bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacotherapy for Agitation Management in a Pediatric Emergency Department
Authors: Brasel Kelsey , LaScala Elizabeth , Weeda Erin , Rarrick Christine 
Published: January 2025

Objectives
In the treatment of agitation in a pediatric emergency department (PED), it is common to use once or as needed (PRN) medications when nonpharmacological management options have failed. Currently, there is limited available evidence on the treatment of pediatric agitation. The objective of this analysis was to characterize the prescribing practices of once or PRN medications for the treatment of agitation in a PED at an academic medical center.

Methods
This was a retrospective chart review of all encounters in which a patient was administered once or PRN medications for agitation treatment in the PED from July 1, 2021, to June 30, 2022. Once or PRN medications were defined as any medication in the antipsychotic, benzodiazepine, and barbiturate classes along with diphenhydramine, clonidine, ketamine, and guanfacine. The primary outcome was to describe the prescribing patterns of the most utilized agents for the treatment of agitation in the PED. Secondary outcomes were to assess effectiveness and safety of the agents utilized.

Results
We reviewed 109 patient encounters in which a once or PRN medication was used for agitation treatment. The most common initial regimens were benzodiazepine monotherapy (n = 47; 43%), antipsychotic monotherapy (n = 23; 21%), and concurrent use of an antipsychotic, benzodiazepine, and diphenhydramine (n = 16; 15%). Patients required another administration of a once or PRN medication within 5 to 120 minutes of initial administration 11% (n = 12) of the time. No patients required rapid sequence intubation and one patient (0.9%) needed treatment for extrapyramidal symptoms.

Conclusions
Results indicate that there is not a standard regimen choice in the treatment of agitation in the PED; however, benzodiazepine monotherapy was used most frequently. Few adverse events occurred. Further research is needed to identify the optimal regimen choice for patients presenting with agitation in a PED.
Severe Lymphopenia Predicts Poorer Survival in Patients With Rectal Cancer Undergoing Neoadjuvant Chemoradiation
Authors: Kim Daniel W. , Lee Grace , Cai Elise M. , Ryan David P. , Parikh Aparna R. , Allen Jill N. , Giantonio Bruce J. , Berger David L. , Kunitake Hiroko , Ricciardi Rocco , Cusack James C. , Roberts Hannah J. , Hong Theodore S. , Wo Jennifer Y. 
Published: January 2025

Purpose
Chemoradiation-induced lymphopenia is common and associated with poorer survival in multiple solid malignancies. However, the association between chemoradiation-related lymphopenia and survival outcomes in rectal cancer is yet unclear. The objective of this study was to evaluate the prognostic impact of lymphopenia and its predictors in patients with rectal cancer undergoing neoadjuvant chemoradiation.

Methods
The inclusion criteria for this single-institution retrospective study were as follows: (1) biopsy-proven diagnosis of rectal adenocarcinoma, (2) receipt of neoadjuvant chemoradiation followed by surgery, and (3) absolute lymphocyte count available prior to and within 12 weeks of chemoradiation. In general, chemoradiation consisted of 5-fluorouracil or capecitabine and radiotherapy with 50.4 Gy over 28 fractions. Lymphopenia was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The primary variable of interest was absolute lymphocyte count nadir within 12 weeks of chemoradiation, dichotomized by <500/μL (grade 3 or worse lymphopenia). The primary endpoint was overall survival. Cox modeling and Kaplan-Meier methods were used to perform survival analyses.

Results
A total of 193 patients were identified with a median follow-up of 68 months. Overall clinical stage was 2 in 21% and 3 in 76%. Median baseline lymphocyte count for the entire cohort was 1700/μL. One hundred ten patients (57%) experienced chemoradiation-related severe lymphopenia. Pathologic complete response rate was 21%; 83% received adjuvant chemotherapy. Lower baseline lymphocyte count was significantly associated with increased risk for chemoradiation-related severe lymphopenia (odds ratio, 1.71). On multivariable Cox regression analysis, chemoradiation-related severe lymphopenia was significantly associated with worse disease-free survival (hazard ratio, 2.64) and overall survival (hazard ratio, 4.32). Five-year overall survival was 79% versus 92%, and 5-year disease-free survival was 70% versus 86% in the cohort that experienced versus did not experience severe lymphopenia, respectively.

