bluuebunny/crossref_metadata_2025_split huggingface dataset:
High affinity chimeric antigen receptor signaling induces an inflammatory program in human regulatory T cells
Authors: Cochrane Russell W. , Robino Rob A. , Granger Bryan , Allen Eva , Vaena Silvia , Romeo Martin J. , de Cubas Aguirre A. , Berto Stefano , Ferreira Leonardo M.R. 
Published: April 2024

SUMMARYRegulatory T cells (Tregs) are promising cellular therapies to induce immune tolerance in organ transplantation and autoimmune disease. The success of chimeric antigen receptor (CAR) T-cell therapy for cancer has sparked interest in using CARs to generate antigen-specific Tregs. Here, we compared CAR with endogenous T cell receptor (TCR)/CD28 activation in human Tregs. Strikingly, CAR Tregs displayed increased cytotoxicity and diminished suppression of antigen-presenting cells and effector T (Teff) cells compared with TCR/CD28 activated Tregs. RNA sequencing revealed that CAR Tregs activate Teff cell gene programs. Indeed, CAR Tregs secreted high levels of inflammatory cytokines, with a subset of FOXP3+CAR Tregs uniquely acquiring CD40L surface expression and producing IFNγ. Interestingly, decreasing CAR antigen affinity reduced Teff cell gene expression and inflammatory cytokine production by CAR Tregs. Our findings showcase the impact of engineered receptor activation on Treg biology and support tailoring CAR constructs to Tregs for maximal therapeutic efficacy.Graphical Abstract
Discovering cancer stem-like cells using Spatial transcriptomic analysis: Nuclear factor I X as a novel therapeutic target for gastric cancer
Authors: Ishikawa Akira , Fukui Takafumi , Kido Aya , Katsuya Narutaka , Kuraoka Kazuya , Uraoka Naohiro , Suzuki Takahisa , Oka Shiro , Kotachi Takahiro , Ashktorab Hassan , Smoot Duane , Yasui Wataru 
Published: April 2024

ABSTRACTBackgroundGastric cancer (GC) is characterized by significant intratumoral heterogeneity and stem cells presenting as promising therapeutic targets. Despite advancements in spatial transcriptome analysis, unexplored targets for addressing cancer stemness remain unknown. This study aims to identify Nuclear Factor IX (NFIX) as a critical regulator of cancer stemness in GC and evaluate its clinicopathological significance and function.MethodsSpatial transcriptome analysis was conducted on GC. NFIX expression’s correlation with clinicopathological factors and prognosis was assessed through immunostaining in 127 GC cases. Functional analyses in cancer cell lines validated these findings.ResultsSpatial transcriptome analysis stratified GC tissues based on genetic profiles, pinpointing CSC-like cells and further refined the classification to identify and highlight the NFIX’s significance, validated by Monocle 3 and CytoTRACE analyses. Knockdown experiments in cancer cell lines demonstrated the involvement of NFIX in cancer cell proliferation and kinase activity.ConclusionsThis study underscores spatial transcriptome analysis’s role in refining GC tissue classification and identifying therapeutic targets, highlighting NFIX as pivotal. NFIX expression correlates with poor prognosis and drives GC progression, suggesting its potential as a novel therapeutic target for personalized GC therapies.
EAP: a versatile cloud-based platform for comprehensive and interactive analysis of large-scale ChIP/ATAC-seq data sets
Authors: Chen Haojie , Huang Tao , Guo Zhijie , Zheng Anqin , Chen Weiran , Ma Liangxiao , Tu Shiqi , Zheng Guangyong , Li Yixue , Shao Zhen 
Published: April 2024

AbstractEpigenome profiling techniques such as ChIP-seq and ATAC-seq have revolutionized our understanding of gene expression regulation in tissue development and disease progression. However, increasing amount of ChIP/ATAC-seq data poses challenges in computational resources, and the absence of systematic tools for epigenomic analysis underscores the necessity for an efficient analysis platform. To address these issues, we developed the Epigenomic Analysis Platform (EAP,https://www.biosino.org/epigenetics), a scalable cloud-based tool that efficiently analyzes large-scale ChIP/ATAC-seq data sets. EAP employs advanced computational algorithms to derive biologically meaningful insights from heterogeneous datasets and automatically generates publication-ready figures and tabular results, enabling comprehensive epigenomic analysis and data mining in areas like cancer subtyping and therapeutic target discovery.
A paired analysis of mercury among non-invasive tissues to inform bat conservation monitoring
Authors: Simonis Molly C , Whitmore Kimberlee , Dyer Kristin E , Allira Meagan , Demory Bret , Chumchal Matthew M , Becker Daniel J 
Published: April 2024

