bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular Complications with Delivery Hospitalizations in Patients with Pulmonary Hypertension: A Nationwide Study from 2011-2020
Authors: Agrawal Ankit , Bajaj Suryansh , Bhagat Umesh , Chandna Sanya , Arockiam Aro Daniela , Jamil Yasser , Iskandarani Mahmoud El , Gupta Rahul , Nayar Divya , Michos Erin D. 
Published: July 2023

AbstractBackgroundPregnancy in patients with pulmonary hypertension (PH) is associated with heightened risk of various medical complications. Our study aims to understand the patient characteristics and investigate the association between PH and these complications in pregnant patients during delivery.MethodsThe National Inpatient Sample (NIS) was used to identify delivery hospitalizations from 2011 to 2020. The primary outcomes were in-hospital medical and obstetric complications. Multivariate logistic regression was performed to study the association of PH with these complications.ResultsA total of 37,482,207 delivery hospitalizations in women ≥18 years were identified from the NIS database out of which 9,593 patients had PH. Pregnant patients with PH had a higher incidence of complications during delivery including preeclampsia/eclampsia, cardiac arrhythmias, pulmonary edema amongst others, compared to pregnant patients without PH. Pregnant patients with PH had a higher incidence of in-hospital mortality compared to those without PH (0.51% vs 0.007%). In adjusted analyses, PH was independently associated with a higher risk of pulmonary edema (OR: 18.65 [95% CI: 13.71-25.38]), peripartum cardiomyopathy (14.06 [9.15-21.60]), venous thromboembolism (12.25 [7.80-19.24]), cardiac arrhythmias (11.75 [10.11-13.67]), acute kidney injury (7.53 [5.36-10.58]), preeclampsia/eclampsia (4.61 [4.04-5.25]), and acute coronary syndrome (2.83 [1.17-6.85]), compared with pregnant patients without PH. In-hospital mortality in patients with PH was associated with stroke (127.33 [78.49-206.57]), acute kidney injury (51.25 [34.40-76.36]), cardiac arrhythmias (24.80 [19.43-31.65]), peripartum cardiomyopathy (6.47 [3.23-12.97]), pulmonary edema (4.27 [2.18-8.37]), venous thromboembolism (2.75 [1.07-7.10]), and preeclampsia/eclampsia (1.87 [1.35-2.60]) compared to pregnant patients without PH.ConclusionDelivery hospitalizations in patients with PH are associated with high risk of various complications. Prenatal counseling and multidisciplinary care are essential to help mitigate unfavorable outcomes in these patients.
Association of Chronotype and Shiftwork with COVID-19 Infection
Authors: Quan Stuart F. , Weaver Matthew D. , Czeisler Mark É. , Barger Laura K. , Booker Lauren A. , Howard Mark E. , Jackson Melinda L. , Lane Rashon I. , McDonald Christine F. , Ridgers Anna , Robbins Rebecca , Varma Prerna , Rajaratnam Shantha M.W. , Czeisler Charles A. 
Published: July 2023

AbstractObjectiveThis study assesses whether chronotype is related to COVID-19 infection and whether there is an interaction with shift work.MethodsCross-sectional survey of 19,821 U.S. adultsResultsCOVID-19 infection occurred in 40% of participants, 32.6% morning and 17.2% evening chronotypes. After adjusting for demographic and socioeconomic factors, shift work, sleep duration and comorbidities, morning chronotype was associated with a higher (aOR: 1.15, 95% CI 1.10-1.21) and evening chronotype with a lower (aOR: 0.82, 95% CI: 0.78-0.87) prevalence of COVID-19 infection in comparison to an intermediate chronotype. Working exclusively night shifts was not associated with higher prevalence of COVID-19. Morning chronotype and working some evening shifts was associated with the highest prevalence of previous COVID-19 infection (aOR: 1.87, 95% CI: 1.28-2.74).ConclusionMorning chronotype and working a mixture of shifts increase risk of COVID-19 infection.Learning OutcomesDescribe the association between chronotype and prevalence of COVID-19 infectionSummarize the combined effect of chronotype and shift work on the prevalence of COVID-19 infection
Single cell susceptibility to SARS-CoV-2 infection is driven by variable cell states
Authors: Reffsin Sam , Miller Jesse , Ayyanathan Kasirajan , Dunagin Margaret C. , Jain Naveen , Schultz David C. , Cherry Sara , Raj Arjun 
Published: July 2023

