bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in Stenotrophomonas maltophilia antibiotic resistance rates in the United States Veterans Affairs Health System
Authors: Appaneal Haley J. , Lopes Vrishali V. , LaPlante Kerry L. , Caffrey Aisling R. 
Published: October 2022

Introduction.Stenotrophomonas maltophiliais an important multidrug-resistant Gram-negative pathogen. While largely a hospital-acquired pathogen, there have been increasing reports of the pathogen in the community.Gap Statement. Trends inS. maltophiliaprevalence and resistance rates that include outpatient isolates are unknown.Aim. We described recent trends in prevalence and resistance ofS. maltophiliain the national Veterans Affairs (VA) Healthcare system.Methodology. The study identified positiveS. maltophiliaclinical cultures among VA adult patients from 2010 to 2018 across all VA hospitals, long-term care facilities/units, and outpatient settings. AnnualS. maltophiliaresistance rates were evaluated. Multidrug resistant (MDR) was defined as resistance to sulfamethoxazole/trimethoprim (SMX/TMP) and minocycline or levofloxacin. Time trends were assessed with regression analyses to estimate annual average percent changes (AAPC) with 95 % confidence intervals using Joinpoint software.Results. Over the 9 year study period, 18 285 S.maltophiliacultures were identified (57 % hospital, 3 % long-term care, 40 % outpatient). The most common source ofS. maltophiliacultures were respiratory cultures (34.6 %) followed by urine cultures (30.4 %). In VA hospitals and long-term care facilities, the number ofS. maltophiliacultures decreased significantly (by 5.4% and 8.4 % per year respectively). Overall, 3.1 % of isolates were MDR which remained stable over the study period. Resistance to other antibiotics assessed mostly remained stable, except SMX/TMP resistance decreased significantly by 8.5 % (2010, 15 %; 2018, 6 %) per year in VA hospitals.Conclusion. While previous work has recognizedS. maltophiliaas primarily a nosocomial pathogen, the present study found that 40 % of cultures collected were among outpatients. Between 2010 and 2018, the number of positiveS. maltophiliacultures decreased significantly in the national VA Healthcare System. Resistance to SMX/TMP decreased over the study period in VA hospitals and now more closely reflects previously reported resistance rates worldwide (0–10 %). MDRS. maltophiliaremained stable and low in the national VA Healthcare System.
Fingerprinting of Mycobacterium tuberculosis isolates by MIRU-VNTR genotyping and detection of isoniazid resistance by real-time PCR
Authors: Gaballah Ahmed , Ghazal Abeer , Almiry Reda , Hussein Somaya , Emad Rasha , El-Sherbini Eglal 
Published: October 2022

Introduction.Tuberculosis (TB) is a great public health problem in developing countries such as Egypt. Genotyping ofMycobacterium tuberculosisisolates has a prominent role in the field of TB prevention.Aim.This study aimed to evaluate real-time PCR using Minor Groove Binder (MGB) probes and to identify circulating lineages/sub-lineages ofM. tuberculosisand their transmission patterns.Hypothesis.We hypothesize that MIRU-VNTR technique is efficient in identifying circulatingM. tuberculosislineages in Egypt.Methodology.Fifty sputum specimens positive for acid-fast bacilli were included. Isoniazid (INH) resistance was detected using the 1 % proportion method. Real-time PCR using MGB-probes was used for simultaneous detection of TB infection and INH resistance. Partial sequencing of thekatGgene was used to confirm INH resistance results. A standard 15 Mycobacterial Interspersed Repetitive Unit Variable Number Tandem Repeat (15-MIRU-VNTR) approach was used for genotyping through the MIRU-VNTRplusonline platform.Results.Only seven specimens showed phenotypic resistance to INH.M. tuberculosiswas detected in all samples, while a mutation in thekatGgene codon 315 was detected only in five samples, which were also phenotypically INH-resistant. Sequencing of thekatGgene showed codon 315 mutation genotypically and phenotypically in the five INH-resistant isolates. Molecular genotyping ofM. tuberculosisisolates revealed that the majority of isolates (26/50, 52 %) belonged to the S family of lineage_4. A low clustering rate (2 %) was observed among our isolates. According to the Hunter-Gaston Discriminatory Index (HGDI), 11 MIRU-VNTR loci were highly or moderately discriminative, while four loci were less polymorphic.Conclusion.MIRU-VNTR genotyping revealed a low clustering rate with a low recent transmission rate ofM. tuberculosisstrains in Alexandria, Egypt.
Did Risk-based or Age-based Vaccine Prioritization for Covid-19 Save More Lives?
Authors: Smits Joeri , Malik Amyn A. , Elharake Jad A. , Mobarak Ahmed Mushfiq , Omer Saad B. 
Published: October 2022