AbstractContaminant exposure can harm wildlife. However, measuring contaminant exposure in wildlife can be challenging due to accessibility of species and/or sampling tissue matrices needed to answer research questions regarding exposure. For example, in bats and other taxa that roost, it may be best to collect pooled feces from colonies for minimal disturbance to species of conservation concern, but fecal contaminant concentrations do not provide contaminant bioaccumulation estimates. Thus, there is a need for quantifying relationships between sample matrices for measuring contaminant exposure to answer research questions pertaining to wildlife health and addressing conservation needs. Our goal was to determine relationships between fecal and fur total mercury (THg). To do so, we collected paired feces and fur from Mexican free-tailed bats (Tadarida brasiliensis) in summer 2023 in western Oklahoma at a maternity roost with no known Hg point source. We analyzed THg in each sample matrix for each individual (n = 48). We found no relationship between individual fecal and fur THg. However, when averaged, fur THg was 6.11 times greater than fecal THg. This factor can be used as a screening-level risk assessment of under-roost feces, which could then be followed by direct assessments of fur THg concentrations and health impacts. We encourage the use of this conversion factor across other insectivorous bat species and sites for estimating initial risks of contaminant exposure with minimal disturbance to species of conservation concern, when timely research for conservation actions are needed, and when a contaminant point source is not yet known.Graphical AbstractGraphical abstract created in BioRender under a free subscription. Cave icon created by artist Freepik athttps://www.flaticon.com/free-icons/cave.HighlightsUnder-roost sampling for contaminant exposure minimizes species disturbanceContaminant exposure relationships in tissues can aide in measuring wildlife healthWe sampledTadarida brasilliensisfor paired fecal and fur total Hg (THg)THg in fur averaged 6.11 times greater than fecesThis factor can be used as an initial risk assessment for under-roost fecal samplingMore invasive follow-up sampling (bat fur) can be justified following risk assessment
Artificial Intelligence for Hemodynamic Monitoring with a Wearable Electrocardiogram Monitor
Authors: Schlesinger Daphne E. , Alam Ridwan , Ringel Roey , Pomerantsev Eugene , Devireddy Srikanth , Shah Pinak , Garasic Joseph , Stultz Collin M. 
Published: April 2024

AbstractBackgroundThe ability to non-invasively measure left atrial pressure would facilitate the identification of patients at risk of pulmonary congestion and guide proactive heart failure care. Wearable cardiac monitors, which record single-lead electrocardiogram data, provide information that can be leveraged to infer left atrial pressures.MethodsWe developed a deep neural network using single-lead electrocardiogram data to determine when the left atrial pressure is elevated. The model was developed and internally evaluated using a cohort of 6739 samples from the Massachusetts General Hospital (MGH) and externally validated on a cohort of 4620 samples from a second institution. We then evaluated model on patch-monitor electrocardiographic data on a small prospective cohort.ResultsThe model achieves an area under the receiver operating characteristic curve of 0.80 for detecting elevated left atrial pressures on an internal holdout dataset from MGH and 0.76 on an external validation set from a second institution. A further prospective dataset was obtained using single-lead electrocardiogram data with a patch-monitor from patients who underwent right heart catheterization at MGH. Evaluation of the model on this dataset yielded an area under the receiver operating characteristic curve of 0.875 for identifying elevated left atrial pressures for electrocardiogram signals acquired close to the time of the right heart catheterization procedure.ConclusionsThese results demonstrate the utility and the potential of ambulatory cardiac hemodynamic monitoring with electrocardiogram patch-monitors.Plain Language SummaryHeart failure is a prevalent disorder that is challenging to manage. Part of what makes heart failure management challenging is that the onset of symptoms can be insidious as there are few robust tools that a clinical can leverage to estimate when a patient is likely to experience an episode of acute heart failure. While elevated intracardiac pressures are a reliable harbinger of worsening heart failure, these pressures are typically measured using an invasive, gold-standard approach, which can only be performed in an inpatient setting. A non-invasive method for detecting higher pressures inside of heart would be especially helpful for identifying worsening heart failure in an expeditious manner in the home environment. For this reason, we developed an artificial intelligence model to detect elevated pressures inside the heart using a non-invasive signal, the electrocardiogram (ECG, or EKG), which can be acquired from a wearable patch monitor device. Our results demonstrate that the model provides a reliable platform for the non-invasive assessment of cardiac pressures using data that can be obtained in the outpatient setting.
Barriers influencing the care of survivors of gender-based violence in the context of forced displacement in Kaya, Burkina Faso: a qualitative study
Authors: Bayoulou Souleymane , Ngangue Patrice , Kaboré Soutongnoma Safiata , Nteungue Boris Arnaud Kouomogne , Pafadnam Yacouba , Yopa Danièle Sandra , Seu Josiane , Kiki Gbètogo Maxime 
Published: April 2024

