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Data-driven models of neurons and circuits are important for understanding how the properties of membrane conductances, synapses, dendrites, and the anatomical connectivity between neurons generate the complex dynamical behaviors of brain circuits in health and disease. However, the inherent complexity of these biological processes makes the construction and reuse of biologically detailed models challenging. A wide range of tools have been developed to aid their construction and simulation, but differences in design and internal representation act as technical barriers to those who wish to use data-driven models in their research workflows. NeuroML, a model description language for computational neuroscience, was developed to address this fragmentation in modeling tools. Since its inception, NeuroML has evolved into a mature community standard that encompasses a wide range of model types and approaches in computational neuroscience. It has enabled the development of a large ecosystem of interoperable open-source software tools for the creation, visualization, validation, and simulation of data-driven models. Here, we describe how the NeuroML ecosystem can be incorporated into research workflows to simplify the construction, testing, and analysis of standardized models of neural systems, and supports the FAIR (Findability, Accessibility, Interoperability, and Reusability) principles, thus promoting open, transparent and reproducible science.

Cellular identity and fate are determined by the proteins synthesized. Initiation of mRNA translation requires an important translation factor, eIF4G ( ifg-1 in C. elegans ). Embryos use mRNA translational control for spatial and temporal regulation of protein synthesis. Using CRISPR engineering, we added in-frame epitope and fluorescent tags (V5, Myc, Flag, GFP, and mCherry) to IFG-1 . Tagged forms containing the V5 epitope caused embryonic arrest. Internal disruption of the V5 tag restored viability at 25°C. This study demonstrates that the molecular nature of a small epitope tag is sufficient to disrupt C. elegans embryogenesis., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2025 by the authors.)

Introduction: Cardiovascular disease (CVD) is a leading cause of death among transgender women and people with HIV. Exogenous estrogen and psychosocial stressors are known risk factors for CVD. Yet, few studies have used biomarkers to examine the role of stress in CVD risk among transgender women with HIV (TWHIV). This analysis examined whether stress moderates relationships between gender-affirming hormone therapy (GAHT) duration and CVD risk among TWHIV., Methods: This cross-sectional analysis of baseline data from an observational cohort of 108 Black and Latina TWHIV in Boston, New York, and Washington, DC, enrolled December 2020 to June 2022, measured sociodemographics, medical diagnoses, medications, smoking history, and perceived stress via interviewer-administered surveys. Physiological stress was measured with 14 biomarkers to calculate allostatic load indices (ALI). Forty participants provided saliva samples used to calculate cortisol awakening response and cortisol daily decline. The 2018 American College of Cardiology Revised Pooled Cohort Equation estimated 10-year CVD risk. Data were analyzed in 2024., Results: GAHT duration was positively associated with CVD risk scores in bivariate regression. In multivariable linear regression models (adjusting for age, income, education), only age and ALI remained significantly associated with CVD risk scores (β 1.13, CI: 1.05, 1.21). No stress measure significantly interacted with GAHT duration to affect CVD risk scores. In visual plots, GAHT duration increased CVD risk scores only for TWHIV experiencing the highest ALI., Conclusions: Stress plays an important role in CVD in TWHIV. More research is needed on non-GAHT factors, which influence CVD health among transgender women., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Raoultella planticola is an emerging opportunistic pathogen closely related to members of the Klebsiella genus. Genomic characterization of R. planticola isolates recovered from food animals is lacking. Here we describe the antimicrobial resistance genes, virulence factors, plasmid replicons, and phylogeny of three antimicrobial-resistant R. planticola isolates recovered from the feces of three dairy calves within 48 hours of birth., Methods: The genomes of the three R. planticola isolates were sequenced on a NextSeq 2000 platform using paired-end sequencing. The raw reads were trimmed using Trimmomatic and assembled using SPAdes v 3.15.4. Antimicrobial resistance genes, virulence factors and plasmid replicons were identified using ABRicate. Single nucleotide polymorphisms were identified among the genomes using the Harvest package and phylogenies were inferred using RAxML., Results: In total, nine different ARGs known to confer resistance to at least five different classes of antibiotics were detected among the three R. planticola genomes. These include bla PLA , a β-lactamase found only in R. planticola, fosfomycin resistance gene fosA, and a sequence aligned with oxqAB, an efflux pump conferring resistance to antibiotics including fluoroquinolones. Each genome encoded between four and seven ARGs, with three considered genotypically to be multidrug-resistant (MDR). Two of the three genomes harbored plasmids, and all three encoded 41 to 42 virulence factors, including iron scavenging genes sitABCD., Conclusions: Results of this study demonstrate the presence of diverse antimicrobial-resistant R. planticola, isolated from the feces of healthy dairy calves, that had some virulence factors that may cause human disease., (Copyright © 2025. Published by Elsevier Ltd.)

