bluuebunny/crossref_metadata_2025_split huggingface dataset:
Skin Necrosis After Methylene Blue Dye Use in Immediate Breast Reconstruction
Authors: Panopoulou Georgina , Fotiou Antonia 
Published: February 2025

Summary:
Skin-sparing mastectomy or nipple-sparing mastectomy is usually combined with sentinel lymph node biopsy and often followed by immediate breast reconstruction. Currently, methylene blue dye (MBD) is being used for the localization of the sentinel lymph node during mastectomy in patients with early breast cancer. However, MBD has been associated with skin complications. Two patients underwent a nipple-sparing mastectomy followed by immediate reconstruction with silicone implants. MBD was injected into the subareolar area to identify the sentinel lymph node. The 2 cases were complicated by MBD. The first case developed 2 gangrenous areas on the site of the MBD injection. The second one developed skin necrosis as well. The use of MBD is responsible for skin complications, such as skin necrosis. In detail, discussion before surgery must be done when organizing immediate breast reconstruction using silicone implants.
Reciprocal Causation Among Pain, Physical Health, and Mental Health 1 Year Post-Traumatic Brain Injury: A Cross-Lagged Panel Model From the TRACK-TBI Study
Authors: Wender Carly , Perrin Paul B. , Krch Denise 
Published: February 2025

Objective:
To estimate the relative causal influence of physical and mental health on pain in persons with traumatic brain injury (TBI) within the year following injury.

Setting:
Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) was a multicenter study that collected data from 18 level 1 trauma centers around the United States.

Participants:
TRACK-TBI recruited adults who experienced an acute TBI. For this secondary analysis, participants were included if they endorsed pain during at least 1 follow-up within 1 year post-TBI.

Design:
Secondary analysis using structural equation modeling of the longitudinal TRACK-TBI dataset of an inception cohort.

Interventions:
None.

Main Outcomes and Measures:
The primary outcomes are pain, physical health, and mental health. Pain was measured by averaging the T-scores of the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity and Pain Interference scales. Physical and mental health were measured with the raw component scores (physical component score and mental component score, respectively) on the Short Form Health Survey.

Results:
Eighty-nine percent of the TRACK-TBI cohort (n = 2022) reported pain throughout 1 year postinjury. This sample (n = 1796) was primarily white (77%) men (67%) in their early forties with mild (87%) closed head injuries (99%) related to motor or road vehicle accidents (57%). Based on the final trimmed model, there was a stronger dominance of pain on physical and mental health than physical and mental health on pain. Thus, pain is a bigger driver of physical and mental health than vice versa.

Conclusions:
Persistent pain is highly prevalent post-TBI and is a bigger driver of physical and mental health 1 year post-TBI than the other way round. Future research should aim to better understand the causes of pain post-TBI to inform what treatments are most effective at reducing pain intensity and interference post-TBI.
The impact of environmental changes on infectious diseases among children in North America
Authors: Bastug Kristen A. , Schwartz Elizabeth L. , Sam-Agudu Nadia A. 
Published: February 2025

Purpose of review
Climate change is no longer a distant threat but a present and accelerating force reshaping the epidemiology of infectious diseases in North America and elsewhere. Rising temperatures, shifting precipitation patterns, and extreme weather events are impacting the geographic distribution of pathogens and their vectors. Understanding these environmental influences on infectious diseases in children is essential for equipping healthcare providers to deliver competent care in the era of climate change.

Recent findings
The northward spread of vector-borne diseases, warming waters and soils, and disease outbreaks following extreme weather events highlight the complex and multifactorial ways through which the environment influences the spread of infectious diseases.

