keywords_in string | keywords_not_in string | title string | abstract string | PMC_ID string | sub_domains string | primary_domain string |
|---|---|---|---|---|---|---|
['nanocurcumin', 'NF-ΞΊB', 'Bax', 'DNA degradation', 'gene expressions'] | ['CYP450', 'IL-10'] | Prophylactic Administration of Nanocurcumin Abates the Incidence of Liver Toxicity Induced by an Overdose of Copper Sulfate: Role of CYP4502E1, NF-ΞΊB and Bax Expressions | The consequences of excess copper in human tissue are the alterations in the oxidative stress markers and peroxidative damage of membrane lipids. Unselective copper binding may be the clue to damaging impact to protein construction and hence modifying their biological functions. The aim of this study is to match the hepatoprotective efficacy of curcumin (CM) or nanocurcumin (NCM) with that of desferrioxamine (DSF; standard heavy metal chelator) against toxic doses of copper sulphate (CuSO 4 ). All treatments were given simultaneously with CuSO 4 for 7 days. CuSO 4 administration elevated serum alanine transaminase, and hepatic nitric oxide (NO), lipid peroxide, and caspase-3 as well as protein expression of cytochrome P4502E1, and nuclear factor-ΞΊB (NF-ΞΊB) and Bax gene expressions. On the other hand, hepatic levels of reduced glutathione, superoxide dismutase, and interleukin-10 were decreased, whereas DNA degradation was increased as well compared with the control group. The administration of the aforementioned antioxidants ameliorated all the previous altered measured parameters. Interestingly, NCM achieved the most pronounced hepatoprotective effect nearly equivalent to that of DSF. It was concluded that NCM is considered a promising candidate against CuSO 4 toxicity, and cytochrome P450, NF-ΞΊB, and Bax are involved in its toxicity and treatment. | PMC6302274 | ['genomics'] | ['genomics'] |
['Toxoplasma gondii', 'Seroprevalence', 'Heart disease', 'Case-control study', 'Alcohol'] | ['Epidemiology'] | Association Between Toxoplasma gondii Exposure and Heart Disease: A Case-Control Study | The parasite Toxoplasma gondii causes infections all around the world. Infections with T. gondii are systemic and the parasite can persist in the heart muscle. Very little is known about the impact of T. gondii on patients with heart disease. We determined the association between T. gondii exposure and patients suffering from heart diseases attending in a public hospital in Durango, Mexico; the association of T. gondii exposure with socio-demographic, behavioral, and clinical characteristics of these patients was also investigated. Through a case-control study, we examined the seroprevalence of anti- T. gondii IgG and IgM antibodies in 400 patients with heart diseases and 400 age- and gender-matched controls using enzyme-linked immunoassays. In addition, we analyzed the association of patient characteristics as determined by a standardized questionnaire with T. gondii exposure by bivariate and multivariate analyses. Fifty-five (13.8%) of 400 patients and 32 (8.0%) of 400 controls had anti- T. gondii IgG antibodies (odds ratio (OR) = 1.83; 95% confidence interval (CI): 1.15 - 2.90; P = 0.01). High anti- T. gondii IgG levels (> 150 IU/mL) were found in 28 (50.9%) of the 55 positive cases and in 14 (43.8%) of the 32 positive controls (P = 0.51). Anti- T. gondii IgM antibodies were found in 13 (23.6%) of the 55 anti- T. gondii IgG positive patients and in 19 (59.4%) of 32 anti- T. gondii IgG positive controls (OR = 0.21; 95% CI: 0.08 - 0.54; P = 0.0008). Multivariate analysis showed that T. gondii exposure was positively associated with being born out of Durango State (OR = 2.93; 95% CI: 1.40 - 6.13; P = 0.004), and with consumption of alcohol (OR = 2.04; 95% CI: 1.01 - 4.12; P = 0.04). Results obtained in this study indicate that T. gondii infection is associated with heart disease, and suggest that heart disease might be related with a chronic infection. This is the first report of an association of T. gondii exposure with alcohol consumption in this population. Results warrant for further research to determine the epidemiological impact of T. gondii exposure on patients with heart diseases. Risk factors associated with T. gondii exposure are critical to design future prevention strategies against T. gondii exposure. | PMC4817581 | ['epidemiology'] | ['epidemiology'] |
['4-hydroxyisoleucine', 'cyclooxygenase-2', 'microsomal prostaglandin E synthase-2', 'phytic acid', 'tyrosinase'] | ['molecular docking'] | Molecular Docking Analysis of Phytic Acid and 4-hydroxyisoleucine as Cyclooxygenase-2, Microsomal Prostaglandin E Synthase-2, Tyrosinase, Human Neutrophil Elastase, Matrix Metalloproteinase-2 and -9, Xanthine Oxidase, Squalene Synthase, Nitric Oxide Synthase, Human Aldose Reductase, and Lipoxygenase Inhibitors | The phytoconstituents phytic acid and 4-hydroxyisoleucine have been reported to posses various biological properties. This prompted us to carry out the docking study on these two ligands (phytic acid & 4-hydroxyisoleucine) against eleven targeted enzymes. Phytic acid & 4-hydroxyisoleucine were evaluated on the docking behaviour of cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-2 (mPGES-2), tyrosinase, human neutrophil elastase (HNE), matrix metalloproteinase (MMP 2 and 9), xanthine oxidase (XO), squalene synthase (SQS), nitric oxide synthase (NOS), human aldose reductase (HAR) and lipoxygenase (LOX) using Discovery Studio Version 3.1 (except for LOX, where Autodock 4.2 tool was used). Docking and binding free energy analysis revealed that phytic acid exhibited the maximum binding energy for four target enzymes such as COX-2, mPGES-2, tyrosinase and HNE. Interestingly, we found that 4-hydroxyisoleucine has the potential to dock and bind with all of the eleven targeted enzymes. This present study has paved a new insight in understanding 4-hydroxyisoleucine as potential inhibitor against COX-2, mPGES-2, tyrosinase, HNE, MMP 2, MMP 9, XO, SQS, NOS, HAR and LOX. 4-hydroxyisoleucine has the potential to dock and bind with all 11targeted enzymes such as (cyclooxygenase-2 [COX-2], microsomal prostaglandin E synthase-2 [mPGES-2], tyrosinase, human neutrophil elastase [HNE], matrix metalloproteinase [MMP-2 and -9], xanthine oxidase, squalene synthase, nitric oxide synthase, human aldose reductase, and lipoxygenase) Moreover, docking studies and binding free energy calculations revealed that phytic acid exhibited the maximum binding energy for four target enzymes such as COX-2, mPGES-2, tyrosinase, and HNE; however, for other six target enzymes, it fails to dock. 4-hydroxyisoleucine has the potential to dock and bind with all 11targeted enzymes such as (cyclooxygenase-2 [COX-2], microsomal prostaglandin E synthase-2 [mPGES-2], tyrosinase, human neutrophil elastase [HNE], matrix metalloproteinase [MMP-2 and -9], xanthine oxidase, squalene synthase, nitric oxide synthase, human aldose reductase, and lipoxygenase) Moreover, docking studies and binding free energy calculations revealed that phytic acid exhibited the maximum binding energy for four target enzymes such as COX-2, mPGES-2, tyrosinase, and HNE; however, for other six target enzymes, it fails to dock. Abbreviations used: COX-2: Cyclooxygenase-2, mPGES-2: Microsomal prostaglandin E synthase-2, HNE: Human neutrophil elastase, MMP-2 and -9: Matrix metalloproteinase-2 and -9, XO: Xanthine oxidase, SQS: Squalene synthase, NOS: Nitric oxide synthase, HAR: Human aldose reductase, LOX: Lipoxygenase, ADME: Absorption, distribution, metabolism, and excretion, TOPKAT: Toxicity Prediction by Computer-assisted Technology. | PMC5669090 | ['drug_discovery'] | ['drug_discovery'] |
['norovirus', 'surveillance network', 'outbreaks', 'viruses', 'CaliciNet', 'United States'] | ['gastroenteritis', 'research'] | Novel Surveillance Network for Norovirus Gastroenteritis Outbreaks, United States 1 | TOC Summary: The launch of CaliciNet in March 2009 was a milestone. CaliciNet, the outbreak surveillance network for noroviruses in the United States, was launched in March 2009. As of January 2011, twenty state and local health laboratories had been certified to submit norovirus sequences and epidemiologic outbreak data to CaliciNet. During the networkβs first year, 552 outbreaks were submitted to CaliciNet, of which 78 (14%) were associated with foodborne transmission. A total of 395 (72%) outbreaks were typed as GII.4, of which 298 (75%) belonged to a new variant, GII.4 New Orleans, which first emerged in October 2009. Analysis of the complete capsid and P2 region sequences confirmed that GII.4 New Orleans is distinct from previous GII.4 variants, including GII.4 Minerva (2006b). | PMC3381557 | ['epidemiology'] | ['epidemiology'] |
['West Nile virus', 'Core protein', 'Flaviviruses', 'Genome cyclization', 'RNA chaperoning'] | ['CS, conserved sequence', 'DAR, downstream AUG region', 'DB, dumbbell-like structure', 'DENV, dengue virus', 'JEV, Japanese encephalitis virus', 'ORF, open reading frame', 'RdRp, RNA-dependent RNA polymerase', 'sfRNA, subgenomic flavivirus RNA', 'TBEV, tick-borne encephalitis virus', 'UAR, upstream AUG region', 'UTR, untranslated region', 'WNV, West Nile virus', 'YFV, yellow fever virus', 'Viral replication'] | Core protein-mediated 5β²β3β² annealing of the West Nile virus genomic RNA in vitro | βΊ WNV is a member of the flavivirus family. βΊ Alexander the Great died of WNV infection in Babylon, around 325 years BC. βΊ WNV core protein mediates genomic RNA circularization by virtue of its RNA chaperoning activity. Genome cyclization through conserved RNA sequences located in the 5β² and 3β² terminal regions of flavivirus genomic RNA is essential for virus replication. Although the role of various cis -acting RNA elements in panhandle formation is well characterized, almost nothing is known about the potential contribution of protein cofactors to viral RNA cyclization. Proteins with nucleic acid chaperone activities are encoded by many viruses ( e.g. , retroviruses, coronaviruses) to facilitate RNA structural rearrangements and RNAβRNA interactions during the viral replicative cycle. Since the core protein of flaviviruses is also endowed with potent RNA chaperone activities, we decided to examine the effect of West Nile virus (WNV) core on 5β²β3β² genomic RNA annealing in vitro . Core protein binding resulted in a dramatic, dose-dependent increase in 5β²β3β² complex formation. Mutations introduced in either the UAR (upstream AUG region) or CS (conserved sequence) elements of the viral RNA diminished core protein-dependent annealing, while compensatory mutations restored the 5β²β3β² RNA interaction. The activity responsible for stimulating RNA annealing was mapped to the C-terminal RNA-binding region of WNV core protein. These results indicate that core protein β besides its function in viral particle formation β might be involved in the regulation of flavivirus genomic RNA cyclization, and thus virus replication. | PMC7172325 | ['genomics'] | ['genomics'] |
['Clopidogrel', 'Diabetes', 'Aspirin', 'Meta-analysis', 'Randomized controlled trial'] | [] | Long-term effect of clopidogrel in patients with and without diabetes: A systematic review and meta-analysis of randomized controlled trials | Previous studies have shown that patients with diabetes mellitus (DM) respond poorly to clopidogrel treatment. To systematically evaluate the efficacy of clopidogrel for the treatment of acute coronary syndromes or ischemic stroke in patients with or without DM. PubMed, the Cochrane Central Register of Controlled Trials, and EMBASE were searched from 1980 on 27 June 2019 to identify relevant randomized controlled trials that compared the effect of a combination of clopidogrel and aspirin with aspirin alone. A random-effects meta-analysis was used to estimate the hazard ratio (HR) and its 95% confidence interval (CI). Sensitivity analysis was performed using a fixed-effect model. The I 2 statistic was used to evaluate the heterogeneity of the study data. Six randomized controlled trials, comprising 43352 participants (13491 with and 29861 without DM) who had received antiplatelet therapy for β₯ 3 mo, were included in the meta-analysis. Compared with aspirin alone, a combination of clopidogrel and aspirin significantly reduced the risk of any cardiovascular event in patients without DM (HR = 0.78, 95%CI: 0.71β0.86, P < 0.001; I 2 = 23%, P = 0.26). Clopidogrel plus aspirin also significantly reduced cardiovascular risk in patients with DM, although the effect was smaller (HR = 0.89, 95%CI: 0.81β0.99, P = 0.030; I 2 = 0%, P = 0.74). Nevertheless, there was no significant difference in the efficacy of clopidogrel at reducing the risk of cardiovascular events in patients with DM vs those without ( P for interaction = 0.062). Thus, the present study shows that the addition of clopidogrel to aspirin significantly lowers cardiovascular risk in patients with or without DM who have experienced ischemic cardiovascular disease. The beneficial effect of the addition of clopidogrel to aspirin for patients with DM was lower than that in patients without DM, although the modifying effect of DM did not reach significance. | PMC7156296 | ['clinical_trials'] | ['clinical_trials'] |
['Chicken', 'Coronavirus', 'Infectious bronchitis virus', 'Immune response', 'Genome-wide association study', 'Single nucleotide polymorphism'] | [] | A genome-wide association study identifies major loci affecting the immune response against infectious bronchitis virus in chicken | β’ The genetic basis of host responses to infectious bronchitis virus is unclear. β’ We detected 20 significant markers for the antibody response to infectious bronchitis virus in chicken. β’ Loci on chromosomes 1 and 5 explained 12% and 13% of phenotypic variation. β’ The host immune response cluster had 13 beta-defensin and interleukin-17F genes. β’ Our results will contribute to the control of outbreaks of infectious bronchitis. The genetic basis of host responses to infectious bronchitis virus is unclear. We detected 20 significant markers for the antibody response to infectious bronchitis virus in chicken. Loci on chromosomes 1 and 5 explained 12% and 13% of phenotypic variation. The host immune response cluster had 13 beta-defensin and interleukin-17F genes. Our results will contribute to the control of outbreaks of infectious bronchitis. Coronaviruses are a hot research topic because they can cause severe diseases in humans and animals. Infectious bronchitis virus (IBV), belonging to gamma-coronaviruses, causes a highly infectious respiratory viral disease and can result in catastrophic economic losses to the poultry industry worldwide. Unfortunately, the genetic basis of the host immune responses against IBV is poorly understood. In the present study, the antibody levels against IBV post-immunization were measured by an enzyme-linked immunosorbent assay in the serum of 511 individuals from a commercial chicken ( Gallus gallus ) population. A genome-wide association study using 43,211 single nucleotide polymorphism markers was performed to identify the major loci affecting the immune response against IBV. This study detected 20 significant ( P <Β 1.16Β ΓΒ 10 β6 ) effect single nucleotide polymorphisms for the antibody level against IBV. These single nucleotide polymorphisms were distributed on five chicken chromosomes (GGA), involving GGA1, GGA3, GGA5, GGA8, and GGA9. The genes in the 1-Mb windows surrounding each single nucleotide polymorphism with significant effect for the antibody level against IBV were associated with many biological processes or pathways related to immunity, such as the defense response and mTOR signaling pathway. A genomic region containing a cluster of 13 beta-defensin ( GAL1 β 13 ) and interleukin-17F genes on GGA3 probably plays an important role in the immune response against IBV. In addition, the major loci significantly associated with the antibody level against IBV on GGA1 and GGA5 could explain about 12% and 13% of the phenotypic variation, respectively. This study suggested that the chicken genome has several important loci affecting the immune response against IBV, and increases our knowledge of how to control outbreaks of infectious bronchitis. | PMC7106259 | ['genomics'] | ['genomics'] |
['cancer', 'incidence', 'predictions', 'demography', 'risk'] | [] | Predictions of cancer incidence in Wielkopolska in 2018 | The cancer incidence in Wielkopolska in 2008 was one of the highest in the country and was higher than in Poland by 21% in men and by 14% in women. We can quantify the future burden of cancer from two different perspectives: the number of new cancer cases due to population change and new cases due to risk change. Making predictions of number of new cancer cases in Wielkopolska in 2018. These projections of number of cancer cases, age specific rates and age-standardized rates for 2018 (all cancers and the most frequent cancers for men and women) has been based on the historical trends of cancer incidence in Wielkopolska in 1999-2008 and demographical prognosis of Central Statistical Office using the method of Hakulinen and Dyba. There will be over 8000 new cancer cases in men in Wielkopolska in 2018 and over 7000 in women. Compare to the period 2004-2008 the number of cancer cases will increase by 45% for men and by nearly 30% for women. About 2/3 of the increase in Wielkopolska is predicted to be connected with demography change, 1/3 with risk change. The predicted increase of number of cancer cases in Wielkopolska in 2018 will be the result of: changes in the population (bigger impact of the older age groups), an influence of the risk factors (mainly smoking) and a participation in the screening programs. | PMC3687375 | ['epidemiology'] | ['epidemiology'] |
['Emergency room', 'infection', 'pediatric hospital', 'respiratory', 'transmission', 'viral'] | ['nosocomial'] | Extremely low risk for acquisition of a respiratory viral infection in the emergency room of a large pediatric hospital during the winter season | Please cite this paper as: Maltezou etΒ al. (2012). Extremely low risk for acquisition of a respiratory viral infection in the emergency room of a large pediatric hospital during the winter season. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750β2659.2012.00355.x. The aim of this study was to investigate the rate of transmission of respiratory viral infections to children visiting the emergency room of a large pediatric hospital during winter. A total of 615 children were prospectively studied. Twentyβtwo (3Β·6%) children developed at least one symptom compatible with a respiratory viral infection within 1β7βdays after the visit, including cough (12 children), fever (8), rhinorrhea (7), and/or respiratory distress (1). Three children (0Β·49%) developed an influenzaβlike illness. These findings indicate that transmission of respiratory viral infections to children visiting an emergency room during the winter season is extremely low. | PMC5780729 | ['epidemiology'] | ['epidemiology'] |
['Coronary Reperfusion', 'Cyclooxygenase-2', 'Troponin', 'Myocardial Infarction', 'Rofecoxib'] | [] | Selective Cyclooxygenase-2 Inhibition Protects Against Myocardial Damage in Experimental Acute Ischemia | Acute myocardial infarction is associated with tissue inflammation. Early coronary reperfusion clearly improves the outcome but may help propagate the inflammatory response and enhance tissue damage. Cyclooxygenase-2 is an enzyme that catalyzes the initial step in the formation of inflammatory prostaglandins from arachidonic acid. Cyclooxygenase-2 levels are increased when ischemic cardiac events occur. The overall function of COX-2 in the inflammatory process generated by myocardial ischemic damage has not yet been elucidated. The objective of this study was to determine whether a selective cyclooxygenase-2 inhibitor (rofecoxib) could alter the evolution of acute myocardial infarction after reperfusion. This study was performed with 48 mongrel dogs divided into two groups: controls and those treated with the drug. All animals were prepared for left anterior descending coronary artery occlusion. The dogs then underwent 180 minutes of coronary occlusion, followed by 30 minutes of reperfusion. Blood samples were collected from the venous sinus immediately before coronary occlusion and after 30 minutes of reperfusion for measurements of CPK-MB, CPK-MBm and troponin I. During the experiment we observed the mean blood pressure, heart rate and coronary flow. The coronary flow and heart rate did not change, but in the control group, there was blood pressure instability, in addition to maximal levels of CPK-MB post-infarction. The same results were observed for CPK-MBm and troponin I. In a canine model of myocardial ischemia-reperfusion, selective inhibition of Cyclooxygenase-2 with rofecoxib was not associated with early detrimental effects on the hemodynamic profile or the gross extent of infarction; in fact, it may be beneficial by limiting cell necrosis. | PMC2666458 | ['clinical_trials'] | ['clinical_trials'] |
['Γ
land eye disease', 'iCSNB', 'CACNA1F', 'CABP4', 'prevalence'] | ['CSNB2A', 'OCT'] | Clinical Characteristics, Mutation Spectrum, and Prevalence of Γ
land Eye Disease/Incomplete Congenital Stationary Night Blindness in Denmark | To assess clinical characteristics, foveal structure, mutation spectrum, and prevalence rate of Γ
land eye disease (AED)/incomplete congenital stationary night blindness (iCSNB). A retrospective survey included individuals diagnosed with AED at a national low-vision center from 1980 to 2014. A subset of affected males underwent ophthalmologic examinations including psychophysical tests, full-field electroretinography, and spectral-domain optical coherence tomography. Over the 34-year period, 74 individuals from 35 families were diagnosed with AED. Sixty individuals from 29 families participated in a follow-up study of whom 59 harbored a CACNA1F mutation and 1 harbored a CABP4 mutation. Among the subjects with a CACNA1F mutation, subnormal visual acuity was present in all, nystagmus was present in 63%, and foveal hypoplasia was observed in 25/43 subjects. Foveal pit volume was significantly reduced as compared to normal ( P < 0.0001). Additionally, outer segment length at the fovea was measured in 46 subjects and found to be significantly reduced as compared to normal ( P < 0.001). Twenty-nine CACNA1F variations were detected among 34 families in the total cohort, and a novel CABP4 variation was identified in one family. The estimated mean birth prevalence rate was 1 per 22,000 live-born males. Our data support the viewpoint that AED, iCSNB, and X-linked coneβrod dystrophy 3 are designations that refer to a broad, continuous spectrum of clinical appearances caused in the majority by a variety of mutations in CACNA1F . We argue that the original designation AED should be used for this entity. | PMC5215230 | ['epidemiology'] | ['epidemiology'] |