AbstractImportanceAll U.S. states provided Covid-19 vaccine access to frontline healthcare workers first, but after that, states varied in whether they gave earlier access to the elderly, versus the vulnerable with comorbidities, or school employees or essential workers, reflecting the underlying scientific and policy uncertainty.ObjectiveTo evaluate if risk-based or age-based prioritization is more effective at reducing reported Covid-19 cases and deaths.DesignA serial cross-sectional studySetting50 U.S. states and Washington D.C.Participants60+ years of age, high-risk individuals, K-12 school employees, and essential workersMain Outcomes and MeasuresHospitalizations and deathsResultsSeven to nine weeks after 60-year-olds became eligible for a vaccine, there was a statistically significant 40-50% decline in Covid-19 hospitalizations in that state. In contrast, there was no statistically detectable change in hospitalizations in the 7-9 weeks after K-12 employees become eligible for vaccines. Vaccine eligibility of “high-risk adults” and “essential workers” produces effects somewhere in the middle, with reductions in hospitalization of about 25%. There was a large statistically significant decline in death rates (25-38%) 10 to 11 weeks after people aged over 60 became vaccine-eligible. These effects were generally statistically larger than high risk individuals, K-12 school employees, and essential workers.Conclusions and RelevancePanel data analysis of weekly variation in Covid-19 health outcomes reveals that prioritizing adults 60+ years of age is associated with the largest reduction in hospitalizations and Covid-19 cases, followed by vaccines for adults with high-risk comorbidities. Vaccinations extended to K-12 school employees and essential workers is associated with the smallest reductions in hospitalizations and deaths.Key PointsQuestionDid Risk-based or Age-based Vaccine Prioritization for Covid-19 Save More Lives?FindingsPanel data analysis of weekly variation in Covid-19 health outcomes reveals that prioritizing adults 60+ years of age is associated with the largest reduction in hospitalizations and Covid-19 cases, followed by vaccines for adults with high-risk comorbidities. Vaccinations extended to K-12 school employees and essential workers is associated with the smallest reductions in hospitalizations and deaths.MeaningPrioritizing adults 60+ years of age can lead to a higher estimated reduction in hospitalizations and deaths, followed by a strategy of prioritizing adults with high-risk comorbidities. Our findings add to the limited evidence for the roadmap for prioritizing use of Covid-19 vaccines, and help address uncertainties about the relative effectiveness of different vaccine strategies.
Evidence of epistasis in regions of long-range linkage disequilibrium across five complex diseases in the UK Biobank and eMERGE datasets
Authors: Singhal Pankhuri , Veturi Yogasudha , Dudek Scott M. , Lucas Anastasia , Frase Alex , Schrodi Steven J. , Fasel David , Weng Chunhua , Pendergrass Rion , Schaid Daniel J. , Kullo Iftikhar J. , Dikilitas Ozan , Sleiman Patrick M.A. , Hakonarson Hakon , Moore Jason H. , Williams Scott M. , Ritchie Marylyn D. , Verma Shefali S. 
Published: October 2022