Discussion
Chemoradiation-induced lymphopenia is common and a prognostic marker of poorer survival in rectal cancer. Closer observation in high-risk patients and treatment modifications may be potential approaches to mitigating treatment-related lymphopenia. Our findings also suggest an important role of the host immunity in rectal cancer outcomes and support future studies investigating ways to reduce treatment-induced lymphopenia.
Treatment Crossover Following Advanced Therapy for Overactive Bladder Syndrome
Authors: Edge Preston , Yanek Lisa R. , Patterson Danielle , Chen Chi Chiung Grace , Handa Victoria L. 
Published: January 2025

Importance
Patients deciding between advanced therapies for overactive bladder syndrome may be interested to know the likelihood of treatment crossover after sacral neuromodulation, intradetrusor OnabotulinumtoxinA, or percutaneous tibial nerve stimulation. Treatment crossover was defined as a switch from one advanced therapy to another.

Objectives
The aim of this study was to estimate the rate of treatment crossover after each advanced therapy for nonneurogenic overactive bladder syndrome. Our secondary objective was to compare medication use after each advanced therapy.

Study Design
Using claims data from the MarketScan database, privately insured women 18–65 years old with overactive bladder syndrome were identified for this retrospective cohort study. For all patients who received an advanced therapy between 2013 and 2019, we calculated the proportion who subsequently crossed over to a different advanced treatment. For each advanced therapy, we also calculated the proportion who subsequently utilized overactive bladder medication.

Results
We identified 7,231 adult women who underwent index advanced therapy for overactive bladder syndrome between 2013 and 2019. Treatment crossover occurred in 309 women (4.3%) and was significantly more likely following percutaneous tibial nerve stimulation (8.0%) compared to sacral neuromodulation (4.2%) or intradetrusor OnabotulinumtoxinA (2.6%, P < 0.01). Treatment crossover was also more likely following sacral neuromodulation compared to intradetrusor OnabotulinumtoxinA (P < 0.01). Medication use after advanced therapy was more common after percutaneous tibial nerve stimulation (29.2%) compared to intradetrusor OnabotulinumtoxinA (20.4%) or sacral neuromodulation (18.8%, P < 0.01).

Conclusions
Treatment crossover following advanced therapy for overactive bladder syndrome was uncommon but was significantly more likely after percutaneous tibial nerve stimulation. Medication use following advanced treatment occurred in a substantial minority in all cohorts.
Liver Injury as a Risk Factor for Post-Traumatic Venous Thromboembolism
Authors: Cobler-Lichter Michael D , Delamater Jessica M , Lyons Nicole B , Collie Brianna L , Meizoso Jonathan P , Pizano Louis R , Proctor Kenneth G , Namias Nicholas , Carter Nicholas H 
Published: January 2025

Background:
Venous thromboembolism (VTE) remains a major source of morbidity and mortality in severely injured patients despite current methods of risk stratification and prophylaxis, suggesting incomplete understanding of VTE risk factors. Given the liver’s role in coagulation, we hypothesized that liver injury (LI) is associated with increased rates of VTE in severely injured patients.

Study Design:
The American College of Surgeons Trauma Quality Improvement Project database (TQIP) 2017-2021 was retrospectively reviewed for patients with a maximum abdominal Abbreviated Injury Score (AIS) ≥ 4 with or without LI. Transfers, burns, all deaths, and patients < 18 years of age were excluded. Logistic regression was performed to assess the independent effect of LI on development of pulmonary embolism (PE) and deep venous thrombosis (DVT) while controlling for potential confounding variables.

Results:
In 44,506 patients, there were 1,736 (3.9%) 890 (2.0%), and 18,642 patients (41.9%) with DVT, PE, and LI, respectively. After controlling for potential confounders, LI was independently associated with PE (aOR 1.279 [95% CI 1.088-1.504]) but was not associated with DVT (aOR 1.011 [95% CI 0.897-1.140]).

