bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population Performance and Individual Agreement of Coronary Artery Disease Polygenic Risk Scores
Authors: Abramowitz Sarah A. , Boulier Kristin , Keat Karl , Cardone Katie M. , Shivakumar Manu , DePaolo John , Judy Renae , Kim Dokyoon , Rader Daniel J. , Ritchie Marylyn D. , Voight Benjamin F. , Pasaniuc Bogdan , Levin Michael G. , Damrauer Scott M. 
Published: July 2024

AbstractImportancePolygenic risk scores (PRSs) for coronary artery disease (CAD) are a growing clinical and commercial reality. Whether existing scores provide similar individual-level assessments of disease liability is a critical consideration for clinical implementation that remains uncharacterized.ObjectiveCharacterize the reliability of CAD PRSs that perform equivalently at the population level at predicting individual-level risk.DesignCross-sectional Study.SettingAll of Us Research Program (AOU), Penn Medicine Biobank (PMBB), and UCLA ATLAS Precision Health Biobank.ParticipantsVolunteers of diverse genetic backgrounds enrolled in AOU, PMBB, and UCLA with available electronic health record and genotyping data.ExposuresPolygenic risk for CAD from previously published PRSs and new PRSs developed separately from the testing cohorts.Main Outcomes and MeasuresSets of CAD PRSs that perform population prediction equivalently were identified by comparing calibration and discrimination (Brier score and AUROC) of generalized linear models of prevalent CAD using Bayesian analysis of variance. Among equivalently performing scores, individual-level agreement between risk estimates was tested with intraclass correlation (ICC) and Light’s Kappa, measures of inter-rater reliability.Results50 PRSs were calculated for 171,095 AOU participants. When included in a model of prevalent CAD, 48 scores had practically equivalent Brier scores and AUROCs (region of practical equivalence = 0.02). Across these scores, 84% of participants had at least one score in both the top and bottom risk quintile. Continuous agreement of individual risk predictions from the 48 scores was poor, with an ICC of 0.351 (95% CI; 0.349, 0.352). Agreement between two statistically equivalent scores was moderate, with an ICC of 0.649 (95% CI; 0.646, 0.652). Light’s Kappa, used to evaluate consistency of assignment to high-risk thresholds, did not exceed 0.56 (interpreted as ‘fair’) across statistically and practically equivalent scores. Repeating the analysis among 41,193 PMBB and 50,748 UCLA participants yielded different sets of statistically and practically equivalent scores which also lacked strong individual agreement.Conclusions and RelevanceAcross three diverse biobanks, CAD PRSs that performed equivalently at the population level produced unreliable individual risk estimates. Approaches to clinical implementation of CAD PRSs must consider the potential for discordant individual risk estimates from otherwise indistinguishable scores.
Rationale of acupuncture for stabilizing blood pressure fluctuation during total laparoscopic hysterectomy (ASBP): a parallel grouped, randomized clinical trial
Authors: Lee Joohyun , Roh Ju-Won , Han Kyung-Hee , Kim Min-Jeong , Na Young Jeong , Yun Bo Seong , Lee Jee Young 
Published: July 2024

