bluuebunny/crossref_metadata_2025_split huggingface dataset:
Workplace Violence in the Pediatric Emergency Department
Authors: Huang Craig James , Boulos Andrew Kamal , Field Steven , Wang Vincent J. , Yen Kenneth 
Published: April 2024

Objectives
Previous work shows that health care workers, and particularly emergency department (ED) staff, are at an above average risk of workplace violence (WPV), defined as verbal threats or physical violence in the workplace. Previous data suggest that staff of a single pediatric ED frequently feel unsafe. The objective of this study was to conduct the first national survey study to assess the prevalence and incidence of WPV in the pediatric ED.

Methods
In this cross-sectional survey study, a representative sample of US pediatric emergency medicine physicians were invited to participate in a national survey adapted from the previously validated Workplace Violence in the Health Sector questionnaire from the World Health Organization. The primary outcome measure was the proportion of physicians who have been exposed to WPV. Rates of exposure to violence, reporting habits, and physician perception of various violence prevention strategies were studied secondarily.

Results
Surveys were completed by 207 (45%) invited participants, representing 31 US children's hospitals. The prevalence of WPV exposure was 96%. Physical violence with a weapon was witnessed by 20% of participants. Injuries requiring medical attention or time off work were experienced by 10% of participants. Half of participants never reported violent events. Security guards were welcome by 99%, armed law enforcement officers by 70%, and metal detectors by 81% of physicians. Self-arming was opposed by 85% of respondents.

Conclusions
Exposure to WPV is frequent among pediatric emergency medicine physicians with a prevalence similar to that of general emergency departments. Workplace violence remains underreported. This national survey contributes to the objective evaluation of individual- and systems-level violence prevention interventions.
Gynecomastia Surgery Patient Education
Authors: Paidisetty Praneet S. , Wang Leonard K. , Shin Ashley , Urbina Jacob , Mitchell David , Quan Amy , Obinero Chioma G. , Chen Wendy 
Published: April 2024

Background
YouTube is a platform for many topics, including plastic surgery. Previous studies have shown poor educational value in YouTube videos of plastic surgery procedures. The purpose of this study was to evaluate the quality and accuracy of YouTube videos concerning gynecomastia surgery (GS).

Methods
The phrases “gynecomastia surgery” (GS) and “man boobs surgery” (MB) were queried on YouTube. The first 50 videos for each search term were examined. The videos were rated using our novel Gynecomastia Surgery Specific Score to measure gynecomastia-specific information, the Patient Education Materials Assessment Tool (PEMAT) to measure understandability and actionability, and the Global Quality Scale to measure general quality.

Results
The most common upload source was a board-certified plastic surgeon (35%), and content category was surgery techniques and consultations (51%). Average scores for the Global Quality Scale (x̄ = 2.25), Gynecomastia Surgery Specific Score (x̄ = 3.50), and PEMAT Actionability (x̄ = 44.8%) were low, whereas PEMAT Understandability (x̄ = 77.4%) was moderate to high. There was no difference in all scoring modalities between the GS and MB groups. Internationally uploaded MB videos tended to originate from Asian countries, whereas GS videos tended to originate from non-US Western countries. Patient uploaders had higher PEMAT Actionability scores than plastic surgeon uploaders.

Conclusions
The quality and amount of gynecomastia-specific information in GS videos on YouTube are low and contain few practical, take-home points for patients. However, understandability is adequate. Plastic surgeons and professional societies should strive to create high-quality medical media on platforms such as YouTube.
A Comparative Study of Large Language Models, Human Experts, and Expert-Edited Large Language Models to Neuro-Ophthalmology Questions
Authors: Tailor Prashant D. , Dalvin Lauren A. , Starr Matthew R. , Tajfirouz Deena A. , Chodnicki Kevin D. , Brodsky Michael C. , Mansukhani Sasha A. , Moss Heather E. , Lai Kevin E. , Ko Melissa W. , Mackay Devin D. , Di Nome Marie A. , Dumitrascu Oana M. , Pless Misha L. , Eggenberger Eric R. , Chen John J. 
Published: April 2024

Background:
While large language models (LLMs) are increasingly used in medicine, their effectiveness compared with human experts remains unclear. This study evaluates the quality and empathy of Expert + AI, human experts, and LLM responses in neuro-ophthalmology.