Conclusion:
In severely injured patients, LI is an independent predictor of PE, but not DVT, suggesting LI is the source of either emboli or a more complex locally prothrombotic focus leading to downstream thrombi in the lung without causing upstream systemic venous thrombi. Further work should focus on elucidation of mechanisms including the portal venous blood coagulation profile, endothelial injury in the liver, and the potential for stasis of venous blood traversing an injured liver as well as the role for including LI in VTE risk stratification.
Decoding ladybird’s colours: structural mechanisms of colour production and pigment modulation
Authors: Carrada Marzia , Haddad Mohamed , San José Luis , Agez Gonzague , Poumirol Jean-Marie , Magro Alexandra 
Published: January 2025

AbstractThis study investigates the mechanisms underlying colour production in the family Coccinellidae, focusing on two model species:A. bipunctata (L)andC. quatuordecimguttata (L). In this family, colours have traditionally been attributed primarily to pigments such as carotenoids and melanins. We propose an alternative perspective, considering the elytra as an integrated optical medium whose optical properties result from both its architectural design and the properties of its constituent materials, including matrix and pigments. In the present work, several methods were used, ranging from optical and electron microscopies, light-based techniques, to LC-HRMS analyses. Through local pigment analyses, microstructural examination of elytra, and modelling of interaction of elytra with light, we show that, while pigments are central to patterning and contribute to colour, overall colour also results from one or more physical mechanisms that may operate simultaneously. In the light of these results, we assume that the complex and diverse colouration in the Coccinellidae can only be elucidated by considering the interplay of pigments and the optical properties of the elytron cuticle.
A nonhuman primate model mirrors human congenital cytomegalovirus infection and reveals a spectrum of vertical transmission outcomes
Authors: Manuel Tabitha , Moström Matilda , Crooks Chelsea M. , Davalos Angel , Barfield Richard , Scheef Elizabeth , Kendall Savannah , Midkiff Cecily C. , Sprehe Lesli , Trexler Macey , Boquet Francis , Shroyer Monica , Danner Victoria , Doyle-Myers Lara , Weinbaum Carolyn , Mirza Anne , Lammi Stephen , Otero Claire , Lee Marissa R. , Rogers Layne W. , Granek Joshua , Owzar Kouros , Malouli Daniel , Früh Klaus , Kowalik Timothy , Chan Cliburn , Permar Sallie R. , Blair Robert V. , Kaur Amitinder 
Published: January 2025

AbstractCongenital cytomegalovirus (cCMV) is the leading infectious cause of birth defects worldwide, yet immune determinants of protection to inform design of a maternal vaccine remain elusive. Here, we characterized the outcome of primary rhesus CMV (RhCMV) infection during pregnancy in an immune competent nonhuman primate (NHP) model. RhCMV DNA was detected in amniotic fluid and/or fetal tissues in six of 12 (50% placental transmission) CMV-naive rhesus macaque dams inoculated intravenously with RhCMV in early second trimester gestation. Widespread tissue dissemination dominated by one of two inoculated RhCMV strains was present in one fetus (8.3% cCMV disease). Placental RhCMV transmission was associated with elevated fetal and maternal plasma TNF-alpha and reduced maternal brain-derived neurotrophic factor and IL-10 levels. CMV exposure during pregnancy had a broad impact on the placenta and fetus even in the absence of congenital infection as evidenced by RhCMV infection at the maternal-fetal interface in all 12 dams, along with significantly reduced placental efficiency and fetal growth metrics compared to gestation-matched control pregnancies. This NHP model recapitulates key aspects of human cCMV and provides new insight into barriers and biomarkers of successful vertical transmission.One sentence summary:The nonhuman primate model mirrors the epidemiology of human congenital CMV (cCMV) after primary infection and reveals its transmission bottlenecks.
Sequencing complete plasmids on Oxford Nanopore Technology Sequencers usingR2C2andChopper
Authors: Schimke Kayla D. , Vollmers Christopher 
Published: January 2025