AbstractThe ability of a virus to infect a cell type is at least in part determined by the presence of host factors required for the viral life cycle. However, even within cell types that express known factors needed for infection, not every cell is equally susceptible, suggesting that our knowledge of the full spectrum of factors that promote infection is incomplete. Profiling the most susceptible subsets of cells within a population may reveal additional factors that promote infection. However, because viral infection dramatically alters the state of the cell, new approaches are needed to reveal the state of these cells prior to infection with virus. Here, we used single-cell clone tracing to retrospectively identify and characterize lung epithelial cells that are highly susceptible to infection with SARS-CoV-2. The transcriptional state of these highly susceptible cells includes markers of retinoic acid signaling and epithelial differentiation. Loss of candidate factors identified by our approach revealed that many of these factors play roles in viral entry. Moreover, a subset of these factors exert control over the infectable cell state itself, regulating the expression of key factors associated with viral infection and entry. Analysis of patient samples revealed the heterogeneous expression of these factors across both cells and patientsin vivo. Further, the expression of these factors is upregulated in particular inflammatory pathologies. Altogether, our results show that the variable expression of intrinsic cell states is a major determinant of whether a cell can be infected by SARS-CoV-2.
Bottom-up and top-down contributions to impaired motion processing in schizophrenia
Authors: Martínez Antígona , Gaspar Pablo A. , Bermudez Dalton H. , Aburto-Ponce M. Belen , Javitt Daniel C. 
Published: July 2023

AbstractBackground and HypothesisMotion processing deficits in schizophrenia have been linked to impairments in higher-order social-cognitive processes. The neural underpinnings are not fully understood but it has been hypothesized that middle temporal area (MT+) may serve as a bridge between purely sensory and more cognitive proceseses. We investigated the interrelationship between MT+ sensory processing deficits and impairments in higher-order processing using naturalistic videos with explicit motion and static images with implied-motion cues.Study DesignFunctional magnetic resonance imaging was used to evaluate cortical and subcortical brain regions associated with real- and implied-motion processing in 28 individuals with schizophrenia and 20 neurotypical controls. These measures were related to face emotion recognition and motion-perception deficits, as measured behaviorally.Study ResultsActivation of MT+ was abnormal in schizophrenia during both real- and implied-motion processing. Dysfunction of early visual cortex and pulvinar were also associated with impaired real-motion processing. During implied-motion-perception, MT+ participated in a wider network involving sensorimotor and prefrontal nodes of the human mirror neuron system, known to play a role in social-cognitive processes. Perception of both real- and implied-motion engaged the posterior superior temporal sulcus, a key node of the social brain network.ConclusionsThe findings support concepts of MT+ as a bridge between visual sensory areas and higher-order brain regions especially in relationship to face emotion recognition and social cognition. Our data argue for greater focus on MT+ contributions to social-cognitive processing, in addition to its well-documented role in visual motion processing.
Perioperative mortality in low-, middle-, and high-income countries: Protocol for a multi-level meta-regression analysis
Authors: McIntyre Kevin J. , Choi Yun-Hee , John-Baptiste Ava , Lizotte Daniel J. , Chan Eunice Y.S. , Moodie Jessica , Stranges Saverio , Martin Janet 
Published: July 2023