ABSTRACTIntroductionReducing blood pressure fluctuations during surgery is a significant goal for anesthesiologists. Acupuncture may be a non-invasive intervention to reduce blood pressure fluctuations but has not yet been studied. This study aims to determine whether acupuncture can be used to reduce blood pressure fluctuations during surgery, especially in the early stages.Methods and analysisThis is a prospective, single-center, randomized controlled clinical trial with a parallel-group design. Thirty adult patients scheduled to undergo total laparoscopic hysterectomy are eligible. Participants who consent will be randomly assigned in a 1:1 ratio to the acupuncture or placebo group. They will be followed up for at least 14 days to assess the safety of the intervention, general anesthesia, and surgery. We will compare the differences between the highest and lowest mean blood pressures from anesthesia induction to the post-incision period as the primary endpoint. As secondary outcomes, systolic, diastolic, and mean blood pressures will be compared at each pre-determined time point. Incidence of hypotension, hypertension, tachycardia, and bradycardia will be counted separately. The use of remifentanil at the early stage of surgery, the rate of surgical discontinuation, and the length of hospital stay will be assessed as surrogate indicators of stable general anesthesia and surgical procedures. For patient-reported outcomes, Spielberger’s State-Trait Anxiety Inventory and EuroQoL-5 Dimensions–5 Levels will evaluate the change in anxiety and overall quality of life. Another non-pharmacological intervention may contribute to surgery by maintaining blood pressure within a stable range during the early postoperative period.Ethics and disseminationThe study will be conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board of CHA Ilsan Medical Center (ICHA 2022-11-010, date of approval 2023-01-03). This study was registered atClinicaltrials.gov(registration identifier:NCT05720884) and CRiS (registration identifier: KCT0009149). The publication is scheduled for December 2025. Data deposition is scheduled to occur.Strengths and limitations of this studyReducing blood pressure fluctuation is important during surgical process.Considering pharmacological interactions, non-pharmacological interventions are preferable for managing blood pressure fluctuation.Acupuncture has some potential for stabilizing blood pressure.
National Assessment on the Frequency of Pain Medication Prescribed for Intrauterine Device Insertion Procedures within the Veterans Affairs Health Care System
Authors: Ware Anna D. , Blumke Terri L. , Hoover Peter J. , Veigulis Zach P. , Ferguson Jacqueline M. , Pillai Malvika , Osborne Thomas F. 
Published: July 2024

AbstractBackgroundThe intrauterine device (IUD) is a highly effective form of long-acting reversible contraception, widely recognized for its convenience and efficacy. Despite its benefits, many patients report moderate to severe pain during and after their IUD insertion procedure. Furthermore, reports suggest significant variability in pain control medications, including no adequate pain medication. The aim of this evaluation was to assess the pharmaceutical pain medication types, proportions, and trends related to IUD insertion procedures within the Veterans Health Administration (VHA).MethodsIUD insertion procedures documented in the VA electronic health record were assessed from 1/1/2018 to 10/13/2023. Descriptive statistics described patient and facility characteristics while annual trends were assessed using linear regression.ResultsOut of the 28,717 procedures captured, only 11.4% had any form of prescribed pain medication identified. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) were the most frequently prescribed pain medication category (8.3%), with ibuprofen being the most common pain medication overall (6.1%). Over the assessment period, there was an average annual increase of 0.52% (p=0.038) of procedures with prescribed pain medication, increasing from 10.3% in 2018 to 13.3% in 2023.ConclusionsAlthough IUD insertion procedures have been seeing an increase in prescribed pain medication, the overall proportion remains disproportionality low relative to the pain experienced. Additionally, when pain interventions were initiated, they disproportionally utilized medication that have been shown to be ineffective. The intent of the work is that the information will help guide data driven pain medication strategies for patients undergoing IUD insertion procedures within the VHA.
A machine learning approach to predict mortality and pulmonary hypertension severity in newborns with congenital diaphragmatic hernia
Authors: Conte Luana , Amodeo Ilaria , De Nunzio Giorgio , Raffaeli Genny , Borzani Irene , Persico Nicola , Griggio Alice , Como Giuseppe , Colnaghi Mariarosa , Fumagalli Monica , Cascio Donato , Cavallaro Giacomo 
Published: July 2024