Objectives: Exploiting the complete blood count (CBC) with differential (CBC-diff) for early sepsis detection has practical value for emergency department (ED) care, especially for those without obvious presentations. The objective of this study was to develop the CBC Sepsis Index (CBC-SI) that incorporates monocyte distribution width (MDW) to enhance rapid sepsis screening., Design: A retrospective observational study., Setting: The ED of the University of Kansas Medical Center, United States., Patients: All adult patients (age 18 or over) presenting to the ED between August 8, 2020, and April 1, 2022, that received a CBC-diff as part of routine clinical care., Interventions: MDW, WBC count, and neutrophil-to-lymphocyte ratio were used to develop a CBC-SI (0 low to 5 high risk) for early sepsis detection. The diagnostic performance of CBC-SI was evaluated for patients with and without obvious early signs of sepsis., Measurements and Main Results: In a cohort of 51,407 ED visits, 1,683 (3.3%) met sepsis criteria; 1,343 (79.8%) septic patients presented with obvious signs and 340 (20.2%) without. The overall area under the curve of the CBC-SI was 0.83 (95% CI, 0.81-0.85). A CBC-SI of greater than or equal to 1 point exhibited a sensitivity of 83.1% (95% CI, 79.9-86.2%) and specificity of 64.8% (95% CI, 64.0-65.5%). Superior performance was observed in the patient subgroup presenting without obvious signs; greater than or equal to 1 point, 81.1% (95% CI, 73.2-88.9%) sensitivity and 69.1% (95% CI, 68.3-69.9%) specificity. Septic patients without obvious signs exhibited delays in antibiotic administration from arrival (median 4.7 vs. 3.4 hr; p < 0.001) and higher rates of ICU admission (43.8% vs. 27.9%; p < 0.001) and in-hospital mortality (14.7% vs. 9.8%; p = 0.011) compared with the septic subgroup presenting with obvious signs., Conclusions: The CBC-SI demonstrated strong performance for early sepsis detection. Its performance was best for nonobvious presentations, suggesting highest utility in a subgroup that is most susceptible to delayed interventions and poorer outcomes., Competing Interests: Dr. Levin, Dr. Hinson, Dr. Naiman, Ms. Smith, Mr. Steinhart, and Mr. DeBraine are employed by Beckman Coulter. Drs. Sarani, Taribichi, and Badaki-Makun have performed other research or consulting for Beckman Coulter. Dr. Kehoe is an employee of Danaher Diagnostics, an indirectly wholly owned subsidiary of Danaher Corporation (NYSE: DHR). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2025 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Pancreatic ductal adenocarcinoma (PDAC) carries an extremely poor prognosis, in part resulting from cellular heterogeneity that supports overall tumorigenicity. Cancer associated fibroblasts (CAF) are key determinants of PDAC biology and response to systemic therapy. While CAF subtypes have been defined, the effects of patient-specific CAF heterogeneity and plasticity on tumor cell behavior remain unclear. Here, multi-omics was used to characterize the tumor microenvironment (TME) in tumors from patients undergoing curative-intent surgery for PDAC. In these same patients, matched tumor organoid and CAF lines were established to functionally validate the impact of CAFs on the tumor cells. CAFs were found to drive epithelial-mesenchymal transition (EMT) and a switch in tumor cell classificiaton from classical to basal subtype. Furthermore, we identified CAF-specific interleukin 8 (IL-8) as an important modulator of tumor cell subtype. Finally, we defined neighborhood relationships between tumor cell and T cell subsets., Competing Interests: Conflict of Interest Statement E.M.J is a paid consultant for Adaptive Biotech, Achilles, DragonFly, Candel Therapeutics, Genocea, and Roche. She receives funding from Lustgarten Foundation and Bristol Myer Squibb. She is the Chief Medical Advisor for Lustgarten and SAB advisor to the Parker Institute for Cancer Immunotherapy (PICI) and for the C3 Cancer Institute. She is a founding member of Abmeta. E.J.F is on the SAB for Resistance Biology, Consultant for Mestag Therapeutics and Merck. L.Z. reports personal fees from Biosion, Alphamab, NovaRock, Xilio, Ambrx, Novagenesis, and Snow Lake Capitals; and other support from Alphamab and Mingruizhiyao outside the submitted work. D.J.Z. reports grant support (to Johns Hopkins) and travel from Roche/Genentech, and honoraria from Omni Health Media, Sermo, Atheneum, Escientiq, Deerfield Institute, ZoomRx, and NeuCore Bio.W.J.H. reports patent royalties from Rodeo/Amgen; grants from Sanofi, NeoTX, and Riboscience; speaking/travel honoraria from Exelixis and Standard BioTools. J.W.Z. report grant funding support (to Johns Hopkins) and travel from Roche/Genentch outside the submitted work.

