bluuebunny/crossref_metadata_2025_split huggingface dataset:
When Is It Safe to Start VTE Prophylaxis after Blunt Solid Organ Injury? A Prospective AAST Multi-Institutional Trial
Authors: Schellenberg Morgan , Owattanapanich Natthida , Emigh Brent , Van Gent Jan-Michael , Egodage Tanya , Murphy Patrick B. , Ball Chad G. , Spencer Audrey L. , Vogt Kelly N. , Keeley Jessica A. , Doris Stephanie , Beiling Marissa , Donnelly Megan , Ghneim Mira , Schroeppel Thomas , Bradford James , Breinholt Connor S. , Coimbra Raul , Berndtson Allison E. , Anding Catherine , Charles Michael S. , Rieger William , Inaba Kenji ,   The AAST VTE Prophylaxis Study Group
Published: October 2023

Abstract

Background
The optimal time to initiate venous thromboembolism (VTE) chemoprophylaxis (VTEp) after blunt solid organ injury remains controversial as VTE mitigation must be balanced against bleeding promulgation. Evidence from primarily small, retrospective, single-center work suggests VTEp ≤48 h is safe and effective. This study was undertaken to validate this clinical practice.

Methods
Blunt trauma patients presenting to 19 participating trauma centers in North America were screened over a one-year study period beginning between August 1 and October 1, 2021. Inclusions were age > 15 years; ≥1 liver, spleen, or kidney injury; and initial nonoperative management (NOM). Exclusions were transfers, ED death, pregnancy, and concomitant bleeding disorder/anticoagulation/antiplatelet medication. A priori power calculation stipulated the need for 1,158 patients. Time of VTEp initiation defined study groups: Early (≤48 h of admission) vs. Late (>48 h). Bivariate and multivariable analyses compared outcomes.

Results
In total, 1,173 patients satisfied study criteria with 571 (49%) liver, 557 (47%) spleen, and 277 (24%) kidney injuries. Median patient age was 34 [25-49] years and 67% (n = 780) were male. Median ISS was 22 [14-29] with AIS Abdomen 3 [2-3] and median AAST grade of solid organ injury 2 [2-3]. Early VTEp patients (n = 838, 74%) had significantly lower rates of VTE (n = 28, 3% vs. n = 21, 7%, p = 0.008); comparable rates of NOM failure (n = 21, 3% vs. n = 12, 4%, p = 0.228); and lower rates of post-VTEp blood transfusion (n = 145, 17% vs. n = 71, 23%, p = 0.024) when compared to Late VTEp patients (n = 301, 26%). Late VTEp was independently associated with VTE (OR 2.251, p = 0.046).

Conclusion
Early initiation of VTE chemoprophylaxis was associated with significantly reduced rates of VTE with no increase in bleeding complications. VTEp initiation ≤48 hours is therefore safe and effective and should be the standard of care for patients with blunt solid organ injury.

Level of Evidence
II, Therapeutic and Care Management
Firearm injuries treated at trauma centers in the United States
Authors: Rivara Frederick P. , Hink Ashley B. , Kuhls Deborah A. , Banks Samantha , Agoubi Lauren L. , Kirkendoll Shelbie , Winchester Alex , Hoeft Christopher , Patel Bhavin , Nathens Avery 
Published: October 2023

BACKGROUND
While firearm injuries and deaths continue to be a major public health problem, the number of nonfatal firearm injuries and the characteristics of patients are not well-known. The American College of Surgeons Committee on Trauma leveraged an existing data system to collect additional data on fatal and nonfatal firearm injuries presenting to trauma centers. This report provides an overview of this initiative and highlights the challenges associated with capturing actionable data on firearm-injured patients.

METHODS
A total of 128 trauma centers that are part of the American College of Surgeons Trauma Quality Improvement Program collected data on individuals of any age arriving alive between March 1, 2021, and February 28, 2022, with a firearm injury. In addition to the standard data collected for Trauma Quality Improvement Program, abstractors also extracted additional data specific to this study. We linked data from the Distressed Community Index to patient records using zip code of residence.