Methods:
This randomized, masked, multicenter cross-sectional study was conducted from June to July 2023. We randomly assigned 21 neuro-ophthalmology questions to 13 experts. Each expert provided an answer and then edited a ChatGPT-4–generated response, timing both tasks. In addition, 5 LLMs (ChatGPT-3.5, ChatGPT-4, Claude 2, Bing, Bard) generated responses. Anonymized and randomized responses from Expert + AI, human experts, and LLMs were evaluated by the remaining 12 experts. The main outcome was the mean score for quality and empathy, rated on a 1–5 scale.

Results:
Significant differences existed between response types for both quality and empathy (P < 0.0001, P < 0.0001). For quality, Expert + AI (4.16 ± 0.81) performed the best, followed by GPT-4 (4.04 ± 0.92), GPT-3.5 (3.99 ± 0.87), Claude (3.6 ± 1.09), Expert (3.56 ± 1.01), Bard (3.5 ± 1.15), and Bing (3.04 ± 1.12). For empathy, Expert + AI (3.63 ± 0.87) had the highest score, followed by GPT-4 (3.6 ± 0.88), Bard (3.54 ± 0.89), GPT-3.5 (3.5 ± 0.83), Bing (3.27 ± 1.03), Expert (3.26 ± 1.08), and Claude (3.11 ± 0.78). For quality (P < 0.0001) and empathy (P = 0.002), Expert + AI performed better than Expert. Time taken for expert-created and expert-edited LLM responses was similar (P = 0.75).

Conclusions:
Expert-edited LLM responses had the highest expert-determined ratings of quality and empathy warranting further exploration of their potential benefits in clinical settings.
3D Imaging Reveals Changes in the Neurovascular Architecture of the Murine Calvarium with Aging
Authors: Horenberg Allison L. , Ren Yunke , Rindone Alexandra N. , Pathak Arvind P. , Grayson Warren L. 
Published: April 2024

AbstractCalvarial nerves, along with vasculature, influence skull formation during development and following injury, but it remains unclear how calvarial nerves are spatially distributed during postnatal growth and aging. Studying the spatial distribution of nerves in the skull remains challenging due to a lack of methods to image and quantify 3D structures in intact bone. To visualize calvarial 3D neurovascular architecture, we imaged nerves and endothelial cells with lightsheet microscopy. We employed machine-learning-based segmentation to facilitate high-resolution characterization from post-natal day 0 (P0) to Week 80 (80wk). We found that TUBB3+ nerve density decreased with aging with the frontal bone demonstrating earlier onset age-related nerve loss than the parietal bone. In addition, nerves in the periosteum and dura mater exhibited similar yet distinct temporal patterns of nerve growth and loss. While no difference was observed in TUBB3+ nerves during skeletal maturation (P0 ⟶ 12wk), we did observe an increase in the volume of unmyelinated nerves in the dura mater. Regarding calvarial vasculature, larger CD31hiEmcn-vessel density increased with aging, while CD31hiEmcnhivessel density was reduced. For all nerve markers studied, calvarial nerves maintained a preferential spatial association with CD31hiEmcnhivessels that decreased with aging. Additionally, we used a model of Apert syndrome that demonstrates early coronal suture fusion to explore the impact of suture-related disease on neurovascular architecture. We identified a mild dysregulation of dural nerves and minor shifts in vessel populations. Collectively, this 3D, spatiotemporal characterization of calvarial nerves throughout the lifespan and provides new insights into age-induced neurovascular architecture.
Combining lineage correlations and a small molecule inhibitor to detect circadian control of the cell cycle
Authors: Nikhat Anjoom , Chakrabarti Shaon 
Published: April 2024

