bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pretreatment of patients with ST-segment elevation myocardial infarction with heparin: a systematic review and meta-analysis
Authors: Costa Gonçalo , Resende Bernardo , Oliveiros Bárbara , Gonçalves Lino , Teixeira Rogério 
Published: January 2024

ABSTRACTBackgroundUnfractionated heparin (UFH) is frequently administered before percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). However, current guidelines do not provide clear recommendations for UFH pretreatment before arrival at the coronary catheterisation laboratory.MethodsBetween June and July 2023, we systematically searched PubMed, Embase and Cochrane databases for studies comparing UFH pretreatments in patients with STEMI. A random-effects meta-analysis and meta-regression analyses were performed.ResultsFourteen studies were included, of which four were randomised clinical trials (RCTs). A total of 76446 patients were included: 31238 in the pretreatment group and 39208 in the control group. Our meta-analysis revealed a lower all-cause mortality for the pretreatment strategy when compared with the control group, albeit with high heterogeneity (pooled odds ratio (OR) = 0.61, 95% confidence interval (CI) [0.49 - 0.76],P< 0.01; I² = 77%); lower in-hospital cardiogenic shock (pooled OR = 0.68, 95% CI [0.58, 0.78],P< 0.21; I² = 27%) and a higher rate of spontaneous reperfusion events (pooled OR = 1.68, 95% CI [1.47, 1.91],P< 0.01; I² = 79%). In terms of major bleeding, the UFH pretreatment strategy further revealed a decreased rate of events (pooled OR = 0.85, 95% CI [0.73, 0.99],P= 0.40; I² = 4%).ConclusionsOur study suggests that UFH pretreatment in patients with STEMI undergoing primary PCI was associated to reduced all-cause mortality, cardiogenic shock, enhancing reperfusion rates, whilst diminishing major bleeding events.
Single-Cell Local Stress Analysis in Tumoroids
Authors: Rodrigues de Mercado Rick , Beslmüller Klara , Vorselen Daan , Danen Erik H.J. , Schmidt Thomas 
Published: January 2024

AbstractThe reciprocal interplay between cancer cells and their local environment, mediated by mechanical forces, necessitates a deeper experimental understanding. This requires precise quantitative measurements of cellular forces within the intricate three-dimensional context of the extracellular matrix. While methods such as traction-force microscopy and micropillar-array technology have effectively reported on cellular forces in two-dimensional cell culture, extending these techniques to three dimensions has proven exceedingly challenging. In the current study, we introduced a novel approach utilizing soft, elastic hydrogel microparticles, resembling the size of cells, to serve as specific and sensitive traction probes in three-dimensional cell culture of collagen-embedded tumoroids. Our methodology relies on high-resolution detection of microparticle deformations. These deformations are translated into spatially resolved traction fields, reaching a spatial resolution down to 1 µm and thereby detecting traction forces as low as 30 Pa. By integrating this high-resolution traction analysis with three-dimensional cell segmentation, we reconstructed the traction fields originating from individual cells. Our methodology enables us to explore the relationships between cellular characteristics, extracellular traction fields, and cellular responses. We observed that cellular stresses ranged from 10 to 100 Pa, integrating to cellular forces from 0.1 to 100 nN, which correlated with the localization of the cells actin skeleton, and the interaction area that cells developed towards the microparticles. Interestingly, the interaction of cells with inert microparticles appeared to be governed by contact mechanics resembling that of two soft spheres. The methodology presented here not only addresses the challenges of extending traditional stress-probe techniques to three dimensions, but also opens a strategy for the study of specific interactions between cells and the local tumoroid environment in a strive to further understand cell-matrix reciprocity in tissue.Here, we present a novel methodology that permits the measurement of quantitative surface stresses on small, inert, elastic, deformable microparticles. Our approach tackles the involved task of mapping local three-dimensional stress fields within tissue. Our methodology was successfully applied to analyze local stresses within a tumor spheroid. We foresee that our research represents a significant advancement toward comprehending the intricate dynamics of cell-matrix reciprocity within tissue.
BaYaka mothers balance childcare and subsistence tasks during collaborative foraging in Congo Basin
Authors: Visine Amandine E. S. , Boyette Adam H. , Ouamba Yann Reische , Lew-Levy Sheina , Sarma Mallika , Jang Haneul 
Published: January 2024