RESULTS
A total of 17,395 patients were included, with mean (SD) age of 30.2 (13.5) years, 82.5% were male, and the majority were Black and non-Hispanic. The mean proportion of variables with missing data varied among trauma centers, with a mean of 20.7% missing data. Injuries occurred most commonly in homes (31.2%) or on the street (26.6%); 70.4% of injuries were due to assaults. Nearly one third of patients were discharged from the emergency department, 25.9% were admitted directly to the operating room, and 10.9% were admitted to the intensive care unit; 5.9% died in the emergency department, and 10.3% died overall during their course of care. Nearly two thirds of patients lived in the two highest distressed categories of communities; only 7.5% lived in the least distressed quintile.

CONCLUSION
Using trauma center data can be a valuable tool to improve our knowledge of firearm injuries if clinical practices and documentation of patient risks and circumstances are standardized.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level III.
CXCR5+CD8+ T Cell–Mediated Suppression of Humoral Alloimmunity and AMR in Mice Is Optimized With mTOR and Impaired With Calcineurin Inhibition
Authors: Han Jing L. , Zimmerer Jason M. , Zeng Qiang , Chaudhari Sachi R. , Hart Madison , Satoskar Anjali A. , Abdel-Rasoul Mahmoud , Breuer Christopher K. , Bumgardner Ginny L. 
Published: October 2023

Background.
Adoptive cellular therapy (ACT) with antibody-suppressor CXCR5+CD8+ T cells (CD8+ TAb-supp) inhibits alloantibody production, antibody-mediated rejection (AMR), and prolongs graft survival in multiple transplant mouse models. However, it is not known how conventional immunosuppressive agents impact the efficacy of CD8+ TAb-supp ACT.

Methods.
We investigated the efficacy of CD8+ TAb-supp cell ACT when combined with calcineurin inhibitor (CNi) or mammalian target of rapamycin inhibitor (mTORi) in a murine model of kidney transplant.

Results.
ACT-mediated decrease in germinal center B cells, posttransplant alloantibody titer, and amelioration of AMR in high alloantibody-producing CCR5 knockout kidney transplant recipients were impaired when ACT was combined with CNi and enhanced when combined with mTORi. CNi (but not mTORi) reduced ACT-mediated in vivo cytotoxicity of IgG+ B cells and was associated with increased quantity of germinal center B cells. Neither CNi nor mTORi treatment impacted the expression of cytotoxic effector molecules (FasL, Lamp1, perforin, granzyme B) by CD8+ TAb-supp after ACT. Concurrent treatment with CNi (but not mTORi) reduced in vivo proliferation of CD8+ TAb-supp after ACT. The increase in quantity of splenic CD44+CXCR5+CD8+ T cells that occurs after ACT was reduced by concurrent treatment with CNi but not by concurrent treatment with mTORi (dose-dependent).

Conclusions.
Impaired efficacy of ACT by CNi is attributed to reduced persistence and/or expansion of CD8+ TAb-supp cells after ACT. In contrast, concurrent immunosuppression with mTORi preserves CD8+ TAb-supp cells quantity, in vivo proliferation, and in vivo cytotoxic effector function after ACT and enhances suppression of humoral alloimmunity and AMR.
Association of non-HDL-C/apoB ratio with long-term mortality in the general population: a cohort study
Authors: Zhang Kerui , Wei Chenchen , Shao Yaqing , Wang Li , Zhao Zongquan , Yin Song , Tang Xuejun , Li Yuan , Gou Zhongshan 
Published: October 2023