AbstractBackgroundSurgery is an indispensable component of a functional healthcare system. To date there is limited information regarding how many people die during the perioperative period globally. This study describes a protocol for a systematic review and multilevel meta-regression to evaluate time trends regarding the odds of perioperative mortality among adults undergoing a bellwether surgical procedure while accounting for higher order clustering at the national level.MethodsPublished studies reporting the number of perioperative deaths from bellwether surgical procedures among adults will be identified from MEDLINE, Embase, Cochrane CENTRAL, LILACS and Global Index Medicus. The primary outcome will be the rate of perioperative mortality across time and the secondary outcome will be investigating cause of death over time as a proportion of overall perioperative mortality. Two reviewers will independently conduct full text screening and extract the data. Disagreements will first be resolved via consensus. If consensus cannot be reached a third reviewer will be included to arbitrate. Due to human resource limitations, a risk of bias appraisal will not be conducted. From the included studies a multilevel meta-regression will be constructed to synthesize the results. This model will conceptualize patients as nested in studies which are in turn nested within countries while taking into account potential confounding variables at all levels.DiscussionThe systematic review and multilevel meta-regression that will be conducted based on this protocol will provide synthesized global evidence regarding the trends of perioperative mortality. This eventual study may help policymakers and other key stakeholders with benchmarking surgical safety initiatives as well as identify key gaps in our current understanding of global perioperative mortality.Systematic review registrationPROSPERO registration number 429040.
A novel nomogram based on serum lipid for identifying the patients at risk for rapid progression of advanced hormone-sensitive prostate cancer
Authors: Wu Mingshuang , He Yi , Pan Chenxi , Zhang Yue , Yang Bo 
Published: July 2023

AbstractBackgroundSerum lipids were reported to be significant predictive factors in various tumors. In order to develop and validate a nomogram for predicting castration-resistant prostate cancer (CRPC) free survival in advanced hormone-sensitive prostate cancer (HSPC) patients, the goal of this study was to assess the prognostic impact of the lipid profiles.Material and MethodsThe follow-up information of 146 CRPC patients who received androgen deprivation therapy as the first and only therapy before progression were retrospectively examined. To evaluate prognostic variables, univariate and multivariate Cox regression analyses were used. The concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves, and decision curve analyses (DCA) were used to design and evaluate a novel nomogram model.ResultsTotal cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), N stage and Gleason sum were determined to be independent prognostic markers and were combined to create a nomogram. This nomogram performed well in the customized prediction of CRPC development at 6th, 12th, 18th and 24th month. The C-indexes in training and validation sets were 0.740 and 0.755, respectively. ROC curves, calibration plots, and DCA all suggested favorable discrimination and predictive ability. Besides, the nomogram also performed better predictive ability than N stage and Gleason sum. The Nomogram-related risk score divided the patient population into two groups with significant progression disparities.ConclusionsThe established nomogram could aid in identifying the patients at high risk for rapid progression of advanced HSPC, so as to formulate individualized therapeutic regimens and follow-up strategies in time.
Nightshift Imposes Irregular Lifestyle Behaviors in Police Academy Trainees
Authors: Erickson Melissa L. , North Rebecca , Counts Julie , Wang Will , Porter Starr Kathryn N. , Wideman Laurie , Pieper Carl , Dunn Jessilyn , Kraus William E. 
Published: July 2023

ABSTRACTStudy ObjectiveShiftwork increases risk for numerous chronic diseases, which is hypothesized to be linked to disruption of circadian timing of lifestyle behaviors. However, empirical data on timing of lifestyle behaviors in real-world shift workers are lacking. To address this, we characterized the regularity of timing of lifestyle behaviors in shift-working police trainees.MethodsUsing a two-group observational study design (N=18), we compared lifestyle behavior timing during 6 weeks of in-class training during dayshift, followed by 6 weeks of field-based training duringeitherdayshift or nightshift. Lifestyle behavior timing, including sleep/wake patterns, physical activity, and meals, was captured using wearable activity trackers and mobile devices. The regularity of lifestyle behavior timing was quantified as an index score, which reflects day-to-day stability on a 24h time scale: Sleep Regularity Index (SRI), Physical Activity Regularity Index (PARI) and Mealtime Regularity Index (MRI). Logistic regression was applied to these indices to develop a composite score, termed the Behavior Regularity Index (BRI).ResultsTransitioning from dayshift to nightshift significantly worsened the BRI, relative to maintaining a dayshift schedule. Specifically, nightshift led to more irregular sleep/wake timing and meal timing; physical activity timing was not impacted. In contrast, maintaining a dayshift schedule did not impact regularity indices.ConclusionNightshift imposed irregular timing of lifestyle behaviors, which is consistent with the hypothesis that circadian disruption contributes to chronic disease risk in shift workers. How to mitigate the negative impact of shiftwork on human health as mediated by irregular timing of sleep/wake patterns and meals deserves exploration.
Automated segmentation of brain metastases in T1-weighted contrast-enhanced MR images pre and post Stereotactic Radiosurgery
Authors: Kanakarajan Hemalatha , De Baene Wouter , Hanssens Patrick , Sitskoorn Margriet 
Published: July 2023