['SARS-CoV-2', 'nanopore sequencing', 'influenza', 'wastewater', 'isothermal amplification', 'adenovirus', 'mutation surveillance', 'co-infection'] | ['variant virus sequencing', 'real-time pathogen detection'] | Simultaneous detection and mutation surveillance of SARS-CoV-2 and multiple respiratory viruses by rapid field-deployable sequencing | Strategies for monitoring the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are crucial for combating the pandemic. Detection and mutation surveillance of SARS-CoV-2 and other respiratory viruses require separate and complex workflows that rely on highly specialized facilities, personnel, and reagents. To date, no method can rapidly diagnose multiple viral infections and determine variants in a high-throughput manner. We describe a method for multiplex isothermal amplification-based sequencing and real-time analysis of multiple viral genomes, termed nanopore sequencing of isothermal rapid viral amplification for near real-time analysis (NIRVANA). It can simultaneously detect SARS-CoV-2, influenza A, human adenovirus, and human coronavirus and monitor mutations for up to 96 samples in real time. NIRVANA showed high sensitivity and specificity for SARS-CoV-2 in 70 clinical samples with a detection limit of 20 viral RNA copies per ΞΌL of extracted nucleic acid. It also detected the influenza A co-infection in two samples. The variant analysis results of SARS-CoV-2-positive samples mirror the epidemiology of coronavirus disease 2019 (COVID-19). Additionally, NIRVANA could simultaneously detect SARS-CoV-2 and pepper mild mottle virus (PMMoV) (an omnipresent virus and water-quality indicator) in municipal wastewater samples. NIRVANA provides high-confidence detection of both SARS-CoV-2 and other respiratory viruses and mutation surveillance of SARS-CoV-2 on the fly. We expect it to offer a promising solution for rapid field-deployable detection and mutational surveillance of pandemic viruses. M.L. is supported by KAUST Office of Sponsored Research (BAS/1/1080-01). This work is supported by KAUST Competitive Research Grant (URF/1/3412-01-01; M.L. and J.C.I.B.) and Universidad Catolica San Antonio de Murcia (J.C.I.B.). A.M.H. is supported by Saudi Ministry of Education (project 436). It is challenging to simultaneously identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and detect viral mutations. Bi etΒ al. develop a convenient sequencing-based method that can simultaneously detect SARS-CoV-2, influenza A (FluA), human adenovirus, and human coronavirus and monitor viral mutations for up to 96 samples in real time. The method not only showed high sensitivity and specificity for SARS-CoV-2 in 70 clinical samples but also detected cases of FluA co-infection. Additionally, it could simultaneously detect SARS-CoV-2 and other viruses in municipal wastewater samples. This rapid and field-deployable method promises to help contain the spread of coronavirus disease 2019 (COVID-19) and ensure the effectiveness of current vaccines. Bi etΒ al. develop a convenient sequencing-based method that can simultaneously detect SARS-CoV-2, influenza A, human adenovirus, and human coronavirus and monitor viral mutations for up to 96 samples in real time. This rapid and field-deployable method promises to help contain the spread of COVID-19 and ensure the effectiveness of vaccines. | PMC8011639 | ['genomics', 'epidemiology'] | ['genomics' |
['mortality', 'myocardial infarction', 'revascularization', 'survival', 'Revascularization'] | ['elderly', 'Mortality/Survival', 'Cardiovascular Disease'] | LongβTerm Mortality of Older Patients With Acute Myocardial Infarction Treated in US Clinical Practice | There is limited information about the longβterm survival of older patients after myocardial infarction ( MI ). CRUSADE (Can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines) was a registry of MI patients treated at 568 US hospitals from 2001 to 2006. We linked MI patients aged β₯65Β years in CRUSADE to their Medicare data to ascertain longβterm mortality (defined as 8 years post index event). Longβterm unadjusted KaplanβMeier mortality curves were examined among patients stratified by revascularization status. A landmark analysis conditioned on surviving the first year postβ MI was conducted. We used multivariable Cox regression to compare mortality risks between STβsegmentβelevation myocardial infarction and nonβSTβsegmentβelevation myocardial infarction patients. Among 22Β 295 MI patients β₯ age 65 years (median age 77Β years), we observed high rates of evidenceβbased medication use at discharge: aspirin 95%, Ξ²βblockers 94%, and statins 81%. Despite this, mortality rates were high: 24% at 1Β year, 51% at 5Β years, and 65% at 8Β years. Eightβyear mortality remained high among patients who underwent percutaneous coronary intervention (49%), coronary artery bypass graft (46%), and among patients who survived the first year postβ MI (59%). Median survival was 4.8Β years (25th, 75th percentiles 1.1, 8.5); among patients aged 65β74Β years it was 8.2Β years (3.3, 8.9) while for patients aged β₯75Β years it was 3.1Β years (0.6, 7.6). Eightβyear mortality was lower among STβsegmentβelevation myocardial infarction than nonβSTβsegmentβelevation myocardial infarction patients (53% versus 67%); this difference was not significant after adjustment (hazard ratio 0.94, 95% confidence interval, 0.88β1.00). Longβterm mortality remains high among patients with MI in routine clinical practice, even among revascularized patients and those who survived the first year. | PMC6064921 | ['clinical_trials'] | ['clinical_trials'] |
['hemolytic uremic syndrome', 'Shiga toxin', 'thrombotic microangiopathy', 'Escherichia coli', 'Shiga toxinβproducing Escherichia coli', 'STEC', 'France'] | ['E. coli', 'bacteria', 'enteric infections', 'food-borne infections', 'food safety', 'HUS'] | Shiga ToxinβAssociated Hemolytic Uremic Syndrome in Adults, France, 2009β2017 | We conducted a retrospective study on hemolytic uremic syndrome caused by Shiga toxinβproducing Escherichia coli (STEC) in 96 adults enrolled in the cohort of the National Reference Center for Thrombotic Microangiopathies network in France during 2009β2017. Most infections were caused by STEC strains not belonging to the O157 or O104 serogroups. Thirty (31.3%) patients had multiple risk factors for thrombotic microangiopathy. In total, 61 (63.5%) patients required dialysis, 50 (52.1%) had a serious neurologic complication, 34 (35.4%) required mechanical ventilation, and 19 (19.8%) died during hospitalization. We used multivariate analysis to determine that the greatest risk factors for death were underlying immunodeficiency (hazard ratioΒ 3.54) and severe neurologic events (hazard ratioΒ 3.40). According to multivariate analysis and propensity score-matching, eculizumab treatment was not associated with survival. We found that underlying conditions, especially immunodeficiency, are strongly associated with decreased survival in adults who have hemolytic uremic syndrome caused by STEC. | PMC8237898 | ['clinical_trials'] | ['clinical_trials'] |
['Influenza', 'vaccine', 'quadrivalent influenza vaccine', 'immunogenicity', 'safety'] | ['elderly'] | Safety and immunogenicity of a quadrivalent influenza vaccine in adults 65Β y of age and older | Frequent mismatches between the predominant circulating B strain lineage and the B strain lineage in trivalent influenza vaccines have resulted in missed opportunities to prevent influenza illness. Quadrivalent influenza vaccines containing B strains from each of the 2 lineages have been developed for improved prevention of influenza B infections. Here, we describe the results of a phase III, randomized, double-blind, active-controlled, multicenter trial examining the safety and immunogenicity of a split-virion inactivated quadrivalent influenza vaccine (IIV4) in 675 adults β₯ 65Β y of age (NCT01218646). Participants were randomly assigned 1:1:1 to receive a single intramuscular injection with the investigational IIV4, or one of 2 split-virion trivalent inactivated influenza vaccines (IIV3s): a licensed IIV3 containing a B Victoria-lineage strain or an investigational IIV3 containing a B Yamagata-lineage strain. Post-vaccination (day 21) hemagglutinin inhibition titers to all strains induced by IIV4 were statistically non-inferior to those induced by the 2 IIV3s. In addition, for each B strain, rates of seroconversion in the IIV4 group were superior to those induced by the comparator IIV3 not containing that B strain. For all vaccines, the most common solicited reaction was injection-site pain, and most reactions were mild to moderate in intensity and transient. Overall safety profiles were similar between IIV4 and the IIV3s, and no vaccine-related serious adverse events were reported. These results confirm that in adults β₯ 65Β y of age, IIV4 was well tolerated and immunogenic against the additional B lineage strain without compromising the immunogenicity of the other 3 vaccine strains. | PMC5612218 | ['clinical_trials'] | ['clinical_trials'] |
['randomized', 'double-blinded', 'placebo-controlled', 'crossover trial', 'hydrogen gas', '8-OHdG', 'oxidative stress', 'hormesis'] | ["Parkinson's disease", 'smell test', '8-hydroxy-2β- deoxyguanine'] | Inhalation of hydrogen gas elevates urinary 8-hydroxy-2β²-deoxyguanine in Parkinsonβs disease | Hyposmia is one of the earliest and the most common symptoms in Parkinsonβs disease (PD). The benefits of hydrogen water on motor deficits have been reported in animal PD models and PD patients, but the effects of hydrogen gas on PD patients have not been studied. We evaluated the effect of inhalation of hydrogen gas on olfactory function, non-motor symptoms, activities of daily living, and urinary 8-hydroxy-2β²-deoxyguanine (8-OHdG) levels by a randomized, double-blinded, placebo-controlled, crossover trial with an 8-week washout period in 20 patients with PD. Patients inhaled either ~1.2β1.4% hydrogen-air mixture or placebo for 10 minutes twice a day for 4 weeks. Inhalation of low dose hydrogen did not significantly influence the PD clinical parameters, but it did increase urinary 8-OHdG levels by 16%. This increase in 8-OHdG is markedly less than the over 300% increase in diabetes, and is more comparable to the increase after a bout of strenuous exercise. Although increased reactive oxygen species is often associated with toxicity and disease, they also play essential roles in mediating cytoprotective cellular adaptations in a process known as hormesis. Increases of oxidative stress by hydrogen have been previously reported, along with its ability to activate the Nrf2, NF-ΞΊB pathways, and heat shock responses. Although we did not observe any beneficial effect of hydrogen in our short trial, we propose that the increased 8-OHdG and other reported stress responses from hydrogen may indicate that its beneficial effects are partly or largely mediated by hormetic mechanisms. The study was approved by the ethics review committee of Nagoya University Graduate School of Medicine (approval number 2015-0295). The clinical trial was registered at the University Hospital Medical Information Network (identifier UMIN000019082). | PMC6352570 | ['clinical_trials'] | ['clinical_trials'] |
['methanotrophs', 'Methylocystis', 'finished genome', 'methane monooxygenase', 'nitrogenase'] | ['comparative genomics'] | Unusual Genomic Traits Suggest Methylocystis bryophila S285 to Be Well Adapted for Life in Peatlands | The genus Methylocystis belongs to the class Alphaproteobacteria , the family Methylocystaceae , and encompasses aerobic methanotrophic bacteria with the serine pathway of carbon assimilation. All Methylocystis species are able to fix dinitrogen and several members of this genus are also capable of using acetate or ethanol in the absence of methane, which explains their wide distribution in various habitats. One additional trait that enables their survival in the environment is possession of two methane-oxidizing isozymes, the conventional particulate methane monooxygenase (pMMO) with low-affinity to substrate (pMMO1) and the high-affinity enzyme (pMMO2). Here, we report the finished genome sequence of Methylocystis bryophila S285, a pMMO2-possessing methanotroph from a Sphagnum -dominated wetland, and compare it to the genome of Methylocystis sp. strain SC2, which is the first methanotroph with confirmed high-affinity methane oxidation potential. The complete genome of Methylocystis bryophila S285 consists of a 4.53βMb chromosome and one plasmid, 175βkb in size. The genome encodes two types of particulate MMO (pMMO1 and pMMO2), soluble MMO and, in addition, contains a pxmABC -like gene cluster similar to that present in some gammaproteobacterial methanotrophs. The full set of genes related to the serine pathway, the tricarboxylic acid cycle as well as the ethylmalonyl-CoA pathway is present. In contrast to most described methanotrophs including Methylocystis sp. strain SC2, two different types of nitrogenases, that is, molybdenumβiron and vanadiumβiron types, are encoded in the genome of strain S285. This unique combination of genome-based traits makes Methylocystis bryophila well adapted to the fluctuation of carbon and nitrogen sources in wetlands. | PMC5808792 | ['genomics'] | ['genomics'] |
['RNA viruses', 'DNA viruses', 'marine', 'seawater', 'abundance'] | ['virioplankton', 'metagenome'] | Are we missing half of the viruses in the ocean? | Viruses are abundant in the ocean and a major driving force in plankton ecology and evolution. It has been assumed that most of the viruses in seawater contain DNA and infect bacteria, but RNA-containing viruses in the ocean, which almost exclusively infect eukaryotes, have never been quantified. We compared the total mass of RNA and DNA in the viral fraction harvested from seawater and using data on the mass of nucleic acid per RNA- or DNA-containing virion, estimated the abundances of each. Our data suggest that the abundance of RNA viruses rivaled or exceeded that of DNA viruses in samples of coastal seawater. The dominant RNA viruses in the samples were marine picorna-like viruses, which have small genomes and are at or below the detection limit of common fluorescence-based counting methods. If our results are typical, this means that counts of viruses and the rate measurements that depend on them, such as viral production, are significantly underestimated by current practices. As these RNA viruses infect eukaryotes, our data imply that protists contribute more to marine viral dynamics than one might expect based on their relatively low abundance. This conclusion is a departure from the prevailing view of viruses in the ocean, but is consistent with earlier theoretical predictions. | PMC3578568 | ['genomics'] | ['genomics'] |
['COVID-19', 'SARS-CoV-2', 'Carrageenan', 'Iota-carrageenan', 'Clinical trial'] | ['Nasal spray'] | The antiviral activity of iota-, kappa-, and lambda-carrageenan against COVID-19: A critical review | There is no specific antiviral treatment available for coronavirus disease 2019 (COVID-19). Among the possible natural constituents is carrageenan, a polymer derived from marine algae that possesses a variety of antiviral properties. The purpose of this review was to summarize the evidence supporting carrageenan subtypes' antiviral activity against the emerging severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19. PubMed/MEDLINE and Google Scholar searches were conducted for publications using the terms βcarrageenanβ, βiota carrageenanβ, βkappa carrageenanβ, lambda-carrageenanβ, 'coronavirus', βcommon coldβ, 'rhinovirus', and βSARS-CoV-2β² search was also done in grey literature to increase our understanding. A search for the word βcarrageenanβ was also carried out. Most of the publications were discussed in narrative. Carrageenan has been shown to have potent antiviral activity against both coronaviruses (coronavirus NL63, SARS-CoV-2) and non-coronaviruses such as dengue virus, herpes simplex virus, cytomegalovirus, vaccinia virus, vesicular stomatitis virus, sindbis virus, human immunodeficiency virus, influenza virus, human papillomavirus, rabies virus, junin virus, tacaribe virus, African swine fever, bovine herpes virus, suid herpes virus, and rhinovirus. No in vivo study has been conducted using carrageenan as an anti-SARS-CoV-2 agent. The majority of the in vivo research was done on influenza, a respiratory virus that causes common cold together with coronavirus. Thus, various clinical trials were conducted to determine the transferability of these in vitro data to clinical effectiveness against SARS-CoV-2. When combined with oral ivermectin, nasally administered iota-carrageenan improved outcome in COVID-19 patients. It is still being tested in clinics for single-dose administration. Though the carrageenan exhibited potent antiviral activity against SARS-CoV-2 and was used to treat COVID-19 under emergency protocol in conjunction with oral medications such as ivermectin, there is no solid evidence from clinical trials to support its efficacy. Thus, clinical trials are required to assess its efficacy for COVID-19 treatment prior to broad application. | PMC8240443 | ['clinical_trials'] | ['clinical_trials'] |
['measles', 'France', 'children', 'adolescents', 'young adults'] | ['epidemiology', 'elimination', 'viruses', 'vaccines', 'immunization', 'Suggested citation for this article: Antona D', 'LΓ©vy-Bruhl D', 'Baudon C', 'Freymuth F', 'Lamy M', 'Maine C', 'et al. Measles elimination efforts and 2008β2011 outbreak', 'France. Emerg Infect Dis [Internet]. 2013 Mar [date cited].http://dx.doi.org/10.3201/eid1903.121360'] | Measles Elimination Efforts and 2008β2011 Outbreak, France | Although few measles cases were reported in France during 2006 and 2007, suggesting the country might have been close to eliminating the disease, a dramatic outbreak of >20,000 cases occurred during 2008β2011. Adolescents and young adults accounted for more than half of cases; median patient age increased from 12 to 16 years during the outbreak. The highest incidence rate was observed in children <1 year of age, reaching 135 cases/100,000 infants during the last epidemic wave. Almost 5,000 patients were hospitalized, including 1,023 for severe pneumonia and 27 for encephalitis/myelitis; 10 patients died. More than 80% of the cases during this period occurred in unvaccinated persons, reflecting heterogeneous vaccination coverage, where pockets of susceptible persons still remain. Although vaccine coverage among children improved, convincing susceptible young adults to get vaccinated remains a critical issue if the target to eliminate the disease by 2015 is to be met. | PMC3647670 | ['epidemiology'] | ['epidemiology'] |
['family cluster', 'outbreak', 'restaurant', 'droplet transmission', '2019 novel coronavirus disease'] | ['COVID-19', 'severe acute respiratory syndrome coronavirus 2', 'SARS-CoV-2', 'viruses', 'respiratory infections', 'zoonoses'] | COVID-19 Outbreak Associated with Air Conditioning in Restaurant, Guangzhou, China, 2020 | During January 26βFebruary 10, 2020, an outbreak of 2019 novel coronavirus disease in an air-conditioned restaurant in Guangzhou, China, involved 3 family clusters. The airflow direction was consistent with droplet transmission. To prevent the spread of the virus in restaurants, we recommend increasing the distance between tables and improving ventilation. | PMC7323555 | ['epidemiology'] | ['epidemiology'] |
['Hemoglobin', 'in-hospital cardiac arrest', 'incidence', 'predictor', 'acute coronary syndrome', 'cardiogenic shock'] | [] | Association of hemoglobin with incidence of in-hospital cardiac arrest in patients with acute coronary syndrome complicated by cardiogenic shock | This study was performed to investigate the association of the admission hemoglobin level with the incidence of in-hospital cardiac arrest (IHCA) in patients with acute coronary syndrome (ACS) complicated by cardiogenic shock (CS). In this retrospective study, we reviewed the medical records of consecutive patients with ACS complicated by CS admitted to the coronary care unit from January 2014 to October 2017. Logistic regression models were carried out to evaluate the association between hemoglobin and the incidence of IHCA. Interaction and subgroup analyses were also performed. In total, 211 patients were included in the study, and 61 (28.9%) patients developed IHCA. In the multivariable analysis, hemoglobin was a strong independent predictor of IHCA (odds ratio, 0.971; 95% confidence interval, 0.954β0.989). In the fully adjusted model, patients in the higher hemoglobin tertile were less likely to develop IHCA than patients in the lowest hemoglobin tertile (odds ratio, 0.194; 95% confidence interval, 0.071β0.530). The relationship remained stable in most subgroups except patients aged β₯70 years. In patients with ACS complicated by CS, the incidence of IHCA is related to the hemoglobin concentration, and a high hemoglobin concentration is a protective factor against the development of IHCA. | PMC6753539 | ['epidemiology'] | ['epidemiology'] |
['Cultural adaptation', 'Depression', 'Internet-based intervention', 'Latin America', 'Randomized Controlled Trial', 'Public Health Care'] | ['AQoL-6D, Assessment of Quality of Life 6 Dimensions', 'APOI, Attitudes Towards Psychological Online Interventions', 'BDI-II, Beck Depression Inventory-II', 'CEQ, Credibility and Expectancy Questionnaire', 'CONSORT, Consolidated Standards of Reporting Trials', 'CRQ, Cultural Relevance Questionnaire', 'CSQ, Client Satisfaction Questionnaire', 'EBPTs, Evidence-Based Psychological Treatments', 'E-SF, Ecuadorian Cultural Version of Smiling is Fun', 'GAD-7, Generalized Anxiety Disorder-7', 'IBIs, Internet-Based Interventions', 'ICERs, Incremental Cost-Effectiveness Ratios', 'ICD-10, International Classification of Diseases-10', 'MCAR, Missing Completely at Random', 'M.I.N.I. 5.0, MINI International Neuropsychiatric Interview 5.0', 'OASIS, Overall Anxiety Severity and Impairment Scale', 'ODSIS, Overall Depression Severity and Impairment Scale', 'PANAS, Positive and Negative Affect Schedule', 'PC, Primary Care', 'PHC, Public Health Care', 'PHQ-9, Patient Health Questionnaire-9', 'QALYs, Quality-Adjusted Life-Years', 'RCI, Reliable Change Index', 'RCT, Randomized Control Trial', 'SPIRIT, Recommendations for Interventional Trials', 'SUS, System Usability Scale', 'TiC-P, Trimbos/iMTA Questionnaire on Costs on Psychiatric Illnesses', 'WL, Waiting List', 'WAI-TECH-SF, Working Alliance Inventory for Online Intervention-Short Form'] | Cultural adaptation of the Smil ing is Fun program for the treatment of depression in the Ecuadorian public health care system: A study protocol for a randomized controlled trial | Depression is one of the world's major health problems. Due to its high prevalence, it constitutes the first cause of disability among the Americas, where only a very low percentage of the population receives the adequate evidence-based psychological treatment. Internet-Based Interventions (IBIs) are a great alternative to reduce the treatment gap for mental disorders. Although there are several studies in low-and middle-income countries proving IBIs' feasibility and acceptability, there is still little evidence of the effectiveness in diverse social and cultural contexts such as Latin America. Two studies will be described: Study 1 is focused on the cultural adaptation of a cognitive-behavioral IBI Smiling is Fun (Botella et al. 2012, 2015) for Ecuadorian population with depression based on the procedure by Salamanca-Sanabria et al. (2018). Study 2 describes the design of a randomized controlled trial to test the preliminary efficacy of the culturally adapted intervention in a Public Health Care setting. A total of 153 patients with mild to moderate degree of depression as assessed with the Mini-International Neuropsychiatric Interview (M.I.N.I.) and the Patient Health Questionnaire-9 (PHQ-9) will be randomly assigned to either an IBI group using only automated support by the system; an IBI group including also minimal human support; or a waiting list group. The primary outcome (depression) and secondary outcomes (e.g., anxiety, affect, quality of life) will be collected at baseline, 3, 6 and 12Β months. Mixed-model analyses with no ad hoc imputations will be conducted. This paper is pioneering in exploring the role of an Internet-based culturally adapted intervention for depression in a public care context in Ecuador. Results obtained will offer new insights into the viability and effectiveness of digital technologies for the psychological treatment of mental illnesses in developing countries. β’ Cultural adaptation of an Internet-based intervention for depression in Ecuador. β’ Efficacy of a culturally adapted intervention in the public health system. β’ Potential of Internet-based interventions in resource-limited health-care countries. Cultural adaptation of an Internet-based intervention for depression in Ecuador. Efficacy of a culturally adapted intervention in the public health system. Potential of Internet-based interventions in resource-limited health-care countries. | PMC7733006 | ['clinical_trials', 'epidemiology'] | ['clinical_trials' |