AbstractBackgroundIn general, the identification of cholesterol-depleted lipid particles can be inferred from non-high-density lipoprotein cholesterol (non-HDL-C) concentration to apolipoprotein B (apoB) concentration ratio, which serves as a reliable indicator for assessing the risk of cardiovascular disease. However, the ability of non-HDL-C/apoB ratio to predict the risk of long-term mortality among the general population remains uncertain. The objective of this study is to explore the association of non-HDL-C/apoB ratio with long-term all-cause and cardiovascular mortality in the adult population of the United States.MethodsThis retrospective cohort study was a further analysis of existing information from the National Health and Nutrition Examination Survey (NHANES). In the ultimate analysis, 12,697 participants from 2005 to 2014 were included. Kaplan-Meier (K-M) curves and the log-rank test were applied to visualize survival differences between groups. Multivariate Cox regression and restricted cubic spline (RCS) models were applied to evaluate the association of non-HDL-C/apoB ratio with all-cause and cardiovascular mortality. Subgroup analysis was conducted for the variables of age, sex, presence of coronary artery disease, diabetes and hypertriglyceridemia and usage of lipid-lowering drugs.ResultsThe average age of the cohort was 46.8 ± 18.6 years, with 6,215 (48.9%) participants being male. During a median follow-up lasting 68.0 months, 891 (7.0%) deaths were documented and 156 (1.2%) patients died of cardiovascular disease. Individuals who experienced all-cause and cardiovascular deaths had a lower non-HDL-C/apoB ratio compared with those without events (1.45 ± 0.16vs.1.50 ± 0.17 and 1.43 ± 0.17vs.1.50 ± 0.17, bothP< 0.001). The results of adjusted Cox regression models revealed that non-HDL-C/apoB ratio exhibited independent significance as a risk factor for both long-term all-cause mortality [hazard ratio (HR) = 0.51, 95% confidence interval (CI): 0.33-0.80] and cardiovascular mortality (HR = 0.33, 95% CI: 0.12-0.90). Additionally, a significant sex interaction was discovered (Pfor interaction < 0.05), indicating a robust association between non-HDL-C/apoB ratio and long-term mortality among females. The RCS curve showed that non-HDL-C/apoB ratio had a negative linear association with long-term all-cause and cardiovascular mortality (Pfor non-linearity was 0.098 and 0.314).ConclusionsThe non-HDL-C/apoB ratio may serve as a potential biomarker for predicting long-term mortality among the general population, independent of traditional risk factors.
Context-invariant socioemotional encoding by prefrontal ensembles
Authors: Frost Nicholas A. , Donohue Kevin C. , Sohal Vikaas 
Published: October 2023

AbstractThe prefrontal cortex plays a key role in social interactions, anxiety-related avoidance, and flexible context- dependent behaviors, raising the question: how do prefrontal neurons represent socioemotional information across different environments? Are contextual and socioemotional representations segregated or intermixed, and does this cause socioemotional encoding to remap or generalize across environments? To address this, we imaged neuronal activity in the medial prefrontal cortex of mice engaged in social interactions or anxiety-related avoidance within different environments. Neuronal ensembles representing context and social interaction overlapped more than expected while remaining orthogonal. Anxiety-related representations similarly generalized across environments while remaining orthogonal to contextual information. This shows how prefrontal cortex multiplexes parallel information streams using the same neurons, rather than distinct subcircuits, achieving context-invariant encoding despite context-specific reorganization of population-level activity.
Targeted memory reactivation is not more effective during slow wave sleep than sleep stage 2
Authors: Carbone Julia , Bibian Carlos , Born Jan , Forcato Cecilia , Diekelmann Susanne 
Published: October 2023

AbstractSleep facilitates memory consolidation, which is assumed to rely on the reactivation of newly encoded memories orchestrated by the temporal interplay of slow oscillations (SO), fast spindles and ripples. SO as well as the number of spindles coupled to SO are more frequent during slow wave sleep (SWS) compared to lighter sleep stage 2 (S2). But, it is unclear whether memory reactivation is more effective during SWS than during S2. To test this question, we applied Targeted Memory Reactivation (TMR) by presenting learning-associated sound cues during SWS vs. S2 in a counterbalanced within-subject design. Contrary to our hypothesis, memory performance was not significantly better when cues were presented during SWS. Event-related potential (ERP) amplitudes were significantly higher for cues presented during SWS than S2, and the density of SO and SO-spindle complexes was generally higher during SWS than during S2. Whereas SO density increased during and after the TMR period, SO-spindle complexes decreased. None of the parameters were associated with memory performance. These findings suggest that the efficacy of TMR does not depend on whether it is administered during SWS or S2, despite differential processing of memory cues in these sleep stages.
Spontaneous network transitions predict somatosensory perception
Authors: Sharma Abhinav , Lange Joachim , Vidaurre Diego , Florin Esther 
Published: October 2023

