bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Free Triiodothyronine with Long-Term Prognosis in Hypertrophic cardiomyopathy patients with HFpEF: A Dual center research study
Authors: Meng Xiangbin , Wang Jing-Jia , Gao Jun , Zhang Kuo , Wen Jun , Wang Xu-Liang , Wang Yuan-Geng-Shuo , Zheng Ji-Lin , Liu Yu-Peng , Song Jing-Jing , Yang Jie , Zheng Yi-Tian , Li Chen , Wang Wen-Yao , Shao Chunli , Tang Yi-Da 
Published: April 2023

AbstractObjectiveThe objective of this study was to identify prognostic factors in Hypertrophic cardiomyopathy patients with HFpEF, with a particular focus on the role of FT3 levels.Research Design and MethodsWe conducted a retrospective cohort study of 992 patients with HFpEF who were admitted to our two medical centers between 2009 and 2019. We collected demographic and clinical data, including FT3 levels, and conducted univariate and multivariate Cox analyses, KM survival curve analysis, and RSC curve analysis to identify prognostic factors and evaluate the non-linear predictive value of FT3.ResultsWe found that age, atrial fibrillation, and NT-proBNP levels were all significant prognostic factors in patients with heart failure. Additionally, FT3 levels were a significant independent predictor of all-cause mortality and cardiac transplantation. Patients with lower FT3 levels had worse long-term prognoses, and the critical value of FT3 was 2.885.ConclusionsOur findings suggest that FT3 levels are an important prognostic factor in patients with heart failure and should be considered when evaluating patient outcomes. Clinicians should monitor FT3 levels and consider interventions to maintain or improve thyroid function in patients with heart failure.Article HighlightsFT3 levels are a significant independent predictor of all-cause mortality and cardiac transplantation in Hypertrophic cardiomyopathy patients with HFpEFPatients with hypertrophic cardiomyopathy combined with HFpEF have a poorer long-term prognosis with lower FT3 levels, with a critical FT3 value of 2.885Age, atrial fibrillation, and NT-proBNP levels were also significant prognostic factors in Hypertrophic cardiomyopathy patients with HFpEFClinicians should monitor FT3 levels and consider interventions to maintain or improve thyroid function in Hypertrophic cardiomyopathy patients with HFpEF.
A diagnostic and economic evaluation of the complex artificial intelligence algorithm aimed to detect 10 pathologies on the chest CT images
Authors: Chernina V. Yu. , Belyaev M.G. , Silin A.Yu. , Avetisov I.O. , Pyatnitskiy I.A. , Petrash E.A. , Basova M.V. , Sinitsyn V.E. , Omelyanovsky V.V. , Gombolevskiy V.A. 
Published: April 2023