ABSTRACTGender-based violence (GBV) is a serious international health problem that challenges fundamental human rights. In addition to violating fundamental rights, it is an attack on the principles of gender equality. GBV is exacerbated in situations of conflict and forced displacement because of the vulnerability it engenders, particularly among women and children. Therefore, caring for victims of GBV in the context of a humanitarian crisis is special because of the specific nature of the context itself. This study aimed to explore the factors that negatively influence the care of survivors of GBV in the context of forced displacement. This was a descriptive and analytical-qualitative study. A total of 26 participants participated in the individual interviews. Most participants were healthcare workers (53,8%). The findings show that barriers to care are sociocultural (fear of stigmatization, ignorance of the benefits of seeking appropriate care and support, self-censorship among GBV survivors, fear or risk of reprisal, honor denied, fear of the aggressor punishment, shame and fear of being repudiated), institutional (lack of qualified human resources to care for GBV survivors, insufficient information on the availability of care services, geographical inaccessibility of care services, lack of confidentiality from service providers, inadequate health care and support systems, low availability of care services, poor quality of care) and financial. Bringing all care services together in one place, such as a one-stop center, is imperative to overcome these obstacles. In this way, it will be possible to improve accessibility to services and enhance the quality of care through effective coordination.
BENEFITS OF PALLIATIVE CARE IN ADULTS WITH A DIAGNOSIS OF HEART FAILURE: AN EXPLORATORY LITERATURE REVIEW
Authors: Herrera Obando Aura Cristina , Larrañaga Guerrero Jhaina Isabella , Mejia Montehermoso William Antonio , Giraldo Oliveros Simon Andres 
Published: April 2024

ABSTRACTIntroductionHeart Failure is a clinical syndrome characterized by a series of symptoms such as dyspnea, orthopnea and edema in the lower limbs. This pathology continues to have a high prevalence despite advances in pharmacotherapy and device therapy and given that it is a pathology that significantly impairs the quality of life of patients, the implementation of care is of vital importance. However, these are underused due to lack of knowledge on the part of health personnel and also due to poor implementation in the different health providers.ObjectiveAn exploratory review of the literature was carried out regarding the benefits of palliative care in patients with advanced heart failure, in order to synthesize the available and updated evidence.MethodologySearched for articles published from 2017 to 2022 related to palliative care in patients with heart failure and using the PRISMA 2020 methodology for this study. This inquiry of articles was carried out in the following databases: UpToDate, PubMed, MESH, PMC (US National Library of Medicine National Institutes of health).ResultsA total of 5 articles were obtained, from which they concluded that palliative care has a positive impact on the quality of life of patients with heart failure, there was a lower rate of hospital readmissions, improvements in physical, psychological and existential.
Circulating biomarkers of kidney tumors in TSC (tuberous sclerosis complex) patients
Authors: Rubtsova Varvara I. , Chun Yujin , Kim Joohwan , Ramirez Cuauhtemoc B. , Jung Sunhee , Cassidy Elizabeth , Rushing Gabrielle , Aguiar Dean J. , Lau Wei Ling , Ahdoot Rebecca S. , Smith Moyra , Lee Sang-Guk , Jang Cholsoon , Lee Gina 
Published: April 2024

