bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics and Long-term Mortality in Patients with ST-Segment Elevation Myocardial Infarction with Non-Obstructive Coronary Arteries (STE-MINOCA): A High Risk Cohort
Authors: Quesada Odayme , Yildiz Mehmet , Henry Timothy D. , Okeson Brynn K. , Chambers Jenny , Shah Ananya , Stanberry Larissa , Volpenhein Lucas , Aziz Dalia , Lantz Rebekah , Palmer Cassady , Ugwu Justin , Ahsan Muhammad J. , Garberich Ross F. , Rohm Heather S. , Aguirre Frank V. , Garcia Santiago , Sharkey Scott W. 
Published: February 2023

ABSTRACTBackgroundThe prognosis of ST-segment elevation myocardial infarction with non-obstructive coronaries (STE-MINOCA) is largely unknown.MethodsThe objective of this study is to evaluate the prevalence, characteristics, and 5-year mortality of patients with STE-MINOCA compared to STEMI with coronary artery obstruction (STEMI-Obstruction) using a multicenter cohort of consecutive STEMI patients at 3 regional Midwest STEMI programs from 2003 to 2020. STE-MINOCA was defined based on (1) coronary stenosis < 60% by visual estimation, (2) ischemia with elevated troponin, and (3) no alternative diagnosis. STE-MINOCA was further classified based on American Heart Association (AHA) definition as AHA STE-MINOCA and AHA STE-MINOCA Mimicker.Results8,566 STEMI patients, including 420 (4.9%) STE-MINOCA (26.9% AHA STE-MINOCA and 73.1% AHA STE-MINOCA Mimicker) were followed for a median of 7.1 years. Compared to STEMI-Obstruction, STE-MINOCA were younger, more often female, had fewer cardiovascular risk factors, and were less likely to be discharged on cardiac medications. At five years, mortality was higher in STE-MINOCA compared with STEMI-Obstruction (18% vs. 15%, p=0.033). In propensity score-matched analysis, STE-MINOCA had a 1.4-fold (95% CI: 1.04-1.89, p=0.028) higher risk of 5-year all-cause mortality compared with STEMI-Obstruction. Furthermore, 5-year mortality risk was significantly higher in AHA STE-MINOCA Mimicker (19% vs. 15%, p=0.043) but similar in AHA STE-MINOCA (17% vs. 15%, p=0.42) compared with STEMI-Obstruction.ConclusionsIn this large multicenter STEMI cohort, nearly 5% of patients presented with STE-MINOCA. At five years, mortality approached 20% among patients with STE-MINOCA. Despite the lower risk profile, STE-MINOCA patients were at 40% higher risk of 5-year all-cause mortality compared with STEMI-Obstruction. Additionally, 5-year all-cause mortality risk was higher in AHA STE-MINOCA Mimicker but similar in AHA STE-MINOCA compared to STEMI-Obstruction.
Contributions of rare and common variation to early-onset and atypical dementia risk
Authors: Wright Carter A. , Taylor Jared W. , Cochran Meagan , Lawlor James M.J. , Moyers Belle A. , Amaral Michelle D. , Bonnstetter Zachary T. , Carter Princess , Solomon Veronika , Myers Richard M. , Love Marissa Natelson , Geldmacher David S. , Cooper Sara J. , Roberson Erik D. , Cochran J. Nicholas 
Published: February 2023

AbstractWe collected and analyzed genomic sequencing data from individuals with clinician- diagnosed early-onset or atypical dementia. Thirty-two patients were previously described, with sixty-eight newly described in this report. Of those sixty-eight, sixty-two patients reported Caucasian, non-Hispanic ethnicity and six reported as African American, non-Hispanic. Fifty-three percent of patients had a returnable variant. Five patients harbored a pathogenic variant as defined by the American College of Medical Genetics criteria for pathogenicity. A polygenic risk score was calculated for Alzheimer’s patients in the total cohort and compared to the scores of a late-onset Alzheimer’s cohort and a control set. Patients with early-onset Alzheimer’s had higher non-APOEpolygenic risk scores than patients with late onset Alzheimer’s, supporting the conclusion that both rare and common genetic variation associate with early-onset neurodegenerative disease risk.
Mental distress among Norwegian adults during the Covid-19 pandemic: predictors of initial response and subsequent trajectories
Authors: Lu Li , Hannigan Laurie J. , Brandlistuen Ragnhild E , Nesvåg Ragnar , Trogstad Lill , Magnus Per , Unnarsdóttir Anna Bára , Valdimarsdóttir Unnur A. , Andreassen Ole A , Ask Helga 
Published: February 2023