AbstractLeveraging linkage disequilibrium (LD) patterns as representative of population substructure enables the discovery of additive association signals in genome-wide association studies (GWAS). Standard GWAS are well-powered to interrogate additive models; however, new approaches are required to investigate other modes of inheritance such as dominance and epistasis. Epistasis, or non-additive interaction between genes, exists across the genome but often goes undetected due to lack of statistical power. Furthermore, the adoption of LD pruning as customary in standard GWAS excludes detection of sites in LD that may underlie the genetic architecture of complex traits. We hypothesize that uncovering long-range interactions between loci with strong LD due to epistatic selection can elucidate genetic mechanisms underlying common diseases. To investigate this hypothesis, we tested for associations between 23 common diseases and 5,625,845 epistatic SNP-SNP pairs (determined by Ohta’sDstatistics) in long-range LD (> 0.25cM). We identified five significant associations across five disease phenotypes that replicated in two large genotype-phenotype datasets (UK Biobank and eMERGE). The genes that were most likely involved in the replicated associations were 1) members of highly conserved gene families with complex roles in multiple pathways, 2) essential genes, and/or 3) associated in the literature with complex traits that display variable expressivity. These results support the highly pleiotropic and conserved nature of variants in long-range under epistatic selection. Our work supports the hypothesis that epistatic interactions regulate diverse clinical mechanisms and may especially be driving factors in conditions with a wide range of phenotypic outcomes.SignificanceCurrent knowledge of genotype-phenotype relationships is largely contingent on traditional univariate approaches to genomic analysis. Yet substantial evidence supports non-additive modes of inheritance and regulation, such as epistasis, as being abundant across the genome. In this genome-wide study, we probe the biomolecular mechanisms underlying complex human diseases by testing the association of pairwise genetic interactions with disease occurrence in large-scale biobank data. Specifically, we tested intrachromosomal and interchrosomal long-range interactions between regions of the genome in high linkage disequilibrium, these regions are typically excluded from genomic analyses. The results from this study suggest that essential gene, members of highly conserved gene families, and phenotypes with variable expressivity, are particularly enriched with epistatic and pleiotropic activity.
Selective mutism in China: a nationwide survey and case-control study
Authors: Hu Xinwen , Reitman Junhua , Pan Stephen W. 
Published: October 2022

AbstractBackgroundSelective mutism (SM) is an anxiety disorder characterized by a consistent failure to speak in particular public settings despite speaking normally in other situations. However, quantitative SM research from China remains scanty at best. In response, this study aimed (1) to describe the sociodemographics and experiences of children and families with SM in China and (2) to identify sociodemographic and environmental correlates of SM in China.MethodsThis case-control mixed-methods study was composed of 172 cases with SM and 179 controls, recruited by online surveys. Multilevel logistic regression was performed to examine the association between potential correlates and SM.ResultsOnly 51.2% of SM cases were diagnosed by a professional, and 31.1% of SM cases that received treatment were guided by a professional. Child SM was associated with: having two parents with an introverted personality (Adjusted odds ratio (AOR): 15.05, (95% confidence interval (CI): 5.39 – 42.07), being born to a mothers aged ≥ 35 (AOR 6.44, 95%CI: 1.24-33.43), and having a sibling (AOR 1.92, 95% CI: 1.00 – 3.70). However, child SM was inversely associated with ever receiving bilingual (AOR 0.20, 95% CI 0.10-0.39) education or being enrolled in an international school (AOR 0.12, 95% CI 0.04-0.35).ConclusionsFindings suggest that many children with SM in China have not received professional treatment or interventions. Hereditary and social environmental factors may be contributing to childhood onset of SM in China. Novel policies such as access to special education resources, SM-training for therapists, and school support are needed to enhance the early detection and treatment of SM in China.
Effects of PM2.5 Air Pollutants on Cardiovascular Health in Ohio: A Secondary Data Analysis
Authors: Finkle Peyton G. , Gillespie Jahasia W. , Piper Brian J. 
Published: October 2022