ABSTRACTPatients with tuberous sclerosis complex (TSC) develop an array of multi-organ disease manifestations, with angiomyolipomas (AML) and cysts in the kidneys being one of the most common and deadly. Early and regular AML/cyst detection and monitoring are vital in lowering TSC patient morbidity and mortality. However, current standard of care for imaging-based methods are not designed for rapid screening, posing challenges for early detection. To identify potential diagnostic screening biomarkers of AML/cysts, we performed global untargeted metabolomics in blood samples from 283 kidney AML/cyst-positive or -negative TSC patients using mass spectrometry. We identified seven highly sensitive chemical features, including octanoic acid, that predict kidney AML/cysts in TSC patients. Patients with elevated octanoic acid have lower levels of very long-chain fatty acids (VLCFAs), suggesting that dysregulated peroxisome activity leads to overproduction of octanoic acid via VLCFA oxidation. This study highlights serum metabolites as novel biomarkers for TSC kidney tumor diagnosis and offers valuable metabolic insights into the disease.
Laminar multi-contrast fMRI at 7T allows differentiation of neuronal excitation and inhibition underlying positive and negative BOLD responses
Authors: Shao Xingfeng , Guo Fanhua , Kim JungHwan , Ress David , Zhao Chenyang , Shou Qinyang , Jann Kay , Wang Danny JJ 
Published: April 2024

AbstractA major challenge for human neuroimaging using functional MRI is the differentiation of neuronal excitation and inhibition which may induce positive and negative BOLD responses. Here we present an innovative multi-contrast laminar functional MRI technique that offers comprehensive and quantitative imaging of neurovascular (CBF, CBV, BOLD) and metabolic (CMRO2) responses across cortical layers at 7 Tesla. This technique was first validated through a finger-tapping experiment, revealing ’double-peak’ laminar activation patterns within the primary motor cortex. By employing a ring-shaped visual stimulus that elicited positive and negative BOLD responses, we further observed distinct neurovascular and metabolic responses across cortical layers and eccentricities in the primary visual cortex. This suggests potential feedback inhibition of neuronal activities in both superficial and deep cortical layers underlying the negative BOLD signals in the fovea, and also illustrates the neuronal activities in visual areas adjacent to the activated eccentricities.
TrajectoryViz: Interactive visualization of treatment trajectories
Authors: Pajusalu Maarja , Mooses Kerli , Oja Marek , Tamm Sirli , Haug Markus , Kolde Raivo 
Published: April 2024

AbstractBackground and objectivesWith the proliferation of real-world or observational health data, there is increasing interest in studying treatment trajectories. The real-life treatment trajectories can be complex, and one has to simplify the patterns to draw any conclusions; however, oversimplification will cause the loss of essential details. Thus, the visualization challenge is to strike a balance between the two extremes.MethodsWe have implemented the observation of treatment trajectories starting from cohort definitions in cooperation with medical specialists, data processing, and then generating the interactive visualizations and detailed data tables within an open-source R package as a Shiny dashboard. The created R package called TrajectoryViz (https://github.com/HealthInformaticsUT/TrajectoryViz) enables reproducible visual analysis and visual content generation for various data investigations.ResultsWe illustrate the use of the tool by assessing the sequence of events present within the data of cervical cancer prevention pathways, as well as the proportions of timely follow-up procedure events.ConclusionBuilding a toolset to access, manage, and analyze observational health data enables more accessible visual analysis of complicated data, adding time dimension to otherwise simplified event sequences that make up trajectories.
Pacemaker implantation after cardiac surgery: a contemporary, nationwide perspective
Authors: Taha Amar , David Alice , Ragnarsson Sigurdur , Szamlewski Piotr , Jamaly Shabbar , Smith J. Gustav , Nielsen Susanne J. , Jeppsson Anders , Martinsson Andreas 
Published: April 2024