SummaryBackgroundUnderstanding factors associated with mental distress during a pandemic is imperative for planning interventions to reduce the negative mental health impact of future crises. Our aim was to identify factors associated with change in levels of mental distress in the Norwegian adult population at the onset of the Covid-19 pandemic, relative to pre-pandemic levels, and with longitudinal changes in mental distress until vaccination against Covid-19 became widespread in Norway (the first 1.5 years of the pandemic).MethodsThe Norwegian Mother, Father and Child Cohort Study (MoBa) is a prospective longitudinal study with baseline recruitment from 1999-2009. Baseline characteristics and eight waves of data collection during the pandemic (between March 2020 and September 2021) were used for this analysis. Mental distress was measured with the 5-item version of Hopkins Symptoms Checklist (HSCL-5). A piecewise latent growth model was fitted to identify initial change in mental distress (March-early April 2020, adjusting for pre-pandemic mental distress measured during prior years of data collection) and longitudinal changes across the pandemic in three distinct periods.FindingsOur sample consisted of 105 972 adult participants (59.6% females). Mental distress levels peaked at the beginning of the pandemic. Several factors were associated with initial increases in distress: chronic medical conditions, living alone, history of psychiatric disorders, relatively lower educational background, female sex, younger age, and obesity. Several of these factors were also associated with long-term change. Being quarantined or having to isolate was associated with the likelihood of increasing distress during the pandemic. We observed a reduction in distress associated with Covid-19 vaccination status, while being infected with SARS-CoV-2 was associated with increasing distress late in the pandemic.InterpretationPre-pandemic vulnerability factors – like having a chronic disease – as well as Covid-19-related factors – like being quarantined or infected by SARS-CoV-2 – were associated with increased mental distress during the pandemic. This knowledge is important for planning of interventions to support vulnerable individuals during pandemics and other health crises.FundingThe Norwegian Ministry of Health, and Care Services and the Ministry of Education and Research. NordForsk, The Research Council of Norway, The South-Eastern Norway Regional Health Authority.
Systemic administration of the antisense oligonucleotide NS-089/NCNP-02 for skipping of exon 44 in patients with Duchenne muscular dystrophy: study protocol for a phase I/II clinical trial
Authors: Ishizuka Takami , Komaki Hirofumi , Asahina Yasuko , Nakamura Harumasa , Motohashi Norio , Takeshita Eri , Shimizu-Motohashi Yuko , Ishiyama Akihiko , Yonee Chihiro , Maruyama Shinsuke , Hida Eisuke , Aoki Yoshitsugu 
Published: February 2023

AbstractAimThe purpose of this study is to evaluate the safety and pharmacokinetics of the novel morpholino oligomer NS-089/NCNP-02 which can induce exon 44 skipping, in patients with DMD. Additionally, we aimed to identify markers predictive of therapeutic efficacy and determine the optimal dosing for future studies.MethodsThis is an open-label, dose-escalation, two-center phase I/II trial in ambulant patients with DMD, presence of an out-of-frame deletion, and a mutation amenable to exon 44 skipping. Part 1 is a stepwise dose-finding stage (4 weeks) during which NS-089/NCNP-02 will be administered intravenously at four dose levels once weekly (1.62, 10, 40, and 80 mg/kg); Part 2 is a 24-week evaluation period based on the dosages determined during Part 1. The primary (safety) endpoints are the results of physical examinations, vital signs, 12-lead electrocardiogram and echocardiography tests, and adverse event reporting. Secondary endpoints include expression of dystrophin protein, motor function assessment, exon 44 skipping efficiency, plasma and urinary NS-089/NCNP-02 concentrations, and changes in blood creatine kinase levels.DiscussionExon-skipping therapy using ASOs shows promise in selected patients, and this first-in-human study is expected to provide critical information for subsequent clinical development of NS-089/NCNP-02.
Are metastatic tumours histologically similar to the primary? Result of a blinded experiment
Authors: Singh Akshita , Jambhekar Nirmala , Shet Tanuja , Ramadwar Mukta , Dikshit Rajesh , Mittra Indraneel 
Published: February 2023