ABSTRACTAcross cultures, mothers face trade-offs between childcare and other labor. In hunter-gatherer societies, mothers face this choice on a daily basis when deciding either to take infants on foraging trips or to leave them with caregivers in the village. Yet, it remains unclear how the presence of infants in foraging groups constrains mothers’ mobility during foraging. Here, we present GPS, energy expenditure and food returns data of 359 foraging trips of 23 BaYaka mothers in the Republic of the Congo. We find that mothers spent more time on out-of-village foraging activities when they took infants along, compared to when they left infants behind. However, infant presence in foraging groups does not affect mothers’ travel distance, travel range, energy expenditure or food returns. Regardless of infant presence, women travel longer and further in a larger area when foraging in groups, compared to when foraging alone, especially in groups with more adults, females and both kin and non-kin. Our results suggest that BaYaka mothers develop ways to accommodate childcare with foraging activities by combining individual-level and group-level behavioural strategies. Our study highlights that group foraging may allow mothers with infants to maintain high mobility, which may have been a key to human range expansion.
Activation of HIF2 leads to vascular remodeling and inflammation, coronary thrombosis and arterial dilation, recapitulating cardiac involvement of Kawasaki disease
Authors: Escobar B , Menendez-Montes I , Albendea-Gomez T , Mendoza-Tamajón S , Castro-Mecinas R , Diaz-Diaz C , Palacios B , Ruiz-Cabello J , Jimenez-Borreguero LJ , Cid MC , Takahashi K , Martin-Puig S 
Published: January 2024

ABSTRACTBackgroundglobal deletion ofVhlleads to vascular defects and early lethality, precluding the study of VHL/HIF signaling during coronary formation and homeostasis. Hypoxia pathway has been associated with cardiovascular diseases involving inflammation and vascular remodeling like atherosclerosis, but its role in Kawasaki Disease (KD) remains unknown. Coronary dilatation and vessel rupture are the most serious complications of KD, while the molecular mechanisms underlying these cardiac events remain poorly understood. Here we aim to determine the function of VHL/HIF pathway in the development of cardiovascular defects and its role in KD.MethodsWe generated a new mouse model to genetically hyperactivate hypoxia pathway in progenitors contributing to coronary vessels and cardiac fibroblasts (Vhl/Wt1). We characterized the model by means of echocardiography, magnetic resonance imaging, histological analysis and molecular approaches. Human cardiac tissue from KD individuals suffering fatal coronary aneurysm were screened for HIF signaling and inflammatory markers by immunohistochemistry.ResultsconditionalVhlKO do not undergo developmental abnormalities but displays cardiomegaly and epicardial vascular defects, with cardiac hypertrophy and progressive coronary diameter increase, as well as pericardial hemorrhage and systemic inflammation early after birth. Histological characterization reveals inflammation of coronary arteries, vascular remodeling with elastin breaks and dilatation, increased perivascular fibrosis and smooth muscle cells death, together with high incidence of intracoronary thrombus formation. In addition, the mutants display vascular calcification and severe cardiac inflammation and interstitial hemorrhages, dying suddenly between 15-20 weeks of age due to vessel rupture. Simultaneous elimination of HIF2 and VHL prevents the cardiovascular abnormalities displayed by single cVhlKO, highlighting the essential role of HIF2 in coronary instability and vascular inflammation. Histological characterization of human cardiac samples shows positive signal for HIF1 and specially HIF2, in the coronary lesions and its surroundings in regions with high inflammatory infiltration, confirming the activation of hypoxia signaling in KD patients with cardiovascular complications.ConclusionsOur data demonstrate the importance of HIF2 signaling in the development of coronary inflammation and vascular remodeling and provide new evidences connecting low oxygen tensions with cardiovascular lesions occurring during the onset of the most severe cases of KD. Furthermore, theVhl/Wt1 mouse generated recapitulates cardiac features of KD with critical heart complications, providing a new platform to uncover unknown aspects of KD pathogenesis.
GeneSelectR: An R Package Workflow for Enhanced Feature Selection from RNA Sequencing Data
Authors: Zhakparov Damir , Moriarty Kathleen , Roqueiro Damian , Baerenfaller Katja 
Published: January 2024