AbstractSensory perception is essential for transforming incoming information in the brain into targeted behavior. Our brains are everlastingly active, and variations in perception are ubiquitously associated with human behavioral performance. Previous studies indicate that changes in spontaneous neural activity within local sensory areas correlate with the perception of ambiguous stimuli. However, the contribution of whole brain spontaneous networks to perception is not well understood. Using an ambiguous tactile temporal discrimination task, we demonstrate that the interaction between wholebrain networks in the seconds of the spontaneous pre-stimulus period also contributes to perception during the task. Transitions to a frontal and a multi-frequency network across the brain are essential for the correct percept. Conversely, incorrect percepts are mainly preceded by transitions to an alphaparietal network. Brain transitions occur faster during the period before stimulus presentation for correct stimuli detection, suggesting the need for enhanced network flexibility during this phase.Significance statementOur brain is constantly engaged in processing sensory input and translating it into sensory perceptions. When confronted with ambiguous sensory information, individuals do not always have the same perceptual experience. We demonstrate that brain network transitions to frontal areas are essential for the correct percept. Conversely, incorrect percepts are mainly preceded by transitions to an alpha-parietal network. Correct stimuli detections are characterized by faster transitions, suggesting the need for enhanced network flexibility. These results extend our knowledge of perception by pointing to the relevance of whole-brain spontaneous networks and their dynamic properties.
Pharmacological and behavioral effects of tryptamines present in psilocybin-containing mushrooms
Authors: Rakoczy Ryan J. , Runge Grace N. , Sen Abhishek K. , Sandoval Oscar , Nguyen Quynh , Roberts Brianna R. , Sciortino Jon H. , Gibbons William J. , Friedberg Lucas M. , Andrew Jones J. , McMurray Matthew S. 
Published: October 2023

ABSTRACTDemand for more efficacious antidepressants, particularly those with a rapid onset of action, has resulted in a reevaluation of psychedelic drugs for their therapeutic potential. Several tryptamines found in psilocybin-containing ‘magic’ mushrooms share chemical similarities with psilocybin, and early work suggests they may also share receptor targets. However, few studies have explored their pharmacological and behavioral effects. To accomplish this, we compared baeocystin, norbaeocystin, and aeruginascin with psilocybin to determine if they are metabolized by the same enzymes, penetrate the blood brain barrier, serve as ligands for similar centrally located receptors, and modulate behavior in rodents similarly. We first assessed the stability and optimal storage and handling conditions for each compound.In vitroenzyme kinetics assays then found that all compounds shared nearly identical rates of dephosphorylation via alkaline phosphatase and metabolism by monoamine oxidase. Further, we found that only the dephosphorylated products of baeocystin and norbaeocystin could cross a blood brain barrier mimetic to a similar degree as the dephosphorylated form of psilocybin, psilocin. Behaviorally, only psilocybin was found to induce head twitch responses in rats, a marker of 5HT2A agonism and indicator of the compound’s hallucinogenic potential. However, like psilocybin, norbaeocystin was also found to improve outcomes in the forced swim test. All compounds were found to cause minimal changes to metrics of renal and hepatic health, suggesting innocuous safety profiles. Collectively, this work suggests that other naturally-occurring tryptamines, especially norbaeocystin, may share the same therapeutic potential as psilocybin, but without causing hallucinations.HIGHLIGHTSBaeocystin, norbaeocystin, and aeruginascin may have similar therapeutic value to psilocybin, but are understudiedCompound stability varied widely, with dephosphorylated forms showing lowest stabilityRates of metabolism by alkaline phosphatase and monoamine oxidase were similar across compoundsBlood brain barrier penetration was limited to dephosphorylated forms of psilocybin, baeocystin, and norbaeocystinRat behavioral testing suggested norbaeocystin may have therapeutic utility similar to psilocybin, without causing hallucinations
Pan-cortical 2-photon mesoscopic imaging and neurobehavioral alignment in awake, behaving mice
Authors: Vickers Evan D. , McCormick David A. 
Published: October 2023

AbstractThe flow of neural activity across the neocortex during active sensory discrimination is constrained by task-specific cognitive demands, movements, and internal states. During behavior, the brain appears to sample from a broad repertoire of activation motifs. Understanding how these patterns of local and global activity are selected in relation to both spontaneous and task-dependent behavior requires in-depth study of densely sampled activity at single neuron resolution across large regions of cortex. In a significant advance toward this goal, we developed procedures to record mesoscale 2-photon Ca2+imaging data from two novelin vivopreparations that, between them, allow simultaneous access to nearly all of the mouse dorsal and lateral neocortex. As a proof of principle, we aligned neural activity with both behavioral primitives and high-level motifs to reveal the existence of large populations of neurons that coordinated their activity across cortical areas with spontaneous changes in movement and/or arousal. The methods we detail here facilitate the identification and exploration of widespread, spatially heterogeneous neural ensembles whose activity is related to diverse aspects of behavior.
From mice to humans: Cross-species transcriptomics analysis to uncover distinct mechanisms of Diabetic Retinopathy (DR)
Authors: Adda Siddharth , Legendre Christophe , Rangasamy Sampath 
Published: October 2023