Summary
Continuing medical education and training on the evolving epidemiology of climate-sensitive diseases is critical for clinicians to address emerging health threats effectively. We advocate for more equitable funding and resource allocation to support innovative pediatric research on climate change and infectious diseases in the United States and other countries in North America.
Changes in Care in Spanish Pediatric Emergency Departments After the First Immunization With Nirsevimab
Authors: Vazquez-Lopez Paula , Rivas-Garcia Aristides , Luaces-Cubells Carles , Perez-Gonzalez Elena , Ales-Palmer María Luisa , Cahis-Vela Nuria , Lera-Carballo Esther , Solano-Navarro Carmen , Romero-Castillo Estefanía , Torres-Begara Eva Patricia , Sanchez-Alvarez Maria Jesus , Benito-Fernandez Javier , Sanz-Rueda Laura , Garcia-Herrero María Angeles , Henares-Rodriguez Alba , Yañez-Mesia Sandra , de Francisco-Profumo Antonio , Martinez-Mejias Abel , May-Llanas Maria Elena , Mesa-Garcia Sofia , Aranda-Mora Alejandro , Baquero-Gomez Concepcion , de la Rosa-Sanchez Daniel , de Ceano–Vivas Maria , de la Torre Espí Mercedes , Oliva-Rodriguez-Pastor Silvia , Guerra-Diez Jo﻿se Lorenzo , Pons-Morales Sara , Gomez-Carabaza Arantxa , Campos-Calleja Carmen , Torres-Torres Antonio Ramon 
Published: February 2025

Objectives:
The aim of the study is to assess the changes in the pediatric care of patients seen in the Pediatric Emergency Departments (PED) during the bronchiolitis season following the introduction of immunization with a monoclonal antibody against RSV (nirsevimab).

Methods:
An observational, retrospective, multicenter study was conducted, analyzing the Bronchiolitis Registry of the Spanish Society of Pediatric Emergency Medicine. This registry, containing data on bronchiolitis cases, was initiated in December 2022. A total of 30 hospitals participated, all of which are members of the Spanish Society of Pediatric Emergency Medicine. Data from a 26-day period in 2 bronchiolitis seasons (2022: preimmunization and 2023: postimmunization) were included. Variables regarding health care burden were recorded for both periods. Quantitative variables were described using mean and SD, and the Student t test was used for comparisons between the 2 periods.

Results:
Twenty-five hospitals from 11 autonomous communities were included with a mean of 47,811 PED visits/year (SD: 26,675). The number of bronchiolitis cases presenting to the PED and bronchiolitis-related admissions decreased by 41.6%(95% CI: 34.9%-48.2%) and 55.4% (95% CI: 46.6%-64.2%), respectively, while admissions for RSV bronchiolitis decreased by 60.3% (95% CI: 51.9%-68.7%). Admissions to pediatric intensive care units decreased by 81.3% (95% CI: 57.9%-100%). Furthermore, the occupancy rate in the pediatric intensive care units decreased by 30% (95% CI: 22.8%-37.3%), while a reduction of 22.4% (95% CI: 13.2%-31.5%) was observed in the occupancy rate of observation units. The number of bronchiolitis cases transferred to other hospitals decreased by 73.4% (95% CI: 29.0%-100%). Finally, there was a 60.9% (95% CI: 26.5%-95.3%) reduction in the need for high-flow oxygen therapy among bronchiolitis patients.

Conclusions:
After the introduction of nirsevimab, a large portion of indicators related to the burden of care associated with bronchiolitis during its epidemic season decreased significantly.
The Aberrantly Expressed Nuclear Factor (Erythroid-derived 2)-Like 2 Participates in aGVHD by Modulating the Activation and Differentiation of CD4+ T Lymphocytes
Authors: Chen Xu , Zhang Yue , Chen Yan , Qin Wei , Cheng Tingting , Wang Shiyu , Xu Yajing 
Published: February 2025

Background.
Current investigation indicates that nuclear factor (erythroid-derived 2)-like 2 (NRF2) possesses both proinflammatory and anti-inflammatory capabilities in T cells, yet its exact function in acute graft-versus-host disease (aGVHD) CD4+ T cells remains unexplored.

Methods.
This study aims to determine NRF2 levels within CD4+ T cells of patients with or without aGVHD and analyze the correlation between T-cell receptor activation and NRF2 expression. RNA sequencing was used to detect changes in the expression profile of CD4+ T cells after overexpression of NRF2, and functional enrichment analysis was performed on the sequencing results. Finally, after treating aGVHD CD4+ T cells with NRF2 inhibitor, the expression of related pathway molecules was detected.