AbstractBackgroundArtificial intelligence (AI) technologies can help solve the significant problem of missed findings in radiology studies. An important issue is assessing the economic benefits of implementing AI.Aimto evaluate the frequency of missed pathologies detection and the economic potential of AI technology for chest CT, validated by expert radiologists, compared with radiologists without access to AI in a private medical center.MethodsAn observational, single-center retrospective study was conducted. The study included chest CTs without IV contrast performed from 01.06.2022 to 31.07.2022 in "Yauza Hospital" LLC, Moscow. The CTs were processed using a complex AI algorithm for ten pathologies: pulmonary infiltrates, typical for viral pneumonia (COVID-19 in pandemic conditions); lung nodules; pleural effusion; pulmonary emphysema; thoracic aortic dilatation; pulmonary trunk dilatation; coronary artery calcification; adrenal hyperplasia; osteoporosis (vertebral body height and density changes). Two experts analyzed CTs and compared results with AI. Further routing was determined according to clinical guidelines for all findings initially detected and missed by radiologists. The lost potential revenue (LPR) was calculated for each patient according to the hospital price list.ResultsFrom the final 160 CTs, the AI identified 90 studies (56%) with pathologies, of which 81 studies (51%) were missing at least one pathology in the report. The "second-stage" LPR for all pathologies from 81 patients was RUB 2,847,760 ($37,251 or CNY 256,218). LPR only for those pathologies missed by radiologists but detected by AI was RUB 2,065,360 ($27,017 or CNY 185,824).ConclusionUsing AI for chest CTs as an "assistant" to the radiologist can significantly reduce the number of missed abnormalities. AI usage can bring 3.6 times more benefits compared to the standard model without AI. The use of complex AI for chest CT can be cost-effective.
COL6A3-derived endotrophin mediates the effect of obesity on coronary artery disease: an integrative proteogenomics analysis
Authors: Yoshiji Satoshi , Lu Tianyuan , Butler-Laporte Guillaume , Carrasco-Zanini-Sanchez Julia , Chen Yiheng , Liang Kevin , Willett Julian Daniel Sunday , Su Chen-Yang , Wang Shidong , Adra Darin , Ilboudo Yann , Sasako Takayoshi , Forgetta Vincenzo , Farjoun Yossi , Zeberg Hugo , Zhou Sirui , Hultström Michael , Machiela Mitchell , Wareham Nicholas J. , Mooser Vincent , Timpson Nicholas J. , Langenberg Claudia , Richards J. Brent 
Published: April 2023

AbstractObesity strongly increases the risk of cardiometabolic diseases, yet the underlying mediators of this relationship are not fully understood. Given that obesity has broad effects on circulating protein levels, we investigated circulating proteins that mediate the effects of obesity on coronary artery disease (CAD), stroke, and type 2 diabetes—since doing so may prioritize targets for therapeutic intervention. By integrating proteome-wide Mendelian randomization (MR) screening 4,907 plasma proteins, colocalization, and mediation analyses, we identified seven plasma proteins, including collagen type VI α3 (COL6A3). COL6A3 was strongly increased by body mass index (BMI) (β= 0.32, 95% CI: 0.26–0.38,P= 3.7 × 10-8per s.d. increase in BMI) and increased the risk of CAD (OR = 1.47, 95% CI:1.26–1.70,P= 4.5 × 10-7per s.d. increase in COL6A3). Notably, COL6A3 is cleaved at its C-terminus to produce endotrophin, which was found to mediate this effect on CAD. In single-cell RNA sequencing of adipose tissues and coronary arteries,COL6A3was highly expressed in cell types involved in metabolic dysfunction and fibrosis. Finally, we found that body fat reduction can reduce plasma levels of COL6A3-derived endotrophin, thereby highlighting a tractable way to modify endotrophin levels. In summary, we provide actionable insights into how circulating proteins mediate the effect of obesity on cardiometabolic diseases and prioritize endotrophin as a potential therapeutic target.
Time series analysis of daily data of COVID-19 reported cases in Japan from January 2020 to February 2023
Authors: Sumi Ayako 
Published: April 2023

AbstractThis study investigatbed temporal variational structures of the COVID-19 pandemic in Japan using a time series analysis incorporating maximum entropy method (MEM) spectral analysis, which produces power spectral densities (PSDs). This method was applied to daily data of COVID-19 cases in Japan from January 2020 to February 2023. The analyses confirmed that the PSDs for data in both the pre- and post-Tokyo Olympics periods show exponential characteristics, which are universally observed in PSDs for time series generated from nonlinear dynamical systems, including the so-called susceptible/exposed/infectious/recovered (SEIR) model, well-established as a mathematical model of temporal variational structures of infectious disease outbreaks. The magnitude of the gradient of exponential PSD for the pre-Olympics period was smaller than that of the post-Olympics period, because of the relatively high complex variations of the data in the pre-Olympics period caused by a deterministic, nonlinear dynamical system and/or undeterministic noise. A 3-dimensional spectral array obtained by segment time series analysis indicates that temporal changes in the periodic structures of the COVID-19 data are already observable before the commencement of the Tokyo Olympics and immediately after the introduction of mass and workplace vaccination programs. Lessons from theoretical studies for measles control programs may be applicable to COVID-19.
Detection of distant familial relatedness in biobanks for identification of undiagnosed carriers of a Mendelian disease variant: application to Long QT syndrome
Authors: Lancaster Megan C. , Chen Hung-Hsin , Shoemaker M. Benjamin , Fleming Matthew R. , Baker James T. , Polikowsky Hannah G. , Samuels David C. , Huff Chad D. , Roden Dan M. , Below Jennifer E. 
Published: April 2023

