bluuebunny/crossref_metadata_2025_split huggingface dataset:
The PS4-Likelihood Ratio Calculator: Flexible allocation of evidence weighting for case-control data in variant classification
Authors: Rowlands Charlie F. , Garrett Alice , Allen Sophie , Durkie Miranda , Burghel George J. , Robinson Rachel , Callaway Alison , Field Joanne , Frugtniet Bethan , Palmer-Smith Sheila , Grant Jonathan , Pagan Judith , McDevitt Trudi , McVeigh Terri , Hanson Helen , Whiffin Nicola , Jones Michael , Turnbull Clare ,   CanVIG-UK
Published: April 2024

AbstractBackgroundWithin the 2015 American College of Medical Genetics/Association of Molecular Pathology (ACMG/AMP) variant classification framework, case-control observations can only be scored dichotomously as ‘strong’ evidence (PS4) towards pathogenicity or ‘nil’.MethodsWe developed the PS4-likelihood ratio calculator (PS4-LRCalc) for quantitative evidence assignment based on the observed variant frequencies in cases and controls. Binomial likelihoods are computed for two models, each defined by pre-specified odds ratio (OR) thresholds. Model one represents the hypothesis of association between variant and phenotype (e.g. OR≥5) and model two represents the hypothesis of non-association (e.g. OR≤1).ResultsPS4-LRCalc enables continuous quantitation of evidence for variant classification expressed as a likelihood ratio (LR), which can be log-converted into log LR (evidence points). Using PS4-LRCalc, observed data can be used to quantify evidence towards either pathogenicity or benignity. Variants can also be evaluated against models of different penetrance. The approach is applicable to balanced datasets generated for more common phenotypes and smaller datasets more typical in very rare disease variant evaluation.ConclusionPS4-LRCalc enables flexible evidence quantitation on a continuous scale for observed case-control data. The converted LR is amenable to incorporation into the now widely used 2018 updated Bayesian ACMG/AMP framework.
MONITORING OF RESPIRATORY VIRUS COINFECTION IN SOUTHERN BRAZIL DURING COVID-19 PANDEMIC
Authors: Padilha Dayane Azevedo , Barazzetti Fernando Hartmann , Schörner Marcos André , Filho Vilmar Benetti , Kawagoe Eric Kazuo , Marques Souza Doris Sobral , Bazzo Maria Luiza , Wagner Glauber , Fongaro Gislaine 
Published: April 2024

ABSTRACTSince December 2019, the COVID-19 pandemic caused by SARS-CoV-2 has reached approximately 769 million people, leading to more than 7 million deaths worldwide. Faced with the possible presence of other respiratory pathogens that could co-infect and modify the clinical response of patients detected for SARS-CoV-2, some researchers have explored this line of investigation. The relationship between these co-infections remains unclear, leading to a need to deepen our knowledge about interactions among pathogens, and between pathogens and the host. Thus, the present study employed RT-qPCR to assess the presence of Human Adenovirus (HAdV), Influenza A (Flu A), Influenza B (Flu B), Human Metapneumovirus (HMPV), Respiratory Syncytial Virus (RSV), Human Rhinovirus (HRV), and Parainfluenza Virus (PIV). A total of 187 nasopharyngeal samples from adult patients exhibiting respiratory symptoms were collected between February 2021 and November 2022 at the University Hospital Polydoro Ernani de Sao Thiago in Florianopolis, SC, Brazil. Our findings revealed that 25.16% of samples tested positive for non-SARS-CoV-2 respiratory viruses (29.8% - HRV, 5.3% - PIV, 4.3%-RSV, and 1.1% - HMPV). From the 74.84% of SARS-CoV-2 positive patients, the presence of co-infection was observed in 9,7% of patients, with 7.5% being HRV, 1.1% HAdV and 1.1% Flu A. Since co-infections can potentially alter patient prognoses and impact local epidemiological dynamics, this study highlights the significance of ongoing monitoring and epidemiological assessment through genomic surveillance of other clinically relevant respiratory pathogens.
Conditional Survival and Nomogram for Elderly Non-Metastatic Colon Cancer Patients Following Colectomy
Authors: Gao Yadong , Wang Huimin , Zhang Yi , Zhao Jing , Feng Sujuan , Qiu Jianwei 
Published: April 2024

