bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in Pediatric Firearm-Related Encounters during the COVID-19 Pandemic by Age Group, Race/Ethnicity, and Schooling Mode in Tennessee
Authors: McKay Tara , Gastineau Kelsey , Wrenn Jesse O. , Han Jin H. , Storrow Alan B. 
Published: March 2023

AbstractPurposeIncreases in pediatric firearm-related injuries during the COVID-19 pandemic may be due to changes in where children and adolescents spent their time. This paper examines changes in the frequency of pediatric firearm-related encounters as a function of schooling mode overall and by race/ethnicity and age group at a large trauma center through 2021.MethodsWe use data from a large pediatric and adult trauma center in Tennessee from January 2018 to December 2021 (N=211 encounters) and geographically linked schooling mode data. We use Poisson regressions to estimate smoothed monthly pediatric firearm-related encounters as a function of schooling mode overall and stratified by race and age.ResultsCompared to pre-pandemic, we find a 42% increase in pediatric encounters per month during March 2020 to August 2020, when schools were closed, and a 23% increase in encounters after schools returned to in-person instruction. Effects of schooling mode are heterogeneous by race. Encounters increased among non-Hispanic Black children and adolescents across all periods relative to pre-pandemic. Among non-Hispanic white children and adolescents, encounters increased during the closure period and decreased on return to in-person instruction. Effects of schooling mode are also heterogeneous by age. Relative to pre-pandemic, pediatric firearm-related encounters increased 205% for children aged 5 to 11 and 69% for adolescents aged 12 to 15 during the school closure period.ConclusionCOVID-19-related changes to school instruction mode in 2020 and 2021 are associated with changes in the frequency and composition of pediatric firearm-related encounters at a major trauma center in Tennessee.
Chest CT findings and outcomes of COVID-19 in second wave: A cross-sectional study in a tertiary care centre in Northern India
Authors: Cheema Taranjeet , Saroha Amit , Kumar Arjun , Panda Prasan Kumar , Saxena Sudhir 
Published: March 2023

AbstractIntroductionThe COVID-19 pandemic has posed a serious threat to global health, with developing nations like India being amongst the worst affected. Chest CT scans play a pivotal role in the diagnosis and evaluation of COVID-19, and certain CT features may aid in predicting the prognosis of COVID-19 illness.MethodsThis was a single-centre, hospital-based, cross-sectional study conducted at a tertiary care centre in Northern India during the second wave of the COVID-19 pandemic from May-June 2021. The study included 473 patients who tested positive for COVID-19. A high-resolution chest CT scan was performed within five days of hospitalization, and patient-related information was extracted retrospectively from medical records. Univariable and Multivariable analysis was done to study the predictors of poor outcome.ResultsA total of 473 patients were included in the study, with 75.5% being males. The mean total CT score was 29.89 ± 9.06. Fibrosis was present in 17.1% of patients, crazy paving in 3.6%, pneumomediastinum in 8.9%, and pneumothorax in 3.6%. Males had a significantly higher total score, while the patients who survived (30.00 ± 9.55 vs 35.00 v 6.21, p value - <.001), received Steroids at day 2 (28.04 ± 9.71 vs 31.66 ± 7.12, p value – 0.002) or Remdesivir had lower total scores (28.04 ± 9.71 vs 31.66 ± 7.12, p-value – 0.002). Total CT score (aHR 1.05, 95% CI 1.02 – 1.08, p – 0.001), pneumothorax (aHR 1.38, 95 % CI 0.67 – 2.87, p – 0.385), pneumomediastinum (aHR 1.20, 95% CI 0.71 - 2.03, p=0.298) and cardiovascular accident (CVA, aHR 4.75, 95% CI 0.84 – 26.72, p – 0.077) were associated with increased mortality, but the results were not significant after adjusting with other variables on multiple regression analysis.ConclusionThis study identifies several radiological parameters, including fibrosis, crazy paving, pneumomediastinum, and pneumothorax, that are associated with poor prognosis in COVID-19. These findings highlight the role of CT thorax in COVID-19 illness and the importance of timely identification and interventions in severe and critical cases of COVID-19 to reduce mortality and morbidity.
Surgical and percutaneous coronary revascularization in patients with multivessel or left main disease; what happens beyond five years? A systematic review and study level meta-analysis of randomized trials
Authors: Formica Francesco , Hernandez-Vaquero Daniel , Tuttolomondo Domenico , Gallingani Alan , Singh Gurmeet , Pattuzzi Claudia , Niccoli Giampaolo , Lorusso Roberto , Nicolini Francesco 
Published: March 2023