['Acylspermidine', 'polyamine', 'anticancer', 'RNA-Seq', 'gene expression', 'Jurkat', 'ALL'] | [] | Identification of Deregulated Signaling Pathways in Jurkat Cells in Response to a Novel Acylspermidine Analogue-N 4 -Erucoyl Spermidine | Natural polyamines such as putrescine, spermidine, and spermine are crucial in the cell proliferation and maintenance in all the eukaryotes. However, the requirement of polyamines in tumor cells is stepped up to maintain tumorigenicity. Many synthetic polyamine analogues have been designed recently to target the polyamine metabolism in tumors to induce apoptosis. N 4 -Erucoyl spermidine (designed as N 4 -Eru), a novel acylspermidine derivative, has been shown to exert selective inhibitory effects on both hematological and solid tumors, but its mechanisms of action are unknown. In this study, RNA sequencing was performed to investigate the anticancer mechanisms of N 4 -Eru-treated T-cell acute lymphoblastic leukemia (ALL) cell line (Jurkat cells), and gene expression was examined through different tools. We could show that many key oncogenes including NDRG1, CACNA1G, TGFBR2, NOTCH1,2,3, UHRF1, DNMT1,3, HDAC1,3, KDM3A, KDM4B, KDM4C, FOS , and SATB1 were downregulated, whereas several tumor suppressor genes such as CDKN2AIPNL, KISS1, DDIT3, TP53I13, PPARG, FOXP1 were upregulated. Data obtained through RNA-Seq further showed that N 4 -Eru inhibited the NOTCH/Wnt/JAK-STAT axis. This study also indicated that N 4 -Eru-induced apoptosis could involve several key signaling pathways in cancer. Altogether, our results suggest that N 4 -Eru is a promising drug to treat ALL. | PMC6262497 | ['genomics'] | ['genomics'] |
['Alternate day fasting', 'Blood pressure', 'Cohort study', 'Endothelial function', 'Healthy subjects', 'Intermittent fasting'] | ['Cell death', 'Cell signalling', 'Glucose metabolism', 'Insulin sensitivity'] | Intermittent Fasting (Alternate Day Fasting) in Healthy, Non-obese Adults: Protocol for a Cohort Trial with an Embedded Randomized Controlled Pilot Trial | Alternate day fasting (ADF) is a subtype of intermittent fasting and is defined as a continuous sequence of a fast day (100% energy restriction, zero calories) and a feed day (ad libitum food consumption), resulting in roughly 36-h fasting periods. Previous studies demonstrated weight reductions and improvements of cardiovascular risk factors with ADF in obese subjects. However, rigorous data on potential endocrine, metabolic and cardiovascular effects, besides weight loss, are lacking. Therefore we aim to investigate the short- and mid- to long-term clinical and molecular effects of ADF in healthy non-obese subjects. We will perform a prospective cohort study with an embedded randomized controlled trial (RCT) including 90 healthy subjects. Thirty of them will have performed ADF for at least 6Β months (mid-term group). Sixty healthy subjects without a particular diet before enrolment will serve as the control group. These subjects will be 1:1 randomized to either continuing their current diet or performing ADF for 4Β weeks. All subjects will undergo study procedures that will be repeated in RCT participants after 4Β weeks. These procedures will include assessment of outcome parameters, dual-energy X-ray absorptiometry, measurement of endothelial function, an oral glucose tolerance test, 24-h blood pressure measurement, retinal vessel analysis, echocardiography and physical activity measurement by an accelerometer. Blood, sputum, buccal mucosa and faeces will be collected for laboratory analyses. Participants in the RCT will wear a continuous glucose monitor to verify adherence to the study intervention. The aim of this project is to investigate the effects of ADF on human physiology and molecular cellular processes. This investigation should gain in-depth mechanistic insights into the concept of ADF and form the basis for larger subsequent cohort recruitment and consecutive intervention studies. NCT02673515; registered 24 November 2015. Current protocol date/version: 7 February 2017/version 1.8. | PMC6096974 | ['epidemiology'] | ['epidemiology'] |
['Inflammatory bowel disease', 'Ulcerative colitis', "Crohn's disease", 'Psychiatric disorder', 'Depression', 'Anxiety', 'Prevalence'] | ['Mental health disorder', 'Adjustment disorder', 'Population based analysis'] | Burden of Psychiatric Disorders among Pediatric and Young Adults with Inflammatory Bowel Disease: A Population-Based Analysis | There is increasing prevalence of psychiatric disorders among inflammatory bowel Disease (IBD) population. Further, presence of psychiatric disorders has been shown as an independent predictor of quality of life among patients with IBD. We intended to explore the prevalence of various psychiatric disorders among pediatric and young adult population with IBD as a population-based analysis. We did a retrospective case control analysis using a deidentified cloud-based database including health care data across 26 health care networks comprising of more than 360 hospitals across USA. Data collected across different hospitals were classified and stored according to Systematized Nomenclature of Medicine-Clinical Terms. We preidentified 10 psychiatric disorders and the queried the database for the presence of at least one of the ten psychiatric disorders among IBD patients between 5 and 24 years of age and compared with controls. Total of 11,316,450 patients in the age group between 5 and 24 years and the number of patients with a diagnosis of IBD, Crohn's disease or ulcerative colitis were 58,020. The prevalence of psychiatric disorders was 21.6% among IBD mainly comprising of depression and anxiety disorder. Multiple logistic regression analysis showed, IBD is 5 times more likely associated with psychiatric disorders than controls, p <0.001). We showed a steady increasing trend in the incidence of psychiatric disorders among IBD patients (2% in 2006 to 15% in 2017). Largest population-based analysis demonstrated an increased prevalence of psychiatric disorders among IBD patients. Our study emphasizes the need for psychological and mental health services to be incorporated as a part of the routine IBD clinic. | PMC6856511 | ['epidemiology'] | ['epidemiology'] |
['Glasgow coma scale', 'infarct volume', 'ischemic stroke', 'modified Rankin scale', 'neuron specific enolase'] | [] | Correlation between serum neuron specific enolase and functional neurological outcome in patients of acute ischemic stroke | The use of biomarkers to predict stroke prognosis is gaining particular attention nowadays. Neuron specific enolase (NSE), which is a dimeric isoenzyme of the glycolytic enzyme enolase and is found mainly in the neurons is one such biomarker. This study was carried out on patients of acute ischemic stroke with the aims to determine the correlation between NSE levels on the day of admission with infarct volume, stroke severity, and functional neurological outcome on day 30. Seventy five patients of acute ischemic stroke admitted in the Department of Medicine were included in the study. Levels of NSE were determined on day 1 using the human NSE ELISA kit (Alpha Diagnostic International Texas 78244, USA). Volume of infarct was measured by computed tomography (CT) scan using the preinstalled software Syngo (version A40A) of Siemen's medical solutions (Forchheim, Germany). Stroke severity at admission was assessed using Glasgow coma scale (GCS) and functional neurological outcome was assessed using modified Rankin scale (mRS) on day 30. Statistical analysis was performed using the SPSS software for windows version 15.0 (SPSS). A positive correlation was found between concentration of NSE on day 1 and infarct volume determined by CT scan ( r = 0.955, P < 0.001). A strong negative correlation was found between GCS at presentation and concentration of NSE on day 1 ( r = β0.806, P < 0.001). There was a positive correlation between NSE levels at day 1 and functional neurological outcome assessed by mRS at day 30 ( r = 0.744, P < 0.001). Serum levels of NSE in first few days of ischemic stroke can serve as a useful marker to predict stroke severity and early functional outcome. However, larger studies with serial estimation of NSE are needed to establish these observations more firmly. | PMC3841589 | ['clinical_trials'] | ['clinical_trials'] |
['SARS-CoV-2', 'COVID-19', 'MERS', 'SARS', 'morin', 'molecular docking'] | ['coronaviruses', 'flavonols'] | Flavonol morin targets host ACE2, IMP-Ξ±, PARP-1 and viral proteins of SARS-CoV-2, SARS-CoV and MERS-CoV critical for infection and survival: a computational analysis | A sudden outbreak of a novel coronavirus SARS-CoV-2 in 2019 has now emerged as a pandemic threatening to efface the existence of mankind. In absence of any valid and appropriate vaccines to combat this newly evolved agent, there is need of novel resource molecules for treatment and prophylaxis. To this effect, flavonol morin which is found in fruits, vegetables and various medicinal herbs has been evaluated for its antiviral potential in the present study. PASS analysis of morin versus reference antiviral drugs baricitinib, remdesivir and hydroxychloroquine revealed that morin displayed no violations of Lipinskiβs rule of five and other druglikeness filters. Morin also displayed no tumorigenic, reproductive or irritant effects and exhibited good absorption and permeation through GI (clogP <5). In principal component analysis, morin appeared closest to baricitinib in 3D space. Morin displayed potent binding to spike glycoprotein, main protease 3CLPro and papain-like protease PLPro of SARS-CoV-2, SARS-CoV and MERS-CoV using molecular docking and significant binding to three viral-specific host proteins viz. human ACE2, importin-Ξ± and poly (ADP-ribose) polymerase (PARP)-1, further lending support to its antiviral efficacy. Additionally, morin displayed potent binding to pro-inflammatory cytokines IL-6, 8 and 10 also supporting its anti-inflammatory activity. MD simulation of morin with SARS-CoV-2 3CLPro and PLPro displayed strong stability at 300βK. Both complexes exhibited constant RMSDs of protein side chains and CΞ± atoms throughout the simulation run time. In conclusion, morin might hold considerable therapeutic potential for the treatment and management of not only COVID-19, but also SARS and MERS if studied further. Communicated by Ramaswamy H. Sarma | PMC7869441 | ['drug_discovery'] | ['drug_discovery'] |
['SARS-CoV-2', 'Nsp1', 'drug designing', 'virtual screening', 'docking', 'molecular dynamics simulations'] | ['virulence factors'] | Identification of the binding interactions of some novel antiviral compounds against Nsp1 protein from SARS-CoV-2 (COVID-19) through high throughput screening | The SARS-CoV-2 pandemic has become a global threat. It has become very difficult to control the spreading of the virus. The virus is a RNA virus and the virulence of the virus is mediated by three virulence causing proteins, viz., Nsp1, Nsp3c and ORF7. So far the drug designing endeavors against the virus have been being targeted towards the spike protein which is responsible for the entry of the virus inside human host as well as the RNA dependent RNA polymerase. However, no effective treatment against the virus has so far been developed. In the present situation, an attempt has been made to target the virulence protein factor Nsp1 which binds to the 40S ribosomal subunit of the human host. We tried to target the Nsp1 by in-silico virtual screening of ligand libraries. We built the three dimensional structure of Nsp1 and used the structure to screen the ChEMBL drug library. We used molecular docking simulations of the top6 screened ligands with Nsp1 and subjected the liagnd-Nsp1 complexes to molecular dynamics simulations to analyze the behaviors of the ligands in a virtual cell. From our analysis we could predict that the ligands bearing the ChEMBL identifiers, CHEMBL1096281, CHEMBL2022920, CHEMBL175656, had the best binding affinity values with Nsp1. Therefore, these ligand molecules may be tested in wet-lab for further analysis. This is the first report to target the virulence factor Nsp1 from SARS-CoV-2. Communicated by Ramaswamy H. Sarma | PMC7899154 | ['drug_discovery'] | ['drug_discovery'] |
['cardiovascular disease', 'heart failure', 'highβsensitivity troponin', 'mortality', 'NTβproBNP', 'orthostatic hypotension', 'stroke', 'Heart Failure', 'Myocardial Infarction'] | ['High Blood Pressure', 'Ischemic Stroke', 'Epidemiology'] | Orthostatic Hypotension and Risk of Clinical and Subclinical Cardiovascular Disease in MiddleβAged Adults | Although orthostatic hypotension ( OH ) is a wellβrecognized manifestation of neuropathy and hypovolemia, its contribution to cardiovascular disease ( CVD ) risk is controversial. Participants with OH , defined as a decrease in blood pressure (systolic β₯20Β mmΒ Hg or diastolic β₯10Β mmΒ Hg) from the supine to standing position, were identified during the first visit of the ARIC (Atherosclerosis Risk in Communities) Study (1987β1989) within 2Β minutes of standing. All participants were followed up for the development of myocardial infarction, heart failure, stroke, fatal coronary heart disease ( CHD ), any CHD (combination of silent, nonfatal, and fatal CHD or cardiac procedures), and allβcause mortality. Participants were assessed for carotid intimal thickness and plaque during the first visit. Detectable highβsensitivity troponin T (β₯5Β ng/L) and elevated NTβproBNP (Nβterminal proβBβtype natriuretic peptide; β₯100Β pg/mL) were determined in blood collected during the second visit (1990β1992). All associations were adjusted for known CVD risk factors. In 9139 participants (57% women; 23% black; mean age, 54Β±5.7Β years), 3% had OH . During followβup (median, 26Β years), OH was associated with myocardial infarction (hazard ratio [ HR ], 1.88; 95% confidence interval [ CI ], 1.44β2.46), congestive heart failure ( HR , 1.65; 95% CI , 1.34β2.04), stroke ( HR , 1.83; 95% CI , 1.35β2.48), fatal CHD ( HR , 2.77; 95% CI , 1.93β3.98), any CHD ( HR , 2.00; 95% CI , 1.64β2.44), and allβcause mortality ( HR , 1.68; 95% CI , 1.45β1.95). OH was also associated with carotid intimal thickness (Ξ², 0.05Β mm; 95% CI , 0.04β0.07 mm), carotid plaque (odds ratio, 1.51; 95% CI , 1.18β1.93), detectable highβsensitivity troponin T (odds ratio, 1.49; 95% CI , 1.16β1.93), and elevated NT βpro BNP (odds ratio, 1.92; 95% CI , 1.48β2.49). OH identified in communityβdwelling middleβaged adults was associated with future CVD events and subclinical CVD . Further research is necessary to establish a causal role for OH in the pathogenesis of CVD . | PMC6015335 | ['clinical_trials', 'epidemiology'] | ['clinical_trials' |
['adolescent girls', 'young women', 'transactional sex', 'mediation analysis', 'HIV incidence', 'older partners', 'multiple partners'] | ['causal pathways'] | The Mediating Role of Partner Selection in the Association Between Transactional Sex and HIV Incidence Among Young Women | Supplemental Digital Content is Available in the Text. In sub-Saharan Africa, transactional sex is associated with an increased risk of HIV infection in adolescent girls and young women, but the mechanisms for this relationship remain unclear. We hypothesize that young women who report transactional sex may have multiple partners and older partners, thereby increasing their HIV risk. We used longitudinal data from the HPTN 068 trial in rural South Africa where young women aged 13β20 who were HIV-negative at enrolment (n = 2362) were followed approximately annually for up to 6 years. We used the parametric g-formula to estimate the total effect of time-varying, frequent transactional sex (receipt of gifts/money at least weekly versus monthly or less) on HIV incidence and the controlled direct effect for mediation in a simulated cohort using 20,000 bootstrapped observations. We calculated rates and hazard ratios (HRs) over the entire study period. The HR for the total effect of frequent transactional sex on HIV incidence was 1.56 (95% confidence interval: 1.28 to 1.85). However, this effect was mediated by partner age (>5+) and number of partners (>1) and the HR was attenuated to 1.09 (95% confidence interval: 0.90 to 1.28) when setting both partner age and partner number constant. Both partner age difference and partner number mediate the relationship between transactional sex and incident HIV infection. Through this mediation analysis, we provide important longitudinal evidence to suggest that young women who engage in frequent transactional sex select multiple partners, often older male partners that may be part of higher risk sexual networks. | PMC6970545 | ['epidemiology'] | ['epidemiology'] |
['ST-segment elevation myocardial infarction', 'Duodenal ulcer perforation', 'Primary percutaneous coronary intervention', 'Excimer laser coronary angioplasty', 'Drug-coated stent'] | ['Case report'] | Primary percutaneous coronary intervention without stenting using excimer laser and manual thrombectomy in STEMI with duodenal ulcer perforation: a case report | ST-segment elevation myocardial infarction (STEMI) and peptic ulcer perforation are both medical emergencies that require urgent intervention. In case that these time-sensitive medical emergencies present concomitantly, it remains unclear which one should be treated first. An 85-year-old man with melaena, epigastric pain, and severe anaemia was transferred to our emergency department and diagnosed as having inferior STEMI based on electrocardiogram. Emergency coronary angiography (CAG) revealed severe stenosis with thrombus in the proximal right coronary artery. Immediate oesophagogastroduodenoscopy and abdominal computed tomography detected the presence of duodenal ulcer perforation. Primary percutaneous coronary intervention (PCI) without stenting using excimer laser coronary angioplasty and manual thrombectomy was performed under intravascular ultrasound (IVUS) guidance to avoid dual antiplatelet therapy (DAPT). After successful PCI, the perforated viscus was surgically repaired with a laparoscopic omental patch. On Day 7, endoscopic haemostasis treated the oozing of blood from the duodenal ulcer. On Day 21, follow-up CAG and IVUS showed residual stenosis with organized thrombus in the culprit lesion, in which a drug-coated stent was directly implanted. He was discharged with a favourable clinical course on Day 23. We judged that PCI should take precedence over the surgical repair of perforated duodenal ulcer in our case since STEMI was an immediate life-threatening compared to the perforated viscus which had no active exsanguination. Excimer laser coronary angioplasty with manual thrombectomy might be an adequate option to avoid stent deployment and subsequent DAPT in such complex scenarios. | PMC7793135 | ['clinical_trials'] | ['clinical_trials'] |
['natural language processing', 'big data', 'public health', 'computed tomography', 'chest CT'] | ['machine learning', 'viral outbreak'] | Natural Language Processing and Machine Learning for Detection of Respiratory Illness by Chest CT Imaging and Tracking of COVID-19 Pandemic in the US | Coronavirus disease 2019 (COVID-19) has spread quickly throughout the United States (US) causing significant disruption in healthcare and society. Tools to identify hot spots are important for public health planning. The goal of our study was to determine if natural language processing (NLP) algorithm assessment of thoracic computed tomography (CT) imaging reports correlated with the incidence of official COVID-19 cases in the US. Using de-identified HIPAA compliant patient data from our common imaging platform interconnected with over 2,100 facilities covering all 50 states, we developed three NLP algorithms to track positive CT imaging features of respiratory illness typical in SARS-CoV-2 viral infection. We compared our findings against the number of official COVID-19 daily, weekly and state-wide. The NLP algorithms were applied to 450,114 patient chest CT comprehensive reports gathered from January 1 st to October 3 rd , 2020. The best performing NLP model exhibited strong correlation with daily official COVID-19 cases (r 2 =0.82, p<0.005). The NLP models demonstrated an early rise in cases followed by the increase of official cases, suggesting the possibility of an early predictive marker, with strong correlation to official cases on a weekly basis (r 2 =0.91, p<0.005). There was also substantial correlation between the NLP and official COVID-19 incidence by state (r 2 =0.92, p<0.005). Using big data, we developed a novel machine-learning based NLP algorithm that can track imaging findings of respiratory illness detected on chest CT imaging reports with strong correlation with the progression of the COVID-19 pandemic in the US. | PMC7977750 | ['epidemiology'] | ['epidemiology'] |
['adherence', 'sublingual immunotherapy', 'efficacy', 'cost', 'side effects'] | [] | Adherence issues related to sublingual immunotherapy as perceived by allergists | Sublingual immunotherapy (SLIT) is a viable alternative to subcutaneous immunotherapy to treat allergic rhinitis and asthma, and is widely used in clinical practice in many European countries. The clinical efficacy of SLIT has been established in a number of clinical trials and meta-analyses. However, because SLIT is self-administered by patients without medical supervision, the degree of patient adherence with treatment is still a concern. The objective of this study was to evaluate the perception by allergists of issues related to SLIT adherence. We performed a questionnaire-based survey of 296 Italian allergists, based on the adherence issues known from previous studies. The perception of importance of each item was assessed by a VAS scale ranging from 0 to 10. Patient perception of clinical efficacy was considered the most important factor (ranked 1 by 54% of allergists), followed by the possibility of reimbursement (ranked 1 by 34%), and by the absence of side effects (ranked 1 by 21%). Patient education, regular follow-up, and ease of use of SLIT were ranked first by less than 20% of allergists. These findings indicate that clinical efficacy, cost, and side effects are perceived as the major issues influencing patient adherence to SLIT, and that further improvement of adherence is likely to be achieved by improving the patient information provided by prescribers. | PMC2898115 | ['clinical_trials'] | ['clinical_trials'] |