ABSTRACTBackgroundCardiac surgery entails an increased risk for brady-arrhythmias. Currently known rates for permanent pacemaker (PPM) implantation after cardiac surgery are derived from non-contemporary studies. This study aimed to explore the incidence and indications for PPM implantation at 30 days and one year after different cardiac surgical procedures in a modern cohort.MethodsAll first-time coronary artery bypass grafting (CABG) and/or valvular surgery patients in Sweden 2006 - 2020 without previous PPM or implantable cardioverter-defibrillator (ICD) (n= 76,447) were included in this nationwide population-based study using data from four national registries. Patients undergoing heart transplantation and those who subsequently received an ICD were excluded.ResultsA PPM was implanted in 8.2% (n= 6,271) of the patients, 35% (n= 2,196) within the first 30 days and 46.3% (n= 2,647) at one year following surgery. The main indication of PPM implantation was atrioventricular block. Tricuspid valve surgery exhibited the highest cumulative incidence for PPM both at 30 days (6.8% (95% confidence interval 4.3 – 10.0)) and one year (8.8% (95% CI 6.0 – 12.0)) surpassing mitral valve surgery (30-day 5.3% (95% CI 4.7-6.0); one-year 6.5% (95% CI 5.8-7.3)), aortic valve surgery (30-day 4.8% (95% CI 4.5-5.1); one-year 6.0% (95% CI 5.6-6.3)) and CABG (30-day 0.74% (95% CI 0.66-0.83); one-year 1.3% (95% CI 1.2-1.35)). The incidence following combined operations (multiple valves and/or coronary surgery) was 6.5% (95% CI 6.0 – 6.9) and 8.1% (95% CI 7.7 – 8.6) at 30 days and one year respectively. Concomitant ablation surgery increased the risk even further (adjusted Hazard Ratio 9.20 (95% CI 7.96-10.64), p<0.001).ConclusionsThe need for PPM after cardiac surgery is common, primarily due to atrioventricular block. Tricuspid valve surgery is associated with the highest risk for PPM implantation amongst isolated procedures. Combined procedures and concomitant surgical ablation further increase that risk.CLINICAL PERSPECTIVEWhat is new?Permanent pacemaker after cardiac surgery is not uncommon with atrioventricular blocking being the main indication.Tricuspid valve surgery had the highest cumulative incidence at 30 days and one year, exceeding other isolated procedures.Combined cardiac surgical procedures and concomitant ablation surgery increased the risk even further.What are the clinical implications?This information is valuable while informing individual patients awaiting cardiac surgery about potential post-operative complications.Recognizing patients at higher risk enables targeted postoperative care, including closer monitoring for signs of conduction disturbances.Studies investigating and identifying predictors of post-cardiac surgery bradyarrhythmias and subsequent need for permanent pacemakers are needed.
HHIP protein interactions in lung cells provide insight into COPD pathogenesis
Authors: Deritei Dávid , Inuzuka Hiroyuki , Castaldi Peter J. , Yun Jeong Hyun , Xu Zhonghui , Anamika Wardatul Jannat , Asara John M. , Guo Feng , Zhou Xiaobo , Glass Kimberly , Wei Wenyi , Silverman Edwin K. 
Published: April 2024

AbstractChronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. The primary causes of COPD are environmental, including cigarette smoking; however, genetic susceptibility also contributes to COPD risk. Genome-Wide Association Studies (GWASes) have revealed more than 80 genetic loci associated with COPD, leading to the identification of multiple COPD GWAS genes. However, the biological relationships between the identified COPD susceptibility genes are largely unknown. Genes associated with a complex disease are often in close network proximity,i.e.their protein products often interact directly with each other and/or similar proteins. In this study, we use affinity purification mass spectrometry (AP-MS) to identify protein interactions withHHIP, a well-established COPD GWAS gene which is part of the sonic hedgehog pathway, in two disease-relevant lung cell lines (IMR90 and 16HBE). To better understand the network neighborhood ofHHIP, its proximity to the protein products of other COPD GWAS genes, and its functional role in COPD pathogenesis, we create HUBRIS, a protein-protein interaction network compiled from 8 publicly available databases. We identified both common and cell type-specific protein-protein interactors of HHIP. We find that our newly identified interactions shorten the network distance between HHIP and the protein products of several COPD GWAS genes, includingDSP, MFAP2, TET2, andFBLN5. These new shorter paths include proteins that are encoded by genes involved in extracellular matrix and tissue organization. We found and validated interactions to proteins that provide new insights into COPD pathobiology, including CAVIN1 (IMR90) and TP53 (16HBE). The newly discovered HHIP interactions with CAVIN1 and TP53 implicate HHIP in response to oxidative stress.