AbstractMeta-analysis exploring outcomes beyond 5-years of trials comparing coronary artery bypass graft (CABG) with percutaneous coronary intervention (PCI) utilizing drug-eluting stents in patients with coronary artery disease (CAD), are missing. We conducted a meta-analysis to compare very long-term outcomes, between the two interventions.Using electronic databases, we retrieved 4 trials, between January, 2010 and January, 2023. The primary endpoint was all-cause mortality. Kaplan-Meier curves of endpoint was reconstructed. Comparisons were made by Cox-linear regression frailty model and by landmark analysis. A flexible parametric model for survival analysis was used to obtain the time-dependent hazard-ratio. A random-effect method was applied.5180 patients were included and randomized to CABG (n=2586) or PCI with DES (n=2594). During 10-year follow-up, PCI showed an overall higher incidence of all-cause mortality [hazard ratio (HR) 1.19; 95% confidence interval (CI), 1.104-1.32; p=0.008)]. At landmark analysis, PCI showed higher risk of the endpoint within 5-years (HR 1.2; 95% CI, 1.06-1.53; p=0.008) while no difference was found at 5–10-year period (HR,1.03; 95%CI, 0.84-1.26; p=0.76). The time-varying HR analysis of PCI versus CABG was consistent with the results of the landmark analysis. There was no long-term difference between the two interventions for myocardial infarction (MI) (OR,1.42; 95%CI, 0.92-2.18; p=0.11), composite of all-cause mortality, stroke or MI (OR,1.07; 95%CI, 0.84-1.36; p=0.57), stroke (OR,0.97; 95%CI, 0.59-1.59; p=0.91) and cardiovascular death (OR,1.02; 95%CI, 0.75-1.40; p=0.90), while PCI was associated with an increased risk for repeat revascularization (OR,2.11; 95%CI, 1.58-2.81; p<0.001) and major adverse cardiac and cerebrovascular events (OR,1.41; 95%CI, 1.13-1.75; p<0.0001). In conclusion, in patients with CAD, there was a significantly overall higher incidence of all-cause mortality after PCI compared to CABG beyond 5-year follow-up. Specifically, CABG is still favorable beyond 5 years and maintains its gold standard role for the CAD treatment; PCI has an evident higher mortality during the first 5 years and a comparable outcome beyond 5 years.
Off-Label Dosing of Direct Oral Anticoagulants Among Inpatients with Atrial Fibrillation
Authors: Sandhu Amneet , Kaltenbach Lisa A. , Chiswell Karen , Shimoga Vijay , Ashur Carmel , Pribish Abby , Fonarow Gregg C. , Piccini Jonathan P. , Ho P. Michael , Varosy Paul D. , Hess Paul L. 
Published: March 2023

ABSTRACTIntroductionAmong patients hospitalized for atrial fibrillation (AF), the frequency of off-label direct oral anticoagulant (DOAC) dosing, associated factors, hospital-level variation, and temporal trends in contemporary clinical practice are unknown.MethodsUsing the Get With The Guidelines®Atrial Fibrillation (GWTG-AF) registry, patients admitted from January 1st, 2014 to March 31st, 2020, and discharged on DOAC therapy were stratified according to receipt of underdosing, overdosing, or recommended dosing. Factors associated with off-label dosing were identified using logistic regression. Hospital-level variation and temporal trends were assessed.ResultsOf 22,470 patients prescribed a DOAC at discharge from hospitalization for AF (66% apixaban, 29% rivaroxaban, 5% dabigatran), underdosing occurred among 2006 (8.9%), overdosing among 511 (2.3%), and recommended dosing among 19953 (88.8%). Patient-related factors associated with off-label DOAC use included age (underdosing: OR 1.06 per 1-year increase [95% CI 1.06-1.07] and overdosing: OR 1.07 per 1-year increase [1.06-1.09]), dialysis dependence (underdosing: OR 5.50 [3.76-8.05] and overdosing: OR 5.47 [2.74-10.88]), female sex (overdosing: OR 0.79 [0.63-0.99]) and weight (overdosing: OR 0.96 per 1-Kg increase [0.95-1.00]). Across hospitals, the adjusted median odds ratio for off-label DOAC use was 1.45 [95% CI 1.34-1.65] (underdosing: 1.52 [1.39-1.76] and overdosing: 1.32 [1.20-1.84]), indicating significant hospital-level variation. Hospital characteristics associated with underdosing included West vs. Northeast location (OR: 1.55 [1.04-2.31]), rural vs. urban setting (OR: 0.48 [0.28-0.83]), and number of beds (<200 vs. 500+, OR: 1.95 [1.29-2.95]). Recommended dosing significantly increased over time (81.9% in 2014 to 90.9% in 2020, p<0.0001 for trend) with a corresponding decline in underdosing (14.4% in 2014 to 6.6% in 2020, p<0.0001 for trend) and overdosing (3.8% in 2014 to 2.5% in 2020, p=0.001 for trend).ConclusionOne of 10 patients hospitalized for atrial fibrillation is discharged on off-label dosing of DOAC with significant variation across hospitals. While the proportion of patients receiving recommended dosing has significantly improved over time, opportunities to improve DOAC dosing persist.
Breathing pattern and pulmonary gas exchange in elderly patients with and without left ventricular dysfunction - modification with exercise-based cardiac rehabilitation and prognostic value
Authors: Eser Prisca , Marcin Thimo , Prescott Eva , Prins Leonie F. , Kolkman Evelien , Bruins Wendy , van der Velde Astrid E , Gil Carlos Peña , Iliou Marie-Christine , Ardissino Diego , Zeymer Uwe , Meindersma Esther P , Van’t Hof Arnoud W.J. , de Kluiver Ed P. , Wilhelm Matthias 
Published: March 2023