AbstractBackgroundThis study aimed to evaluate the conditional survival (CS) of elderly patients with non-metastatic colon cancer who underwent colectomy and build conditional nomograms that can accommodate varying survival periods and estimate survival rates.MethodsData from 9302 patients between 2004 and 2017 were obtained from the Surveillance, Epidemiology, and End Results database. CS was used to assess overall survival and colon-specific survival rates in patients who survived beyond a certain time period. Cox regression was used to select factors for nomogram development, and performance was evaluated using area under the receiver operating characteristic curve (AUC), calibration plot, and decision curve analysis (DCA).ResultsThe 5-year conditional overall survival rates initially increased slightly but then decreased over time. The rates at different time points after diagnosis (baseline and 1-5 years) were 62.5, 63.2, 62.8, 62.1, 61.6, and 59.8%. In contrast, 5-year conditional colon-specific survival rates consistently improved over the same period. These rates were 78.1, 80.9, 84.2, 86.9, 89.3, and 90.9%, respectively. Nomograms were developed for baseline measurements and for patients who survived 1, 3, and 5 years. The performance of these nomograms, assessed using AUC, calibration curves, and DCA, indicated good predictive capabilities.ConclusionCS provides valuable information on the medium- and long-term survival probabilities of elderly patients with non-metastatic colon cancer who underwent colectomy. The developed conditional nomograms allowed for the estimation of survival probabilities across different timeframes, facilitating a comprehensive understanding of prognosis and collaborative decision making.
Development and Internal Validation of Models Predicting the Health Insurance Status of Participants in the German National Cohort
Authors: Hrudey Ilona , Swart Enno , Baurecht Hansjörg , Becher Heiko , Damms-Machado Antje , Hoffmann Wolfgang , Jöckel Karl-Heinz , Kartschmit Nadja , Katzke Verena , Keil Thomas , Kollhorst Bianca , Leitzmann Michael , Meinke-Franze Claudia , Michels Karin B. , Mikolajczyk Rafael , Niedermaier Tobias , Pigeot Iris , Schipf Sabine , Schmidt Börge , Walter Barbara , Willich Stefan , Wolff Robert , Stallmann Christoph 
Published: April 2024

AbstractBackgroundIn Germany, all citizens must purchase health insurance, in either statutory (SHI) or private health insurance (PHI). Because of the division into SHI and PHI, person insurance’s status is an important variable for studies in the context of public health research. In the German National Cohort (NAKO), the variable on self-reported health insurance status of the participants has a high proportion of missing values (55.4%). The aim of our study was to develop and internally validate models to predict the health insurance status of NAKO baseline survey participants in order to replace missing values. In this respect, our research interest was focused on the question to which extent socio-demographic characteristics are suitable for predicting health insurance status.MethodsWe developed two prediction models including 53,796 participants to estimate the probability that a participant is either member of a SHI (model 1) or PHI (model 2). We identified eight predictors by literature research: occupation, income, education, sex, age, employment status, residential area, and marital status. The predictive performance was determined in the internal validation considering discrimination and calibration. Discrimination was assessed based on the Area Under the Curve (AUC) and the Receiver Operating Characteristic (ROC) curve and calibration was assessed based on the calibration slope and calibration plot.ResultsIn model 1, the AUC was 0.91 (95% CI: 0.91-0.92) and the calibration slope was 0.97 (95% CI: 0.97-0.97). Model 2 had an AUC of 0.91 (95% CI: 0.90-0.91) and a calibration slope of 0.97 (95% CI: 0.97-0.97). Based on the calculated performance parameters both models turned out to show an almost ideal discrimination and calibration. Employment status and household income and to a lesser extent educational level, age, sex, marital status, and residential area are suitable for predicting health insurance status.ConclusionsSocio-demographic characteristics especially employment status and household income assessed at NAKO’s baseline were suitable for predicting the statutory and private health insurance status. However, before applying the prediction models in other studies, an external validation in population-based studies is recommended.
Optimization of1H MR spectroscopy methods for large volume acquisition of low concentration downfield resonances at 3T and 7T
Authors: Wilson Neil E. , Elliott Mark A. , Reddy Nanga Ravi Prakash , Swago Sophia , Witschey Walter R. , Reddy Ravinder 
Published: April 2024