AbstractImportanceThe diagnosis and study of rare genetic disease is often limited to referral populations, leading to underdiagnosis and a biased assessment of penetrance and phenotype.ObjectiveTo develop a generalizable method of genotype inference based on distant relatedness and to deploy this to identify undiagnosed Type 5 Long QT Syndrome (LQT5) rare variant carriers in a non-referral population.ParticipantsWe identified 9 LQT5 probands and 3 first-degree relatives referred to a single Genetic Arrhythmia clinic, each carrying D76N (p.Asp76Asn), the most common variant implicated in LQT5. The non-referral population consisted of 69,879 ancestry-matched subjects in BioVU, a large biobank that links electronic health records to dense array data. Participants were enrolled from 2007-2022. Data analysis was performed in 2022.ExposuresWe developed and applied a novel approach to genotype inference (Distant Relatedness for Identification and Variant Evaluation, or DRIVE) to identify shared, identical-by-descent (IBD) large chromosomal segments in array data.Main Outcomes and MeasuresWe sought to establish genetic relatedness among the probands and to use genomic segments underlying D76N to identify other potential carriers in BioVU. We then further studied the role of D76N in LQT5 pathogenesis.ResultsGenetic reconstruction of pedigrees and distant relatedness detection among clinic probands using DRIVE revealed shared recent common ancestry and identified a single long shared haplotype. Interrogation of the non-referral population in BioVU identified a further 23 subjects sharing this haplotype, and sequencing confirmed D76N carrier status in 22, all previously undiagnosed with LQT5. The QTc was prolonged in D76N carriers compared to BioVU controls, with 40% penetrance of QTc ≥ 480 msec. Among D76N carriers, a QTc polygenic score was additively associated with QTc prolongation.Conclusions and RelevanceDetection of IBD shared chromosomal segments around D76N enabled identification of distantly related and previously undiagnosed rare-variant carriers, demonstrated the contribution of polygenic risk to monogenic disease penetrance, and further established LQT5 as a primary arrhythmia disorder. Analysis of shared chromosomal regions spanning disease-causing mutations can identify undiagnosed cases of genetic diseases.
Epidemiology ofPlasmodium malariaeandPlasmodium ovalespp. in a highly malaria-endemic country: a longitudinal cohort study in Kinshasa Province, Democratic Republic of Congo
Authors: Sendor Rachel , Banek Kristin , Kashamuka Melchior Mwandagalirwa , Mvuama Nono , Bala Joseph A. , Nkalani Marthe , Kihuma Georges , Atibu Joseph , Thwai Kyaw L. , Svec W. Matthew , Goel Varun , Nseka Tommy , Lin Jessica T. , Bailey Jeffrey A. , Emch Michael , Carrel Margaret , Juliano Jonathan J. , Tshefu Antoinette , Parr Jonathan B. 
Published: April 2023