ABSTRACTPrenatal prediction of postnatal outcomes in newborns with congenital diaphragmatic hernia (CDH) remains challenging, especially for mortality and neonatal persistent pulmonary hypertension (PPHN). Despite the increasing utilization of advanced artificial intelligence (AI) technologies in the neonatal field, this study is pioneering in exploring AI methodologies in the context of CDH. It represents an initial attempt to implement a Machine Learning (ML) system to predict postnatal mortality and PPHN severity, using prenatal and early postnatal data as input variables. We enrolled 50 patients with isolated left-sided CDH from singleton pregnancies and retrospectively collected clinical and imaging variables from fetal ultrasound (US) and shape features extracted from magnetic resonance imaging (MRI), combined with gestational age and birth weight. A supervised ML model for predicting mortality and PPHN severity was developed, achieving good accuracy (88% for mortality prediction and 82% for PPHN) and sensitivity (95% for mortality and 85% for PPHN). The area under the curve (AUC) of the ROC curve was 0.88 for mortality and 0.82 for PPHN predictions. Our results may lead to novel AI applications in the neonatal field, focusing on predicting postnatal outcomes based on prenatal data, ultimately improving prognostic assessments and intervention strategies for such a complex disease.Clinical Trial RegistrationThe trial was registered at ClinicalTrials.gov with IdentifierNCT04609163What is Knownprenatal prediction of postnatal mortality and severity of pulmonary hypertension in CDH newborns remains challenging and largely based on imaging through the volumetric assessment of fetal lungs.What is Newdeveloping a ML system for predicting PPHN severity and mortality risk based on the integrated assessment of prenatal and early postnatal variables is feasible, with good accuracy.
Optimal annual COVID-19 vaccine boosting dates following previous booster vaccination or breakthrough infection
Authors: Townsend Jeffrey P. , Hassler Hayley B. , Dornburg Alex 
Published: July 2024

AbstractCOVID-19 booster vaccinations mitigate transmission and reduce the morbidity and mortality associated with infection. However, the optimal date for booster administration remains uncertain. Geographic variation in infection rates throughout the year make it challenging to intuit the best yearly booster administration date to effectively prevent infection, and also challenging to provide best guidance in how to alter booster administration in response to a breakthrough infection. Therefore, we leverage longitudinal antibody and reinfection probabilities with spatiotemporal projections of COVID-19 incidence to develop a geographically-informed approach to optimizing the timing of booster vaccination. Additionally, we assess the delay in booster vaccination that is warranted following breakthrough infections whenever they occur during the year, enabling an approach that acknowledges and respects diverse immune statuses, thereby addressing a substantial barrier to uptake. Our results provide guidance for individual decision-making and healthcare provider recommendations, as well as optimal public health policies.Significance StatementCOVID-19 booster vaccinations are pivotal in reducing disease transmission. However, optimal schedules that would most successfully mitigate adverse health outcomes have not been rigorously determined. Spatial and temporal surges of infections, including breakthrough infections, challenge the implementation of effective boosting strategies. We leverage antibody data and incidence projections to develop a geographically-informed schedule for yearly booster administration and quantify appropriate delays in booster vaccination post-breakthrough infection, thereby accounting for immune status and enhancing vaccination inclusivity. Our findings offer crucial information for individual decision making, healthcare provider guidance, and policy aimed at optimizing the impact of booster vaccination on public health.
Physician experiences of electronic health records interoperability and its practical impact on care delivery in the English NHS: A cross-sectional survey study
Authors: Li Edmond , Lounsbury Olivia , Hasnain Mujtaba , Ashrafian Hutan , Darzi Ara , Neves Ana Luisa , Clarke Jonathan 
Published: July 2024