ABSTRACTPurposeThis goal of this study was to optimize spectrally selective1H MRS methods for large volume acquisition of low concentration metabolites with downfield resonances at 7T and 3T, with particular attention paid to detection of nicotinamide adenine dinucleotide (NAD+) and tryptophan.MethodsSpectrally selective excitation was used to avoid magnetization transfer effects with water, and various sinc pulses were compared to a pure-phase E-BURP pulse. Localization using a single slice selective pulse was compared to voxel-based localization that used three orthogonal refocusing pulses, and low bandwidth refocusing pulses were used to take advantage of the chemical shift displacement of water. A technique for water sideband removal was added, and a method of coil channel combination for large volumes was introduced.ResultsProposed methods were compared qualitatively to previously-reported techniques at 7T. Sinc pulses resulted in reduced water signal excitation and improved spectral quality, with a symmetric, low bandwidth-time product pulse performing best. Single slice localization allowed shorter TEs with large volumes, enhancing signal, while low bandwidth slice selective localization greatly reduced the observed water signal. Gradient cycling helped remove water sidebands, and frequency aligning and pruning individual channels narrowed spectral linewidths. High quality brain spectra of NAD+and tryptophan are shown in four subjects at 3T.ConclusionImproved spectral quality with higher downfield signal, shorter TE, lower nuisance signal, reduced artifacts, and narrower peaks was realized at 7T. These methodological improvements allowed for previously unachievable detection of NAD+and tryptophan in human brain at 3T in under five minutes.
Design of the COMEBACK and BACKHOME Studies, Longitudinal Cohorts for Comprehensive Deep Phenotyping of Adults with Chronic Low-Back Pain (cLBP): a part of the BACPAC Research Program
Authors: Hue Trisha F. , Lotz Jeffrey C. , Zheng Patricia , Black Dennis M. , Bailey Jeannie , Ewing Susan K. , Fields Aaron J. , Mehling Wolf , Scheffler Aaron , Strigo Irina , Petterson Thomas , Wu Lucy A. , O’Neill Conor ,   The UCSF REACH Center,   the CoRe CEnter for PAtient-Centric Mechanistic PHenotyping in Chronic Low Back Pain
Published: April 2024

ABSTRACTObjectiveThe University of California, San Francisco (UCSF) Core Center for Patient-centric, Mechanistic Phenotyping in Chronic Low Back Pain (REACH) is one of the three NIH Back Pain Consortium (BACPAC) Research Programs Mechanistic Research Centers (MRCs). The goal of UCSF REACH is to define cLBP phenotypes and pain mechanisms that can lead to effective, personalized treatments for patients across the population. The primary objective of this research project is to address the critical need for new diagnostic and prognostic markers, and associated patient classification protocols for chronic low back pain (cLBP) treatment.DesignTo meet this objective, REACH is conducting two large investigator-initiated translational research cohort studies called: The Longitudinal Clinical Cohort for Comprehensive Deep Phenotyping of Chronic Low-Back Pain (cLBP) Adults Study (comeBACK) and the Chronic Low-Back Pain (cLBP) in Adults Study (BACKHOME).SettingcomeBACK is a longitudinal multicenter in-person observational study of 450 adults with chronic low back pain designed to perform comprehensive deep phenotyping. While, the BACKHOME study is a site-less longitudinal observational e-cohort of approximately 3000 U.S. adults with cLBP. To our knowledge, BACKHOME is the largest prospective remote registry of nationwide adults with cLBP.MethodsBoth the comeBACK and BACKHOME studies are collecting a robust and comprehensive set of risk factors, outcomes, and covariates in order to perform deep phenotyping of cLBP patients based on combined biopsychosocial variables to: define cLBP subtypes, establish phenotyping tools for routine clinical evaluation, and lead to improved cLBP outcomes in the future. The data from both studies will be used to establish techniques to develop a patient-centric definition of treatment success and to analyze cLBP patient traits to define clinically useful cLBP phenotypes, using a combination of traditional data analyses and deep learning methods.ConclusionsThese 2 pivotal studies, in conjunction with the ancillary studies being performed in both comeBACK and BACKHOME, and the other BACPAC-consortium research projects, we will be able to address a number of diagnostic and therapeutic issues in this complex and diverse patient population with cLBP. These studies will help clarify biopsychosocial mechanisms of cLBP with the aim to provide a foundation to improve the evaluation of treatment effectiveness and to spur new avenues of therapeutic research, including personalized outcome measures that constitute a clinically meaningful treatment effect for individual cLBP patients.
Ablation STrategies for Repeat PrOcedures in Atrial Fibrillation Recurrences despite Durable Pulmonary Vein Isolation ASTRO - AF Trial
Authors: Schmidt Boris , Bordignon Stefano , Metzner Andreas , Sommer Philipp , Steven Daniel , Dahme Tilmann , Busch Matthias , Tilz Roland Richard , Schaack David , Rillig Andreas , Sohns Christian , Sultan Arian , Weinmann-Emhardt Karolina , Hummel Astrid , Vogler Julia , Fink Thomas , Lueker Jakob , Pott Alexander , Heeger Christian , Julian Chun KR 
Published: April 2024