['SNP', 'Genotyping', 'Infinium', 'iScan', 'Illumina'] | ['Basic Protocol', 'Issue 81', 'genomics', 'HiScan'] | Infinium Assay for Large-scale SNP Genotyping Applications | Genotyping variants in the human genome has proven to be an efficient method to identify genetic associations with phenotypes. The distribution of variants within families or populations can facilitate identification of the genetic factors of disease. Illumina's panel of genotyping BeadChips allows investigators to genotype thousands or millions of single nucleotide polymorphisms (SNPs) or to analyze other genomic variants, such as copy number, across a large number of DNA samples. These SNPs can be spread throughout the genome or targeted in specific regions in order to maximize potential discovery. The Infinium assay has been optimized to yield high-quality, accurate results quickly. With proper setup, a single technician can process from a few hundred to over a thousand DNA samples per week, depending on the type of array. This assay guides users through every step, starting with genomic DNA and ending with the scanning of the array. Using propriety reagents, samples are amplified, fragmented, precipitated, resuspended, hybridized to the chip, extended by a single base, stained, and scanned on either an iScan or Hi Scan high-resolution optical imaging system. One overnight step is required to amplify the DNA. The DNA is denatured and isothermally amplified by whole-genome amplification; therefore, no PCR is required. Samples are hybridized to the arrays during a second overnight step. By the third day, the samples are ready to be scanned and analyzed. Amplified DNA may be stockpiled in large quantities, allowing bead arrays to be processed every day of the week, thereby maximizing throughput. | PMC3991437 | ['genomics'] | ['genomics'] |
['Leishmania infantum', 'mitochondrial DNA', 'visceral leishmaniasis', 'Tunisia', 'relapse'] | ['whole genome sequencing', 'comparative genomics', 'antimony resistance'] | Nuclear and mitochondrial genome sequencing of North-African Leishmania infantum isolates from cured and relapsed visceral leishmaniasis patients reveals variations correlating with geography and phenotype | Although several studies have investigated genetic diversity of Leishmania infantum in North Africa, genome-wide analyses are lacking. Here, we conducted comparative analyses of nuclear and mitochondrial genomes of seven L . infantum isolates from Tunisia with the aim to gain insight into factors that drive genomic and phenotypic adaptation. Isolates were from cured ( n =4) and recurrent ( n =3) visceral leishmaniasis (VL) cases, originating from northern ( n =2) and central ( n =5) Tunisia, where respectively stable and emerging VL foci are observed. All isolates from relapsed patients were from Kairouan governorate (Centre); one showing resistance to the anti-leishmanial drug Meglumine antimoniate. Nuclear genome diversity of the isolates was analysed by comparison to the L. infantum JPCM5 reference genome. Kinetoplast maxi and minicircle sequences (1 and 59, respectively) were extracted from unmapped reads and identified by blast analysis against public data sets. The genome variation analysis grouped together isolates from the same geographical origins. Strains from the North were very different from the reference showing more than 34 587 specific single nucleotide variants, with one isolate representing a full genetic hybrid as judged by variant frequency. Composition of minicircle classes within isolates corroborated this geographical population structure. Read depth analysis revealed several significant gene copy number variations correlating with either geographical origin (amastin and Hsp33 genes) or relapse (CLN3 gene). However, no specific gene copy number variation was found in the drug-resistant isolate. In contrast, resistance was associated with a specific minicircle pattern suggesting Leishmania mitochondrial DNA as a potential novel source for biomarker discovery. | PMC7660250 | ['genomics'] | ['genomics'] |
['SARS-CoV-2', 'COVID-19', 'drug repurposing', 'pharmacophore', 'non-structural proteins'] | ['virtual screening', 'nucleocapsid protein'] | Repurposing drugs for treatment of SARS-CoV-2 infection: computational design insights into mechanisms of action | The COVID-19 pandemic has negatively affected human life globally. It has led to economic crises and health emergencies across the world, spreading rapidly among the human population and has caused many deaths. Currently, there are no treatments available for COVID-19 so there is an urgent need to develop therapeutic interventions that could be used against the novel coronavirus infection. In this research, we used computational drug design technologies to repurpose existing drugs as inhibitors of SARS-CoV-2 viral proteins. The Broad Instituteβs Drug Repurposing Hub consists of in-development/approved drugs and was computationally screened to identify potential hits which could inhibit protein targets encoded by the SARS-CoV-2 genome. By virtually screening the Broad collection, using rationally designed pharmacophore features, we identified molecules which may be repurposed against viral nucleocapsid and non-structural proteins. The pharmacophore features were generated after careful visualisation of the interactions between co-crystalised ligands and the protein binding site. The ChEMBL database was used to determine the compoundβs level of inhibition of SARS-CoV-2 and correlate the predicted viral protein target with whole virus in vitro data. The results from this study may help to accelerate drug development against COVID-19 and the hit compounds should be progressed through further in vitro and in vivo studies on SARS-CoV-2. Communicated by Ramaswamy H. Sarma | PMC7544922 | ['drug_discovery'] | ['drug_discovery'] |
['Pharmacogenetics', 'Osteosarcoma', 'Variants', 'FASL', 'ABCC5'] | [] | Variants of FasL and ABCC5 are predictive of outcome after chemotherapy-based treatment in osteosarcoma | Previous pharmacogenetics studies showed that genetic variants could be indicative of the response to chemotherapy. We aimed to investigate whether variants of FasL, MSH2, ABCC5, CASP3 and CYP3A4 are associated with the outcome after chemotherapy-based treatment in osteosarcoma. 132 osteosarcoma patients who had completed the neoadjuvant chemotherapy in our center were included. 5-year progression-free survival (PFS) was assessed from the initial treatment to the earliest sign of disease progression or death from any cause. 5 SNPs were genotyped using TaqMan SNP Genotyping Assay, including rs763110 of FasL, rs4638843 of MSH2, rs939338 of ABCC5, rs2720376 of CASP3 and rs4646437 of CYP3A4. Patients were classified into two groups according to the 5-year PFS (event/no event). The chi-square test was used to analyze difference of genotype frequency. Logistic regression analysis was used to determine the independent predictors of the PFS rate. The overall 5-year PFS was 61.4% (81/132). Genotype TT/CT of rs763110 and genotype GG/AG of rs939338 were significantly associated with the event of 5-year PFS ( p =β―0.028 for rs763110; p =β―0.039 for rs939338). Patients with no risk allele showed a 5-year PFS of 73.7% (42/57), which was significantly higher than a PFS of 54.2% (26/48) for patients with one risk allele and 48.1% (13/27) for patients with two different risk alleles ( p =Β 0.03). Logistic regression analysis showed that allele T of FasL rs763110 and allele G of ABCC5 rs939338 were independent risk factors of the 5-year PFS. The ORs were 2.14 (95%CIβ―=β―1.13β3.35, p =β―0.01) for rs763110 and 1.73 (95%CIβ―=β―1.05β2.52, p =β―0.03) for rs939338, respectively. The association of variants of FASL and ABCC5 with survival outcome after chemotherapy was validated in patients with osteosarcoma. Our findings may provide a new insight into a more personalized treatment for patients with osteosarcoma. | PMC6066469 | ['genomics'] | ['genomics'] |
['personalized medicine', 'isocitrate dehydrogenase', 'capillary sequencing', 'glioma', 'molecular pathology', 'Saudi Arabia'] | ['RT-qPCR', 'molecular diagnostics', 'next-generation DNA sequencing', 'brain cancer'] | EGFRvIII expression and isocitrate dehydrogenase mutations in patients with glioma | Molecular pathology and personalized medicine are still being evolved in Saudi Arabia, and genetic testing for the detection of mutations as cancer markers have not been established in the diagnostics laboratories in Saudi Arabia. The aim of the present study was to determine the prevalence of isocitrate dehydrogenase (IDH1 and IDH2) mutations and epidermal growth factor receptor variant (EGFRv)III transcript expression in Saudi Arabian patients with glioma. Out of 117 brain tumors tested by reverse transcription-quantitative PCR for EGFRvIII, 41 cases tested positive. In the glioblastoma (GBM) category, 28/55 tumors were positive, in astrocytoma tumors 5/22, and in oligodendrogliomas 4/13 cases were positive respectively. EGFRvIII transcript was sequenced by capillary electrophoresis to demonstrate the presence of EGFRvIII-specific junction where exons 2β7 were deleted. In the present study 106 tumors were sequenced for IDH1 exon-4 mutations using the capillary sequencing method. The most common substitution missense mutation c.395G>A was found in 16 tumors. In the case of adamantinomatous craniopharyngioma, a novel missense mutation in c.472C>T was detected in IDH2 gene. Using next-generation sequencing (NGS), 74 tumors were sequenced for the IDH1 gene, and a total of 8 missense variants were identified in 36 tumors in a population of Saudi Arabia. The missense mutation (c.395G>A) was detected in 29/36 of tumors. A novel intronic mutation in c.414+9T>A was found in 13 cases in the IDH1 gene. In addition, one case exhibited a novel synonymous mutation in c.369A>G. Eleven tumors were found to have compound mutations in the IDH1 gene. In IDH2 gene, out of a total of 16 variants found in 6 out of 45 tumors, nine were missense, five were synonymous and one was intronic. This is the first report from Saudi Arabian laboratories analyzing glioma tumors for EGFRvIII expression, and the first study from Saudi Arabia to analyze IDH mutations in gliomas using the capillary and NGS methods. | PMC7656109 | ['genomics'] | ['genomics'] |
['Cancer', 'Hypothalamus', 'Appetite', 'Serotonin', 'Transcriptomics', 'Anorexia'] | [] | Hypothalamic food intake regulation in a cancer-cachectic mouse model | Appetite is frequently affected in cancer patients leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer-cachectic mouse model with increased food intake. In this model, mice bearing C26 tumour have an increased food intake subsequently to the loss of body weight. We hypothesise that in this model, appetite-regulating systems in the hypothalamus, which apparently fail in anorexia, are still able to adapt adequately to changes in energy balance. Therefore, studying changes that occur on appetite regulators in the hypothalamus might reveal targets for treatment of cancer-induced eating disorders. By applying transcriptomics, many appetite-regulating systems in the hypothalamus could be taken into account, providing an overview of changes that occur in the hypothalamus during tumour growth. C26-colon adenocarcinoma cells were subcutaneously inoculated in 6Β weeks old male CDF1 mice. Body weight and food intake were measured three times a week. On day 20, hypothalamus was dissected and used for transcriptomics using Affymetrix chips. Food intake increased significantly in cachectic tumour-bearing mice (TB), synchronously to the loss of body weight. Hypothalamic gene expression of orexigenic neuropeptides NPY and AgRP was higher, whereas expression of anorexigenic genes CCK and POMC were lower in TB compared to controls. In addition, serotonin and dopamine signalling pathways were found to be significantly altered in TB mice. Serotonin levels in brain showed to be lower in TB mice compared to control mice, while dopamine levels did not change. Moreover, serotonin levels inversely correlated with food intake. Transcriptomic analysis of the hypothalamus of cachectic TB mice with an increased food intake showed changes in NPY, AgRP and serotonin signalling. Serotonin levels in the brain showed to correlate with changes in food intake. Further research has to reveal whether targeting these systems will be a good strategy to avoid the development of cancer-induced eating disorders. The online version of this article (doi:10.1007/s13539-013-0121-y) contains supplementary material. | PMC4053566 | ['genomics'] | ['genomics'] |
['Chromatin', 'ChIP-Seq', 'Genetically modified organism', 'Epigenetics', 'DNA'] | ['Histone modifications'] | Chromatin structure analysis enables detection of DNA insertions into the mammalian nuclear genome | Genetically modified organisms (GMOs) have numerous biomedical, agricultural and environmental applications. Development of accurate methods for the detection of GMOs is a prerequisite for the identification and control of authorized and unauthorized release of these engineered organisms into the environment and into the food chain. Current detection methods are unable to detect uncharacterized GMOs, since either the DNA sequence of the transgene or the amino acid sequence of the protein must be known for DNA-based or immunological-based detection, respectively. Here we describe the application of an epigenetics-based approach for the detection of mammalian GMOs via analysis of chromatin structural changes occurring in the host nucleus upon the insertion of foreign or endogenous DNA. Immunological methods combined with DNA next generation sequencing enabled direct interrogation of chromatin structure and identification of insertions of various size foreign (human or viral) DNA sequences, DNA sequences often used as genome modification tools ( e.g . viral sequences, transposon elements), or endogenous DNA sequences into the nuclear genome of a model animal organism. The results provide a proof-of-concept that epigenetic approaches can be used to detect the insertion of endogenous and exogenous sequences into the genome of higher organisms where the method of genetic modification, the sequence of inserted DNA, and the exact genomic insertion site(s) are unknown. Measurement of chromatin dynamics as a sensor for detection of genomic manipulation and, more broadly, organism exposure to environmental or other factors affecting the epigenomic landscape are discussed. β’ Insertion of DNA sequences into a host genome causes chromatin structure remodeling. β’ ChIP-seq identifies molecular signatures of DNA insertion into the mammalian genome. β’ Focus on epigenetic marks limits sequencing data amount required for GMO detection. β’ Proof-of-concept for use of chromatin dynamics as a sensor of genomic manipulation. Insertion of DNA sequences into a host genome causes chromatin structure remodeling. ChIP-seq identifies molecular signatures of DNA insertion into the mammalian genome. Focus on epigenetic marks limits sequencing data amount required for GMO detection. Proof-of-concept for use of chromatin dynamics as a sensor of genomic manipulation. | PMC5668663 | ['genomics'] | ['genomics'] |
['Licorice', 'Herbal medicines', 'Health foods', 'Estrogenic activity', 'Cytochrome P-450 (CYP)'] | ['FOSHU, Foods for Specified Health Uses', 'FNFC, Foods with Nutrient Functional Claim', 'CAA, Consumer Affairs Agency', 'FFC, Foods with Function Claims', 'E2, 17Ξ²-estradiol', 'HPLC, high-performance liquid chromatography', 'ORAC, oxygen radical absorption capacity', 'CYP, cytochrome P-450', 'BMD, bone mineral density', 'TE, Trolox equivalent', 'DGL, deglycyrrhizin', 'Safety assessment'] | Quality evaluation of health foods containing licorice in the Japanese Market | β’ The contents of glabridin and medical component glycyrrhizin were analyzed in herbal medicines and health foods containing licorice. β’ A small amount of glycyrrhizin was detected in some of health foods. β’ Estrogenic activity was detected in some of health food ingredients and health foods. β’ Antioxidant activity was detected in all the materials. β’ Assessment of hepatic CYP activity, liver and uterine weights in estrogen deficient mice was useful for evaluating the safety of estrogenic ingredients. The contents of glabridin and medical component glycyrrhizin were analyzed in herbal medicines and health foods containing licorice. A small amount of glycyrrhizin was detected in some of health foods. Estrogenic activity was detected in some of health food ingredients and health foods. Antioxidant activity was detected in all the materials. Assessment of hepatic CYP activity, liver and uterine weights in estrogen deficient mice was useful for evaluating the safety of estrogenic ingredients. Focusing on licorice, a highly used raw material in health foods, quantitative analysis of functional/medicinal components and a safety and functional evaluation was carried out for herbal medicines, health food ingredients, and so-called health foods. A functional component, glabridin, was detected in herbal medicines from Glycyrrhiza glabra and G. inflata , health food ingredients, and in commercially available health foods that contain licorice. Likewise, glycyrrhizin, a medicinal component, was detected in these sources, except in licorice oil extract. Estrogen activity in vitro was detected in some of the herbal medicines, health food ingredients, and in health foods containing licorice. In the in vivo study, liver weight in ovariectomized (OVX) mice treated with licorice oil extract was significantly higher than that in OVX and sham mice in a dose dependent manner. These results suggest that excessive intake of licorice oil extract from health foods should be avoided, even though these ingredients might be beneficial for medical use in order to maintain bone health in postmenopausal women. Measurement of hepatic cytochrome P-450 (CYP) activity, reproductive organ weight, and fat and bone mass in OVX mice was considered useful for evaluating the safety and efficacy of estrogenic health food ingredients derived from herbal medicines. | PMC6722472 | ['clinical_trials'] | ['clinical_trials'] |
['liver xenograft', 'gene editing', 'AAV', 'miRNA', 'AAT', 'AATD', 'A1AT'] | ['humanized liver mouse model', 'liver regeneration', 'Ξ±-1 antitrypsin deficiency', 'nuclease-free genome editing', 'shRNA', 'RNAi'] | Survival Advantage of Both Human Hepatocyte Xenografts and Genome-Edited Hepatocytes for Treatment of Ξ±-1 Antitrypsin Deficiency | Hepatocytes represent an important target for gene therapy and editing of single-gene disorders. In Ξ±-1 antitrypsin (AAT) deficiency, one missense mutation results in impaired secretion of AAT. In most patients, lung damage occurs due to a lack of AAT-mediated protection of lung elastin from neutrophil elastase. In some patients, accumulation of misfolded PiZ mutant AAT protein triggers hepatocyte injury, leading to inflammation and cirrhosis. We hypothesized that correcting the Z mutant defect in hepatocytes would confer a selective advantage for repopulation of hepatocytes within an intact liver. A human PiZ allele was crossed onto an immune-deficient (NSG) strain to create a recipient strain (NSG-PiZ) for human hepatocyte xenotransplantation. Results indicate that NSG-PiZ recipients support heightened engraftment of normal human primary hepatocytes as compared with NSG recipients. This model can therefore be used to test hepatocyte cell therapies for AATD, but more broadly it serves as a simple, highly reproducible liver xenograft model. Finally, a promoterless adeno-associated virus (AAV) vector, expressing a wild-type AAT and a synthetic miRNA to silence the endogenous allele, was integrated into the albumin locus. This gene-editing approach leads to a selective advantage of edited hepatocytes, by silencing the mutant protein and augmenting normal AAT production, and improvement of the liver pathology. Borel etΒ al. describe two studies based on misfolded human Ξ±-1 antitrypsin (A1AT). First, when A1AT is expressed in livers of NSG, mice it allows for reproducible engraftment of human hepatocytes. Second, gene editing of hepatocytes to decrease misfolded protein results in expansion of corrected cells and amelioration of liver disease. | PMC5675605 | ['genomics'] | ['genomics'] |
['COVID-19', 'Corona virus', 'Pandemic', 'Drug repurposing', 'Medicinal plants'] | [] | Combating COVID-19: The role of drug repurposing and medicinal plants | A novel corona virus-2 disease has spread to 213 countries and territories across the globe. The corona pandemic has claimed more than 548,934 deaths worldwide till the evening of 8th of July 2020 and the number of confirmed cases is increasing at an alarming rate. Therefore, there is an urgent need to find a treatment or a vaccine for COVID-19 at the earliest. The aim of this mini-review is to give an overview of identified repurposed anti-COVID-19 drugs which are currently under clinical trials. A thorough literature survey was done to retrieve relevant information using various web based search engines such as Google, Google scholar, and various other electronic research databases such as PubMed, Medline, MeSh etc . The findings of the recently published articles, clinical trials, COVID-19 update by World Health Organization etc ., and the opinion of the authors is summarized in this brief review. The antiviral medicinal plants were identified based on their use in Chinese/Indian indigenous systems of medicine, traditional use, published scientific phytochemical studies and/or their effectiveness against upper respiratory infections, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). The disease is just over six months old and effective prophylactic or therapeutic agents are yet to be developed for COVID-19. Thus, in the absence of an effective therapy, scientific community has rationally considered the drug repurposing approach for the development of anti COVID-19 drugs. Various studies and clinical trials involving antimalarial drugs, anti-HIV drugs, anti-hepatitis drugs, anti-parasitic drug, anti-inflammatory drugs, the combination of antimalarial and macrolide antibiotic and few other molecules identified through drug repurposing are currently underway to combat COVID-19. Due emphasis is also given to develop novel corona vaccines for the prophylaxis and to identify drugs for adjunct/supportive therapy. Several medicinal plants along with their major phytochemicals exhibiting antiviral activity are identified for further exploration. It is anticipated that these natural products might also play an important role in combating COVID-19. Use of drug repurposing strategy to develop anti COVID-19 drugs and exploring antiviral medicinal plants as adjunct or supportive therapy appears to be a viable option. Therefore, it is the need of the hour to work in parallel on different strategies such as genetic engineering, in silico approach, herbal remedies and drug repositioning to achieve the common goal of finding a safe and effective treatment for COVID-19 at the earliest. | PMC7590838 | ['drug_discovery', 'epidemiology'] | ['drug_discovery' |
['dalfampridine', 'pharmacokinetics', 'moderate renal impairment', 'severe renal impairment', 'multiple sclerosis'] | [] | Pharmacokinetics of Dalfampridine Extended Release 7.5-mg Tablets in Healthy Subjects and Individuals With Mild and Moderate Renal Impairment: An Open-Label Study | Dalfampridine extended release tablets (D-ER; prolonged-release fampridine in Europe) are available to improve walking in patients with multiple sclerosis (MS). D-ER is mainly renally eliminated; the approved 10-mg twice daily dose is contraindicated in the United States in patients with moderate or severe renal impairment. This study evaluated single-dose and steady-state pharmacokinetics of a 7.5-mg dose of D-ER in healthy subjects (nβ=β13) and subjects with mild (nβ=β17) and moderate (nβ=β12) renal impairment. D-ER plasma concentrations were consistently higher in subjects with renal impairment relative to healthy individuals with a significant ( P <β.0001) inverse linear relationship between creatinine clearance and drug exposure. Steady-state AUC 0β12 among healthy subjects, 167.0βΒ±β55.3βngβh/mL, increased 74% and 151% with mild and moderate renal impairment, respectively. The overall incidence of adverse events was 61.5%, 47.1%, and 33.3% in healthy subjects, and subjects with mild and moderate renal impairment, respectively, and for treatment-related adverse events the rates were 0%, 17.6%, and 8.3%, respectively. The most common adverse events were headache, dizziness, and arthralgia. The pharmacokinetics of D-ER 7.5-mg twice daily in subjects with mild renal impairment was comparable to 10-mg twice daily in patients with MS who had normal renal function. Exposure was significantly higher in moderate renal impairment. | PMC4263161 | ['drug_discovery'] | ['drug_discovery'] |