AbstractAimsIn elderly patients with and without left ventricular dysfunction (LVD) we compared ventilatory parameters from before to after exercise-based cardiac rehabilitation (exCR) and assessed their prognostic value for major adverse cardiovascular events (MACE).Methods and ResultsPatients aged ≥65 years with acute or chronic coronary syndromes (ACS, CCS) without cardiac surgery who participated in a multicentre study on effectiveness of exCR from seven European countries were included. Cardiopulmonary exercise testing (CPET) was performed before, at termination of exCR and at 12 months follow-up. Ventilation (VE), breathing frequency (BF), tidal volume (VT) and end-expiratory carbon dioxide pressure (PETCO2) were measured at rest, at first ventilatory threshold and peak exercise.In 818 patients, age was 72.5±5.4 years, 21.9% were women, 79.8% had ACS, and 151 (18%) had LVD. NYHA functional class was not different between LVD and noLVD (86% NYHA I in each group). Compared to noLVD, in LVD resting VE was increased 8%, resting BF 6%, peak VE, peak VT, and peak PETCO2reduced by 6%, 8%, and 5%, respectively, and VE/VVCO2slope increased by 11%. From before to after exCR, resting VE decreased and peak PETCO2increased significantly more in LVD compared to noLVD. In LVD, higher resting BF, higher nadir VE/VCO2, and lower peak PETCO2at baseline were associated with MACEConclusionsIn elderly patients with ischemic LVD, exaggerated resting ventilation and impaired pulmonary gas exchange during exercise was related to worse outcomes. ExCR was associated with an improvement of abnormal breathing patterns and gas exchange parameters.
Medioapical contractile pulses coordinated between cells regulateDrosophilaeye morphogenesis
Authors: Birriel Christian Rosa , Malin Jacob , Hatini Victor 
Published: March 2023

ABSTRACTLattice cells (LCs) in the developingDrosophilaretina constantly move and change shape before attaining final forms. Previously we showed that repeated contraction and expansion of apical cell contacts affect these dynamics. Here we describe a second contributing factor, the assembly of a medioapical actomyosin ring composed of nodes linked by filaments that attract each other, fuse, and contract the LCs’ apical area. This medioapical actomyosin network is dependent on Rho1 and its known effectors. Apical cell area contraction alternates with relaxation, generating pulsatile changes in apical cell area. Strikingly, cycles of contraction and relaxation of cell area are reciprocally synchronized between adjacent LCs. Further, in a genetic screen, we identified RhoGEF2 as an activator of these Rho1 functions and RhoGAP71E/C-GAP as an inhibitor. Thus, Rho1 signaling regulates pulsatile medioapical actomyosin contraction exerting force on neighboring cells, coordinating cell behavior across the epithelium. This ultimately serves to control cell shape and maintain tissue integrity during epithelial morphogenesis of the retina.Short summaryRosa et. al. describe a Rho1-dependent pulsatile medioapical actomyosin network that couples neighboring retina lattice cells biomechanically, creating an adaptive supracellular actomyosin network that coordinates the mechanical behavior of neighboring cells and regulates cell shape and tissue integrity.
Helicobacter pylorimodulates heptose metabolite biosynthesis and heptose-dependent innate immune host cell activation by multiple mechanisms
Authors: Hauke Martina , Metz Felix , Rapp Johanna , Faass Larissa , Bats Simon , Radziej Sandra , Link Hannes , Eisenreich Wolfgang , Josenhans Christine 
Published: March 2023