AbstractThere is an entrenched belief among pathologists, biologists and clinicians alike that metastatic tumours are histologically similar to the primary. Although this belief has never been scientifically tested, it forms the conceptual foundation upon which metastasis research has been based for decades. In order to scientifically test this dogma, we conducted a blinded experiment in which three highly experienced professor grade cancer pathologists were asked to predict the site of origin of 298 metastatic tumours arising at nine different sites. The accuracy of prediction of all three examiners was just under 50%. However, there was very little inter-observer agreement, and Kappa statistic generated the value of 0.27 which is much below the figure of 0.4 required to detect even a moderate level of concordance. In only 56 / 298 (18.8%) cases did the examiners agree with each other’s diagnosis. Thus the possibility cannot be excluded that the correct diagnoses made by the examiners had happened by play of chance. Our finding suggests that histological relationship between primary and metastatic tumours requires further investigation.
Genome-wide association study of blood mercury in European pregnant women and children
Authors: Dack Kyle , Bustamante Mariona , Taylor Caroline M. , Llop Sabrina , Lozano Manuel , Yousefi Paul D , Grazuleviciene Regina , Gutzkow Kristine Bjerve , Brantsæter Anne Lise , Mason Dan , Escaramís Georgia , Lewis Sarah J 
Published: February 2023

AbstractBackgroundMercury (Hg) is a toxic heavy metal which humans are most commonly exposed to through food chain contamination, especially via fish consumption. Even low-level exposure can be harmful because of the poor clearance rate, particularly for methylmercury. It is likely that genetic variation modifies exposure through changes in the absorption, metabolism, and/or removal of mercury. Associations have been reported between Hg and variants at multiple genetic loci, but in many cases these results are not yet replicated.MethodsThis study included two populations: pregnant women from the Avon Longitudinal Study of Parents and Children (ALSPAC, n=2,893) and children from the Human Early Life Exposome (HELIX, n=1,042). Genome-wide testing by cohort was performed by fitting linear regressions models on whole blood Hg levels and Haplotype Reference Consortium imputed single-nucleotide polymorphisms (SNPs). SNP heritability was estimated using linkage disequilibrium (LD)-score regression, and the biological functions of the top variants were investigated using resources which aggregate prior literature.ResultsHg SNP heritability was estimated to be 24.0% (95% CI: 16.9% to 46.4%) for pregnant women. The number of genetic variants independently associated with whole blood mercury levels above a suggestive p-value threshold (P < 1×10−5) was 16 for pregnant women and 21 for children. However, none were replicated in both populations, nor did any pass a stronger genome-wide significant threshold (P < 5×10−8). Several suggestive variants had possible biological links to Hg such as rs146099921 in metal transporterSLC39A14, and two variants (rs28618224, rs7154700) in potassium voltage-gated channels genes.DiscussionThere was evidence for a considerable proportion of Hg variance being attributed to genome-wide variation in pregnant women. However, results between pregnant women and children were highly discordant which could reflect differences in metabolism and a gene-age interaction with Hg levels. There were a large number of SNPs suggestively associated with Hg levels, which likely include both true associations and false positives. These interim findings will be expanded following collaboration with additional study groups.
Prioritization of risk genes for Alzheimer’s disease: an analysis framework using spatial and temporal gene expression data in the human brain based on support vector machine
Authors: Wang Shiyu , Fang Xixian , Wen Xiang , Yang Congying , Yang Ying , Zhang Tianxiao 
Published: February 2023

AbstractBackgroundAlzheimer’s disease (AD) is a complex disorder, and its risk is influenced by multiple genetic and environmental factors. In this study, an AD risk gene prediction framework based on spatial and temporal features of gene expression data (STGE) was proposed.MethodsWe proposed an AD risk gene prediction framework based on spatial and temporal features of gene expression data. The gene expression data of providers of different tissues and ages were used as model features. Human genes were classified as AD risk or non-risk sets based on information extracted from relevant databases. Support vector machine (SVM) models were constructed to capture the expression patterns of genes believed to contribute to the risk of AD.ResultsThe recursive feature elimination (RFE) method was utilized for feature selection. Data for 64 tissue-age features were obtained before feature selection, and this number was reduced to 19 after RFE was performed. The SVM models were built and evaluated using 19 selected and full features. The area under curve (AUC) values for the SVM model based on 19 selected features (0.740 [0.690–0.790]) and full feature sets (0.730 [0.678–0.769]) were very similar. Fifteen genes predicted to be risk genes for AD with a probability greater than 90% were obtained.ConclusionThe newly proposed framework performed comparably to previous prediction methods based on protein-protein interaction (PPI) network properties. A list of 15 candidate genes for AD risk was also generated to provide data support for further studies on the genetic etiology of AD.
Trials underestimate the impact of preventive treatment for household contacts exposed to multidrug-resistant tuberculosis: a simulation study
Authors: Kasaie Parastu , Pennington Jeff , Gupta Amita , Dowdy David W. , Kendall Emily A. 
Published: February 2023