AbstractBackgroundMultiple adverse health outcomes have been linked to air pollution, particularly exposure to particulate matter (PM2.5).JustificationThis research will help to identify the role that socioeconomic and geographical factors have in increased cardiovascular disease and cardiac events due to elevated exposure amounts of PM2.5. Minorities in the United States are more likely to have or die from cardiovascular disease and also are the majority of the occupants in low-income communities with high levels of PM2.5.MethodsPM2.5pollutant concentrations were measured from 2016 to 2018 and collected by air quality monitoring equipment in Ohio. The cardiovascular disease data on adult residents of Ohio from 2016-2018 was from the National Vital Statistics System (NVSS) and the Centers for Medicare and Medicaid Services Medicare Provider Analysis and Review (MEDPAR). R programming was used to find associations between cardiovascular disease and PM2.5in Ohio. Contingency tables compared the consumption of PM2.5and the rate of heart disease mortality. Heat maps indicated areas where heart disease mortality and PM2.5concentrations were highest.ResultsThe average PM2.5concentration in Ohio was determined to be 7.9 μG/m3. The highest PM2.5concentrations were found in Montgomery County, Ohio and the lowest were recorded in Allen County, Ohio. With increased population density, there was also an increase with PM2.5concentrations (P<0.01). The association between cardiovascular disease mortality and PM2.5rates in these counties was nonsignificant (P>0.01). It was also found that 31.8% of counties in Ohio had air monitoring while the remaining 68.2% did not have any form of it.ConclusionKnowing the risk of PM2.5levels in any neighborhood could help community members and leaders pick a more appropriate course of action. Reducing air pollutants in these areas may in turn reduce cardiovascular disease in that population, leading to better health outcomes and longevity. This research also identified gaps in air monitoring that assists in prioritizing areas that need immediate remediation.
ADRA2AandIRX1are putative risk genes for Raynaud’s phenomenon
Authors: Hartmann Sylvia , Yasmeen Summaira , Jacobs Benjamin M , Denaxas Spiros , Pirmohamed Munir , Gamazon Eric R. , Caulfield Mark J. ,   Genes & Health Research Team, Hemingway Harry , Pietzner Maik , Langenberg Claudia 
Published: October 2022

AbstractRaynaud’s phenomenon (RP) is a common vasospastic disorder that causes severe pain and ulcers, but despite its high reported heritability, no causal genes have been robustly identified. We conducted a genome-wide association study including 5,147 RP cases and 439,294 controls, based on diagnoses from electronic health records, and identified three unreported genomic regions associated with the risk of RP (p<5×10−8). We prioritizedADRA2A(rs7090046, odds ratio (OR) per allele: 1.26; 95%-CI: 1.20-1.31; p<9.6×10-27) andIRX1(rs12653958, OR: 1.17; 95%-CI: 1.12-1.22, p<4.8×10-13) as candidate causal genes through integration of gene expression in disease relevant tissues. We further identified a likely causal detrimental effect of low fasting glucose levels on RP risk (rG=-0.21; p-value=2.3×10-3), and systematically highlighted drug repurposing opportunities, like the antidepressant mirtazapine. Our results provide the first robust evidence for a strong genetic contribution to RP and highlight a so far underrated role of α2A-adrenoreceptor signalling, encoded atADRA2A, as a possible mechanism for hypersensitivity to catecholamine-induced vasospasms.
“It is bad because it limits capacity building here back at home”Genetic and genomic researchers’ perspectives on biological sample sharing in collaborative research
Authors: Kaawa-Mafigiri David , Ekusai- Sebatta Deborah , Munabi Ian , Mwaka Erisa Sabakaki 
Published: October 2022

AbstractNumerous ethical, legal and social issues arise with biological sample sharing. The study explored the perspectives of genetic/genomic researchers on the sharing of biological samples in international collaborative research. Qualitative in-depth interviews were conducted with 15 researchers. Participants expressed positive attitudes towards biobanking and appreciated the benefits of cross-border sharing of biological samples but noted that this practice had adversely affected local capacity building efforts. There was limited understanding of the ethico-regulatory frameworks governing sample sharing. Researchers emphasized the importance of respecting cultural values in biobanking research. Issues concerning poor governance and inequitable benefit sharing were also raised. There is a need for fair and equitable international collaborations where all researchers are treated with respect and as equal partners.
Using polygenic risk scores for prioritising individuals at greatest need of a CVD risk assessment
Authors: Chung Ryan , Xu Zhe , Arnold Matthew , Ip Samantha , Harrison Hannah , Barrett Jessica , Pennells Lisa , Kim Lois G. , DiAngelantonio Emanuele , Paige Ellie , Ritchie Scott C. , Inouye Michael , Usher-Smith Juliet A. , Wood Angela M. 
Published: October 2022