AbstractHeptose metabolites including ADP-heptose are involved in bacterial lipopolysaccharide and cell envelope biosynthesis. Recently, heptoses were also identified to have potent pro-inflammatory activity on human cells as novel microbe-associated molecular patterns. The gastric pathogenic bacteriumHelicobacter pyloriproduces heptose metabolites which it transports into human cells through its Cag type 4 secretion system. UsingH. pylorias a model, we have addressed the question, how pro-inflammatory ADP-heptose biosynthesis can be regulated by the bacteria. We have characterized the inter-strain variability and regulation of heptose biosynthesis genes and the modulation of heptose metabolite production byH. pylori, which impact cell-autonomous pro-inflammatory human cell activation. HldE, a central enzyme of heptose metabolite biosynthesis, showed strong sequence variability between strains, and was also strain-variably expressed. Transcript amounts of genes in thehldEgene cluster displayed intra-strain and inter-strain differences, were modulated by host cell contact and the presence of thecagpathogenicity island, and were affected by carbon starvation regulator A (CsrA). We reconstituted four steps of theH. pyloriLPS heptose biosynthetic pathwayin vitrousing recombinant purified GmhA, HldE and GmhB proteins. On the basis of one- and two-dimensional NMR spectroscopy and mass spectrometry, the structures of major reaction products were identified as β-D-ADP-heptose and β-heptose-1-monophosphate. A pro-inflammatory heptose-monophosphate variant was also identified for the first time as a novel cell-active product inH. pyloribacteria. Separate purified HldE subdomains and variant HldE allowed to uncover additional strain variation in generating heptose metabolites.
Perirhinal Cortex Learns A Predictive Map of The Task Environment
Authors: Lee David G. , McLachlan Caroline A. , Nogueira Ramon , Kwon Osung , Carey Alanna E. , House Garrett , Lagani Gavin D. , LaMay Danielle , Fusi Stefano , Chen Jerry L. 
Published: March 2023

ABSTRACTGoal-directed tasks involve acquiring an internal model, known as a predictive map, of relevant stimuli and associated outcomes to guide behavior. Here, we identified neural signatures of a predictive map of task behavior in perirhinal cortex (Prh). Mice learned to perform a tactile working memory task by classifying sequential whisker stimuli over multiple training stages. Chemogenetic inactivation demonstrated that Prh is involved in task learning. Chronic two-photon calcium imaging, population analysis, and computational modeling revealed that Prh encodes stimulus features as sensory prediction errors. Prh forms stable stimulus-outcome associations that expand in a retrospective manner and generalize as animals learn new contingencies. Stimulus-outcome associations are linked to prospective network activity encoding possible expected outcomes. This link is mediated by cholinergic signaling to guide task performance, demonstrated by acetylcholine imaging and perturbation. We propose that Prh combines error-driven and map-like properties to acquire a predictive map of learned task behavior.
Phenotypic and spatial heterogeneity of brain myeloid cells after stroke is associated with cell ontogeny, tissue damage, and brain connectivity
Authors: Patir Anirudh , Barrington Jack , Szymkowiak Stefan , Straus Dana , Alfieri Alessio , Lefevre Lucas , Henderson Neil C , Horsburgh Karen , Ramachandran Prakash , McColl Barry W 
Published: March 2023