AbstractChronotherapy has emerged as an exciting possibility for improving treatment regimens in cancer. A strong influence of the circadian clock on the cell cycle is a crucial requirement for successful chronotherapy. However, though a number of molecular interactions have been discovered between these two oscillators, it remains unclear whether these interactions are sufficient to generate emergent control of cellular proliferation. In this work, we computationally explore a strategy to detect clock control over the cell cycle, by computing lineage correlations in cell cycle times in the presence and absence of the clock inhibitor KL001. Using phenomenological models, we and others have previously suggested that the ‘cousin-mother inequality’ – a phenomenon where cousin cells show stronger cell cycle time correlations than mother-daughter pairs, could be leveraged to probe circadian effects on cellular proliferation. Using stochastic simulations calibrated to match HCT116 colon cancer proliferation datasets, we demonstrate that the established gene-networks giving rise to the cell cycle and circadian oscillations are sufficient to generate the cousin-mother inequality. In the presence of KL001 which stabilizes CRY1, our models predict greater than 50% decrease in the cousin-mother inequality, but counter-intuitively, very little change in population growth rates. Our results predict a range of underlying cell cycle times where the cousin-mother inequality should be observed, and consequently suggest the exciting possibility of combining measurements of lineage correlations with KL001 as a probe of circadian clock – cell cycle interactions.
Graft incompatibility between pepper and tomato can be attributed to genetic incompatibility between diverged immune systems
Authors: Thomas Hannah Rae , Gevorgyan Alice , Hermanson Alexandra , Yanders Samantha , Erndwein Lindsay , Norman-Ariztía Matthew , Sparks Erin E. , Frank Margaret H 
Published: April 2024

SummaryGraft compatibility is the capacity of two plants to form cohesive vascular connections. Tomato and pepper are incompatible graft partners; however, the underlying cause of graft rejection between these two species remains unknown.We diagnosed graft incompatibility between tomato and diverse pepper varieties based on weakened biophysical stability, decreased growth, and persistent cell death using trypan blue and TUNEL assays. Transcriptomic analysis of cell death in the junction was performed using RNA-sequencing, and molecular signatures for incompatible graft response were characterized based on meta-transcriptomic comparisons with other biotic processes.We show that tomato is broadly incompatible with diverse pepper cultivars. These incompatible graft partners activate prolonged transcriptional changes that are highly enriched for defense processes. Amongst these processes was broad NLR upregulation and hypersensitive response. Using transcriptomic datasets for a variety of biotic stress treatments, we identified a significant overlap in the genetic profile of incompatible grafting and plant parasitism. In addition, we found over 1000 genes that are uniquely upregulated in incompatible grafts.Based on NLR overactivity, DNA damage, and prolonged cell death we have determined that tomato and pepper graft incompatibility is likely caused by a form of genetic incompatibility, which triggers a hyperimmune-response.
Directed Evolution of Acoustic Reporter Genes Using High-Throughput Acoustic Screening
Authors: Hurt Robert C. , Jin Zhiyang , Soufi Mohamed , Wong Katie K. , Sawyer Daniel P. , Shen Hao K. , Dutka Przemysław , Deshpande Ramya , Zhang Ruby , Mittelstein David R. , Shapiro Mikhail G. 
Published: April 2024

ABSTRACTA major challenge in the fields of biological imaging and synthetic biology is noninvasively visualizing the functions of natural and engineered cells inside opaque samples such as living animals. One promising technology that addresses this limitation is ultrasound (US), with its penetration depth of several cm and spatial resolution on the order of 100 µm.1Within the past decade, reporter genes for US have been introduced2,3and engineered4,5to link cellular functions to US signals via heterologous expression in commensal bacteria and mammalian cells. These acoustic reporter genes (ARGs) represent a novel class of genetically encoded US contrast agent, and are based on air-filled protein nanostructures called gas vesicles (GVs).6Just as the discovery of fluorescent proteins was followed by the improvement and diversification of their optical properties through directed evolution, here we describe the evolution of GVs as acoustic reporters. To accomplish this task, we establish high-throughput, semi-automated acoustic screening of ARGs in bacterial cultures and use it to screen mutant libraries for variants with increased nonlinear US scattering. Starting with scanning site saturation libraries for two homologs of the primary GV structural protein, GvpA/B, two rounds of evolution resulted in GV variants with 5- and 14-fold stronger acoustic signals than the parent proteins. We anticipate that this and similar approaches will help high-throughput protein engineering play as large a role in the development of acoustic biomolecules as it has for their fluorescent counterparts.
A major effect locus involved in migration timing is shared by pink and sockeye salmon
Authors: Barry Patrick D. , Tallmon David A. , Howe Natasha S. , Baetscher Diana S. , D’Amelio Katie L. , Vulstek Scott C. , Russell Josh R. , Gharrett Anthony J. , Larson Wesley A. 
Published: April 2024