AbstractBackground and purposeAccurate segmentation of brain metastases on Magnetic Resonance Imaging (MRI) is a tedious and time-consuming task for radiologists that could be optimized with deep learning (DL) methods. Previous studies that evaluated the performance of several DL algorithms focused on training and testing the models on the planning MRI only. The purpose of this study is to evaluate well-known DL approaches (nnU-Net and MedNeXt) for their performance on both planning and follow-up MRI.Materials and methodsPre-treatment brain MRIs were collected retrospectively for 263 patients at the Gamma Knife Center of Elisabeth-TweeSteden Hospital (ETZ). The patients were split into 203 patients for training and 60 patients for testing. For these 60 patients, the follow-up MRIs were also retrospectively collected. To increase heterogeneity, we added the publicly available MRI from the Mathematical oncology laboratory for 75 patients to the training data. The performance was compared between the two models, with and without addition of the public data.ResultsAll models obtained a good Dice Similarity Coefficient (all DSC >= 0.928) for planning MRI. MedNeXt trained with combined data was the best performing model for follow-ups at 3, 15 and 21 months (DSC of 0.796, 0.725, and 0.720 respectively) while nnU-Net trained with combined data was the best performing model for follow-ups at 6, 9 and 12 months (DSC of 0.738, 0.740 and 0.713 respectively).ConclusionThe models achieved a good performance score for planning MRI. Though the models performed worse for follow-ups, addition of public data enhanced their performance, providing a viable solution to improve their efficacy for the follow-ups. There was only limited difference in performance of the two algorithms. These algorithms hold promise as a valuable tool for clinicians for automated segmentation of pre- and postsurgical MRI during treatment planning and response evaluations, respectively.
Leveraging Generative AI to Prioritize Drug Repurposing Candidates: Validating Identified Candidates for Alzheimer’s Disease in Real-World Clinical Datasets
Authors: Yan Chao , Grabowska Monika E. , Dickson Alyson L. , Li Bingshan , Wen Zhexing , Roden Dan M. , Stein C. Michael , Embí Peter J. , Peterson Josh F. , Feng QiPing , Malin Bradley A. , Wei Wei-Qi 
Published: July 2023

AbstractDrug repurposing represents an attractive alternative to the costly and time-consuming process of new drug development, particularly for serious, widespread conditions with limited effective treatments, such as Alzheimer’s disease (AD). Emerging generative artificial intelligence (GAI) technologies like ChatGPT offer the promise of expediting the review and summary of scientific knowledge. To examine the feasibility of using GAI for identifying drug repurposing candidates, we iteratively tasked ChatGPT with proposing the twenty most promising drugs for repurposing in AD, and tested the top ten for risk of incident AD in exposed and unexposed individuals over age 65 in two large clinical datasets: 1) Vanderbilt University Medical Center and 2) theAll of UsResearch Program. Among the candidates suggested by ChatGPT, metformin, simvastatin, and losartan were associated with lower AD risk in meta-analysis. These findings suggest GAI technologies can assimilate scientific insights from an extensive Internet-based search space, helping to prioritize drug repurposing candidates and facilitate the treatment of diseases.
CLIPB4 is a central node in the protease network that regulates humoral immunity inAnopheles gambiaemosquitoes
Authors: Zhang Xiufeng , Zhang Shasha , Kuang Junyao , Sellens Kathleen A. , Morejon Bianca , Saab Sally A. , Li Miao , Metto Eve C. , An Chunju , Culbertson Christopher T. , Osta Mike A. , Scoglio Caterina , Michel Kristin 
Published: July 2023