AbstractBackgroundSeveral clinical trials of tuberculosis preventive treatment (TPT) for household contacts of patients with multidrug-resistant tuberculosis (MDR-TB) are nearing completion. The potential benefits of TPT for MDR-TB contacts extend beyond the outcomes that clinical trials can measure.MethodsWe developed an agent-based, household-structured TB and MDR-TB transmission model, calibrated to an illustrative setting in India, the country accounting for 26% of global MDR-TB burden. We simulated household contact investigation for contacts of patients with MDR-TB, comparing an MDR-TPT regimen against alternatives of isoniazid preventive treatment, household contact investigation without TPT, or no household contact intervention. We simulated outcomes of a clinical trial and estimated the patient-level and population-level effects over a longer time horizon.FindingsDuring two years of follow-up per recipient, a simulated 6-month MDR-TPT regimen with 70% efficacy against both DS- and MDR-TB infection could prevent 72% [Interquartile range (IQR): 45 – 100%] of incident MDR-TB among TPT recipients (number needed to treat (NNT) 73 [44 – 176] to prevent one MDR-TB case), compared to household contact investigation without TPT. This NNT decreased to 54 [30 – 183] when median follow-up was increased from two to 16 years, to 27 [11 – Inf] when downstream transmission effects were also considered, and to 12 [8 – 22] when these effects were compared to a scenario of no household contact intervention.InterpretationIf forthcoming trial results demonstrate efficacy, the long-term population impact of MDR-TPT implementation could be much greater than suggested by trial outcomes alone.FundingNIH K01AI138853 and K08AI127908; Johns Hopkins Catalyst Award.
A population-based serological survey ofVibrio choleraeantibody titers in Ouest Department, Haiti in the year prior to the 2022 cholera outbreak
Authors: Clutter Christy H. , Klarman Molly B. , Cajusma Youseline , Cato Emilie T. , Sayeed Md. Abu , Brinkley Lindsey , Jensen Owen , Baril Chantale , Beau De Rochars V. Madsen , Azman Andrew S. , Long Maureen T. , Cummings Derek , Leung Daniel T. , Nelson Eric J. 
Published: February 2023

ABSTRACTAfter three years with no confirmed cholera cases in Haiti, an outbreak ofVibrio choleraeO1 emerged in October 2022. Levels of pre-existing antibodies provide an estimate of prior immunologic exposure, reveal potentially relevant immune responses, and set a baseline for future serosurveillance. We analyzed dried blood spots collected in 2021 from a population-weighted representative cross-sectional serosurvey in two communes in the Ouest Department of Haiti. We found lower levels of circulating IgG and IgA antibodies againstV. choleraelipopolysaccharide (LPS, IgG and IgA p<0.0001) in those below 5 years of age compared to those five years and older. Among a subset of patients with higher titers of antibodies, we were unable to detect any functional (vibriocidal) antibodies. In conclusion, the lack of detectable functional antibodies, and age-discordant levels ofV. choleraeLPS IgG, suggest that populations in Haiti may be highly susceptible to cholera disease, especially among young children.
Effects of joint mobilization combined with acupuncture on pain, physical function, and depression in stroke patients with chronic neuropathic pain: a randomized controlled trial
Authors: Lee Ji-Eun , Akimoto Takayuki , Lee Ho-Seong 
Published: February 2023