AbstractBackgroundAblation strategies for patients with symptomatic atrial fibrillation (AF) and isolated pulmonary veins (PV) vary and their impact on arrhythmia recurrence remains unclear. This prospective randomized German multi—center trial sought to compare two ablation strategies in this patient cohort.MethodsPatients with AF despite durable PV isolation were randomly assigned at seven centers to undergo low-voltage area (LVA) ablation using 3D mapping and irrigated radiofrequency current ablation (group A) or empirical left atrial appendage isolation (LAAI) utilizing the cryoballoon (CB) followed by staged interventional LAA closure (group B). The primary endpoint was freedom from atrial tachyarrhythmias between 91 and 365 days after index ablation. The study was powered for superiority of LAAI compared to LVA.ResultsPatients (40% female, mean age 68.8±8 years) with paroxysmal (32%) or persistent AF (68%) were randomized to undergo LVA ablation (n=79) or CB guided LAAI (n=82). After a planned interim analysis enrollment was halted on January 10th2023.In the LAAI group 77/82 LAAs were successfully isolated with subsequent LAAC in 57 patients. Procedure related complications occurred in 4 (5%) and 11 (13.5%) patients in group A and B, respectively (P=0.10). The median follow-up was 367 (IQR 359-378) days. The Kaplan Meier point estimate for the freedom from a primary endpoint event was 51.7% (CI 40.9-65.4%) for group A and 55.5% (CI 44.4-69.2%; p=0.8069).ConclusionsThe present study did not detect superiority of CB guided LAAI over LVA ablation in patients with AF despite durable PVI.It was registered athttps://clinicaltrials.gov/study/NCT04056390Clinical PerspectivesWhat is new?This is the first randomized multi-center study to compare two different ablation strategies in AF patients with durable PVI.Empirical LAAI was not associated with better outcome in comparison to low-voltage area ablation.What are the clinical implications?LAAI should not be advocated as a stand-alone ablation strategy for patients with AF recurrences after prior ablation.The patient with AF recurrence after prior catheter ablation should be informed that if all PVs are found durably isolated the optimal ablation strategy remains uncertain.
School Neighborhood Deprivation is Associated with a Higher Prevalence of Hypertension
Authors: Onugha Elizabeth A. , Banerjee Ankona , Nobleza Kenneth J. , Nguyen Duc T. , Rosales Omar , Oluyomi Abiodun , Dave Jayna M. , Samuels Joshua 
Published: April 2024