AbstractBackgroundThe lack of interoperability has been a well-recognised limitation associated with the use of electronic health records (EHR). However, less is known about how it manifests for frontline NHS staff when delivering care, how it impacts patient care, and what are its implications on care efficiency.Objectives(1) To capture the perceptions of physicians regarding the current state of EHRs interoperability, (2) to investigate how poor interoperability affects patient care and safety and (3) to determine the effects on care efficiency in the NHS.MethodsAn online survey was conducted to explore how physicians perceived the routine use of EHRs, its effects on patient safety, and impact to care efficiency in NHS healthcare facilities. Descriptive statistics was used to report any notable findings observed.ResultsA total of 636 NHS physicians participated. Participants reported that EHR interoperability is rudimentary across much of the NHS, with limited ability to read but not edit data from within their organisation. Negative perceptions were most pronounced amongst specialties in secondary care settings and those with less than one year of EHR experience or lower self-reported EHR skills. Limited interoperability prolonged hospital stays, lengthened consultation times, and frequently necessitated repeat investigations to be performed. Limited EHR interoperability impaired physician access to clinical data, hampered communication between providers, and was perceived to threatened patient safety.ConclusionAs healthcare data continues to increase in complexity and volume, EHR interoperability must evolve to accommodate these growing changes and ensure the continued delivery of safe care. The experiences of physicians provide valuable insight into the practical challenges limited interoperability poses and can contribute to future policy solutions to better integrate EHRs in the clinical environment.Public Interest/Lay SummaryLimited interoperability between EHR systems has been a longstanding problem since the technology’s introduction in NHS England. However, little research has been done to understand the extent of this problem from the perspective of physicians and the challenges it poses.This study surveyed 636 physicians across England to better understand limited EHR interoperability. Most participants reported that interoperability between NHS facilities was inadequate. Consequences of this included increased duration of hospital stays, lengthened consultation times, and more redundant diagnostic tests performed. Limited interoperability hindered communication between NHS workers and threatened care quality and patient safety. As more healthcare technologies are incorporated into the NHS, gaining greater insight from physicians is critical to finding solutions to address these problems.
Parvalbumin interneuron ErbB4 controls ongoing network oscillations and olfactory behaviors in mice
Authors: Hu Bin , Geng Chi , Guo Feng , Liu Ying , Wang Ran , Chen You-Ting , Hou Xiao-Yu 
Published: July 2024

AbstractParvalbumin (PV)-positive interneurons modulate the processing of odor information. However, less is known about how PV interneurons dynamically remodel neural circuit responses in the olfactory bulb (OB) and its physiological significance. This study showed that a reinforced odor discrimination task up-regulated the activity of ErbB4 kinase in mouse OB. ErbB4 knock-out in the OB impaired dishabituation of odor responses and discrimination of complex odors, whereas odor memory or adaptation had no alteration in mice. RNAscope analysis demonstrated that ErbB4-positive neurons are localized throughout the OB, whereas within the internal and external plexiform layers, ErbB4 mRNA are largely expressed in PV-positive interneurons. ErbB4 knock-out in PV interneurons disrupted odor-evoked responses of mitral/tufted cells, and led to increased power in the ongoing local field potential in awake mice. We also found a decrease in the frequency of miniature inhibitory postsynaptic currents and deficits in stimulus-evoked recurrent and lateral inhibition onto mitral cells, suggesting broad impairments in inhibitory microcircuit following PV-ErbB4 loss. Similarly, ErbB4 ablation in OB PV interneurons disrupted olfactory discrimination and dishabituation in mice. These findings provide novel insights into the role of PV-ErbB4 signaling in inhibitory microcircuit plasticity, ongoing oscillations, and OB output, which underlies normal olfactory behaviors.
Re-analysis of mobile mRNA datasets highlights challenges in the detection of mobile transcripts from short-read RNA-Seq data
Authors: Paajanen Pirita , Tomkins Melissa , Hoerbst Franziska , Veevers Ruth , Heeney Michelle , Thomas Hannah Rae , Apelt Federico , Saplaoura Eleftheria , Gupta Saurabh , Frank Margaret , Walther Dirk , Faulkner Christine , Kehr Julia , Kragler Friedrich , Morris Richard J. 
Published: July 2024

AbstractShort-read RNA-Seq analyses of grafted plants have led to the proposal that large numbers of mRNAs move over long distances between plant tissues, acting as potential signals. The detection of transported transcripts by RNA-Seq is both experimentally and computationally challenging, requiring successful grafting, delicate harvesting, rigorous contamination controls and data processing approaches that can identify rare events in inherently noisy data. Here, we perform a meta-analysis of existing datasets and examine the associated bioinformatic pipelines. Our analysis reveals that technological noise, biological variation and incomplete genome assemblies give rise to features in the data that can distort the interpretation. Taking these considerations into account, we find that a substantial number of transcripts that are currently annotated as mobile are left without support from the available RNA-Seq data. Whilst several annotated mobile mRNAs have been validated, we cannot exclude that others may be false positives. The identified issues may also impact other RNA-Seq studies, in particular those using single nucleotide polymorphisms (SNPs) to detect variants.
The minimal number of genes needed to identify a tumor
Authors: Gil Gabriel , Gonzalez Augusto 
Published: July 2024