SummaryAcute stroke causes substantial mortality and morbidity and provokes extensive changes to myeloid immune cell populations in the brain that may be targets for limiting brain damage and enhancing brain repair. The most effective immunomodulatory approaches will require precise manipulation of discrete myeloid cell phenotypes in time and space to avoid harmful effects of indiscriminate neuroimmune perturbation. We sought to define how stroke alters the composition and phenotypes of mononuclear myeloid cells with particular attention to how cell ontogeny and spatial organisation combine to expand myeloid cell diversity across the brain after stroke. Multiple reactive microglial states and dual monocyte-derived populations contributed to an extensive repertoire of myeloid cells in post-stroke brain. We identified important overlap and distinctions among different cell types and states that involved ontogeny- and spatial-related properties. Notably, brain connectivity with infarcted tissue underpinned the pattern of local and remote altered cell accumulation and reactivity. Our discoveries suggest a global but anatomically-governed brain myeloid cell response to stroke that comprises diverse phenotypes arising through intrinsic cell ontogeny factors interacting with exposure to spatially-organised brain damage and neuroaxonal cues.
Gene recoding by synonymous mutations creates promiscuous intragenic transcription initiation in mycobacteria
Authors: Hegelmeyer Nuri K. , Previti Mary L. , Andrade Joshua , Utama Raditya , Sejour Richard J. , Gardin Justin , Muller Stephanie , Ketchum Steven , Yurovsky Alisa , Futcher Bruce , Goodwin Sara , Ueberheide Beatrix , Seeliger Jessica C. 
Published: March 2023

ABSTRACTEach genome encodes some codons more frequently than their synonyms (codon usage bias), but codons are also arranged more frequently into specific pairs (codon pair bias). Recoding viral genomes and yeast or bacterial genes with non-optimal codon pairs has been shown to decrease gene expression. Gene expression is thus importantly regulated not only by the use of particular codons but by their proper juxtaposition. We therefore hypothesized that non-optimal codon pairing could likewise attenuateMtbgenes. We explored the role of codon pair bias by recodingMtbgenes (rpoB, mmpL3, ndh) and assessing their expression in the closely related and tractable model organismM. smegmatis. To our surprise, recoding caused the expression of multiple smaller protein isoforms from all three genes. We confirmed that these smaller proteins were not due to protein degradation, but instead issued from new transcription initiation sites positioned within the open reading frame. New transcripts gave rise to intragenic translation initiation sites, which in turn led to the expression of smaller proteins. We next identified the nucleotide changes associated with these new sites of transcription and translation. Our results demonstrated that apparently benign, synonymous changes can drastically alter gene expression in mycobacteria. More generally, our work expands our understanding of the codon-level parameters that control translation and transcription initiation.IMPORTANCEMycobacterium tuberculosis(Mtb) is the causative agent of tuberculosis, one of the deadliest infectious diseases worldwide. Previous studies have established that synonymous recoding to introduce rare codon pairings can attenuate viral pathogens. We hypothesized that non-optimal codon pairing could be an effective strategy for attenuating gene expression to create a live vaccine forMtb. We instead discovered that these synonymous changes enabled the transcription of functional mRNA that initiated in the middle of the open reading frame and from which many smaller protein products were expressed. To our knowledge, this is the first report that synonymous recoding of a gene in any organism can create or induce intragenic transcription start sites.
Tracking Early Mammalian Organogenesis – Prediction and Validation of Differentiation Trajectories at Whole Organism Scale
Authors: Imaz-Rosshandler Ivan , Rode Christina , Guibentif Carolina , Ton Mai-Linh N. , Dhapola Parashar , Keitley Daniel , Argelaguet Ricard , Calero-Nieto Fernando J. , Nichols Jennifer , Marioni John C. , de Bruijn Marella F.T.R. , Göttgens Berthold 
Published: March 2023

AbstractEarly organogenesis represents a key step in animal development, where pluripotent cells divide and diversify to initiate formation of all major organs. Here, we used scRNA-Seq to profile over 300,000 single cell transcriptomes sampled in 6 hour intervals from mouse embryos between E8.5 and E9.5. Combining this dataset with our previous E6.5 to E8.5 atlas resulted in a densely sampled time course of over 400,000 cells from early gastrulation to organogenesis. Computational lineage reconstruction at full organismal scale identified complex waves of blood and endothelial development, including a new molecular programme for somite-derived endothelium. To assess developmental fates across the primitive streak, we dissected the E7.5 primitive streak into four adjacent regions, performed scRNA- Seq and predicted cell fates computationally. We next defined early developmental state/fate relationships experimentally by a combination of orthotopic grafting, microscopic analysis of graft contribution as well as scRNA-Seq to transcriptionally determine cell fates of the grafted primitive streak regions after 24h ofin vitroembryo culture. Experimentally determined fate outcomes were in good agreement with the fates predicted computationally, thus demonstrating how classical grafting experiments can be revisited to establish high-resolution cell state/fate relationships. Such interdisciplinary approaches will benefit future studies in both developmental biology as well as guide thein vitroproduction of cells for organ regeneration and repair.