AbstractObjectiveTo investigate the effectiveness of joint mobilization (JM) combined with acupuncture (AC) for treatment pain, physical function and depression in poststroke patients.MethodsA total of 69 poststroke patients were randomly assigned to the JM+AC group (n = 23), the JM group (n = 23), and the control group (n = 23). Patients in the JM+AC group and the JM group received JM for 30 minutes, twice a week for 12 weeks, and the JM+AC group received AC for 30 minutes separately once a week. The control group did not receive JM or AC. Pain (visual analog scale, shoulder pain and disability index, Western Ontario and McMaster universities osteoarthritis index), physical function (range of motion, 10-m walking speed test, functional gait assessment, manual function test, activities of daily living scale, instrumental activities of daily living scale), and depression (center for epidemiologic studies depression scale, Beck depression inventory) were assessed for each patient before and after the 12 weeks of intervention.ResultsPain and physical function were improved significantly in the JM+AC group compared with the JM and control groups. Physical function and depression were improved significantly in the JM+AC and JM groups compared with the control group.ConclusionThe treatment of JM combined with AC improved pain, depression, and physical function of poststroke patients with chronic neuropathic pain in this study. This valuable finding provides empirical evidence for the designing therapeutic interventions and identifying potential therapeutic targets.
Heavy Metals Induced Health Risk Assessment Through Consumption of Selected Commercially Available Spices in Noakhali District of Bangladesh
Authors: Islam Md Shahedul , Chowdhury Akibul Islam , Shill Lincon Chandra , Reza Sompa , Alam Mohammad Rahanur 
Published: February 2023

AbstractThere are growing concerns for food safety due to the risks associated with heavy metal contamination of culinary herbs and spices in developing countries like Bangladesh. The objective of the present cross-sectional study is to determine the concentrations of the heavy metals Lead (Pb), Cadmium (Cd), Chromium (Cr), Copper (Cu), and Iron (Fe) in the branded and non-branded spices collected from the Noakhali district by Atomic absorption spectrophotometry method, as well as to assess the health hazard risk associated with heavy metal intake via consumption of spices. The findings revealed that the greatest concentrations of Pb (15.47 ± 1.93), Cd (1.65 ± 0.011), Cr (31.99 ± 3.97), Cu (18.84 ± 1.97), and Fe (9.29 ± 1.71) were found in Cardamom, Coriander leaf, Bay leaf, Dried chili, and Black pepper respectively. Around 37% of Cr and 5% of Fe Estimated Daily Values (EDI) were greater than reference doses (RfD). All spices had Total Hazard Quotient (THQ) values for Pb, Cd, Cu, and Fe that were below acceptable, and 37% of all spices had TTHQ values for Pb, Cd, Cu, and Fe that were over the standard range, suggesting adverse health impacts for consumers. Green chili, ginger, coriander leaf, and all kinds of chili powder and turmeric powder have been reported to have exceptionally high TTHQ levels of Cr. The estimated carcinogenic risk for unbranded chili, green chili, and coriander leaf was found to be higher than safe levels.
Analysis of electronic health records from three distinct and large populations reveals high prevalence and biases in the co-administration of drugs known to interact
Authors: Sánchez-Valle Jon , Correia Rion Brattig , Camacho-Artacho Marta , Lepore Rosalba , Mattos Mauro M. , Rocha Luis M. , Valencia Alfonso 
Published: February 2023

AbstractThe co-administration of drugs known to interact has a high impact on morbidity, mortality, and health economics. We study the drug-drug interaction (DDI) phenomenon by analyzing drug administrations from population-wide Electronic Health Records (EHR) in Blumenau (Brazil), Catalonia (Spain), and Indianapolis (USA). Despite very different health care systems and drug availability, we find a common large risk of DDI administration that affected 13 to 20% of patients in these populations. In addition, the increasing risk of DDI as patients age is very similar across all three populations but is not explained solely by higher co-administration rates in the elderly. We also find that women are at higher risk of DDI overall— except for men over 50 years old in Indianapolis. Finally, we show that PPI alternatives to Omeprazole can reduce the number of patients affected by known DDIs by up to 21% in both Blumenau and Catalonia, and 2% in Indianapolis, exemplifying how analysis of EHR data can lead to a significant reduction of DDI and its associated human and economic costs. Although the risk of DDIs increases with age, administration patterns point to a complex phenomenon that cannot be solely explained by polypharmacy and multimorbidity. The lack of safer drug alternatives, particularly for chronic conditions, further overburdens health systems, thus highlighting the need for disruptive drug research.