ABSTRACTPlasmids are ubiquitous tools in molecular biology which are used for a large variety of experiments within academic and commercial labs.Both new and old plasmids have to undergo sequencing-based analysis to determine whether or not they are functional, i.e. contain the correct insert in the correct backbone. While traditional Sanger sequencing based analysis was most often limited to the inserts, new high-throughput sequencing based methods and services can now provide the complete sequence of a plasmid. Currently available methods and services vary in throughput and cost.Here, we adapted the Oxford Nanopore Technologies-based R2C2 sequencing method to - rapidly and at low cost - sequence complete plasmids, either individually or in a pool. We also developed an analysis pipeline, Chopper, that produces full-length plasmid sequences. We tested our workflow with commonly used plasmids we ordered from Addgene and produced highly accurate sequences for each plasmid from both their individual and pooled sequencing runs.
Comparative Patterns of Variation on the X Chromosome and Autosomes: The Role of the Breeding Sex Ratio
Authors: Spurley William J. , Payseur Bret A. 
Published: January 2025

AbstractIn many populations, unequal numbers of females and males reproduce each generation. This imbalance in the breeding sex ratio (BSR) shapes patterns of genetic variation on the sex chromosomes and the autosomes in distinct ways. Despite recognition of this phenomenon, effects of the BSR on some aspects of variation remain unclear, especially for populations with non-equilibrium demographic histories. To address this gap in the field, we used coalescent simulations to examine relative patterns of variation at X-linked loci and autosomal loci in populations spanning the range of BSR with historical changes in population size. Shifts in BSR away from 1:1 reduce nucleotide diversity and the number of unique haplotypes and increase linkage disequilibrium and the frequency of the most common haplotype, with contrasting effects on X-linked loci and autosomal loci. Strong population bottlenecks transform relationships between the BSR, the site frequency spectrum, and linkage disequilibrium while relationships between the BSR, nucleotide diversity, and haplotype characteristics are broadly conserved. Our findings indicate that evolutionary interpretations of variation on the X chromosome should consider the combined effects of the BSR and demographic history. The genomic signatures we report could be used to reconstruct these fundamental population parameters from genomic data in natural populations.Significance StatementThe breeding sex ratio is a fundamental evolutionary parameter, but genomic analyses routinely assume it is 1:1. Our research characterizes the relationships between the breeding sex ratio and multiple facets of genomic variation and shows how these relationships change in the context of dynamic demographic histories. In doing so, we provide increasingly realistic expectations for patterns of X-linked and autosomal variation in population genomic datasets collected from natural populations.
Low level contamination confounds population genomic analysis
Authors: Ward Audrey K. , Scopel Eduardo F. C. , Shuman Brent , Momany Michelle , Bensasson Douda 
Published: January 2025

AbstractGenome sequence contamination has a variety of causes and can originate from within or between species. Previous research focused primarily on cross-species contamination or on prokaryotes. This paper visualizes B-allele frequency to test for intra-species contamination, and measures its effects on phylogenetic and admixture analysis in two fungal species. Using a standard base calling pipeline, we found that contaminated genomes superficially appeared to produce good quality genome data. Yet as little as 5-10% genome contamination was enough to change phylogenetic tree topologies and make contaminated strains appear as hybrids between lineages (genetically admixed). We recommend the use of B-allele frequency plots to screen genome resequencing data for intra-species contamination.
ConcurrentPIK3CAmutant drives cachexia through inflammatory signaling inEGFRmutant lung cancer
Authors: Yue Meiting , Qin Zhen , Tang Shijie , Cai Xinlei , Zhao Yikai , Chen Liang , Chen Luonan , Ji Hongbin 
Published: January 2025

AbstractPIK3CAmutation is frequently concurrent with known oncogenic drivers such asEGFRmutation in lung cancer, raising an interesting question about its real function. Cachexia is a systemic disease involving complex interaction between primary tumors and distant organs, significantly contributing to cancer-related mortality. Through integrative study of genetically engineered mouse models (GEMMs) and clinical data, we find concurrentPIK3CAmutant preferentially drives cachexia inEGFR-mutant lung cancer, promoting malignant progression instead of cancer initiation.PIK3CAmutant-mediated cachexia could be overcome by osimertinib (Osi) treatment in Osi-sensitive GEMM. In contrast, chemotherapy, routinely used in clinic for those relapsed from Osi therapy, fails to ameliorate cachexia in Osi-resistant GEMM despite notable tumor suppression.PIK3CAmutant-driven cachexia is mediated through NF-κB activation and could be dampened by combined aspirin treatment. This work uncovers the biological function ofPIK3CAmutant and mechanism behinds its clinical impacts, and proposes a potentially effective strategy for clinical management.
Single-cell decoding of human islet cell type-specific alterations in type 2 diabetes reveals converging genetic- and state-driven β-cell gene expression defects
Authors: Bandesh Khushdeep , Motakis Efthymios , Nargund Siddhi , Kursawe Romy , Selvam Vijay , Bhuiyan Redwan M , Eryilmaz Giray Naim , Krishnan Sai Nivedita , Spracklen Cassandra N. , Ucar Duygu , Stitzel Michael L. 
Published: January 2025