AbstractMotivationHigh-dimensional Bulk RNA sequencing (RNAseq) datasets pose a considerable challenge in identifying biologically relevant features for downstream analyses and data mining efforts. The standard approach involves differential gene expression (DGE) analysis, but its effectiveness can be limited depending on the data due to its univariate nature. In complex datasets, an alternative approach involves employing a variety of machine learning (ML) tools, which attempt to understand non-linear relationships between features and focus on generalizability rather than statistical significance. This approach will result in the generation of multiple feature lists, which might exhibit similarities in terms of classification performance metrics. Therefore, there is an urgent need for a cohesive workflow that seamlessly integrates robust feature selection using diverse ML methods while also evaluating the biological relevance of the resulting feature lists. This combined approach would enable the prioritization of the best-performing list, considering both sets of criteria.ResultsWe introduce GeneSelectR, an open-source R package that innovatively combines ML and bioinformatic data mining approaches for enhanced feature selection. With GeneSelectR, features can be selected from a normalized RNAseq dataset with a variety of ML methods and user-defined parameters. This is followed by an assessment of their biological relevance with Gene Ontology (GO) enrichment analysis, along with a semantic similarity analysis of the resulting GO terms. Additionally, similarity coefficients and fractions of the GO terms of interest are calculated. With this, GeneSelectR optimizes ML performance and rigorously assesses the biological relevance of the various lists, offering a means to prioritize feature lists with regard to the biological question. When applied to the TCGA-BRCA dataset, the GeneSelectR workflow generated several feature lists using different ML methods and a DGE analysis. By leveraging the various functions in GeneSelectR, the different lists could be evaluated based on both ML performance and biological relevance. This comprehensive evaluation facilitated the selection of the best-performing list, which exhibited both strong machine learning performance and high relevance to the biological question while maintaining a manageable number of highly specific features.AvailabilityThe package is available on CRAN. To install it, run: install.packages(‘GeneSelectR’)Contactdzhakparov@gmail.comSupplementary informationSupplementary data are available atBioinformaticsonline.
Genetic characterisation of candidate ecdysteroid kinases inDrosophila melanogaster
Authors: Scanlan Jack L. , Robin Charles 
Published: January 2024

AbstractEcdysteroids are major hormones in insects and control moulting, growth, reproduction, physiology, and behaviour. The biosynthesis of ecdysteroids such as 20-hydroxyecdysone (20E) from dietary sterols is well characterised, but ecdysteroid catabolism is poorly understood. Ecdysteroid kinases (EcKs) mediate the reversible phosphorylation of ecdysteroids, which has been implicated in ecdysteroid recycling during embryogenesis and reproduction in various insects. However, to date only two EcK-encoding genes have been identified, in the silkwormBombyx moriand the mosquitoAnopheles gambiae. Previously, we identified two ecdysteroid kinase-like (EcKL) genes—Wallflower(Wall) andPinkman(pkm)—in the model fruit flyDrosophila melanogasterthat are orthologs of the ecdysteroid 22-kinase geneBmEc22K. Here, using gene knockdown, knockout and misexpression, we exploreWallandpkm’s possible functions and genetically test the hypothesis that they encode EcKs.Wallandpkmnull mutants are viable and fertile, suggesting they are not essential for development or reproduction, whereas phenotypes arising from RNAi and somatic CRISPR appear to derive from off-target effects or other artefacts. However, misexpression ofWallresults in dramatic phenotypes, including developmental arrest, and defects in trachea, cuticle and pigmentation.Wallmisexpression fails to phenocopy irreversible ecdysteroid catabolism through misexpression ofCyp18a1, suggesting Wall does not directly inactivate 20E. Additionally,Wallmisexpression phenotypes are not attenuated inCyp18a1mutants, strongly suggesting Wall is not an ecdysteroid 26-kinase. We hypothesise that the substrate of Wall in this misexpression experiment and possibly generally is an unknown, atypical ecdysteroid that plays essential roles inDrosophiladevelopment, and may highlight aspects of insect endocrinology that are as-yet uncharacterised. We also provide preliminary evidence thatCG5644encodes an ecdysteroid 22-kinase conserved across Diptera.
On the lipid dependence of bacterial mechanosensitive channel gating in situ
Authors: Britt Madolyn , Sawasato Katsuhiro , Moller Elissa , Kidd Gerald , Bogdanov Mikhail , Sukharev Sergei 
Published: January 2024