['sewage', 'wastewater', 'epidemiology', 'public health', 'CoV', 'SARS-CoV-2', 'severe acute respiratory syndrome coronavirus 2', 'viruses', 'Belgium', 'the Netherlands'] | ['Nanopore', 'Illumina', 'zoonoses', 'COVID-19', 'coronavirus disease', 'respiratory infections'] | Monitoring SARS-CoV-2 Circulation and Diversity through Community Wastewater Sequencing, the Netherlands and Belgium | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a major global health problem, and public health surveillance is crucial to monitor and prevent virus spread. Wastewater-based epidemiology has been proposed as an addition to disease-based surveillance because virus is shed in the feces of β40% of infected persons. We used next-generation sequencing of sewage samples to evaluate the diversity of SARS-CoV-2 at the community level in the Netherlands and Belgium. Phylogenetic analysis revealed the presence of the most prevalent clades (19A, 20A, and 20B) and clustering of sewage samples with clinical samples from the same region. We distinguished multiple clades within a single sewage sample by using low-frequency variant analysis. In addition, several novel mutations in the SARS-CoV-2 genome were detected. Our results illustrate how wastewater can be used to investigate the diversity of SARS-CoV-2 viruses circulating in a community and identify new outbreaks. | PMC8084483 | ['epidemiology'] | ['epidemiology'] |
['antibody levels', 'cord blood', 'mother', 'passive immunity', 'predictor'] | ['asymptomatic infection', 'baby', 'convalescent infection', 'COVID-19 infection', 'mother-baby dyads', 'prevalence', 'symptomatic infection', 'time course'] | Severe acute respiratory syndrome coronavirus 2 serology levels in pregnant women and their neonates | Pregnant women and their neonates represent 2 vulnerable populations with an interdependent immune system that are highly susceptible to viral infections. The immune response of pregnant women to severe acute respiratory syndrome coronavirus 2 and the interplay of how the maternal immune response affects the neonatal passive immunity have not been studied systematically. We characterized the serologic response in pregnant women and studied how this serologic response correlates with the maternal clinical presentation and with the rate and level of passive immunity that the neonate received from the mother. Women who gave birth and who tested positive for immunoglobulin M or immunoglobulin G against severe acute respiratory syndrome coronavirus 2 using semiquantitative detection in a New York City hospital between March 22, 2020, and May 31, 2020, were included in this study. A retrospective chart review of the cases that met the inclusion criteria was conducted to determine the presence of coronavirus disease 2019 symptoms and the use of oxygen support. Serology levels were compared between the symptomatic and asymptomatic patients using a Welch 2 sample t test. Further chart review of the same patient cohort was conducted to identify the dates of self-reported onset of coronavirus disease 2019 symptoms and the timing of the peak immunoglobulin M and immunoglobulin G antibody levels after symptom onset was visualized using local polynomial regression smoothing on log 2 -scaled serologic values. To study the neonatal serology response, umbilical cord blood samples of the neonates born to the subset of serology positive pregnant women were tested for serologic antibody responses. The maternal antibody levels of serology positive vs the maternal antibody levels of serology negative neonates were compared using the Welch 2 sample t test. The relationship between the quantitative maternal and quantitative neonatal serologic data was studied using a Pearson correlation and linear regression. A multiple linear regression analysis was conducted using maternal symptoms, maternal serology levels, and maternal use of oxygen support to determine the predictors of neonatal immunoglobulin G levels. A total of 88 serology positive pregnant women were included in this study. The antibody levels were higher in symptomatic pregnant women than in asymptomatic pregnant women. Serology studies in 34 women with symptom onset data revealed that the maternal immunoglobulin M and immunoglobulin G levels peak around 15 and 30 days after the onset of coronavirus disease 2019 symptoms, respectively. Furthermore, studies of 50 neonates born to this subset of serology positive women showed that passive immunity in the form of immunoglobulin G is conferred in 78% of all neonates. The presence of passive immunity is dependent on the maternal antibody levels, and the levels of neonatal immunoglobulin G correlate with maternal immunoglobulin G levels. The maternal immunoglobulin G levels and maternal use of oxygen support were predictive of the neonatal immunoglobulin G levels. We demonstrated that maternal serologies correlate with symptomatic maternal infection, and higher levels of maternal antibodies are associated with passive neonatal immunity. The maternal immunoglobulin G levels and maternal use of oxygen support, a marker of disease severity, predicted the neonatal immunoglobulin G levels. These data will further guide the screening for this uniquely linked population of mothers and their neonates and can aid in developing maternal vaccination strategies. | PMC7825873 | ['epidemiology'] | ['epidemiology'] |
['Retina', 'DNA Methylation', '5-methylcytosine', '5-hydroxymethylcytosine', 'retina', 'development', 'epigenetics', 'DNA methylation', 'mouse', 'chromatin', 'nucleus', 'Photoreceptor'] | ['Developmental Biology', 'Issue 138', 'Eye', 'Pigment Epithelium of Eye', 'Chemical Processes', 'Biochemical Processes', 'Anatomy', 'Sense Organs', 'Phenomena and Processes', 'Chemical Phenomena', 'immunohistochemistry', 'hydrochloric acid', 'denaturation'] | Immunohistochemical Detection of 5-Methylcytosine and 5-Hydroxymethylcytosine in Developing and Postmitotic Mouse Retina | The epigenetics of retinal development is a well-studied research field, which promises to bring a new level of understanding about the mechanisms of a variety of human retinal degenerative diseases and pinpoint new treatment approaches. The nuclear architecture of mouse retina is organized in two different patterns: conventional and inverted. Conventional pattern is universal where heterochromatin is localized to the periphery of the nucleus, while active euchromatin resides in the nuclear interior. In contrast, inverted nuclear pattern is unique to the adult rod photoreceptor cell nuclei where heterochromatin localizes to the nuclear center, and euchromatin resides in the nuclear periphery. DNA methylation is predominantly observed in chromocenters. DNA methylation is a dynamic covalent modification on the cytosine residues (5-methylcytosine, 5mC) of CpG dinucleotides that are enriched in the promoter regions of many genes. Three DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) participate in methylation of DNA during development. Detecting 5mC with immunohistochemical techniques is very challenging, contributing to variability in results, as all DNA bases including 5mC modified bases are hidden within the double-stranded DNA helix. However, detailed delineation of 5mC distribution during development is very informative. Here, we describe a reproducible technique for robust immunohistochemical detection of 5mC and another epigenetic DNA marker 5-hydroxymethylcytosine (5hmC), which colocalizes with the "open", transcriptionally active chromatin in developing and postmitotic mouse retina. | PMC6235063 | ['genomics'] | ['genomics'] |
['Neurodevelopmental disorders', 'Mental disorders', 'Atopic diseases', 'Chronic inflammatory diseases', 'Risk factors'] | ['Substance abuse', 'Childhood diseases', 'Infectious diseases'] | Infectious, atopic and inflammatory diseases, childhood adversities and familial aggregation are independently associated with the risk for mental disorders: Results from a large Swiss epidemiological study | To examine the associations between mental disorders and infectious, atopic, inflammatory diseases while adjusting for other risk factors. We used data from PsyCoLaus, a large Swiss Population Cohort Study ( n = 3720; age range 35-66). Lifetime diagnoses of mental disorders were grouped into the following categories: Neurodevelopmental, anxiety (early and late onset), mood and substance disorders. They were regressed on infectious, atopic and other inflammatory diseases adjusting for sex, educational level, familial aggregation, childhood adversities and traumatic experiences in childhood. A multivariate logistic regression was applied to each group of disorders. In a complementary analysis interactions with sex were introduced via nested effects. Associations with infectious, atopic and other chronic inflammatory diseases were observable together with consistent effects of childhood adversities and familial aggregation, and less consistent effects of trauma in each group of mental disorders. Streptococcal infections were associated with neurodevelopmental disorders (men), and measles/mumps/rubella-infections with early and late anxiety disorders (women). Gastric inflammatory diseases took effect in mood disorders (both sexes) and in early disorders (men). Similarly, irritable bowel syndrome was prominent in a sex-specific way in mood disorders in women, and, moreover, was associated with early and late anxiety disorders. Atopic diseases were associated with late anxiety disorders. Acne (associations with mood disorders in men) and psoriasis (associations with early anxiety disorders in men and mood disorders in women) contributed sex-specific results. Urinary tract infections were associated with mood disorders and, in addition, in a sex-specific way with late anxiety disorders (men), and neurodevelopmental and early anxiety disorders (women). Infectious, atopic and inflammatory diseases are important risk factors for all groups of mental disorders. The sexual dimorphism of the associations is pronounced. | PMC5183994 | ['epidemiology'] | ['epidemiology'] |
['Vitamin D deficiency', 'Reduced sun exposure', 'Fracture', 'Children', 'Teenagers', 'Risk factors for vitamin D deficiency'] | [] | High prevalence of vitamin D deficiency in 2β17Β year olds presenting with acute fractures in southern Australia | To determine vitamin D deficiency risk and other lifestyle factors in children aged 2β17Β years presenting with an acute fracture to Sunshine Hospital. A prospective observational study was undertaken using a convenience sample data collected from children aged 2β17Β years of age presenting with an acute fracture. Recruitment was undertaken over a 3-month period from February to May 2014. Risk factors for vitamin D deficiency (skin pigmentation, hours spent outdoors, sunscreen use and obesity) were identified. Patients providing consent, had measurements of serum 25-hydroxyvitamin D (25-OHD). Vitamin D deficiency was defined as <Β 50Β nmol/L. Of the 163 patients recruited into this study, 134 (82%) had one or more risk factor(s) for vitamin D deficiency. Of these, 109 (81%) consented to 25-OHD testing, with a median of 53Β nmol/l (range 14β110Β nmol/l) obtained. A total of 57 (52% at risk, 35% of total participants) were found to be vitamin D deficient. 45 (80%) had mild deficiency (30β50Β nmol/l) and 11 (20%) had moderate deficiency (12.5β29Β nmol/l). One third of all participants, and the majority participants who had one or more risk factor(s) for vitamin D deficiency, were vitamin D deficient. Based on our findings we recommend that vitamin D status be assessed in all children with risk factor of vitamin D deficiency living in urban environments at higher latitudes presenting with fractures. The effect of vitamin D status on fracture risk and fracture healing in children and teenagers is yet to be determined, as do the effects of vitamin D supplementation in vitamin D deficient paediatric patients presenting with acute fracture. β’ Prevalence of vitamin D deficiency is high in multiethnic children, presenting with fracture with risk factor(s) of vitamin D deficiency. β’ Reduced sun exposure or hyperpigmentation have a strong association with vitamin D deficiency. β’ Screening for vitamin D deficiency and assessment of dietary calcium adequacy are recommended when a child or teenager presents with an acute fracture. Prevalence of vitamin D deficiency is high in multiethnic children, presenting with fracture with risk factor(s) of vitamin D deficiency. Reduced sun exposure or hyperpigmentation have a strong association with vitamin D deficiency. Screening for vitamin D deficiency and assessment of dietary calcium adequacy are recommended when a child or teenager presents with an acute fracture. | PMC4926840 | ['epidemiology'] | ['epidemiology'] |
['glioma', 'GSK1838705A', 'insulin-like growth factor', 'signal transduction', 'small molecule kinase inhibitor'] | ['targeted cancer therapy'] | GSK1838705A, an IGF-1R inhibitor, inhibits glioma cell proliferation and suppresses tumor growth in vivo | Glioma is a type of primary malignant tumor of the central nervous system in humans. At present, standard treatment involves surgical resection, followed by radiation therapy and chemotherapy. However, the prognosis is poor and the long-term survival rate remains low. An improved understanding of the molecular basis for glioma tumorigenesis is in urgently required. The pro-survival effect of the insulin-like growth factor (IGF) signaling pathway has been implicated in progression of the glioma disease state. GSK1838705A is a novel, small molecule kinase inhibitor of IGF-IR, which inhibits IGF signal transduction and downstream target activation. Its anti-proliferative activity has been demonstrated in various tumor cell lines. The present study investigated the potential use of GSK1838705A for the treatment of glioma. Human U87MG glioma cells were used to examine the inhibitory activity of GSK1838705A in cell proliferation, migration and apoptosis. The antitumor activity of GSK1838705A was assessed in a xenograft mouse model. GSK1838705A inhibited the growth and induced the apoptosis of the U87MG glioma cells in a dose-dependent manner. The GSK1838705A-treated cells exhibited reduced migratory activity in response to chemoattractants. The present study further demonstrated the antitumor activity of GSK1838705A in vivo . The administration of GSK1838705A significantly inhibited the growth of glioma tumors by inducing the apoptosis of tumor cells. These results suggested that targeting IGF signaling with GSK1838705A may be a promising therapeutic strategy for the treatment of patients with glioma. | PMC4581800 | ['drug_discovery'] | ['drug_discovery'] |
['COVID-19', 'SARS-CoV-2', 'Papain-like protease', 'Molecular docking', 'Molecular dynamics simulation', 'Computational chemistry', 'Organic chemistry', 'Theoretical chemistry', 'Pharmaceutical chemistry', 'Bioinformatics', 'Pharmaceutical science'] | [] | Structure-based drug designing of naphthalene based SARS-CoV PLpro inhibitors for the treatment of COVID-19 | The emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a greater challenge for the world. Coronavirus has infected over 38.3 million people and caused millions of deaths worldwide. The COVID-19 outbreak has accentuated the need for additional efforts to develop broad-spectrum therapeutics to combat SARS-CoV-2 infection. In the current investigation, an attempt was made to design potential SARS-CoV PLpro inhibitors containing naphthalene and 3,4-dihydro-2H-pyran moieties connected via -NHCO- linker. The ligands obeyed Lipinski's rule and were found to have good drug-likeness and ADMET properties. Docking simulations confirmed strong binding affinity and inhibition potential of the designed ligands against the receptor SARS CoV-2 Papain-like protease (PLpro). LigandL10 incorporating the oxadiazole ring system displayed better binding affinity than the control 5-acetamido-2-methyl- N -[(1 R )-1-naphthalen-1-ylethyl]benzamide. Further, the docked complex of LigandL10 was subjected to molecular dynamics (MD) simulation to examine the molecular mechanisms of protein-ligand interactions. The results of the present study are encouraging. Ligand L10 emerged as the most potent ligand in the series and could be considered for further research for the development of potential therapeutics for the treatment of COVID-19. COVID-19; SARS-CoV-2; papain-like protease; Molecular Docking; molecular dynamics simulation; Computational Chemistry; Organic chemistry; Theoretical chemistry; Pharmaceutical chemistry; Bioinformatics; Pharmaceutical Science | PMC7679114 | ['drug_discovery'] | ['drug_discovery'] |
['biosafety', 'biosecurity', 'legislation', 'governance', 'China'] | [] | Chinaβs evolving biosafety/biosecurity legislations | This paper represents a systematic effort to describe and assess Chinaβs evolving biosafety/biosecurity legislative and regulatory regime. It catalogs and analyzes laws, regulations, and measures, including the newly passed Biosafety/Biosecurity Law. Various reasons are underlying Chinaβs recently accelerating legislative process for such a law, from international attention increasingly turning biosafety/biosecurity governance into a more regular fixture; the emergence of infectious diseases and even pandemics linked with zoonosis; advances in the global frontier of the life sciences and biotechnology and their integration with other technologies, which, while holding great promise for advancements in global health, raises biosafety/biosecurity concerns; to the strengthening of biosafety/biosecurity governance in many countries. Chinese leadershipβs βholistic view of national securityβ encompasses broad areas of concerns of national security with biosafety/biosecurity being an integral part. However, having progressed alongside its development of the life sciences and biotechnology, Chinaβs current biosafety/biosecurity legislative and regulatory regime is far from rising to the challenges and even the newly enacted Biosafety/Biosecurity law still has room for improvement. The paperβs findings have significant policy implications for further enhancing Chinaβs biosafety/biosecurity legislation and governance and making them better serve domestic interests while converging with international norms. | PMC8245076 | ['clinical_trials'] | ['clinical_trials'] |
['Food science', 'Food chemistry', 'Agriculture', 'Alpha glucosidas', 'Enzyme kinetics', 'Anti-diabetic', 'Molecular docking', 'Medicinal plant', 'Hypoglycaemic'] | [] | Alpha glucosidase inhibition activity of phenolic fraction from Simarouba glauca : An in-vitro , in-silico and kinetic study | A phenolic rich fraction purified from Simarouba glauca leaves was effective in alpha glucosidase inhibition. The purified fraction named βfraction-14β had shown significant inhibition of yeast alpha glucosidase enzyme activity (IC 50 = 2.4 Β± 0.4 ΞΌg/mL) when compared to anti-diabetic drug acarbose (IC 50 = 2450 Β± 24 ΞΌg/mL). The purified fraction also had reasonable DPPH (IC 50 = 14.4 Β± 0.1 ΞΌg/mL) and ABTS (IC 50 = 7.6 Β± 0.5 ΞΌg/mL) free radical scavenging activity when compared to the standard ascorbic acid. The LC-MS analysis of bioactive βfraction-14β revealed four compounds, eclalbasaponin-v ( 1 ), cyanidin-3-O-(2β²galloyl)-galactoside ( 2 ), kaempferol-3-O-glucoside ( 3 ) and kaempferol-3-O-pentoside ( 4 ) for the first time in S.Β glauca in this study. The kinetic study of the βfraction-14β indicates a mixed type of inhibition on the alpha glucosidase enzyme with K i , 6.2 ΞΌg/mL. Docking studies showed promising binding energy for the compounds 2 (-7.769 kJ/mol), 3 (-7.04 kJ/mol) and 4 (-7.127 kJ/mol) against yeast alpha glucosidase which was better than acarbose (-6.867 kJ/mol). In conclusion, the phenolic rich fraction from S.Β glauca possessing good in-vitro antioxidant property and alpha glucosidase enzyme inhibition potential along with mixed inhibition kinetics. Also, better binding energy of compounds ( 1, 2 & 3 ) appears to contain potential lead-molecule for antidiabetic therapy. Food Science; Food Chemistry; Agriculture; Alpha Glucosidas; Enzyme Kinetics; Anti-diabetic; Molecular Docking; Medicinal Plant; Hypoglycaemic. | PMC7350133 | ['drug_discovery'] | ['drug_discovery'] |
['Coronavirus', 'COVID-19', 'Pandemic', 'Drug shortage', 'Pharmacist', 'Policymaker'] | [] | Global drug shortages due to COVID-19: Impact on patient care and mitigation strategies | Coronavirus disease 2019 (COVID-19) arising from Wuhan, China, is currently outbreaking worldwide. The World Health Organization (WHO) has declared COVID-19 to be a global pandemic. COVID-19 could cause a wide range of symptoms ranging from self-limiting fever, sore throat, and cough to more severe symptoms that could lead to acute respiratory distress syndrome. As a result of the lockdown and increased demand, drug shortages could become a growing global issue. This article aims to shed light on the potential impact of drug shortages as a result of this pandemic on patient outcomes and the role of pharmacists and pharmacy policymakers in alleviating this emerging problem. | PMC7235598 | ['epidemiology'] | ['epidemiology'] |
['Cataract', 'diabetes', 'incidence', 'progression', 'risk factors', 'visual impairment'] | [] | Four-year incidence and progression of visual impairment in a South Indian population with diabetes | The aim of this study is to investigate the 4-year incidence and progression of visual impairment (VI) and the associated risk factors for incident VI in a South Indian population with type 2 diabetes. A total of 634 participants with type 2 diabetes were found eligible after 4 years. Visual acuity (VA) was estimated using the modified Early Treatment Diabetic Retinopathy Study protocol. VA in the better eye was considered for the assessment of VI based on the World Health Organization criteria. Mild VI was defined as VA <20/40 but up to 20/60, moderate VI as VA <20/60 but up to 20/200, severe VI as VA <20/200 but up to 10/200, and blindness as VA worse than 10/200. The 4-year incidence of any VI, mild VI, moderate VI, severe VI, and blindness was 21.7%, 18.3%, 3.4%, 0.0%, and 0.0%, respectively; of the 13 participants with VI at baseline, 12 (92%) showed worsening/progression of VI on follow-up. Multiple logistic regression showed that nuclear cataract of grades >4.0 (odds ratio [OR]: 2.612 [1.148β5.942], P = 0.022) and lower socioeconomic score (OR: 0.965 [95% confidence interval, (0.933-0.998)], P = 0.040) were associated with the risk of future incident VI. Refractive error (47%) and cataract (30%) were identified as the leading causes of incident VI at follow-up. VI seems to be a significant problem among diabetic participants in the South Indian population. Refractive error and cataract are the leading but treatable causes of incident VI in this population and would benefit from intervention. | PMC5549411 | ['epidemiology'] | ['epidemiology'] |