Results.
Our findings demonstrated a significant upregulation of NRF2 expression in CD4+ T cells from patients in the aGVHD group compared with patients in the non-aGVHD group, and its expression level is correlated with the severity of aGVHD. Additionally, T-cell receptor activation in CD4+ T cells elevates NRF2 expression. Postactivation of NRF2-inhibited CD4+ T cells, the expression levels of T-cell activation markers were notably lower than those in non-NRF2-inhibited CD4+ T cells. Sequencing analysis identified 904 genes that changed after NRF2 overexpression. These genes were categorized into 288 gene subsets, encompassing pathways such as T-cell receptor signaling transduction, Janus kinase 1/signal transducer and activator of transcription 1 (JAK1-STAT1) signaling, T helper cell 17 (Th17) cell differentiation, etc. Ultimately, treating CD4+ T cells of aGVHD patients with an NRF2 inhibitor led to a significant downregulation of JAK1-STAT1 signaling and Th17 cells.

Conclusions.
Elevated NRF2 expression in CD4+ T cells of patients with aGVHD initiates and exacerbates aGVHD by potentiating T-cell activation, amplifying JAK1/STAT1 signaling, and instigating Th17/regulatory T-cell ratio imbalance.
Enhancing Accuracy of Operative Reports with Automated Artificial Intelligence Analysis of Surgical Video
Authors: Khanna Abhinav , Wolf Tamir , Frank Igor , Krueger Alexander , Shah Paras , Sharma Vidit , Gettman Matthew T , Boorjian Stephen A , Asselmann Dotan , Tollefson Matthew K 
Published: February 2025

Background:
The creation of operative reports is a tedious documentation task that increases administrative burden, which is a potential driver of burnout. Additionally, operative reports are inherently subjective and may contain inaccuracies and incomplete information. Recent advances in artificial intelligence (AI) technology have enabled computer-vision systems to accurately detect operative steps on surgical video. We aim to develop a platform for automated creation of video-based AI surgical operative reports in robotic-assisted radical prostatectomy (RARP).

Study Design:
An AI computer-vision algorithm was employed to automatically detect surgical steps. Each step detected on video was mapped to pre-specified text, which was then compiled into a narrative AI operative report. Accuracy of the AI operative reports was compared to operative reports written by surgeons, using expert review of raw surgical video footage as the ground-truth.

Results:
158 cases from a tertiary referral center were included. In surgeon operative reports, 84(53.2%) cases had at least one discrepancy between the operative report and surgical video. Of these, 43(27.2%) cases had a clinically significant discrepancy based on expert video review. In AI operative reports, 46(29.1%) cases had at least one discrepancy between the operative report and surgical video. Of these, 20(12.7%) cases had a clinically significant discrepancy. Overall accuracy was higher for AI operative reports as compared to surgeon operative reports (87.3% versus 72.8%,p=0.001).

Conclusion:
Operative reports created by AI achieved higher accuracy than those written by surgeons. To our knowledge, this is the first report of automated video-based AI surgical documentation. Future studies are warranted to explore the potential for this novel tool to reduce documentation burden, improve operative report accuracy, promote surgical transparency, and decrease subjectivity in surgical documentation.
The association between sleep trajectories throughout pregnancy and postpartum pain in individuals with overweight or obesity: a prospective cohort study
Authors: Hawkins Marquis S. , Chapa Danielle A. N. , Lim Grace , Goldschmidt Andrea B. , Meyer Michelle L. , Avorgbedor Forgive , Levine Michele D. 
Published: February 2025

AbstractBackgroundPain after childbirth affects maternal and infant outcomes. Although sleep influences pain in general adult populations, research on this during the perinatal period is limited. This study examines the association between sleep quality and duration changes from mid to late pregnancy and pain during postpartum hospitalization.MethodsThis secondary data analysis included 118 pregnant individuals (12-20 weeks gestation at enrollment) with a pre-pregnancy BMI ≥ 25 kg/m². The Pittsburgh Sleep Quality Index estimated sleep quality and duration at six prenatal visits. Group-based trajectory models identified distinct sleep patterns. Pain was assessed every 8 hours during the three-day postpartum hospitalization using a 0-10 numeric rating scale and was then calculated as the pain Area Under the Curve (AUC). Multivariable-adjusted linear regression analyzed the relationship between sleep trajectories and postpartum pain.ResultsTwo trajectories for sleep quality and two for sleep duration were identified. The "Consistently poor" group showed increasing PSQI scores from 9 to 11, while the "Late worsening" group’s scores increased from 4 to 6. The "Late decreasing" duration group consistently slept 6-7 hours, while the "Consistently short" group maintained 5-6 hours nightly. No significant associations were found between sleep quality (expβ = 0.77, 95% CI: 0.51 to 1.17, p = 0.22) or duration (expβ = 0.75, 95% CI: 0.46 to 1.21, p = 0.24) and postpartum pain.ConclusionsSleep quality and duration changes during pregnancy were not associated with postpartum pain in this cohort. Future research should explore sleep’s impact on pain later in the postpartum period when chronic pain may develop.
RNAcare: Integrating Clinical Data with Transcriptomic Evidence using Rheumatoid Arthritis as a Case Study
Authors: Tang Mingcan , Haese-Hill William , Morton Fraser , Goodyear Carl , Porter Duncan , Siebert Stefan , Otto Thomas D. 
Published: February 2025