AbstractBackgroundIncreasing reports suggest that non-falciparum species are an underappreciated cause of malaria in sub-Saharan Africa, but their epidemiology is not well-defined. This is particularly true in regions of highP. falciparumendemicity such as the Democratic Republic of Congo (DRC), where 12% of the world’s malaria cases and 13% of deaths occur.Methods and FindingsThe cumulative incidence and prevalence of P. malariae and P. ovale spp. infection detected by real-time PCR were estimated among children and adults within a longitudinal study conducted in seven rural, peri-urban, and urban sites from 2015-2017 in Kinshasa Province, DRC. Participants were sampled at biannual household survey visits (asymptomatic) and during routine health facility visits (symptomatic). Participant-level characteristics associated with non-falciparum infections were estimated for single- and mixed-species infections. Among 9,089 samples collected from 1,565 participants over a 3-year period, the incidence of P. malariae and P. ovale spp. infection was 11% (95% CI: 9%-12%) and 7% (95% CI: 5%-8%) by one year, respectively, compared to a 67% (95% CI: 64%-70%) one-year cumulative incidence of P. falciparum infection. Incidence continued to rise in the second year of follow-up, reaching 26% and 15% in school-age children (5-14yo) for P. malariae and P. ovale spp., respectively. Prevalence of P. malariae, P. ovale spp., and P. falciparum infections during household visits were 3% (95% CI: 3%-4%), 1% (95% CI: 1%-2%), and 35% (95% CI: 33%-36%), respectively. Non-falciparum malaria was more prevalent in rural and peri-urban vs. urban sites, in school-age children, and among those with P. falciparum co-infection. A crude association was detected between P. malariae and any anemia in the symptomatic clinic population, although this association did not hold when stratified by anemia severity. No crude associations were detected between non-falciparum infection and fever prevalence.ConclusionsP. falciparumremains the primary driver of malaria morbidity and mortality in the DRC. However, non-falciparum species also pose an infection risk across sites of varying urbanicity and malaria endemicity within Kinshasa, DRC, particularly among children under 15 years of age. AsP. falciparuminterventions gain traction in high-burden settings like the DRC, continued surveillance and improved understanding of non-falciparum infections are warranted.
Stage-dependent biomarker changes in spinocerebellar ataxia type 3
Authors: Faber Jennifer , Berger Moritz , Carlo Wilke , Hübener-Schmid Jeannette , Schaprian Tamara , Santana Magda M , Grobe-Einsler Marcus , Onder Dement , Koyak Berkan , Giunti Paola , Garcia-Moreno Hector , Gonzalez-Robles Cristina , Lima Manuela , Raposo Mafalda , Vieira Melo Ana Rosa , de Almeida Luís Pereira , Silva Patrick , Pinto Maria M , van de Warrenburg Bart P. , van Gaalen Judith , Jeroen de Vries Jeroen , Oz Gulin , Joers James M. , Synofzik Matthis , Schöls Ludger , Riess Olaf , Infante Jon , Manrique Leire , Timmann Dagmar , Thieme Andreas , Jacobi Heike , Reetz Kathrin , Dogan Imis , Onyike Chiadikaobi , Povazan Michal , Schmahmann Jeremy , Ratai Eva-Maria , Schmid Matthias , Klockgether Thomas 
Published: April 2023

AbstractSpinocerebellar ataxia type 3/Machado–Joseph disease (SCA3) is the most common autosomal dominant ataxia. In view of the development of targeted therapies for SCA3, precise knowledge of stage-dependent fluid and MRI biomarker changes is needed.We analyzed cross-sectional data of 292 SCA3 mutation carriers including 57 pre-ataxic individuals, and 108 healthy controls from the European Spinocerebellar ataxia type 3/Machado-Joseph Disease Initiative (ESMI) cohort. Blood concentrations of mutant ATXN3 and neurofilament light (NfL) were determined, and volumes of pons, cerebellar white matter (CWM) and cerebellar grey matter (CGM) were measured on MRI.Mutant ATXN3 concentrations were high before and after ataxia onset, while NfL continuously increased and deviated from normal 11.9 years before onset. Pons and CWM volumes decreased, but the deviation from normal was only 2.0 years (pons) and 0.3 years (CWM) before ataxia onset. We propose a staging model of SCA3 that includes an initial asymptomatic carrier stage followed by the biomarker stage defined by absence of ataxia, but a significant rise of NfL. The biomarker stage leads into the ataxia stage, defined by manifest ataxia.The present analysis provides a robust framework for further studies aiming at elaboration and differentiation of the staging model of SCA3.
The Bilateral Remote Ischaemic Conditioning in Children (BRICC) trial: a two-centre, double-blind, randomised controlled trial in young children undergoing cardiac surgery
Authors: Drury Nigel E , van Doorn Carin , Woolley Rebecca L , Amos-Hirst Rebecca J , Bi Rehana , Spencer Collette M , Morris Kevin P , Montgomerie James , Stickley John , Crucean Adrian , Gill Alicia , Hill Matt , Weber Ralf J.M. , Najdekr Lukas , Jankevics Andris , Southam Andrew D. , Lloyd Gavin R. , Jaber Osama , Kassai Imre , Pelella Guiseppe , Khan Natasha E , Botha Phil , Barron David J , Madhani Melanie , Dunn Warwick B , Ives Natalie J , Kirchhof Paulus , Jones Timothy J 
Published: April 2023