Background: Inpatient psychiatric facilities have an increased risk of infection transmission. This study evaluated the impact of roommate and unit mate exposures on coronavirus disease-2019 (COVID-19) transmission to inform isolation practices., Methods: A single-center retrospective study was conducted among patients hospitalized in an inpatient behavioral health hospital from July 2020 through August 2023. We compared the risk of COVID-19 acquisition after exposure among patients with a contagious roommate versus those exposed to a contagious unit mate., Results: During the study period, the conversion rate was 10.05% overall, 24.4% for roommates, and 9.3% for unit mates; patients exposed to a roommate were at 3.14 times higher odds (95% confidence interval, 1.42-6.92) of acquiring COVID-19 after exposure. On unit-stratified analysis, patients exposed to a roommate on the geropsychiatric unit had the highest risk of postexposure conversion compared with unit mate exposed patients (odds ratio 6.38, 95% confidence interval 1.75-23.22). Logistic regression analysis identified a nonsignificant risk associated with increased time in group therapy., Conclusions: Exposure to a COVID-19-contagious roommate significantly increases the risk of COVID-19 acquisition among exposed patients receiving inpatient psychiatric care. Cohorting contagious and exposed individuals and avoiding multibedded rooms may mitigate COVID-19 transmission risk during psychiatric care., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Doxycycline post-exposure prophylaxis (doxy-PEP) reduces bacterial sexually transmitted infections among men who have sex with men and transgender women. Although poised for widespread clinical implementation, the impact of doxy-PEP on antimicrobial resistance remains a primary concern as its effects on the gut microbiome and resistome, or the antimicrobial resistance genes (ARGs) present in the gut microbiome, are unknown. To investigate these effects, we studied participants from the DoxyPEP trial, a randomized clinical trial comparing doxy-PEP use, a one-time doxycycline 200-mg dose taken after condomless sex (DP arm, n = 100), to standard of care (SOC arm, n = 50) among men who have sex with men and transgender women. From self-collected rectal swabs at enrollment (day-0) and after 6 months (month-6), we performed metagenomic DNA sequencing (DNA-seq) or metatranscriptomic RNA sequencing (RNA-seq). DNA-seq data were analyzable from 127 samples derived from 89 participants, and RNA-seq data were analyzable from 86 samples derived from 70 participants. We compared the bacterial microbiome and resistome between the two study arms and over time. The median number of doxycycline doses taken since enrollment by participants with DNA-seq data was zero (interquartile range (IQR): 0-7 doses) for the SOC arm and 42 (IQR: 27-64 doses) for the DP arm. Tetracycline ARGs were detected in all day-0 DNA-seq samples and in 85% of day-0 RNA-seq samples. The proportional mass of tetracycline ARGs in the resistome increased between day-0 and month-6 in DP participants from 46% to 51% in the metagenome (P = 2.3 × 10 -2 ) and from 4% to 15% in the metatranscriptome (P = 4.5 × 10 -6 ), but no statistically significant increases in other ARG classes were observed. Exposure to a higher number of doxycycline doses correlated with proportional enrichment of tetracycline ARGs in the metagenome (Spearman's ρ = 0.23, P = 9.0 × 10 -3 ) and metatranscriptome (Spearman's ρ = 0.55, P = 3.7 × 10 -8 ). Bacterial microbiome alpha diversity, beta diversity and total bacterial mass did not differ between day-0 and month-6 samples from DP participants when assessed by either DNA-seq or RNA-seq. In an abundance-based correlation analysis, we observed an increase over time in the strength of the correlation between tetracycline ARGs and specific bacterial taxa, including some common human pathogens. In sum, doxy-PEP use over a 6-month period was associated with an increase in the proportion of tetracycline ARGs comprising the gut resistome and an increase in the expression of tetracycline ARGs. At 6 months of doxy-PEP use, no residual differences were observed in alpha and beta diversity or taxonomic composition of the gut microbiome. As doxy-PEP is implemented as a public health strategy, further studies and population-level surveillance of doxycycline-resistant pathogens are needed to understand the implications of these findings. ClinicalTrials.gov registration number: NCT03980223 ., Competing Interests: Competing interests: Mayne Pharmaceuticals donated doxycycline hyclate to the study, and Cepheid and Hologic provided reagents and STI diagnostic assays. Several authors have served as scientific advisors: to Merck (C. Celum and D.D.), to Gilead Sciences (C. Celum), to GlaxoSmithKline (C. Celum) and to Vir Biotechnology (A.L.). The other authors have no conflict of interests to declare., (© 2024. The Author(s).)