ABSTRACTDiabetic Retinopathy (DR) is the leading risk for vision loss in working adults worldwide, affecting more than 100 million people. While risk factors such as diabetes duration, hyperglycemia, and dyslipidemia are well-acknowledged, the unifying molecular mechanisms underlying the pathogenesis of DR remain incompletely understood across different species. To bridge this gap, we conducted a comprehensive RNA-sequencing (RNA-seq) meta-analysis on retinal tissue samples from mice, rats, and humans with diabetes. Our integrative bioinformatics analysis elucidated both conserved and species-specific transcriptional landscapes associated with DR. Notably, pro-inflammatory pathways were ubiquitously activated in the retinal tissues across all examined species. However, unique human-specific immune-metabolic signatures emerged, which were not observed in rodent models. In summary, our investigation unveils both universal and species-specific molecular underpinnings of DR, enhancing our understanding of its complex pathobiology. These findings validate the utility of animal models in DR research and underscore the importance of human-focused studies to uncover mechanisms uniquely relevant to human pathology.
Expression of Lanthipeptides in Human Cells
Authors: Eslami Sara M. , Rahman Imran R. , van der Donk Wilfred A. 
Published: October 2023

AbstractCyclic peptides represent a burgeoning area of interest in therapeutic and biotechnological research. In opposition to their linear counterparts, cyclic peptides, such as certain ribosomally synthesized and post-translationally modified peptides (RiPPs), are more conformationally constrained and less susceptible to proteolytic degradation. The lanthipeptide RiPP cytolysin L forms a covalently enforced helical structure that may be used to disrupt helical interactions at protein-protein interfaces. Herein, an expression system is reported to produce lanthipeptides and structurally diverse cytolysin L derivatives in mammalian cells. Successful targeting of lanthipeptides to the nucleus is demonstrated. In vivo expression and targeting of such peptides in mammalian cells may allow for screening of lanthipeptide inhibitors of native protein-protein interactions.Table of contents graphic
In vivoaffinity maturation of murine B cells reprogrammed to express human antibodies
Authors: Yin Yiming , Guo Yan , Jiang Yuxuan , Quinlan Brian , Peng Haiyong , Crynen Gogce , He Wenhui , Zhang Lizhou , Ou Tianling , Bailey Charles C. , Farzan Michael 
Published: October 2023

AbstractCRISPR-edited murine B cells engineered to express human antibody variable chains proliferate, class switch, and secrete these antibodies in vaccinated mice. However, current strategies disrupt the heavy-chain locus, resulting in inefficient somatic hypermutation without functional affinity maturation. Here we show that recombined murine heavy- and kappa-variable genes can be directly and simultaneously overwritten, using Cas12a-mediated cuts at their 3’-most J segments and 5’ homology arms complementary to distal V segments. Cells edited in this way to express the HIV-1 broadly neutralizing antibodies 10-1074 or VRC26.25-y robustly hypermutated and generated potent neutralizing plasma in vaccinated recipient mice. 10-1074 variants isolated from these mice bound and neutralized HIV-1 envelope glycoprotein more efficiently than wild-type 10-1074 while maintaining or improving its already low polyreactivity and longin vivohalf-life. We further validated this approach by generating substantially broader and more potent variants of the anti-SARS-CoV-2 antibodies ZCB11 and S309. Thus, B cells edited at their native loci affinity mature, facilitating development of broad, potent, and bioavailable antibodies and expanding the potential applications of engineered B cells.
Noise robustness and metabolic load determine the principles of central dogma regulation
Authors: Lo Teresa W. , Choi Han James , Huang Dean , Wiggins Paul A. 
Published: October 2023

AbstractThe processes of gene expression are inherently stochastic, even for essential genes required for growth. How does the cell maximize fitness in light of noise? To answer this question, we build a mathematical model to explore the trade-off between metabolic load and growth robustness. The model predicts novel principles of central dogma regulation: Optimal protein expression levels for many genes are in vast overabundance. Essential genes are transcribed above a lower limit of one message per cell cycle. Gene expression is achieved by load balancing between transcription and translation. We present evidence that each of these novel regulatory principles is observed. These results reveal that robustness and metabolic load determine the global regulatory principles that govern gene expression processes, and these principles have broad implications for cellular function.One-sentence summaryFitness maximization predicts protein overabundance, a transcriptional floor, and the balancing of transcription and translation.