ABSTRACTBackground and AimsPrevious trials evaluating remote ischaemic preconditioning in children undergoing cardiac surgery showed mixed results. We sought to determine whether adequately delivered bilateral preconditioning is cardioprotective in young children, with or without cyanosis, undergoing surgery.MethodsProspective, double-blind, randomised controlled trial at two UK centres. Children aged 3-36 months undergoing tetralogy of Fallot repair or ventricular septal defect closure were randomised in a 1:1 ratio to receive either bilateral preconditioning or sham intervention. Participants were followed up until hospital discharge or 30 days. The primary outcome was area under the curve for high-sensitivity troponin-T in the first 24 hours after surgery, analysed by intention-to-treat. Right atrial biopsies were obtained in selected patients. Trial registration:ISRCTN12923441.ResultsBetween 24 October 2016 and 8 December 2020, 120 eligible children were randomised to receive either bilateral preconditioning (n=60) or sham intervention (n=60). Participants had a median age of 7 months and 42 (35%) were female. The primary outcome, area under the curve for hs-troponin-T was higher in the preconditioning group (mean: 70.0±50.9µg/L/hr, n=56) than in controls (mean: 55.6±30.1µg/L/hr, n=58), p=0.04. Sub-group analyses did not show a differential treatment effect by oxygen saturations (pinteraction=0.25) but showed evidence of differential treatment effect by underlying defect (pinteraction=0.04). Myocardial metabolism, quantified in atrial biopsies, and secondary outcomes were not different between randomised groups.ConclusionsBilateral remote ischemic preconditioning does not attenuate myocardial injury in children undergoing surgical repair for congenital heart defects, and there was evidence of potential harm in unstented tetralogy of Fallot.
Molecular insight into the mechanism of action of some beneficial flavonoids for the treatment of Parkinson’s Disease
Authors: Biswas Sima , Mitra Anindita , Roy Sreekanya , Ghosh Rita , Bagchi Angshuman 
Published: April 2023

ABSTRACTParkinson’s Disease (PD) is a severe neurodegenerative disorder. It is characterized by the declination of dopaminergic (DA) neurons of substantia nigra pars compacta in the mid brain. Decrease in dopamine level in substantia nigra is a major event in PD. Mutation in Parkin protein is responsible for the onset of Autosomal Recessive Juvenile Parkinson’s (ARJP) Disease. Till date, there is no available treatment of PD without any side-effects. Therefore, the focus has been shifted to identifying natural product inhibitors for the treatment of the disorder. Flavonoids, a class of natural products, have proven neuroprotective effects. Some of the flavonoids have their abilities to influence the activities of central nervous system. Therefore, many studies are being conducted to analyze their activities to lower the progression of neurodegenerative diseases. This study was conducted to identify the flavonoids to be used as potential drugs for PD. From the literature, we picked up the flavonoids active on the nervous systems of human beings. We employed a literature mining approach to build a Structure Activity Relationship (SAR) to measure their efficacies. We performed molecular docking simulations using the flavonoids as the ligands and computed their binding free energy values. Our study would therefore point towards future drug- designing endeavours to come up with plausible therapeutics against PD onset.
BEERS2: RNA-Seq simulation through high fidelityin silicomodeling
Authors: Brooks Thomas G. , Lahens Nicholas F. , Mrčela Antonijo , Sarantopoulou Dimitra , Nayak Soumyashant , Naik Amruta , Sengupta Shaon , Choi Peter S. , Grant Gregory R. 
Published: April 2023