AbstractFor bacterial mechanosensitive channels acting as turgor-adjusting osmolyte release valves, membrane tension is the primary stimulus driving opening transitions. Because tension is transmitted through the surrounding lipid bilayer, it is possible that the presence or absence of different lipid species may influence the function of these channels. In this work, we characterize the lipid dependence of chromosome-encoded MscS and MscL in E. coli strains with genetically altered lipid composition. We use two previously generated strains that lack one or two major lipid species (PE, PG, or CL) and engineer a third strain that is highly enriched in CL due to the presence of hyperactive cardiolipin synthase ClsA. We characterize the functional behavior of these channels using patch-clamp and quantify the relative tension midpoints, closing rates, inactivation depth, and the rate of recovery back to the closed state. We also measure the osmotic survival of lipid-deficient strains, which characterizes the functional consequences of lipid-mediated channel function at the cell level. We find that the opening and closing behavior of MscS and MscL tolerate the absence of specific lipid species remarkably well. The lack of cardiolipin (CL), however, reduces the active MscS population relative to MscL and decreases the closing rate, slightly increasing the propensity of MscS toward inactivation and slowing the recovery process. The data points to the robustness of the osmolyte release system and the importance of cardiolipin for the adaptive behavior of MscS.
Maternal histone methyltransferases antagonistically regulate monoallelic expression inC. elegans
Authors: Sands Bryan , Yun Soo R. , Oshima Junko , Mendenhall Alexander R. 
Published: January 2024

AbstractUndefined epigenetic programs act to probabilistically silence individual autosomal alleles, generating unique individuals, even from genetic clones. This sort of random monoallelic expression can explain variation in traits and diseases that differences in genes and environments cannot. Here, we developed the nematodeCaenorhabditis elegansto study monoallelic expression in whole tissues, and defined a developmental genetic regulation pathway. We found maternal H3K9 histone methyltransferase (HMT) SET-25/SUV39/G9a works with HPL-2/HP1 and LIN-61/L3MBTL2 to randomly silence alleles in the intestinal progenitor E-cell of 8-cell embryos to cause monoallelic expression. SET-25 was antagonized by another maternal H3K9 HMT, MET-2/SETDB1, which works with LIN-65/ATF7ZIP and ARLE-14/ARL14EP to prevent monoallelic expression. The HMT-catalytic SET domains of both MET-2 and SET-25 were required for regulating monoallelic expression. Our data support a model wherein SET-25 and MET-2 regulate histones during development to generate patterns of somatic monoallelic expression that are persistent but not heritable.
Gelatinous matrix, an original strategy to cope with oligotrophy in Nassellaria (Radiolaria)
Authors: Llopis Monferrer Natalia , Romac Sarah , Laget Manon , Nakamura Yasuhide , Biard Tristan , Sandin Miguel M. 
Published: January 2024