['methylenetetrahydrofolate reductase', 'C677T', 'arterial thrombosis', 'gene polymorphism', 'risk factor'] | ['myocardial infarction', 'Georgian population'] | Methylenetetrahydrofolate Reductase Gene Polymorphism (C677T) as a Risk Factor for Arterial Thrombosis in Georgian Patients | Methylenetetrahydrofolate reductase ( MTHFR ) gene polymorphism (C677T)] is a well-recognized genetic risk factor for venous thrombosis; however, its association with arterial thrombosis is still under debate. Herein, we evaluated the prevalence of MTHFR C677T polymorphism in Georgian patients in comparison with healthy individuals and its association with arterial thrombosis. We enrolled 214 participants: 101 with arterial thrombosis (71.3% males; mean age: 66.3 Β± 12.1 years) and 113 controls (67.3% males; mean age: 56.6 Β± 11.3 years). Genomic DNA was extracted from dry blood spot on Whatman filter paper. Polymerase chain reaction was performed to determine MTHFR C677T polymorphism. Frequency of C677T allele polymorphism in controls was 21.2%, which corresponded to heterozygous and homozygous stage frequencies of 35.4% and 3.5%, respectively. In patient group, an allelic frequency of 33.2% was found, which corresponded to the presence of 48.5% of heterozygous and 8.9% of homozygous individuals. Comparing the frequency of mutated alleles between the 2 groups, a significantly high frequency of mutated alleles was found in patient group ( P < .05). In conclusion, high frequency of MTHFR C677T polymorphism found in arterial thrombosis patient group suggests that this polymorphism might increase the risk of arterial thrombosis in Georgian patients. | PMC6714755 | ['clinical_trials', 'epidemiology'] | ['clinical_trials' |
['Viral vector', 'Vaccines', 'Safety', 'Adverse events following immunization (AEFI)', 'Treescan'] | ['Surveillance', 'Duration', 'Adverse event of special interest (AESI)'] | Defining the interval for monitoring potential adverse events following immunization (AEFIs) after receipt of live viral vectored vaccines | Live viral vectors that express heterologous antigens of the target pathogen are being investigated in the development of novel vaccines against serious infectious agents like HIV and Ebola. As some live recombinant vectored vaccines may be replication-competent, a key challenge is defining the length of time for monitoring potential adverse events following immunization (AEFI) in clinical trials and epidemiologic studies. This time period must be chosen with care and based on considerations of pre-clinical and clinical trials data, biological plausibility and practical feasibility. The available options include: (1) adapting from the current relevant regulatory guidelines; (2) convening a panel of experts to review the evidence from a systematic literature search to narrow down a list of likely potential or known AEFI and establish the optimal risk window(s); and (3) conducting βnear real-timeβ prospective monitoring for unknown clusteringβs of AEFI in validated large linked vaccine safety databases using Rapid Cycle Analysis for pre-specified adverse events of special interest (AESI) and Treescan to identify previously unsuspected outcomes. The risk window established by any of these options could be used along with (4) establishing a registry of clinically validated pre-specified AESI to include in case-control studies. Depending on the infrastructure, human resources and databases available in different countries, the appropriate option or combination of options can be determined by regulatory agencies and investigators. | PMC6535369 | ['clinical_trials', 'epidemiology'] | ['clinical_trials' |
['drug change', 'drug shortage', 'hospital', 'patient safety challenges', 'tender'] | ['facilitators and measures'] | Drug change: βa hassle like no otherβ. An in-depth investigation using the Danish patient safety database and focus group interviews with Danish hospital personnel | Drug change (DC) is a common challenge in Danish hospitals. It affects the work of hospital personnel and has potentially serious patient safety consequences. Focus on medication safety is becoming increasingly important in the prevention of adverse events. The aim of this study is to identify and describe patient safety challenges related to DCs, and to explore potential facilitators to improve patient safety in the medication process in Danish hospital setting. Two qualitative methods were combined. Data were obtained from the Danish Patient Safety Database (DPSD) containing incidents reports of adverse events related to DCs. Additionally, five semi-structured focus group interviews with hospital personnel (doctors, nurses, pharmacists and pharmacy technicians) from the five regions of Denmark were held. The DPSD search identified 88 incidents related to DCs due to tender or drug shortage. The incidents were linked to prescribing errors, incorrect dose being dispensed/administered, and delayed/omitted treatment. Four themes from the interviews emerged: (1) challenges related to the drug itself; (2) situational challenges; (3) challenges related to the organization/IT systems/personnel; (4) facilitators/measures to ensure patient safety. DC is as a complex challenge, especially related to drug shortage. The results allow for a deeper understanding of the challenges and possible facilitators of DCs on the individual and organizational level. Pharmacy personnel were identified to play a key role in ensuring patient safety of DCs in hospitals. Indeed, this emphasizes that pharmacy personnel should be engaged in developing patient safety strategies and support hospital personnel around drug changes. | PMC6628512 | ['clinical_trials'] | ['clinical_trials'] |
['gastric cancer', 'cell cycle', 'pharmacophore', 'molecular docking', 'molecular dynamics'] | [] | Development of novel HER2 inhibitors against gastric cancer derived from flavonoid source of Syzygium alternifolium through molecular dynamics and pharmacophore-based screening | Continuous usage of synthetic chemotherapeutic drugs causes adverse effects, which prompted for the development of alternative therapeutics for gastric cancer from natural source. This study was carried out with a specific aim to screen gastroprotective compounds from the fruits of Syzygium alternifolium (Myrtaceae). Three flavonoids, namely, 1) 5-hydroxy-7,4β²-dimethoxy-6,8-di-C-methylflavone, 2) kaempferol-3-O- Ξ² - d -glucopyranoside, and 3) kaempferol-3-O- Ξ± - l -rhamnopyranoside were isolated from the above medicinal plant by employing silica gel column chromatography and are characterized by NMR techniques. Antigastric cancer activity of these flavonoids was examined on AGS cell lines followed by cell cycle progression assay. In addition, pharmacophore-based screening and molecular dynamics of proteinβligand complex were carried out to identify potent scaffolds. The results showed that compounds 2 and 3 exhibited significant cytotoxic effect, whereas compound 1 showed moderate effect on AGS cells by inhibiting G2/M phase of cell cycle. Molecular docking analysis revealed that compound 2 has higher binding energies on human growth factor receptor-2 (HER2). The constructed pharmacophore models reveal that the compounds have more number of H-bond Acc/Don features which contribute to the inhibition of HER2 activity. By selecting these features, 34 hits were retrieved using the query compound 2. Molecular dynamic simulations (MDS) of proteinβligand complexes demonstrated conspicuous inhibition of HER2 as evidenced by dynamic trajectory analysis. Based on these results, the compound ZINC67903192 was identified as promising HER2 inhibitor against gastric cancer. The present work provides a basis for the discovery a new class of scaffolds from natural products for gastric carcinoma. | PMC5104305 | ['drug_discovery'] | ['drug_discovery'] |
['Chlorine disinfectant', 'Color additive', 'Skin irritation', 'Antimicrobial efficacy', 'Skin safety'] | ['Efficacy test'] | Evaluation of the antimicrobial efficacy and skin safety of a novel color additive in combination with chlorine disinfectants | β’ Novel color additive for chlorine disinfectants aids visibility and coverage. β’ Chlorine with and without color additive achieved the same antimicrobial efficacy. β’ The color additive improved the efficacy of 0.5% sodium hypochlorite against coronavirus. β’ Chlorine with and without color additive were negligible skin irritants. β’ The color additive did not adversely affect efficacy or skin safety of chlorine. Novel color additive for chlorine disinfectants aids visibility and coverage. Chlorine with and without color additive achieved the same antimicrobial efficacy. The color additive improved the efficacy of 0.5% sodium hypochlorite against coronavirus. Chlorine with and without color additive were negligible skin irritants. The color additive did not adversely affect efficacy or skin safety of chlorine. A novel color additive colorizes chlorine disinfectants blue to improve visibility and enhance spray surface coverage, and it fades to colorless to indicate elapsed contact time. We investigated its interactions with 3 chlorine disinfectants to determine if the additive would adversely affect the disinfectants' antimicrobial efficacy or skin safety. We tested 0.5% sodium hypochlorite, 0.2% calcium hypochlorite, and 0.5% sodium dichloroisocyanurate (NaDCC) alone versus with color additive. An independent laboratory tested efficacy against Staphylococcus aureus , Pseudomonas aeruginosa , Vibrio cholerae , and human coronavirus 229E. An independent laboratory also tested direct skin irritation. Chlorine disinfectants with and without color additive achieved equal levels of efficacy against the tested pathogens. Against S. aureus , 0.5% sodium hypochlorite with and without color additive met Environmental Protection Agency criteria for disinfection success. Against human coronavirus 229E, 0.5% sodium hypochlorite alone failed disinfection success criteria, whereas 0.5% sodium hypochlorite with color additive achieved full viral inactivation (β₯4.50 log 10 reduction). Against V. cholerae , 0.2% calcium hypochlorite alone and with color additive achieved 5.99 log 10 and >6.03 log 10 reductions, respectively. Against S. aureus and P. aeruginosa, 0.5% NaDCC with and without color additive achieved >4.9 log 10 and >3.54 log 10 reductions, respectively. All 3 chlorine disinfectants with color additive tested as negligible skin irritants. This color additive can be combined with chlorine disinfectants without adversely affecting antimicrobial efficacy or skin safety. | PMC7115331 | ['clinical_trials'] | ['clinical_trials'] |
['CtrA', 'Rhodobacter capsulatus', 'RNA-seq', 'small non-coding RNAs', 'sRNA-Detect'] | ['logistic regression'] | Genome-wide identification and characterization of small RNAs in Rhodobacter capsulatus and identification of small RNAs affected by loss of the response regulator CtrA | Small non-coding RNAs (sRNAs) are involved in the control of numerous cellular processes through various regulatory mechanisms, and in the past decade many studies have identified sRNAs in a multitude of bacterial species using RNA sequencing (RNA-seq). Here, we present the first genome-wide analysis of sRNA sequencing data in Rhodobacter capsulatus , a purple nonsulfur photosynthetic alphaproteobacterium. Using a recently developed bioinformatics approach, sRNA-Detect, we detected 422 putative sRNAs from R. capsulatus RNA-seq data. Based on their sequence similarity to sRNAs in a sRNA collection, consisting of published putative sRNAs from 23 additional bacterial species, and RNA databases, the sequences of 124 putative sRNAs were conserved in at least one other bacterial species; and, 19 putative sRNAs were assigned a predicted function. We bioinformatically characterized all putative sRNAs and applied machine learning approaches to calculate the probability of a nucleotide sequence to be a bona fide sRNA. The resulting quantitative model was able to correctly classify 95.2% of sequences in a validation set. We found that putative cis- targets for antisense and partially overlapping sRNAs were enriched with protein-coding genes involved in primary metabolic processes, photosynthesis, compound binding, and with genes forming part of macromolecular complexes. We performed differential expression analysis to compare the wild type strain to a mutant lacking the response regulator CtrA, an important regulator of gene expression in R. capsulatus , and identified 18 putative sRNAs with differing levels in the two strains. Finally, we validated the existence and expression patterns of four novel sRNAs by Northern blot analysis. | PMC5546546 | ['genomics'] | ['genomics'] |
['African swine fever virus', 'Antiviral', 'Genistein', 'Viral DNA replication', 'Molecular docking'] | [] | Genistein inhibits African swine fever virus replication in vitro by disrupting viral DNA synthesis | African swine fever virus (ASFV) is the causal agent of a highly-contagious and fatal disease of domestic pigs, leading to serious socio-economic consequences in affected countries. Once, neither an anti-viral drug nor an effective vaccines are available, studies on new anti-ASFV molecules are urgently need. Recently, it has been shown that ASFV type II topoisomerase (ASFV-topo II) is inhibited by several fluoroquinolones (bacterial DNA topoisomerase inhibitors), raising the idea that this viral enzyme can be a potential target for drug development against ASFV. Here, we report that genistein hampers ASFV infection at non-cytotoxic concentrations in Vero cells and porcine macrophages. Interestingly, the antiviral activity of this isoflavone, previously described as a topo II poison in eukaryotes, is maximal when it is added to cells at middle-phase of infection (8 hpi), disrupting viral DNA replication, blocking the transcription of late viral genes as well as the synthesis of late viral proteins, reducing viral progeny. Further, the single cell electrophoresis analysis revealed the presence of fragmented ASFV genomes in cells exposed to genistein, suggesting that this molecule also acts as an ASFV-topo II poison and not as a reversible inhibitor. No antiviral effects were detected when genistein was added before or at entry phase of ASFV infection. Molecular docking studies demonstrated that genistein may interact with four residues of the ATP-binding site of ASFV-topo II (Asn-144, Val-146, Gly-147 and Leu-148), showing more binding affinity (β4.62β―kcal/mol) than ATP 4β (β3.02β―kcal/mol), emphasizing the idea that this viral enzyme has an essential role during viral genome replication and can be a good target for drug development against ASFV. Image 1 β’ Genistein shows potent anti-ASFV activity at non-cytotoxic concentrations. β’ Genistein disrupts viral genome replication and viral protein synthesis. β’ It acts as an ASFV-topo II poison promoting irreversible viral genome breaks. β’ Docking studies revealed that genistein interacts with the ATP-binding site of ASFV-topo II with more affinity than ATP 4β . Genistein shows potent anti-ASFV activity at non-cytotoxic concentrations. Genistein disrupts viral genome replication and viral protein synthesis. It acts as an ASFV-topo II poison promoting irreversible viral genome breaks. Docking studies revealed that genistein interacts with the ATP-binding site of ASFV-topo II with more affinity than ATP 4β . | PMC7127377 | ['drug_discovery'] | ['drug_discovery'] |
['hepatocellular carcinoma', 'genomic variations', 'TP53 mutation', 'lncRNA', 'prognosis marker', 'HCC'] | [] | TP53 Mutation Related and Directly Regulated lncRNA Prognosis Markers in Hepatocellular Carcinoma | TP53 mutation is the most common genetic variation type in Hepatocellular carcinoma (HCC). We aim to illustrate the landscape of genomic alterations and TP53 mutation related and directly regulated lncRNA prognosis markers. Utilizing the clinical and transcriptome data from The Cancer Genome Atlas (TCGA) website, we present the landscape of genomic alterations and RNA differential expression profiles. By analyzing the ENCODE TP53 ChIP-seq data, we get the TP53 chromatin binding profiles. By KaplanβMeier (KM) survival analysis and ROC analysis, we identify lncRNA prognosis markers. TP53 ranks the highest mutation frequency gene and the maximum mutation type of TP53 is Missense Mutation (> 2.5Γ10 4 ). TP53 mutation showed poor clinical outcome among the pathological Stage II and Stage III HCC patients. By differential expression analysis of the TP53 wild type and mutation HCC, we find thousands of misregulated genes, including 699 differential expression lncRNAs (p <0.05, |log2FC| β₯1). Functional enrichment analysis of the misregulated genes shows that TP53 mutation events mainly alter DNA replication, cell cycle and immune response signaling pathways. By estimation of tumor-infiltrating immune cells through CIBERSORT, we find that the TP53 mutation events are significantly correlated with the different proportions of nine immune cells. We then integratively analyze the differential expression lncRNAs in TP53 wild type and mutation groups and the TP53 ChIP-seq binding lncRNAs, and get 112 overlap lncRNAs. By KaplanβMeier survival analysis and ROC analysis, we identify two lncRNAs (RP4-736L20.3 and SNRK-AS1) that show significant prognosis value. Using the collected HCC samples, we validate the misregulated expression of RP4-736L20.3 and SNRK-AS1. The work presents the landscape of genomic variations and two TP53 mutation related and directly regulated lncRNA prognosis markers of HCC. | PMC8364375 | ['genomics'] | ['genomics'] |
['cholera', 'Haiti', 'community health worker', 'public health', 'training'] | ['bacteria', 'waterborne infections', 'material development', 'ORS', 'oral rehydration solution', 'evaluation', 'dispatch'] | Cholera Prevention Training Materials for Community Health Workers, Haiti, 2010β2011 | Stopping the spread of the cholera epidemic in Haiti required engaging community health workers (CHWs) in prevention and treatment activities. The Centers for Disease Control and Prevention collaborated with the Haitian Ministry of Public Health and Population to develop CHW educational materials, train >1,100 CHWs, and evaluate training efforts. | PMC3310581 | ['epidemiology'] | ['epidemiology'] |
['Remdesivir', 'GS-441524', 'COVID-19', 'Nucleoside', 'Antiviral', 'Oral bioavailability', 'Drug metabolism'] | ['SARS-CoV-2', 'ADK, adenosine kinase', 'Cobi, cobicistat', 'CYP, cytochrome P450', 'DMPK, drug metabolism and pharmacokinetics', 'EMS, enhanced mass scan', 'EPI, enhanced product ion', 'FIPV, feline infectious peritonitis coronavirus', 'HINTs, histidine triad nucleotide binding proteins', 'HLMs, human liver microsomes', 'IDA, information dependent acquisition', 'MLMs, mouse liver microsomes', 'MRM, multiple reaction monitoring', 'RdRp, RNA-dependent RNA-polymerases', 'RDV, remdesivir', 'SOF, sofosbuvir', 'TAF, tenofovir alafenamide'] | Can remdesivir and its parent nucleoside GS-441524 be potential oral drugs? An inΒ vitro and inΒ vivo DMPK assessment | Remdesivir (RDV) is the only US Food and Drug Administration (FDA)-approved drug for treating COVID-19. However, RDV can only be given by intravenous route, and there is a pressing medical need for oral antivirals. Significant evidence suggests that the role of the parent nucleoside GS-441524 in the clinical outcomes of RDV could be largely underestimated. We performed an inΒ vitro and inΒ vivo drug metabolism and pharmacokinetics (DMPK) assessment to examine the potential of RDV, and particularly GS-441524, as oral drugs. In our inΒ vitro assessments, RDV exhibited prohibitively low stability in human liver microsomes (HLMs, t 1/2 =Β βΌ1Β min), with the primary CYP-mediated metabolism being the mono-oxidation likely on the phosphoramidate moiety. This observation is poorly aligned with any potential oral use of RDV, though in the presence of cobicistat, the microsomal stability was drastically boosted to the level observed without enzyme cofactor NADPH. Conversely, GS-441524 showed excellent metabolic stability in human plasma and HLMs. In further inΒ vivo studies in CD-1 mice, GS-441524 displayed a favorable oral bioavailability of 57%. Importantly, GS-441524 produced adequate drug exposure in the mice plasma and lung, and was effectively converted to the active triphosphate, suggesting that it could be a promising oral antiviral drug for treating COVID-19. While extensive hydrolysis and CYP-mediated metabolism in liver render remdesivir (RDV) unsuitable as an oral drug, GS-441524 exhibited favorable oral bioavailability and effective bioactivation in mice toward oral use. Image 1 | PMC8245906 | ['drug_discovery'] | ['drug_discovery'] |
['Healthcare workers', 'high risk', 'immunoassay', 'pandemic', 'SARS-CoV-2', 'seroprevalence'] | [] | Seroprevalence of antibodies to SARS-CoV-2 in healthcare workers & implications of infection control practice in India | Healthcare workers (HCWs) are considered to be at a high risk of contracting COVID-19 infection. Besides, control of nosocomial infections transmitted from HCWs to the patients is also a cause of concern. This study was undertaken to investigate the seroprevalence of antibodies against the SARS-CoV-2 virus among the hospital staff of a tertiary care health facility in north India. The HCWs were tested for SARS-CoV-2 serology (IgG+IgM) using chemiluminescence immunoassay between June 22 and July 24, 2020. Venous blood (2 ml) was collected and tested for SARS-CoV-2 IgG and IgM antibodies. Of the 3739 HCWs tested, 487 (13%) were positive for total SARS-CoV-2 antibodies. The highest seroprevalence was observed in administrative staff (19.6%) and least in physicians (5.4%). The staff who used public (20%) and hospital transportation (16.9%) showed higher seroprevalence compared to staff using personal transportation (12.4%). No difference was observed between HCWs posted in COVID versus non-COVID areas. All seropositive symptomatic HCWs in our study (53.6%) had mild symptoms, and the remaining 46.4 per cent were asymptomatic. The antibody positivity rate progressively increased from 7.0 per cent in the first week to 18.6 per cent in the fourth week during the study. The presence of antibodies to SARS-CoV-2 in a significant number of asymptomatic HCWs, association with the use of public transport, relatively lower seroprevalence compared with the non-HCWs and rising trend during the period of the study highlight the need for serosurveillance, creating awareness for infection control practices including social distancing and study of infection dynamics in the community for effective control of an infectious pandemic. | PMC8184075 | ['epidemiology'] | ['epidemiology'] |