ABSTRACTBackgroundGene expression analysis is a crucial tool for uncovering the biological mechanisms that underlie differences between patient subgroups, offering insights that can inform clinical decisions. However, despite its potential, gene expression analysis remains challenging for clinicians due to the specialised skills required to access, integrate, and analyse large datasets. Existing tools primarily focus on RNA-Seq data analysis, providing user-friendly interfaces but often falling short in several critical areas: they typically do not integrate clinical data, lack support for patient-specific analyses, and offer limited flexibility in exploring relationships between gene expression and clinical outcomes in disease cohorts. Users, including clinicians with a general knowledge of transcriptomics, however, who may have limited programming experience, are increasingly seeking tools that go beyond traditional analysis. To overcome these issues, computational tools must incorporate advanced techniques, such as machine learning, to better understand how gene expression correlates with patient symptoms of interest.ResultsOur RNAcare platform, addresses these limitations by offering an interactive and reproducible solution specifically designed for analysing bulk RNA-Seq data from patient samples in a clinical context. This enables researchers to directly integrate gene expression data with clinical features, perform exploratory data analysis, and identify patterns among patients with similar diseases. By enabling users to integrate transcriptomic and clinical data, and customise the target label, the platform facilitates the analysis of the relationships between gene expression and clinical symptoms, like pain and fatigue. This allows users to generate hypotheses and illustrative visualisations/reports to support their research.As proof of concept, we use RNAcare to link inflammation-related genes to pain and fatigue in rheumatoid arthritis (RA) and detect signatures in the drug response group, confirming previous findings and generating new hypotheses.ConclusionWe present a novel computational platform allowing the interpretation of clinical and transcriptomics data in real-time. The platform can be used for data generated by the user, such as the patient data presented here or using published datasets.The platform is available athttps://rna-care.mvls.gla.ac.uk/, with its source code athttps://github.com/sii-scRNA-Seq/RNAcare/.
Neural correlates of boundary extension during visual imagination
Authors: Vickery Timothy , Singh Banjit , Levy Alyssa , Sweetman Kallie , Cronin Zoe , Intraub Helene 
Published: February 2025

AbstractPeople typically remember seeing a greater expanse of a scene than was visible in a studied close-up (boundary extension, BE). Multivoxel pattern analysis was used to test the neural correlates of BE. Classifiers were trained using a whole-brain searchlight method to discriminate between close-up and wider-angle versions of 16 scenes during repeated perceptual exposures. Earlier, each subject studied either the close or wide version of each scene and then visually imagined it from memory. If a brain region reflects BE, then unlike classification during perception, visual images of close views should sometimes be misclassified as wide (capturing false memory beyond the view), whereas visual images of wide views should be correctly classified. BE-consistent patterns during imagery were found in high-level visual regions, including posterior superior parietal cortex. This pattern did not reflect a brain-wide bias toward better classification of wider-angle views: the pattern reversed (better classification of close views) in the early visual cortex, presenting a novel distinction between early and late visual representations in imagery. We propose that this method reflects active maintenance of boundary-extended scene representations in memory and that it holds promise as a general purpose tool for decoding false memory in the brain.
Genome-wide identification and characterization of QTLs for transcriptional noise in human midbrain cells
Authors: Hirose Naoki , Mizuno Shota , Niwa Yuki , Hara Tomonori , Yamamoto Hirona , Koyama Emiko , Ueda Junko , Tsuboi Takashi , Takata Atsushi 
Published: February 2025