ABSTRACTMigration is an important component of the life cycles of many organisms and differences in migration timing can greatly influence fitness. Variation in migration timing (hereafter referred to as run timing) is found in many salmon species and contributes to the portfolio of life history diversity that is vital for maintaining healthy populations. Pink salmon (Oncorhynchus gorbuscha) are composed of temporally isolated lineages that spawn in even and odd years. Here, we focus on early and late runs of pink salmon in Auke Creek, Alaska, which spawn a few weeks apart in the same ≈50m stretch of stream. We conducted low coverage, whole genome sequencing on pink salmon from the early and late runs of both even and odd lineages to investigate the genetic basis of run timing in this system. Within the even lineage we detected a major effect locus displaying high genetic divergence between early and late run individuals on chromosome 10 of the pink salmon genome. This same locus showed a lower - but still elevated - amount of genetic divergence in the odd lineage. The region of high divergence includes the Leucine Rich Repeat Containing 9 gene (lrrc9), and genetic divergence was substantially reduced outside of this gene. Thelrrc9gene also shows high divergence between two ecotypes of sockeye salmon (Oncorhynchus nerka) that differ in both run timing and spawning habitat. Comparison of thelrrc9gene region in pink and sockeye salmon shows that variation within this gene is associated with run timing in both species. However, the polymorphic sites (i.e, SNPs) and run timing alleles are unique to each species and arose from independent mutations following divergence from a common ancestor. These results demonstrate that adaptation in pink salmon can occur at small temporal scales and that complex traits can be controlled by similar genetic mechanisms in multiple species.
Novel 4,400-year-old ancestral component in a tribe speaking a Dravidian language
Authors: Sequeira Jaison Jeevan , Krishna Swathy , van Driem George , Mustak Mohammed Shafiul , Das Ranajit 
Published: April 2024

AbstractResearch has shown that the present-day population on the Indian subcontinent derives its ancestry from at least three components identified with pre-Indo-Iranian agriculturalists once inhabiting the Iranian plateau, pastoralists originating from the Pontic-Caspian steppe and ancient hunter-gatherer related to the Andamanese Islanders. The present-day Indian gene pool represents a gradient of mixtures from these three sources. However, with more sequences of ancient and modern genomes and fine structure analyses, we can expect a more complex picture of ancestry to emerge. In this study, we focus on Dravidian linguistic groups to propose a fourth putative source which may have branched out from the basal Middle Eastern component that gave rise to the Iranian plateau farmer related ancestry. The Elamo-Dravidian theory and the linguistic phylogeny of the Dravidian family tree provide chronological fits for the genetic findings presented here. Our findings show a correlation between the linguistic and genetic lineages in language communities speaking Dravidian languages when they are modelled together. We suggest that this source, which we shall call ‘Proto-Dravidian’ ancestry, emerged around the dawn of the Indus Valley civilisation. This ancestry is distinct from all other sources described so far, and its plausible origin not later than 4,400 years ago on the region between the Iranian plateau and the Indus valley supports a Dravidian heartland before the arrival of Indo-European languages on the Indian subcontinent. Admixture analysis shows that this Proto-Dravidian ancestry is still carried by most modern inhabitants of the Indian subcontinent other than the tribal populations. This momentous finding underscores the importance of population-specific fine structure studies. We also recommend informed sampling strategies for biobanks and to avoid oversimplification of ancestral reconstruction. Achieving this requires interdisciplinary collaboration.
Observational activation of anterior cingulate cortical neurons coordinates hippocampal replay in social learning
Authors: Mou Xiang , Ji Daoyun 
Published: April 2024

AbstractSocial learning enables a subject to make decisions by observing the actions of another. How neural circuits acquire relevant information during observation to guide subsequent behavior is unknown. Utilizing an observational spatial working memory task, we show that neurons in the rat anterior cingulate cortex (ACC) associated with spatial trajectories during self-running in a maze are activated when observing another rat running the same maze. The observation-induced ACC activities are reduced in error trials and are correlated with activities of hippocampal place cells representing the same trajectories. The ACC activities during observation also predict subsequent hippocampal place cell activities during sharp-wave ripples and spatial contents of hippocampal replay prior to self-running. The results support that ACC neurons involved in decisions during self-running are reactivated during observation and coordinate hippocampal replay to guide subsequent spatial navigation.
Gli2 Facilitates Tumor Immune Evasion and Immunotherapeutic Resistance by Coordinating Wnt Ligand and Prostaglandin Signaling
Authors: DeVito Nicholas C. , Nguyen Y-Van , Sturdivant Michael , Plebanek Michael P. , Howell Kaylee , Yarla Nagendra , Jain Vaibhav , Aksu Michael , Beasley Georgia , Theivanthiran Balamayooran , Hanks Brent A. 
Published: April 2024