['Hepatocellular carcinoma (HCC)', 'Transcatheter arterial chemoembolization (TACE)', 'Transcatheter arterial chemotherapy infusion (TACI)', 'Efficacy', 'Safety', 'Cohort studies', 'Meta-analysis'] | ['Randomized clinical trials'] | Efficacy and Safety of Transcatheter Arterial Chemoembolization and Transcatheter Arterial Chemotherapy Infusion in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis | Hepatocellular carcinoma (HCC) is a worldwide health threat with increasing incidence and a high mortality rate. Most HCC patients are diagnosed at an advanced stage and are unable to undergo potential curative surgery. Transcatheter arterial chemoembolization (TACE) and transcatheter arterial chemotherapy infusion (TACI) are two of the main palliative treatments for advanced HCC patients. The clinical efficacy and safety of TACE and TACI are controversial. For this reason, we conducted a systematic review and meta-analysis to summarize the current evidence. We searched for randomized controlled trials (RCTs) and cohort studies that compared the clinical outcomes and adverse effects in HCC patients who received TACE or TACI treatments. The database search was performed and last updated on November 1, 2016. Overall survival and clinical response were compared using a hazard ratio (HR) with a 95% confidence interval (CI). A total of 11 clinical studies that included 13,090 patients were included based on the inclusion/exclusion criteria, of which 9 were cohort studies and 2 were RCTs. TACE was associated with a 23% lower hazard of death compared to TACI (pooled HRβ=β0.77, 95% CIβ=β0.67β0.88, p =β0.0002). Patients receiving TACE had a 28% higher disease control rate (DCR) and 162% higher objective response rate (ORR). Only the increase in ORR associated with TACE was statistically significant [DCR: odds ratio (OR)β=β1.28, 95% CIβ=β0.35β4.64, p =β0.71; ORR: ORβ=β2.62, 95% CIβ=β1.33β5.15, p =β0.002]. TACE is associated with more favorable survival and response rate than TACI in patients with intermediate or advanced HCC. | PMC7844720 | ['clinical_trials'] | ['clinical_trials'] |
['Diabetes', 'Obesity', 'COVID-19', 'Pandemic', 'Management'] | ['Consensus'] | Management of patients with diabetes and obesity in the COVID-19 era: Experiences and learnings from South and East Europe, the Middle East, and Africa | The COVID-19 pandemic has had a major effect on healthcare during 2020. Current evidence suggests that, while individuals with diabetes and obesity are no more prone to SARS-CoV-2 infection than those without, the risk of hospitalisation if someone has diabetes or obesity and then contracts COVID-19 is three times higher β and 4.5 times higher if they have diabetes and obesity. We assembled a panel of experts from South and East Europe, the Middle East, and Africa to discuss the challenges to management of diabetes and obesity during and post the COVID-19 pandemic. The experience and learnings of this panel cover a heterogeneous patient population, wide range of clinical settings, healthcare organisations, disease management strategies, and social factors. We discuss the importance of timely and effective disease management via telemedicine, providing reassurance and guidance for patients unable or unwilling to visit healthcare settings at this time. We address the use of novel therapies and their role in managing diabetes and obesity during the pandemic, as well as the importance of controlling hypoglycaemia and preventing cardiovascular complications, particularly in vulnerable people. Finally, we consider post-COVID-19 management of diabetes and obesity, and how these learnings and experiences should impact upon future clinical guidelines. | PMC7728417 | ['epidemiology'] | ['epidemiology'] |
['Nonhuman primates', 'humans', 'bacteria', 'Africa', 'surveillance'] | ['infectious diseases', 'emergence'] | Bacterial Infections in Humans and Nonhuman Primates from Africa: Expanding the Knowledge | The close phylogenetic relationship between humans and other primates creates exceptionally high potential for pathogen exchange. The surveillance of pathogens in primates plays an important role in anticipating possible outbreaks. In this study, we conducted a molecular investigation of pathogenic bacteria in feces from African nonhuman primates (NHPs). We also investigated the pathogens shared by the human population and gorillas living in the same territory in the Republic of Congo. In total, 93% of NHPs (n=176) and 95% (n=38) of humans were found to carry at least one bacterium. Non- pallidum Treponema spp. (including T. succinifaciens , T. berlinense , and several potential new species) were recovered from stools of 70% of great apes, 88% of monkeys, and 79% of humans. Non- tuberculosis Mycobacterium spp. were also common in almost all NHP species as well as in humans. In addition, Acinetobacter spp., members of the primate gut microbiota, were mainly prevalent in human and gorilla. Pathogenic Leptospira spp. were highly present in humans (82%) and gorillas (66%) stool samples in Congo, but were absent in the other NHPs, therefore suggesting a possible gorillas-humans exchange. Particular attention will be necessary for enteropathogenic bacteria detected in humans such as Helicobacter pylori , Salmonella spp. (including S. typhi/paratyphi ), Staphyloccocus aureus , and Tropheryma whipplei , some of which were also present in gorillas in the same territory ( S. aureus and T. whipplei ). This study enhances our knowledge of pathogenic bacteria that threaten African NHPs and humans by using a non-invasive sampling technique. Contact between humans and NHPs results in an exchange of pathogens. Ongoing surveillance, prevention, and treatment strategies alone will limit the spread of these infectious agents. | PMC8223552 | ['epidemiology'] | ['epidemiology'] |
['albuminuria', 'chronic kidney disease', 'exercise training', 'glomerular filtration rate', 'physical performance', 'randomized controlled trial'] | [] | Randomized Controlled Trial of Exercise inΒ CKDβThe RENEXC Study | Home-based, clinically feasible trials in nonβdialysis-dependent patients with chronic kidney disease (CKD) are sparse. We compared the effects of 2 different exercise training programs on physical performance, and measured glomerular filtration rate (mGFR) and albuminuria level in patients with CKD stages 3 toΒ 5. This is a single-center, randomized controlled trial (RCT) comprising 151 patients (mGFR: 22 Β± 8 ml/min per 1.73 m 2 ; age 66 Β± 14 years) randomized to either balance or strength training. Both groups were prescribed 30 minutes of exercise per day for 5 days per week for 12 months, comprising 60 minutes per week of endurance training and 90 minutes per week of either strength or balance exercises. The exercises were individually prescribed, and the intensity was monitored with Borgβs rating of perceived exertion (RPE). There were no treatment differences for any of the primary outcomes measuring physical performance. The strength and balance groups showed significantly increased effect sizes after 12 months for the following: walking (31 m and 24 m, P < 0.001) and the 30-second sit-to-stand test (both: 1 time, P < 0.001); quadriceps strength (right/left: strength 1.2/0.8 kg*m, P < 0.003; balance 0.6/0.9, P < 0.01); functional reach (both: 2 cm, P < 0.01); and fine motor skills (open/closed eyes, right/left, both: between 0.3 and 4 seconds faster, P < 0.05). After 12 months, there was a significant treatment difference for albuminuria ( P < 0.02), which decreased by 33% in the strength group. In both groups, mGFR declined by 1.8 ml/min per 1.73 m 2 . Our primary hypothesis that strength training was superior to balance training was not confirmed. Within groups, 12 months of exercise training resulted in significant improvements in most measures of physical performance. Measured GFR declined similarly in the 2 groups. The strength group showed a significant decrease in albuminuria. | PMC6609793 | ['clinical_trials'] | ['clinical_trials'] |
['Streptococcus pneumoniae', 'pneumonia', 'pneumococcal', 'serotype 15A', 'disease outbreak'] | ['pneumococcal infections', 'bacteria', 'antibiotic', 'antibacterial', 'antimicrobial drugs'] | Streptococcus pneumoniae Serotype 15A in Psychiatric Unit, Rhode Island, USA, 2010β2011 | During a pneumococcal disease outbreak in a pediatric psychiatric unit in a hospital in Rhode Island, USA, 6 (30%) of 20 patients and staff were colonized with Streptococcus pneumoniae serotype 15A, which is not included in pneumococcal vaccines. The outbreak subsided after implementation of antimicrobial drug prophylaxis and enhanced infection control measures. | PMC3559171 | ['epidemiology'] | ['epidemiology'] |
['Genistein derivatives', 'Acetylcholinesterase (AChE)', 'Molecular docking', 'Molecular dynamics simulation', 'MM/GBSA'] | ['Kinetics analysis', 'ACh, acetylcholine', 'AChEIs, acetylcholinesterase inhibitors', 'AChE, acetylcholinesterase', 'AD, AlzheimerΧ³s disease', 'BuChE, butyrylcholinesterase', 'BuSCh,S-butyrylthiocholine chloride', 'CAS, catalytic active site', 'DTNB, 5,5β²-dithiobis-(2-nitrobenzoic acid)', 'GAFF, generalized AMBER force field', 'G1, 3-(4-methoxyphenyl)-7-(2-(piperidin-1-yl)ethoxy)-4H-chromen-4-one', 'G2, (S)-3-(4-methoxyphenyl)-7-(2-(2-methylpiperidin-1-yl)ethoxy)-4H-chromen-4-one', 'iso-OMPA, tetraisopropyl pyrophosphoramide', 'MD, molecular dynamics', 'MM/GBSA, molecular mechanics/generalized born surface area', 'PAS, peripheral anionic site', 'PDB, protein data bank', 'PME, particle mesh Ewald', 'RMSD, root-mean-square deviation', 'S-ACh, acetylthiocholine iodide', 'ΞEele, electrostatic energy contribution', 'ΞEMM, gas-phase interaction energy between receptor and ligand', 'ΞEvdw, van der Waals energy contribution', 'SASA, solvent accessible surface area', 'ΞGexp, experimental binding free energy', 'ΞGGB, polar desolvation energy term', 'ΞGpred, total binding free energy', 'ΞGSA, nonpolar desolvation energy term', 'ΞS, conformational entropy contribution'] | Inhibition of acetylcholinesterase by two genistein derivatives: kinetic analysis, molecular docking and molecular dynamics simulation | In this study two genistein derivatives (G1 and G2) are reported as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and differences in the inhibition of AChE are described. Although they differ in structure by a single methyl group, the inhibitory effect of G1 (IC 50 =264Β nmol/L) on AChE was 80 times stronger than that of G2 (IC 50 =21,210Β nmol/L). Enzyme-kinetic analysis, molecular docking and molecular dynamics (MD) simulations were conducted to better understand the molecular basis for this difference. The results obtained by kinetic analysis demonstrated that G1 can interact with both the catalytic active site and peripheral anionic site of AChE. The predicted binding free energies of two complexes calculated by the molecular mechanics/generalized born surface area (MM/GBSA) method were consistent with the experimental data. The analysis of the individual energy terms suggested that a difference between the net electrostatic contributions (Ξ E ele +Ξ G GB ) was responsible for the binding affinities of these two inhibitors. Additionally, analysis of the molecular mechanics and MM/GBSA free energy decomposition revealed that the difference between G1 and G2 originated from interactions with Tyr124, Glu292, Val294 and Phe338 of AChE. In conclusion, the results reveal significant differences at the molecular level in the mechanism of inhibition of AChE by these structurally related compounds. The inhibitory potency of G1 (IC 50 =264Β nmol/L) was 80 times stronger than that of G2 (IC 50 =21,210Β nmol/L) against acetylcholinesterase. The combination of enzyme-kinetic analysis, molecular docking and molecular dynamics simulations was conducted to better understand the molecular basis of the inhibition against AChE. | PMC4629110 | ['drug_discovery'] | ['drug_discovery'] |
['infectious disease', 'epidemiology', 'heritability', 'response to selection', 'indirect genetic effect'] | ['quantitative genetics'] | Why genetic selection to reduce the prevalence of infectious diseases is way more promising than currently believed | Genetic selection for improved disease resistance is an important part of strategies to combat infectious diseases in agriculture. Quantitative genetic analyses of binary disease status, however, indicate low heritability for most diseases, which restricts the rate of genetic reduction in disease prevalence. Moreover, the common liability threshold model suggests that eradication of an infectious disease via genetic selection is impossible because the observed-scale heritability goes to zero when the prevalence approaches zero. From infectious disease epidemiology, however, we know that eradication of infectious diseases is possible, both in theory and practice, because of positive feedback mechanisms leading to the phenomenon known as herd immunity. The common quantitative genetic models, however, ignore these feedback mechanisms. Here, we integrate quantitative genetic analysis of binary disease status with epidemiological models of transmission, aiming to identify the potential response to selection for reducing the prevalence of endemic infectious diseases. The results show that typical heritability values of binary disease status correspond to a very substantial genetic variation in disease susceptibility among individuals. Moreover, our results show that eradication of infectious diseases by genetic selection is possible in principle. These findings strongly disagree with predictions based on common quantitative genetic models, which ignore the positive feedback effects that occur when reducing the transmission of infectious diseases. Those feedback effects are a specific kind of Indirect Genetic Effects; they contribute substantially to the response to selection and the development of herd immunity ( i.e. , an effective reproduction ratio less than one). | PMC8049556 | ['epidemiology'] | ['epidemiology'] |
['pharmacokinetics', 'renal impairment', 'safety', 'selective progesterone receptor modulator', 'vilaprisan'] | [] | Pharmacokinetics and Safety of the Novel Selective Progesterone Receptor Modulator Vilaprisan in Participants With Renal Impairment | This open label, parallelβgroup study investigated the pharmacokinetics and safety of a single oral 2βmg dose of the novel selective progesterone receptor modulator vilaprisan in participants with impaired renal function compared with age, weight, sex, and race matched controls with normal renal function. Systemic exposure (area under the plasma concentrationβtime curve [AUC]) and maximum observed concentrations (C max ) were compared among 9 participants with moderate renal impairment and matched controls by ANOVA. An additional 4 participants, each with severe renal impairment or normal renal function, contributed to a linear regression analysis exploring any monotone relationship between individual variables and the estimated glomerular filtration rate. The geometric mean AUC was increased by a factor of 1.35 in renally impaired participants compared to normal controls (not statistically significant: least squares mean, 1.346; 90% confidence interval, 0.918β1.973). C max was similar in participants with moderate renal impairment and normal renal function (least squares mean, 1.026; 90% confidence interval, 0.779β1.351). Considering the overall variability, there was no correlation between renal function (estimated glomerular filtration rate) and C max or AUC of vilaprisan. Single oral administration of vilaprisan 2Β mg was well tolerated by all participants, both men and women and irrespective of renal function. The incidence of treatmentβemergent adverse events was similar across all groups. Results from this study do not indicate that a dose adjustment will be necessary for vilaprisan when treating patients up to moderate renal impairment. | PMC7496433 | ['clinical_trials', 'drug_discovery'] | ['clinical_trials' |
['morbidity and mortality conferences', 'patient safety', 'quality improvement', 'hospital', 'medical education'] | ['organizational learning'] | Implementation status of morbidity and mortality conferences in Swiss hospitals: a national cross-sectional survey study | To determine the implementation status and current practice of morbidity and mortality conferences (M&MCs) in Switzerland. A national cross-sectional online survey was conducted in spring 2017. The questionnaire focused on overall goals, structure and procedures of hospital M&MCs. Further topics included satisfaction, perceived effectiveness and support requirements. A total of 913 chief physicians of surgery and internal medicine, and specialist fields of obstetrics and gynaecology, anaesthesiology and intensive care from Swiss acute care hospitals were invited to the survey. 321 completed the questionnaire, resulting in a 35.2% response rate. Chief or senior physicians in charge of the M&MCs in their department. No intervention Numbers and percentages of M&MCs within the surveyed disciplines fulfilling certain characteristics and procedural features. Among 321 respondents, the majority are conducting M&MCs in their departments. Within and between the medical disciplines considerable heterogeneity was found in structural and procedural features of M&MCs. Only a small part of the reported M&MCs is following a systematic approach and meeting recommended procedural features. Although the respondents are satisfied and perceive the M&MCs as an efficient tool, they agree that there is a need for professionalization and standardization. M&MCs are widely used to promote medical education, patient safety and quality improvements. However, the term M&MC seems to cover different types of meetings. Although the overall goals are similar, various types of M&MCs are used in practice and different objectives are pursued. Tools such as checklists, guidelines and templates are considered helpful. | PMC5928454 | ['clinical_trials'] | ['clinical_trials'] |
['cognitive impairment', 'myocardial infarction', 'percutaneous coronary intervention', 'Myocardial Infarction', 'Cognitive Impairment'] | ['health services research', 'Mortality/Survival'] | Association of Cognitive Impairment With Treatment and Outcomes inΒ Older Myocardial Infarction Patients: A Report From the NCDRΒ Chest Painβ MI Registry | Little is known regarding use of cardiac therapies and clinical outcomes among older myocardial infarction ( MI ) patients with cognitive impairment. Patients β₯65Β years old with MI in the NCDR (National Cardiovascular Data Registry) Chest Painβ MI Registry between January 2015 and December 2016 were categorized by presence and degree of chartβdocumented cognitive impairment. We evaluated whether cognitive impairment was associated with allβcause inβhospital mortality after adjusting for known prognosticators. Among 43Β 812 STβsegmentβelevation myocardial infarction (STEMI) patients, 3.9% had mild and 2.0% had moderate/severe cognitive impairment; among 90Β 904 nonβSTβsegmentβelevation myocardial infarction (NSTEMI patients, 5.7% had mild and 2.6% had moderate/severe cognitive impairment. A statistically significant but numerically small difference in the use of primary percutaneous coronary intervention was observed between patients with STEMI with and without cognitive impairment (none, 92.1% versus mild, 92.8% versus moderate/severe, 90.4%; P =0.03); use of fibrinolysis was lower among patients with cognitive impairment (none, 40.9% versus mild, 27.4% versus moderate/severe, 24.2%; P <0.001). Compared with NSTEMI patients without cognitive impairment, rates of angiography, percutaneous coronary intervention, and coronary artery bypass grafting were significantly lower among patients with NSTEMI with mild (41%, 45%, and 70% lower, respectively) and moderate/severe cognitive impairment (71%, 74%, and 93% lower, respectively). After adjustment, compared with no cognitive impairment, presence of moderate/severe ( STEMI : odds ratio, 2.2, 95% CI , 1.8β2.7; NSTEMI : odds ratio, 1.7, 95% CI , 1.4β2.0) and mild cognitive impairment ( STEMI : OR , 1.3, 95% CI , 1.1β1.5; NSTEMI : odds ratio, 1.3, 95% CI , 1.2β1.5) was associated with higher inβhospital mortality. Patients with NSTEMI with cognitive impairment are substantially less likely to receive invasive cardiac care, while patients with STEMI with cognitive impairment receive similar primary percutaneous coronary intervention but less fibrinolysis. Presence and degree of cognitive impairment was independently associated with increased inβhospital mortality. Approaching clinical decision making for older patients with MI with cognitive impairment requires further study. | PMC6755847 | ['clinical_trials'] | ['clinical_trials'] |
['adjuvant chemotherapy', 'breast cancer', 'gene expression signature', 'node-positive', 'Oncotype Dx'] | [] | Avoiding over- and undertreatment in patients with resected node-positive breast cancer with the use of gene expression signatures: are we there yet? | Prediction of benefit from adjuvant chemotherapy following resection of early breast cancer and, as a result, proper selection of candidates remains an elusive goal since the relative magnitude of benefit is the same regardless of the presence of clinicopathologic factors. Multiple studies, including randomized trials, establish the role of certain gene expression signatures in node-negative disease since they predict the risk of breast cancer relapse being so low that adjuvant chemotherapy can be omitted. In contrast, more limited data are available in higher risk, node-positive breast cancer patients, making the exclusion of adjuvant chemotherapy potentially hazardous. βProspectiveβretrospectiveβ studies and limited prospective data show that several signatures, namely Oncotype Dx, MammaPrint, Prosigna, EndoPredict and Breast Cancer Index, select with different levels of success node-positive patients at very low risk for distant recurrence despite not receiving chemotherapy, although the long-term follow-up is still awaited. Pending, however the publication of the results from ongoing randomized studies which enroll patients with node-positive disease, major caution is warranted. Improper use and misinterpretation of these transcriptomic profiles can lead to undertreatment and exposure of patients to unnecessary risks resulting in increased breast cancer mortality for patients with axillary node-positive disease. With this review we critically discuss the available data on gene expression signatures that are used in clinical practice and offer practical recommendations regarding the management of patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive breast cancer. | PMC6695578 | ['genomics'] | ['genomics'] |
['simulation', 'genome evolution', 'indel', 'lateral gene transfer', 'GC-content amelioration'] | ['codon models'] | ALFβA Simulation Framework for Genome Evolution | In computational evolutionary biology, verification and benchmarking is a challenging task because the evolutionary history of studied biological entities is usually not known. Computer programs for simulating sequence evolution in silico have shown to be viable test beds for the verification of newly developed methods and to compare different algorithms. However, current simulation packages tend to focus either on gene-level aspects of genome evolution such as character substitutions and insertions and deletions (indels) or on genome-level aspects such as genome rearrangement and speciation events. Here, we introduce Artificial Life Framework (ALF), which aims at simulating the entire range of evolutionary forces that act on genomes: nucleotide, codon, or amino acid substitution (under simple or mixture models), indels, GC-content amelioration, gene duplication, gene loss, gene fusion, gene fission, genome rearrangement, lateral gene transfer (LGT), or speciation. The other distinctive feature of ALF is its user-friendly yet powerful web interface. We illustrate the utility of ALF with two possible applications: 1) we reanalyze data from a study of selection after globin gene duplication and test the statistical significance of the original conclusions and 2) we demonstrate that LGT can dramatically decrease the accuracy of two well-established orthology inference methods. ALF is available as a stand-alone application or via a web interface at http://www.cbrg.ethz.ch/alf . | PMC3341827 | ['genomics'] | ['genomics'] |