ABSTRACTBackgroundTo provide quantitative evidence of the use of polygenic risk scores (PRS) for systematically identifying individuals for invitation for full formal cardiovascular disease (CVD) risk assessment.Methods108,685 participants aged 40-69, with measured biomarkers, linked primary care records and genetic data in UK Biobank were used for model derivation and population health modelling. Prioritisation tools using age, PRS for coronary artery disease and stroke, and conventional risk factors for CVD available within longitudinal primary care records were derived using sex-specific Cox models. Rescaling to account for the healthy cohort effect, we modelled the implications of initiating guideline-recommended statin therapy after prioritising individuals for invitation to a formal CVD risk assessment.Results1,838 CVD events were observed over median follow up of 8.2 years. If primary care records were used to prioritise individuals for formal risk assessment using age- and sex-specific thresholds corresponding to 5% false negative rates then we would capture 65% and 43% events amongst men and women respectively. The numbers of men and women needed to be screened to prevent one CVD event (NNS) are 74 and 140 respectively. In contrast, adding PRS to both prioritisation and formal assessments, and selecting thresholds to capture the same number of events resulted in a NNS of 60 for men and 90 for women.ConclusionThe use of PRS together with primary care records to prioritise individuals at highest risk of a CVD event for a formal CVD risk assessment can more efficiently prioritise those who need interventions the most than using primary care records alone. This could lead to better allocation of resources by reducing the number of formal risk assessments in primary care while still preventing the same number CVD events.
Association between cancer and dementia risk in the UK Biobank: evidence of diagnostic bias
Authors: Wang Jingxuan , Buto Peter , Ackley Sarah F. , Kobayashi Lindsay C. , Graff Rebecca E. , Zimmerman Scott C. , Hayes-Larson Eleanor , Mayeda Elizabeth Rose , Asiimwe Stephen B. , Calmasini Camilla , Glymour M. Maria 
Published: October 2022

AbstractIntroductionEpidemiological studies have identified an inverse association between cancer and dementia. Underlying methodological biases have been postulated, yet no studies have systematically investigated the potential for each source of bias within a single dataset. We used the UK Biobank to compare estimates for the cancer-dementia association using different analytical specifications designed to sequentially address multiple sources of bias, including competing risk of death, selective survival, confounding bias, and diagnostic bias.MethodsWe included 140,959 UK Biobank participants aged ≥55 without dementia before enrollment and with linked primary care data. We used cancer registry data to identify cases of prevalent cancer before UK Biobank enrollment and incident cancer diagnosed after enrollment. We used Cox models to evaluate associations of prevalent and incident cancer with all-cause dementia, Alzheimer’s disease (AD), and vascular dementia. We used time-varying models to evaluate diagnostic bias.ResultsThe cohort accumulated 3,310 incident dementia diagnoses over a median of 12.3 years of follow-up. All-site incident cancer was positively associated with all-cause dementia incidence (hazard ratio [HR]=1.15, 95% CI: 1.02-1.29), but prevalent cancer was not (HR=1.04, 95% CI: 0.92-1.17). Results were similar for vascular dementia. AD was not associated with prevalent or incident cancer. Dementia diagnosis was substantially elevated in the first year after cancer diagnosis (HR=1.83, 95% CI: 1.42-2.36), after which the association attenuated to null, suggesting diagnostic bias.ConclusionHealth care utilization after a cancer diagnosis may increase chance of a dementia diagnosis, creating potential diagnostic bias in electronic health records-based studies.
Global prediction for monkeypox epidemic
Authors: Zhang Li , Huang Jianping , Chen Bin , Zhao Yingjie , Wang Danfen , Yan Wei 
Published: October 2022

AbstractThe monkeypox epidemic has now spread all over the world and has become an epidemic of widespread concern in the international community. Before the emergence of targeted vaccines and specific drugs, it is necessary to numerically simulate and predict the epidemic. In order to better understand and grasp its transmission situation, and put forward some countermeasures accordingly, we predicted and simulated monkeypox transmission and vaccination scenarios using models developed for COVID-19 predictions. The results suggest the monkeypox epidemic will spread to almost all countries in the world by the end of 2022 based on modified SEIR model prediction. The total number of people infected with monkeypox will reach 100,000. The top five countries will be the United States, Brazil, Germany, France and Britain with more than 28000, 20000, 4000, 4500 and 4000 cases respectively. If 30% of the population is vaccinated, the number of infected people will drop by 35%.