AbstractWe demonstrate that the global state of a Gene Regulatory Network[1]may be labeled by a few genes in spite of the fact that there are thousands of genes participating in it. For example, the expression values of only 3 genes are enough to discriminate between a tissue sample coming from a normal lung or a lung adenocarcinoma. We follow a pragmatic procedure, dependent on the sample set, but which is expected to become exact for large enough sets of samples. The proof relies on a scheme for the construction of perfect classification panels of genes[2], inspired by rough set theory[3].
A review of co-occurrence and hybridization as neglected factors in studies of Syrian WoodpeckerDendrocopos syriacusand Great Spotted WoodpeckerDendrocopos major
Authors: Bakai Antonii , Gorman Gerard , Kajtoch Łukasz 
Published: July 2024

AbstractSome species of woodpecker (Picidae), such as in the genusDendrocopos, are known to occasionally hybridize. The distribution, biology and ecology of the Syrian Woodpecker (D. syriacus) and the Great Spotted Woodpecker (D. major) are fairly well-known (less so in the case of Syrian), but these closely related species are seldom treated together in studies. This review summarizes the published data on these species in order to evaluate the omissions and inaccuracies in research and surveys on their sympatric populations. As research that deals with both species together is scant, the need to examine interactions, both antagonistic and hybridization, is advisable in order to properly understanding their ecology, ethology, breeding biology and demography.
Resistance of estrogen receptor function to BET bromodomain inhibition is mediated by transcriptional coactivator cooperativity
Authors: Zhang Sicong , Roeder Robert G. 
Published: July 2024

AbstractThe Bromodomain and Extra-Terminal Domain (BET) family of proteins are critical chromatin readers that bind to acetylated histones through their bromodomains to activate transcription. Here, we reveal that bromodomain inhibition fails to repress oncogenic targets of estrogen receptor due to an intrinsic transcriptional mechanism. While bromodomains are necessary for the transcription of many genes, BRD4 binds to estrogen receptor binding sites and activates transcription of critical oncogenes independently of its bromodomains. BRD4 associates with the Mediator complex and disruption of Mediator complex reduces BRD4’s enhancer occupancy. Profiling changes in the post-initiation RNA polymerase II (Pol II)-associated factors revealed that BET proteins regulate interactions between Pol II and elongation factors SPT5, SPT6, and PAF1 complex, which associate with BET proteins independently of their bromodomains and mediate their transcription elongation effect. Our findings highlight the importance of bromodomain-independent functions and interactions of BET proteins in the development of future therapeutic strategies.
Cross-view graph neural networks for spatial domain identification by integrating gene expression, spatial locations with histological images
Authors: Liu Songyan , Guo Yin , Zhang Zixuan , Zhang Shuqin , Li Limin 
Published: July 2024

AbstractThe latest developments in spatial transcriptomics technology provide an unprecedented opportunity for in situ elucidation of tissue structure and function. Spatial transcriptomics can provide simultaneous, multi-modal, and complementary information, including gene expression profiles, spatial positions, and histological images. Despite these capabilities, current methodologies often fall short in fully integrating these multi-modal datasets, thereby limiting their ability to fully understand tissue heterogeneity. In this study, we propose XVGAE (cross-view graph autoencoders), a novel approach that integrates gene expression data, spatial coordinates, and histological images to identify spatial domains. XVGAE constructs two distinct graphs: a spatial graph from spatial coordinates and a histological graph from histological images, and these graphs enable XVGAE to learn specific representations for each view and propagate information between them using cross-view graph convolutional networks. The experiments on benchmark datasets of the human dorsolateral prefrontal cortex show demonstrate that the XVGAE could achieve better clustering accuracy than state-of-the-art methods, and further experiments on four real spatial transcriptomics datasets on different sequencing platforms show that the XVGAE could identify biologically meaningful spatial domains with smoother boundary than other methods.