AbstractTherapeutic resistance to immune checkpoint blockade has been commonly linked to the process of mesenchymal transformation (MT) and remains a prevalent obstacle across many cancer types. An improved mechanistic understanding for MT-mediated immune evasion promises to lead to more effective combination therapeutic regimens. Herein, we identify the Hedgehog transcription factor, Gli2, as a key node of tumor-mediated immune evasion and immunotherapy resistance during MT. Mechanistic studies reveal that Gli2 generates an immunotolerant tumor microenvironment through the upregulation of Wnt ligand production and increased prostaglandin synthesis. This pathway drives the recruitment, viability, and function of granulocytic myeloid-derived suppressor cells (PMN-MDSCs) while also impairing type I conventional dendritic cell, CD8+T cell, and NK cell functionality. Pharmacologic EP2/EP4 prostaglandin receptor inhibition and Wnt ligand inhibition each reverses a subset of these effects, while preventing primary and adaptive resistance to anti-PD-1 immunotherapy, respectively. A transcriptional Gli2 signature correlates with resistance to anti-PD-1 immunotherapy in stage IV melanoma patients, providing a translational roadmap to direct combination immunotherapeutics in the clinic.SIGNIFICANCEGli2-induced EMT promotes immune evasion and immunotherapeutic resistance via coordinated prostaglandin and Wnt signaling.
Assessing a Role for Sarcospan in Immune Function
Authors: Valera Isela C. , Kahmini Aida Rahimi , Smith Kyle A. , Crawford Rhiannon Q. , Parvatiyar Michelle S. 
Published: April 2024

AbstractSarcospan (SSPN) is a tetraspanin-like member of the dystrophin-glycoprotein complex (DGC) with expression reported at the transcript level in B cells and several other immune cell populations. SSPN is best known for its expression in skeletal, cardiac, and vascular smooth muscle, however it is expressed in other cell types and its roles in non-muscle cells have not been well described. Analysis of functional interactions of SSPN with effectors of hematopoietic cell lineages uncovered strong associations with several proteins with known roles in hematopoiesis and immune response. In this study, we utilized flow cytometry to uncover SSPN+ immune cell populations expressing the SSPN protein. We performed immunophenotyping of global SSPN-deficient (SSPN-/-) C57BL/6J male and female mice to assess whether SSPN plays an essential role in generation of specific immune cells. By flow cytometry we found that B cells, CD11b+ and CD11c+ (monocytes, tissue macrophages, and a subset of dendritic cells) express the highest levels of SSPN at their cell membranes. To pinpoint potential roles for SSPN in B cell development, SSPN-/-bone marrow cells were isolated and differentiated using phorbol myristate acetate (PMA). To test B cell effector functions, antibody isotype analysis was performed to assess whether SSPN influences antibody class switching. Blood serum of WT and SSPN-/-mice were tested for presence of important developmental signals for B cell maturation, development and isotype switching. Our study is the first to document SSPN protein expression on distinct classes of immune cells including CD11b+, CD11c+ and B cells (CD19+). Immunophenotyping revealed several differences in immune cell populations in the murine spleens: 1) a significant increase in % T cells in SSPN-/-males, 2) slight reduction of % B cells in SSPN-/-females, 3) a significant increase % of dendritic cells in SSPN-/-females, and 4) no significant alterations in NK cells. Under unstimulated conditions, SSPN-/-female mice had a significantly lower IgG2b titers compared to WT. Overall, the observation of SSPN expression in distinct immune cells, potential role(s) in hematopoiesis and B cell effector function is intriguing and warrants further investigation.HighlightsThe sarcospan protein has an established role in stabilization of striated muscle membranes and is an essential member of the dystrophin-glycoprotein complex. This study investigates the reported presence ofSspnin B cells and examines potential roles in immune function including:Determining a connection with hematopoiesis and establishment of ‘niches’Impact on immune content in spleens of sarcospan-deficient miceIdentifying a role in B cell effector functions