AbstractPancreatic islets maintain glucose homeostasis through coordinated action of their constituent endocrine and affiliate cell types and are central to type 2 diabetes (T2D) genetics and pathophysiology. Our understanding of robust human islet cell type-specific alterations in T2D remains limited. Here, we report comprehensive single cell transcriptome profiling of 245,878 human islet cells from a 48-donor cohort spanning non-diabetic (ND), pre-diabetic (PD), and T2D states, identifying 14 distinct cell types detected in every donor from each glycemic state. Cohort analysis reveals ∼25-30% loss of functional beta cell mass in T2D vs. ND or PD donors resulting from (1) reduced total beta cell numbers/proportions and (2) reciprocal loss of ‘high function’ and gain of senescent β-cell subpopulations. We identify in T2D β-cells 511 differentially expressed genes (DEGs), including new (66.5%) and validated genes (e.g.,FXYD2, SLC2A2, SYT1), and significant neuronal transmission and vitamin A metabolism pathway alterations. Importantly, we demonstrate newly identified DEG roles in human β-cell viability and/or insulin secretion and link 47 DEGs to diabetes-relevant phenotypes in knockout mice, implicating them as potential causal islet dysfunction genes. Additionally, we nominate as candidate T2D causal genes and therapeutic targets 27 DEGs for which T2D genetic risk variants (GWAS SNPs) and pathophysiology (T2D vs. ND) exert concordant expression effects. We provide this freely accessible atlas for data exploration, analysis, and hypothesis testing. Together, this study provides new genomic resources for and insights into T2D pathophysiology and human islet dysfunction.
Recruiting ESCRT to single-chain heterotrimer peptide-MHCI releases antigen-presenting vesicles that stimulate T cells selectively
Authors: Olson Blade A. , Huey-Tubman Kathryn E. , Mao Zhiyuan , Hoffmann Magnus A. G. , Murray Richard M. , Mayo Stephen L. 
Published: January 2025

AbstractImmune cells naturally secrete extracellular antigen-presenting vesicles (APVs) displaying peptide:MHC complexes to facilitate the initiation, expansion, maintenance, or silencing of immune responses. Previous work has sought to manufacture and purify these vesicles for cell-free immunotherapies. In this study, APV assembly and release is achieved in non-immune cells by transfecting HEK293T or Expi293F cells with a single-chain heterotrimer (SCT) peptide/major histocompatibility complex I (pMHCI) construct containing an ESCRT- and ALIX-binding region (EABR) sequence appended to the cytoplasmic tail; this EABR sequence recruits ESCRT proteins to induce the budding of APVs displaying SCT pMHCI. A comparison of multiple pMHCI constructs shows that inducing the release of APVs by the addition of an EABR sequence generalizes across SCT pMHCI constructs. Purified pMHCI/EABR APVs selectively stimulate IFN-γ release from T cells presenting their cognate T cell receptor, demonstrating the potential use of these vesicles as a form of cell-free immunotherapy.Significance StatementImmune cells are known to naturally release pMHC-displaying extracellular vesicles (EVs), called antigen-presenting vesicles (APVs), which can orchestrate immune responses either directly or with the aid of antigen-presenting cells (APCs). For decades, researchers have pursued ways to replicate these APVs for immunotherapy by using chemically modified nanoparticles or by engineering the increased expression of APVs from immune cells which are typically low yield. Here we presents a broadly applicable platform for generating high concentrations of pMHCI-displaying APVs that can selectively modulate T cells, demonstrating a significant advance in the engineering of APVs for cell-free immunotherapy. The APVs presented here, and related APVs, could be translated into clinical therapies for modulating cancer progression or regulating autoimmunity in addition to their use as a tool to help characterize how endogenous extracellular vesicles influence the immune system.