AbstractInsect humoral immune responses are regulated in part by protease cascades, whose components circulate as zymogens in the hemolymph. In mosquitoes, these cascades consist ofclip domainserineproteases (cSPs) and/or their non-catalytichomologs (cSPHs), which form a complex network, whose molecular make-up is not fully understood. Using a systems biology approach, based on a co-expression network of gene family members that function in melanization and co-immunoprecipitation using the serine protease inhibitor (SRPN)2, a key negative regulator of the melanization response in mosquitoes, we identify the cSP CLIPB4 from the African malaria mosquitoAnopheles gambiaeas a central node in this protease network.CLIPB4is tightly co-expressed withSRPN2and forms protein complexes with SRPN2 in the hemolymph of immune-challenged female mosquitoes. Genetic and biochemical approaches validate our network analysis and show that CLIPB4 is required for melanization and antibacterial immunity, acting as a prophenoloxidase (proPO)-activating protease, which is inhibited by SRPN2. In addition, we provide novel insight into the structural organization of the cSP network inAn. gambiae, by demonstrating that CLIPB4 is able to activate proCLIPB8, a cSP upstream of the proPO-activating protease CLIPB9. These data provide the first evidence that, in mosquitoes, cSPs provide branching points in immune protease networks and deliver positive reinforcement in proPO activation cascades.
Antisense transcription and PRC2 repression function in parallel during vernalization
Authors: Nielsen Mathias , Menon Govind , Zhao Yusheng , Mateo-Bonmati Eduardo , Wolff Philip , Zhou Shaoli , Howard Martin , Dean Caroline 
Published: July 2023

Non-coding transcription induces chromatin changes that can mediate environmental responsiveness, but the causes and consequences of these mechanisms are still unclear. Here, we investigate how antisense transcription interfaces with Polycomb Repressive Complex 2 silencing during winter-induced epigenetic regulation of ArabidopsisFLOWERING LOCUS C(FLC). Through genetic, chromatin, and computational analyses, we show thatFLCis silenced through pathways that function with different dynamics: an antisense transcription-mediated pathway capable of fast response; and in parallel a slow Polycomb Repressive Complex 2 (PRC2) switching mechanism that maintains each allele in an epigenetically silenced state. Components of both the antisense and PRC2 pathways are regulated by a common transcriptional regulator (NTL8), which accumulates slowly due to reduced growth at low temperatures. The parallel activities of the regulatory steps, which we encapsulate in a mathematical model, creates a flexible system for registering widely fluctuating natural temperature conditions that change year on year, and yet ensure robust epigenetic silencing ofFLC.SignificanceThe role of non-coding transcription in establishing and maintaining chromatin states is controversial, mainly because of extensive feedbacks complicating analysis of the relationship between co-transcriptional processing, chromatin state and transcription. This controversy has extended to the role of antisense transcription in the Polycomb-mediated epigenetic silencing of ArabidopsisFLC, a key step in the process of vernalization. Here, we show that antisense transcription and PRC2 silenceFLCin parallel pathways that are affected by growth dynamics and temperature fluctuations. These features explain the varied importance of antisense transcription in cold-inducedFLCepigenetic silencing seen in various studies using different environmental and growth conditions. The parallel repressive inputs and extensive feedbacks make the mechanism counter-intuitive but provide great flexibility to the plant.
Exploring alternative quorum sensing model structures and quorum quenching strategies
Authors: Cimolato Chiara , Bellato Massimo , Selvaggio Gianluca , Marchetti Luca , Giordano Giulia , Schenato Luca 
Published: July 2023

AbstractBacterial quorum sensing (QS) is a cell-to-cell communication mechanism through which bacteria share information about cell density, and tune gene expression accordingly. Pathogens exploit QS to orchestrate virulence and regulate the expression of genes related to antimicrobial resistance. Despite the vast literature on QS, the properties of the underlying molecular network are not entirely clear. We compare two synthetic QS circuit architectures: in the first, a single positive feedback loop autoinduces the synthesis of the signal molecule; the second includes an additional positive feedback loop enhancing the synthesis of the signal molecule receptor. Our comprehensive analysis of the two systems and their equilibria highlights the differences in the bistable and hysteretic behaviors of the alternative QS structures. Finally, we investigate three different QS inhibition approaches; numerical analysis predicts their effect on the steady-state behavior of the two different QS models, revealing critical parameter thresholds that guarantee an effective QS suppression.