AbstractSimulation of RNA-seq reads is critical in the assessment, comparison, benchmarking, and development of bioinformatics tools. Yet the field of RNA-seq simulators has progressed little in the last decade. To address this need we have developed BEERS2, which combines a flexible and highly configurable design with detailed simulation of the entire library preparation and sequencing pipeline. BEERS2 takes input transcripts (typically fully-length mRNA transcripts with polyA tails) from either customizable input or from CAMPAREE simulated RNA samples. It produces realistic reads of these transcripts as FASTQ, SAM, or BAM formats with the SAM or BAM formats containing the true alignment to the reference genome. It also produces true transcript-level quantification values. BEERS2 combines a flexible and highly configurable design with detailed simulation of the entire library preparation and sequencing pipeline and is designed to include the effects of polyA selection and RiboZero for ribosomal depletion, hexamer priming sequence biases, GC-content biases in PCR amplification, barcode read errors, and errors during PCR amplification. These characteristics combine to make BEERS2 the most complete simulation of RNA-seq to date. Finally, we demonstrate the use of BEERS2 by measuring the effect of several settings on the popular Salmon pseudoalignment algorithm.
Inosine Induces Stemness Features in CAR T cells and Enhances Potency
Authors: Klysz Dorota D. , Fowler Carley , Malipatlolla Meena , Stuani Lucille , Freitas Katherine A. , Meier Stefanie , Daniel Bence , Sandor Katalin , Xu Peng , Huang Jing , Labanieh Louai , Leruste Amaury , Bashti Malek , Keerthi Vimal , Mata-Alcazar Janette , Gkitsas Nikolaos , Guerrero Justin A. , Fisher Chris , Patel Sunny , Asano Kyle , Patel Shabnum , Davis Kara L. , Satpathy Ansuman T. , Feldman Steven A. , Sotillo Elena , Mackall Crystal L. 
Published: April 2023

AbstractAdenosine (Ado) mediates immune suppression in the tumor microenvironment and exhausted CD8+CAR T cells mediate Ado-induced immunosuppression through CD39/73-dependent Ado production. Knockout of CD39, CD73 or A2aR had modest effects on exhausted CAR T cells, whereas overexpression of Ado deaminase (ADA), which metabolizes Ado to inosine (INO), induced stemness features and potently enhanced functionality. Similarly, and to a greater extent, exposure of CAR T cells to INO augmented CAR T cell function and induced hallmark features of T cell stemness. INO induced a profound metabolic reprogramming, diminishing glycolysis and increasing oxidative phosphorylation, glutaminolysis and polyamine synthesis, and modulated the epigenome toward greater stemness. Clinical scale manufacturing using INO generated enhanced potency CAR T cell products meeting criteria for clinical dosing. These data identify INO as a potent modulator of T cell metabolism and epigenetic stemness programming and deliver a new enhanced potency platform for immune cell manufacturing.Statement of SignificanceAdenosine is well known to inhibit T cell function and substantial effort has focused on inhibiting adenosine generation and signaling. Here, we show that exhausted T cells are suppressed by adenosine, which is only modestly impacted by inhibiting adenosine generation or signaling. In contrast, metabolism of adenosine to inosine augmented T cell function and culture of T cells with inosine induced multi-level reprogramming leading to stemness and improved anti-tumor potency. We demonstrate the feasibility of introducing inosine during GMP cell manufacturing as a novel strategy to generate enhanced CAR-T cells.