AbstractBackgroundHypertension, a major modifiable risk factor for cardiovascular disease, is increasing among adolescents. While socioeconomic factors have been shown to contribute to hypertension risk in adults, similar data in children is lacking. We examined the association between socioeconomic characteristics of school neighborhoods and the prevalence of hypertension in adolescents.MethodsSchool neighborhood socioeconomic status (SES) was assessed via the area deprivation index (ADI), a composite measure of area-level socioeconomic deprivation. Using data from a school BP surveillance program implemented in the Houston metropolitan area, we performed a cross-sectional analysis using both univariate and multivariable regression analyses.ResultsAmong 21,392 students aged 10 to 19 years during the 2000 through 2017 academic years, the prevalence of sustained hypertension was 2.6%. Although 85% of students attended schools located in neighborhoods in quartiles 1 (Q1) and 2 (Q2) (higher ADI represents more deprivation), Hispanics and African Americans were overrepresented in the schools located inside more deprived neighborhoods. The highest sustained hypertension rate (4.6%) was observed among students attending Q 3 and Q4 schools compared to 2.3% in Q 1 and Q2 schools (p < 0.001). Multivariable regression analysis showed that being male, obese, and attending school in a disadvantaged neighborhood were significantly associated with an increased prevalence of hypertension.ConclusionsAttending school in neighborhoods with lower SES may account for the increased hypertension prevalence in minority adolescents. Characteristics of school neighborhoods play an important role in the disparities observed in hypertension prevalence, providing direct opportunities to encourage improved dietary intake and physical activity, both of which are important determinants of hypertension.
Microbiota-derived inosine programs protective CD8+T cell responses against influenza in newborns
Authors: Stevens Joseph , Culberson Erica , Kinder Jeremy , Ramiriqui Alicia , Gray Jerilyn , Bonfield Madeline , Shao Tzu-Yu , Al Gharabieh Faris , Peterson Laura , Steinmeyer Shelby , Zacharias William , Pryhuber Gloria , Paul Oindrila , Sengupta Shaon , Alenghat Theresa , Way Sing Sing , Deshmukh Hitesh 
Published: April 2024

AbstractThe immunological defects causing susceptibility to severe viral respiratory infections due to early-life dysbiosis remain ill-defined. Here, we show that influenza virus susceptibility in dysbiotic infant mice is caused by CD8+T cell hyporesponsiveness and diminished persistence as tissue-resident memory cells. We describe a previously unknown role for nuclear factor interleukin 3 (NFIL3) in repression of memory differentiation of CD8+T cells in dysbiotic mice involving epigenetic regulation of T cell factor 1 (TCF 1) expression. Pulmonary CD8+T cells from dysbiotic human infants share these transcriptional signatures and functional phenotypes. Mechanistically, intestinal inosine was reduced in dysbiotic human infants and newborn mice, and inosine replacement reversed epigenetic dysregulation ofTcf7and increased memory differentiation and responsiveness of pulmonary CD8+T cells. Our data unveils new developmental layers controlling immune cell activation and identifies microbial metabolites that may be used therapeutically in the future to protect at-risk newborns.
PGC-1α drives small cell neuroendocrine cancer progression towards an ASCL1-expressing subtype with increased mitochondrial capacity
Authors: Varuzhanyan Grigor , Chen Chia-Chun , Freeland Jack , He Tian , Tran Wendy , Song Kai , Wang Liang , Cheng Donghui , Xu Shili , Dibernardo Gabriella A. , Esedebe Favour N , Bhatia Vipul , Han Mingqi , Abt Evan R. , Park Jung Wook , Memarzadeh Sanaz , Shackelford David , Lee John K. , Graeber Thomas , Shirihai Orian , Witte Owen 
Published: April 2024

ABSTRACTAdenocarcinomas from multiple tissues can evolve into lethal, treatment-resistant small cell neuroendocrine (SCN) cancers comprising multiple subtypes with poorly defined metabolic characteristics. The role of metabolism in directly driving subtype determination remains unclear. Through bioinformatics analyses of thousands of patient tumors, we identified enhanced PGC-1α—a potent regulator of oxidative phosphorylation (OXPHOS)—in various SCN cancers (SCNCs), closely linked with neuroendocrine differentiation. In a patient-derived prostate tissue SCNC transformation system, the ASCL1-expressing neuroendocrine subtype showed elevated PGC-1α expression and increased OXPHOS activity. Inhibition of PGC-1α and OXPHOS reduced the proliferation of SCN lung and prostate cancer cell lines and blocked SCN prostate tumor formation. Conversely, enhancing PGC- 1α and OXPHOS, validated by small-animal Positron Emission Tomography mitochondrial imaging, tripled the SCN prostate tumor formation rate and promoted commitment to the ASCL1 lineage. These results establish PGC-1α as a driver of SCNC progression and subtype determination, highlighting novel metabolic vulnerabilities in SCNCs across different tissues.STATEMENT OF SIGNIFICANCEOur study provides functional evidence that metabolic reprogramming can directly impact cancer phenotypes and establishes PGC-1α-induced mitochondrial metabolism as a driver of SCNC progression and lineage determination. These mechanistic insights reveal common metabolic vulnerabilities across SCNCs originating from multiple tissues, opening new avenues for pan-SCN cancer therapeutic strategies.