['Intensive Care Units', 'medication errors', 'nurses', 'patient safety', 'pharmacists', 'physicians'] | [] | Causes of Medication Errors in Intensive Care Units from the Perspective of Healthcare Professionals | This study was conducted to explore and to describe the causes of medication errors in Intensive Care Units (ICUs) from the perspective of physicians, nurses, and clinical pharmacists. The study was conducted using a descriptive qualitative method in 2016. We included 16 ICUs of seven educational hospitals affiliated to Isfahan University of Medical Sciences. Participants included 19 members of the healthcare team (physician, nurse, and clinical pharmacist) with at least 1 year of work experience in the ICUs. Participants were selected using purposeful sampling method. Data were collected through semi-structured individual interviews and were used for qualitative content analysis. The four main categories and ten subcategories were extracted from interviews. The four categories were as follows: βlow attention of healthcare professionals to medication safety,β βlack of professional communication and collaboration,β βenvironmental determinants,β and βmanagement determinants.β Incorrect prescribing of physicians, unsafe drug administration of nurses, the lack of pharmaceutical knowledge of the healthcare team, and the weak professional collaboration lead to medication errors. To improve patient safety in the ICUs, healthcare center managers need to promote interprofessional collaboration and participation of clinical pharmacists in the ICUs. Furthermore, interprofessional programs to prevent and reduce medication errors should be developed and implemented. | PMC5632936 | ['clinical_trials'] | ['clinical_trials'] |
['Bovine', 'Bovine herpesvirus 1', 'Bovine viral diarrhea virus', 'Risk factor', 'Seroprevalence'] | [] | Seroprevalence and risk factors associated with bovine herpesvirus 1 and bovine viral diarrhea virus in North-Eastern Mexico | Bovine herpesvirus 1 (BoHV-1) and bovine viral diarrhea virus (BVDV) are well known etiological agents of cattle that produce important economic losses due to reproductive failures and calf mortality, as well as enteric and respiratory disease. Tamaulipas is located northeast of Mexico, an important cattle production and the principal exporter of calf and heifer to the United States. The objectives of this study were to estimate the seroprevalence of BoHV-1 and of BVDV, and to determine the effects of risk factors on these infections. Blood samples of cattle from 57 farms from rural districts of Tamaulipas were collected. The samples were tested for antibodies against BoHV-1 and BVDV using commercial ELISA kits. Data on potential risk factors were obtained using a questionnaire administered to the farmer at the time the blood samples were taken. The seroprevalences for BoHV-1 and BVDV were 64.4% and 47.8%, respectively. In the logistic regression analysis, the significant risk factors were rural district, herd size and cattle introduced to the farm. This study confirms the high seroprevalence of BoHV-1 and BVDV in unvaccinated cattle in Tamaulipas, Mexico. The results of this study could be used for the development of BoHV-1 and BVDV prevention and control program in North-Eastern, Mexico. | PMC5011497 | ['epidemiology'] | ['epidemiology'] |
['genome editing', 'CRISPR', 'zinc-finger nuclease', 'chromatin', 'nucleosomes'] | [] | Nucleosomes inhibit target cleavage by CRISPR-Cas9 in vivo | The efficiency of genome editing with CRISPR-Cas9 can vary widely at different targets and in different cells. Some of this variability may be due to the inherent quality of different guide RNAs, but it may also depend on the cellular context of the genomic target DNA. In this report, we demonstrate that targets bound by nucleosomes are cut much less efficiently than targets from which nucleosomes are absent or have been depleted. This information can inform target selection, particularly in cases where cells are quiescent or nucleosome mobility is limited. Genome editing with CRISPR-Cas nucleases has been applied successfully to a wide range of cells and organisms. There is, however, considerable variation in the efficiency of cleavage and outcomes at different genomic targets, even within the same cell type. Some of this variability is likely due to the inherent quality of the interaction between the guide RNA and the target sequence, but some may also reflect the relative accessibility of the target. We investigated the influence of chromatin structure, particularly the presence or absence of nucleosomes, on cleavage by the Streptococcus pyogenes Cas9 protein. At multiple target sequences in two promoters in the yeast genome, we find that Cas9 cleavage is strongly inhibited when the DNA target is within a nucleosome. This inhibition is relieved when nucleosomes are depleted. Remarkably, the same is not true of zinc-finger nucleases (ZFNs), which cleave equally well at nucleosome-occupied and nucleosome-depleted sites. These results have implications for the choice of specific targets for genome editing, both in research and in clinical and other practical applications. | PMC6156633 | ['genomics'] | ['genomics'] |
['psychotic depression', 'mifepristone', 'serotonin transporter', 'Xenopus oocyte', 'serotonin', 'depression', 'two-electrode voltage clamp'] | ['nerve regeneration', 'current recording', 'antidepressants', 'serotonin transmission', 'NSFC grant', 'neural regeneration'] | Mifepristone modulates serotonin transporter function | Regulating serotonin expression can be used to treat psychotic depression. Mifepristone, a glucocorticoid receptor antagonist, is an effective candidate for psychotic depression treatment. However, the underlying mechanism related to serotonin transporter expression is poorly understood. In this study, we cloned the human brain serotonin transporter into Xenopus oocytes, to establish an in vitro expression system. Two-electrode voltage clamp recordings were used to detect serotonin transporter activity. Our results show that mifepristone attenuates serotonin transporter activity by directly inhibiting the serotonin transporter, and suggests that the serotonin transporter is a pharmacological target of mifepristone for the treatment of psychotic depression. | PMC4146234 | ['epidemiology'] | ['epidemiology'] |
['carboxymethylcellulose', 'acetylated distarch phosphate', 'bentonite', 'boric acid and aluminium sulfate', 'food contact materials'] | ['FCMsubstance Nos\xa01071 and 1072', 'active and intelligent materials', 'safety assessment'] | Safety assessment of the active substances carboxymethylcellulose, acetylated distarch phosphate, bentonite, boric acid and aluminium sulfate, for use in active food contact materials | This scientific opinion of the EFSA PanelΒ on Food Contact Materials, Enzymes, Flavourings and Processing Aids ( CEF Panel) deals with the safety evaluation of the active substances carboxymethylcellulose, acetylated distarch phosphate ( FCM substance NoΒ 1071), bentonite, boric acid and aluminium sulfate ( FCM substance NoΒ 1072). The mixture is intended to be used as a liquid absorber in the packaging of perishable foods to extend their shelfβlife. All substances have been evaluated and approved for use as additives in plastic food contact materials and/or as food additives. Migration of boron into foods was up to 0.7Β mg/kg food. Migration of aluminium was not detected (limit of detection ( LOD ) of 0.001Β mg/kg). The CEF PanelΒ concludes that the substances carboxymethylcellulose, acetylated distarch phosphate, bentonite, boric acid and aluminium sulfate are not of safety concern for the consumer when used as active components in moisture and liquid absorbers. The absorbent pads must be used under conditions in which direct contact between the active mixture and the food is avoided and the fluid absorption capacity of the absorber is not exceeded. | PMC7009366 | ['clinical_trials'] | ['clinical_trials'] |
['Lazarus phenomenon', 'return of spontaneous circulation', 'CPR', 'resuscitation', 'cardiac arrest'] | ['myocardial infarction'] | The Lazarus phenomenon | The Lazarus phenomenon or the unassisted return of spontaneous circulation after cardiac arrest is a grossly underreported phenomenon in medical literature which essentially implies the βresurrectionβ of an individual after cardiac arrest. Although there have been a handful of such cases reported, the clinical incidence and significance may be underestimated. Because of the presumed infrequency of this condition, there are no studies specifically researching Lazarus phenomenon in scientific literature. This review intends to systematically present current and past knowledge on this rare but definitive phenomenon. Research databases namely Google Scholar, Science Direct, Medline and PubMed were utilized. Only articles which identified cases where the return of spontaneous circulation occurred after cessation of Cardiopulmonary Resuscitation (CPR), and review articles on the entity were included. The mentioned databases were searched using the terms βLazarus phenomenonβ, βcardiopulmonary resuscitationβ and βreturn of spontaneous circulationβ. A literature review was synthesised based on articles meeting the eligibility criteria to better understand the phenomenon of return of spontaneous circulation. | PMC4973403 | ['clinical_trials'] | ['clinical_trials'] |
['2019 novel coronavirus disease', 'mental health', 'preparedness', 'response', 'China'] | ['COVID-19', 'SARS-CoV-2', 'severe acute respiratory syndrome coronavirus 2', 'viruses', 'respiratory infections', 'zoonoses', 'public health emergency'] | Public Mental Health Crisis during COVID-19 Pandemic, China | The 2019 novel coronavirus disease emerged in China in late 2019βearly 2020 and spread rapidly. China has been implementing emergency psychological crisis interventions to reduce the negative psychosocial impact on public mental health, but challenges exist. Public mental health interventions should be formally integrated into public health preparedness and emergency response plans. | PMC7323564 | ['epidemiology'] | ['epidemiology'] |
['Influenza', 'vaccine', 'vaccination', 'A(H1N1)pdm09', 'H1N1', 'pandemic'] | ['viruses', 'model'] | Effects of Vaccine Program against Pandemic Influenza A(H1N1) Virus, United States, 2009β2010 | Vaccination likely prevented 700,000β1,500,000 clinical cases, 4,000β10,000 hospitalizations, and 200β500 deaths. In April 2009, the United States began a response to the emergence of a pandemic influenza virus strain: A(H1N1)pdm09. Vaccination began in October 2009. By using US surveillance data (April 12, 2009βApril 10, 2010) and vaccine coverage estimates (October 3, 2009βApril 18, 2010), we estimated that the A(H1N1)pdm09 virus vaccination program prevented 700,000β1,500,000 clinical cases, 4,000β10,000 hospitalizations, and 200β500 deaths. We found that the national health effects were greatly influenced by the timing of vaccine administration and the effectiveness of the vaccine. We estimated that recommendations for priority vaccination of targeted priority groups were not inferior to other vaccination prioritization strategies. These results emphasize the need for relevant surveillance data to facilitate a rapid evaluation of vaccine recommendations and effects. | PMC3647645 | ['epidemiology'] | ['epidemiology'] |
['Fluoroquinolones', 'Multicenter retrospective cohort study', 'Stenotrophomonas maltophilia', 'Tigecycline', 'Ventilator-associated pneumonia'] | ['Levofloxacin', 'Moxifloxacin'] | Tigecycline in the Treatment of Ventilator-Associated Pneumonia Due to Stenotrophomonas maltophilia : A Multicenter Retrospective Cohort Study | Tigecycline is a potential alternative to trimethoprimβsulfamethoxazole in treating Stenotrophomonas maltophilia infections due to its potent in vitro antimicrobial activity. Clinical evidence regarding the use of tigecycline in the treatment of S. maltophilia infections is scarce. In this study, we assessed the efficacy of tigecycline treating ventilator-associated pneumonia (VAP) due to S. maltophilia in comparison with fluoroquinolones. This is a multicenter retrospective cohort study of patients admitted between January 2017 and December 2020 with the diagnosis of VAP caused by S. maltophilia receiving either tigecycline or fluoroquinolones as the definitive therapyββ₯β48Β h. Clinical outcomes including 28-day mortality, clinical cure and microbiological cure were analyzed. Of 82 patients with S. maltophilia VAP included, 46 received tigecycline, and 36 received fluoroquinolones; 70.7% of patients had polymicrobial pneumonia, and the appropriate empiric therapy was applied to only 14.6% of patients. The overall 28-day mortality was 39%. Compared with patients receiving fluoroquinolones, tigecycline therapy resulted in worse clinical cure (32.6% vs. 63.9%, p =β0.009) and microbiological cure (28.6% vs. 59.1%, p =β0.045), while there was no statistical difference between 28-day mortality (47.8% vs. 27.8%, p =β0.105) in the two groups. Similar results were also shown in the inverse probability of treatment weighted univariable regression model and multivariable regression model. The standard dose of tigecycline therapy was associated with a lower clinical and microbiological cure rate but not associated with an increased 28-day mortality in patients with S. maltophilia VAP compared with fluoroquinolones. Considering the unfavorable clinical outcomes, we therefore recommend against using the standard dose of tigecycline in treating S. maltophilia VAP unless new clinical evidence emerges. The online version contains supplementary material available at 10.1007/s40121-021-00516-5. | PMC8354101 | ['epidemiology'] | ['epidemiology'] |
['SARS-CoV-2', 'Nucleotide substitution rate', 'Outbreak', 'Population dynamics', 'Effective reproductive number', 'Cruise ship', 'Confined settings'] | ['COVID-19, Coronavirus disease 2019', 'SARS-CoV-2, severe acute respiratory syndrome coronavirus 2', 'SARS, severe acute respiratory syndrome', 'MERS, Middle East respiratory syndrome', 'RT-PCR, reverse-transcription PCR', 'R0, basic reproductive number', 'Re, effective reproductive number', 'GISAID, Global Initiative on Sharing All Influenza Data', 'MCMC, Markov chain Monte Carlo', 'GTR, general time-reversible', 'ML, maximum likelihood', 'ESS, effective sample size', 'HPD, highest posterior density', 'tMRCA, time to the most recent common ancestor'] | Transmission dynamics of SARS-CoV-2 on the Diamond Princess uncovered using viral genome sequence analysis | An outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred aboard the Diamond Princess cruise ship between her January 20 departure and late February 2020. Here, we used phylodynamic analyses to investigate the transmission dynamics of SARS-CoV-2 during the outbreak. Using a Bayesian coalescent-based method, the estimated mean nucleotide substitution rate of 240 SARS-CoV-2 whole-genome sequences was approximately 7.13Β ΓΒ 10 β4 substitutions per site per year. Population dynamics and the effective reproductive number (R e ) of SARS-CoV-2 infections were estimated using a Bayesian framework. The estimated origin of the outbreak was January 21, 2020. The infection spread substantially before quarantine on February 5. The R e peaked at 6.06 on February 4 and gradually declined to 1.51, suggesting that transmission continued slowly even after quarantine. These findings highlight the high transmissibility of SARS-CoV-2 and the need for effective measures to control outbreaks in confined settings. | PMC7880849 | ['epidemiology'] | ['epidemiology'] |
['neurotropic B vitamins', 'safety', 'thiamine', 'pyridoxine', 'cobalamin', 'neurotoxicity', 'hip fracture', 'lung cancer'] | [] | Update on Safety Profiles of Vitamins B1, B6, and B12: A Narrative Review | The neurotropic B vitamins B1 (thiamine), B6 (pyridoxine), and B12 (cobalamin) are essential for proper functioning of the nervous system. Deficiencies may induce neurological disorders like peripheral neuropathy (PN) and mainly occur in vulnerable populations (eg, elderly, diabetics, alcoholics). As epidemiologic cohort studies raised safety concerns about vitamin B6/B12 intake being potentially associated with increased risks of hip fracture (HF) and lung cancer (LC), we explored these aspects and performed comprehensive literature searches. However, we suggest not to neglect actual high-risk factors (eg, smoking in LC, higher age in HF) by focusing on individual nutrients, but to examine the complex interaction of numerous factors involved in disease development. Because it warrants continued consideration, we also provide an update on neurotoxicity associated with vitamin B6. We consider that neurological side effects due to vitamin B6 intake are rare and only occur with high daily doses and/or longer treatment duration. The benefit-risk ratio of high-dose treatment with neurotropic B vitamins in indications like PN is therefore considered advantageous, particularly if dosing recommendations are followed and serum levels monitored. | PMC7764703 | ['clinical_trials'] | ['clinical_trials'] |
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BiomedKeyRefine: Refined Biomedical Keyword Extraction Benchmark
Version 1.0
Last updated: February 2026
Author: Christian Hoang (@christhoang04)
License: MIT
π Dataset Summary
BiomedKeyRefine is a high-quality, refined subset of the PubMedAKE benchmark (CIKM 2022), specifically curated for biomedical keyword extraction research.
The original PubMedAKE contains 843k+ articles with author-assigned keywords (extractive + abstractive). This version:
- Filters for quality (β₯5 keywords total, abstract β₯200 chars, removed noisy entries >40% stop words).
- Stratifies into multi-label sub-domains (genomics, clinical_trials, drug_discovery, epidemiology).
- Enables evaluation of domain-specific knowledge impact on keyword extraction (correlation with external benchmarks like GUE, CSEDB).
- Supports LLM-as-a-judge with non-expert calibration.
Ideal for:
- Keyword extraction (extractive/abstractive)
- Domain adaptation & knowledge probing
- LLM evaluation in biomedical text mining
- Correlation between domain knowledge and extraction performance
π Dataset Statistics
| Metric | Value | Notes |
|---|---|---|
| Total Articles | 5,000 | Filtered from PubMedAKE small train (~82k) |
| Train Split | ~3,500 (70%) | Stratified by primary domain |
| Validation Split | ~750 (15%) | |
| Test Split | ~750 (15%) | |
| Sub-domains | 4 (multi-label) | genomics, clinical_trials, drug_discovery, epidemiology |
| Avg Keywords/Article | ~6β8 (in + not_in) | Author-assigned ground truth |
| Avg Abstract Length | β₯200 chars | Filtered for sufficient context |
| Languages | English | |
| Modalities | Text | Title + Abstract + Keywords |
Sub-domain Distribution (multi-label occurrences):
- epidemiology: ~1,741
- clinical_trials: ~1,467
- genomics: ~1,414
- drug_discovery: ~740
(Note: Multi-label means some articles belong to multiple domains, reflecting real interdisciplinary nature of biomedical research.)
π οΈ Supported Tasks and Leaderboards
- Keyword Extraction (extractive & abstractive)
- Domain Classification (multi-label from sub_domains)
- Knowledge Correlation (link domain knowledge benchmarks to extraction F1)
- LLM-as-a-Judge Evaluation (with non-expert calibration)
No official leaderboard yet β community contributions welcome!
π Languages
- Primarily English (all abstracts, titles, keywords from PubMed Central English subset).
π Dataset Structure
Data Instances
Each row is one biomedical article with:
- Metadata (PMC_ID, title)
- Content (abstract)
- Ground truth (keywords_in: extractive, keywords_not_in: abstractive)
- Labels (sub_domains: multi-label string, e.g., "genomics, drug_discovery")
Example (from clinical_trials):
{
"keywords_in": ["Clinical trials", "COVID-19", "Estimands", "Missing data", "Pandemic"],
"keywords_not_in": ["Statistical strategy", "Supportive analyses"],
"title": "Statistical Issues and Recommendations for Clinical Trials Conducted During the COVID-19 Pandemic",
"abstract": "The COVID-19 pandemic has had and continues to have major impacts on planned and ongoing clinical trials...",
"PMC_ID": "PMC8011486",
"sub_domains": "clinical_trials, epidemiology"
}
π Data Fields
| Field | Type | Description |
|---|---|---|
| PMC_ID | string | Unique PubMed Central ID |
| title | string | Article title |
| abstract | string | Full abstract text |
| keywords_in | list[str] | Extractive keywords (appear literally in text) |
| keywords_not_in | list[str] | Abstractive keywords (inferred, not literal in text) |
| sub_domains | string | Comma-separated multi-label sub-domains (e.g., "genomics, drug_discovery") |
Data Splits
Split Type 1: Standard Train/Validation/Test Split (70/15/15, stratified by primary domain)
- train: 3,500 articles (70%) β for fine-tuning or training judge
- validation: 750 articles (15%) β for hyperparameter tuning & calibration
- test: 750 articles (15%) β for final evaluation & baseline comparison
Split Type 2: Sub-domain Split (multi-label, with overlap between domains)
Separate files for each primary sub-domain (easy to load domain-specific data):
- subdomain_genomics.csv (~1,414 articles)
- subdomain_clinical_trials.csv (~1,467 articles)
- subdomain_drug_discovery.csv (~740 articles)
- subdomain_epidemiology.csv (~1,741 articles)
Benefit: Convenient for domain-specific testing (e.g., run only on genomics to correlate with GUE benchmark).
All splits are stratified to preserve balance across primary domains.
All splits are stratified by primary domain (first sub-domain in multi-label list) to maintain balance.
π οΈ Dataset Creation
Curation Rationale
Refined from PubMedAKE to create a smaller, higher-quality subset focused on:
- Clean ground truth (β₯5 keywords, long abstract, low noise).
- Sub-domain stratification for domain knowledge studies.
- Feasibility for LLM evaluation and fine-tuning on consumer hardware.
Source Data
- Original: PubMed Open Access Subset (PMC-OA) via PubMedAKE (Zenodo DOI: 10.5281/zenodo.6330817)
- Filtering: β₯5 keywords total, abstract β₯200 chars, removed noisy entries (>40% stop words)
Annotations
- Ground truth: Author-assigned keywords (extractive + abstractive) from original PubMedAKE.
- Sub-domains: Inferred multi-label from keywords using domain-specific terms.
Personal and Sensitive Information
No personal or sensitive data (only public PMC articles).
β οΈ Considerations for Using the Data
Social Impact
Improves biomedical literature search, recommendation, and text mining (PubMed, Semantic Scholar, drug discovery RAG).
Limitations
- Skew toward epidemiology (PubMed OA bias).
- Author keywords can be subjective or noisy.
- English-only.
- Sub-domain inference heuristic (keyword-based) may have minor overlap errors.
Misuse Potential
None foreseen (public scientific abstracts).
π How to Use
from datasets import load_dataset
# Load standard splits
dataset = load_dataset("christian-hoang-04/BiomedKeyRefine")
train_df = dataset["train"].to_pandas()
print(train_df.head())
# Load sub-domain specific file (download from repo)
genomics = pd.read_csv("https://huggingface.co/datasets/christian-hoang-04/BiomedKeyRefine/resolve/main/subdomains/genomics.csv")
π Citation
If you use this dataset in your research, please cite:
@misc{hoang2026biomedkeyrefine,
author = {Christian Hoang},
title = {BiomedKeyRefine: Refined Biomedical Keyword Extraction Benchmark with Sub-domain Stratification},
year = {2026},
publisher = {Hugging Face},
howpublished = {\url{https://huggingface.co/datasets/christian-hoang-04/BiomedKeyRefine}},
}
π References / Related Datasets
- Original PubMedAKE: https://pmc.ncbi.nlm.nih.gov/articles/PMC9652778/
- Zenodo source: https://zenodo.org/records/6330817
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