AbstractRadiolaria are heterotrophic protists abundant in the world’s oceans playing important roles in biogeochemical cycles. Some species host photosynthetic algae also contributing to primary production. Such mixotrophic behaviour is believed to explain their ecological success in oligotrophic waters, notably Collodaria, exclusively mixotrophic radiolarians within a gelatinous matrix. Yet, our understanding of Radiolaria ecology is limited to direct observations, as they have so far withstood reproduction in culture and their genomes are unexplored. Sampling oligotrophic California Current communities revealed an abundant, rarely observed population of Nassellaria of the genusPhlebarachnium, characterized to live within a gelatinous matrix along with other Radiolaria. Phylogenetic reconstruction of the ribosomal DNA suggests that these distantly related lineages within Nassellaria independently developed the ability to produce a gelatinous matrix ∼150 million years ago. By matching physical samples with their genetic signature, we identified these rarely observed organisms in global metabarcoding datasets, revealing strong biogeographic affinity to oligotrophic water masses. Global ocean co-occurrence networks showed that Radiolaria with a gelatinous matrix have a distinct biogeography compared to those without the matrix. Results suggest that the gelatinous matrix is an adaptation to oligotrophic waters, but further research is needed to evaluate similarities between the gelatinous matrices across different Radiolaria groups. This strategy could increase the effective volume to weight ratio favoring prey capture and create a favorable microenvironment for symbionts, enhancing ecological success in nutrient-depleted waters. This study advances our understanding of eukaryotic diversity evolution, emphasizing specific advantages of certain adaptations, specifically when evolution occurs independently across lineages.
Individual bioenergetic capacity as a potential source of resilience to Alzheimer’s disease
Authors: Arnold Matthias , Buyukozkan Mustafa , Doraiswamy P. Murali , Nho Kwangsik , Wu Tong , Gudnason Vilmundur , Launer Lenore J. , Wang-Sattler Rui , Adamski Jerzy ,   The Alzheimer’s Disease Neuroimaging Initiative,   Alzheimer’s Disease Metabolomics Consortium, De Jager Philip L. , Ertekin-Taner Nilüfer , Bennett David A. , Saykin Andrew J. , Peters Annette , Suhre Karsten , Kaddurah-Daouk Rima , Kastenmüller Gabi , Krumsiek Jan 
Published: January 2024

AbstractImpaired glucose uptake in the brain is one of the earliest presymptomatic manifestations of Alzheimer’s disease (AD). The absence of symptoms for extended periods of time suggests that compensatory metabolic mechanisms can provide resilience. Here, we introduce the concept of a systemic ‘bioenergetic capacity’ as the innate ability to maintain energy homeostasis under pathological conditions, potentially serving as such a compensatory mechanism. We argue that fasting blood acylcarnitine profiles provide an approximate peripheral measure for this capacity that mirrors bioenergetic dysregulation in the brain. Using unsupervised subgroup identification, we show that fasting serum acylcarnitine profiles of participants from the AD Neuroimaging Initiative yields bioenergetically distinct subgroups with significant differences in AD biomarker profiles and cognitive function. To assess the potential clinical relevance of this finding, we examined factors that may offer diagnostic and therapeutic opportunities. First, we identified a genotype affecting the bioenergetic capacity which was linked to succinylcarnitine metabolism and significantly modulated the rate of future cognitive decline. Second, a potentially modifiable influence of beta-oxidation efficiency seemed to decelerate bioenergetic aging and disease progression. Our findings, which are supported by data from more than 9,000 individuals, suggest that interventions tailored to enhance energetic health and to slow bioenergetic aging could mitigate the risk of symptomatic AD, especially in individuals with specific mitochondrial genotypes.
An Empty Scoping Review of Emergency Department to School Transition for Youth with Mental Health Concerns
Authors: Smith Lora Henderson , Warren Emily , Hendrickson Natalie , Joshua Kate 
Published: January 2024

AbstractThe number of youth Emergency Department (ED) visits due to mental health concerns has been steadily increasing with a large number of youth being referred from school. Despite the increase in ED visits, there has not been an increase in the number of students who are actually admitted to the hospital. Further, youth referred from school are more likely to be discharged from the ED. Given the unique relationship between school and ED referrals and the large number of youth who do not require hospitalization, this study sought to understand how schools are supporting students who return to school after an ED visit. We conducted a scoping review to identify programs and practices to support ED to school transition. Two reviewers screened 907 manuscripts, but none of the manuscripts met the inclusion criteria. We discuss the importance of supporting students returning to school from the ED and draw from the literature on hospital to school transition to make recommendations for educators.
WITHDRAWN: Prompt Engineering GPT-4 to Answer Patient Inquiries: A Real-Time Implementation in the Electronic Health Record across Provider Clinics
Authors: Afshar Majid , Gao Yanjun , Wills Graham , Wang Jason , Churpek Matthew M , Westenberger Christa J , Kunstman David T , Gordon Joel E , Liao Frank J , Patterson Brian 
Published: January 2024

Withdrawal StatementThe authors have withdrawn their manuscript owing to needing additional internal review. Therefore, the authors do not wish this work to be cited as a reference for the project. If you have any questions, please contact the corresponding author.