SummaryNot only the abundance of gene expression but also its cell-to-cell variation, referred to as “transcriptional noise”, is known to have certain biological significance. However, the mechanistic basis of transcriptional noise, particularly how it is regulated by genetic variants, remains elusive. In this study, we analyzed single-cell RNA sequencing (scRNA- seq) data of human induced pluripotent stem cell (iPSC)-derived midbrain cells (795,661 cells in 17 conditions) from 155 individuals with their genotypes to perform genome-wide mapping of quantitative trait loci for transcriptional noise (tnQTLs). Our analyses controlling for confounding factors such as gene expression abundance identified a total of 101,024 significant tnQTL-gene pairs. A comparison with QTLs for expression levels (i.e. eQTLs) detected by an equivalent pipeline revealed that the majority (81%) of tnQTLs were also identified as eQTLs, while no significant eQTL effects were observed in the others, and a small portion (7%) of eQTLs were with significant tnQTL effects. The tnQTLs and eQTLs showed distinctive patterns of sharing across cellular conditions, where tnQTL effects were often more condition-specific than those of eQTLs. In particular, tnQTLs without significant eQTL effects (termed tn>eQTLs) were dramatically altered by rotenone-induced oxidative stress. The tn>eQTLs also exhibited unique patterns of enrichment in various functional genomic elements, such as being frequently observed in promoters of non-QTL target genes. In the analysis using summary statistics from genome-wide association studies (GWAS) for various human complex traits, we found nominally significant enrichment of heritability for schizophrenia in tn>eQTLs. Possible contributions of tn>eQTLs to schizophrenia risk were supported by the enrichment of association signals in their target genes. We also identified genes whose transcriptional noise was implicated to be causally associated with a trait by a Mendelian randomization analysis, includingHLAgenes andYWHAEassociated with multiple autoimmune/psychiatric disorders. To further explore the role of transcriptional noise dysregulation in disease, we analyzed scRNA-seq data from human schizophrenia and mouse model brains. Genes exhibiting differential transcriptional noise between cases and controls, i.e. differentially noisy genes (DNGs), were particularly abundant in the superficial and deep layer excitatory neurons, where association signals in schizophrenia GWAS were also enriched in their DNGs. Overall, our comprehensive mapping of tnQTLs provides a resource for a new class of regulatory genetic variants, deepens our understanding of the mechanistic basis of how genetic variants regulate transcriptional noise, and highlights the roles of tnQTLs and transcriptional noise dysregulation in human complex traits.
Multivalency controls the growth and dynamics of a biomolecular condensate
Authors: von Hofe Julian , Abacousnac Jatin , Chen Mechi , Sasazawa Moeka , Kristiansen Ida Javér , Westrey Soren , Grier David G. , Saurabh Saumya 
Published: February 2025

AbstractBiomolecular condensates are essential for cellular organization and function, yet understanding how chemical and physical factors govern their formation and dynamics has been limited by a lack of non-invasive measurement techniques. Conventional microscopy methods often rely on fluorescent labeling and sub-strate immobilization, which can perturb the intrinsic properties of condensates. To overcome these challenges, we apply label-free, contact-free holographic video microscopy to study the behavior of a condensate-forming proteinin vitro. This technique enables rapid, high-throughput, and precise measurements of individual condensate diameters and refractive indexes, providing unprecedented insight into size distributions and dense-phase macromolecular concentrations over time. Using this method, we investigate the kinetics of droplet growth, aging, and equilibrium dynamics in the model condensate-forming protein PopZ. By systematically varying the concentration and valence of cations, we uncover how multivalent ions influence condensate organization and dynamics, a hypothesis we further test using super-resolution microscopy. Our findings reveal that PopZ droplet growth deviates from classical models such as Smoluchowski coalescence and Ostwald ripening. Instead, we show that condensate growth is consistent with gelation at the critical overlap concentration. Holographic microscopy offers significant advantages over traditional techniques, such as differential interference contrast (DIC) microscopy, delivering reproducible measurements and capturing condensate dynamics with unparalleled precision. This work highlights the power of holographic microscopy to probe the material properties and mechanistic underpinnings of biomolecular condensates, paving the way for deeper insights into their roles in synthetic systems.