bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advancing systemic toxicity risk assessment: Evaluation of a NAM-based toolbox approach
Authors: Cable Sophie , Baltazar Maria Teresa , Bunglawala Fazila , Carmichael Paul L , Contreas Leonardo , Dent Matthew Philip , Houghton Jade , Kukic Predrag , Malcomber Sophie , Nicol Beate , Przybylak Katarzyna R , Punt Ans , Reynolds Georgia , Reynolds Joe , Scott Sharon , Tang Dawei , Middleton Alistair M 
Published: December 2024

Abstract
For many years, a method that allowed systemic toxicity safety assessments to be conducted without generating new animal test data, seemed out of reach. However, several different research groups and regulatory authorities are beginning to use a variety of in silico, in chemico, and in vitro techniques to inform safety decisions. To manage this transition to animal-free safety assessments responsibly, it is important to ensure that the level of protection offered by a safety assessment based on new approach methodologies (NAMs), is at least as high as that provided by a safety assessment based on traditional animal studies. To this end, we have developed an evaluation strategy to assess both the level of protection and the utility offered by a NAM-based systemic safety “toolbox.” The toolbox comprises physiologically based kinetic models to predict internal exposures, and bioactivity NAMs designed to give broad coverage across many different toxicity modes of action. The output of the toolbox is the calculation of a bioactivity:exposure ratio (analogous to a margin of internal exposure), which can be used to inform decision-making. In this work, we have expanded upon an initial pilot study of 10 chemicals with an additional 38 chemicals and 70 consumer exposure scenarios. We found that, for the majority of these (&gt;90%), the NAM-based workflow is protective of human health, enabling us to make animal-free safety decisions for systemic toxicity and preventing unnecessary animal use. We have also identified critical areas for improvement to further increase our confidence in the robustness of the approach.
Assessment of Relationship Between Dietary Factors, Socioeconomic Factors, Behavioral Factors, Physical Measurement, and Risk of Migraine
Authors: Zhang Yanhua , Liu Hongwei , Chen Xuan , Dong Defu 
Published: December 2024

Objective:
Although numerous studies have identified associations between socioeconomic, behavioral, dietary, and physical factors and migraine, the causal nature of these relationships has yet to be adequately established.

Materials and Methods:
We utilized 2-sample Mendelian randomization (MR) to elucidate the causal associations of 28 distinct traits for socioeconomic factors, behavioral factors, dietary factors, and physical measurement with migraine. In the univariable MR analysis, the inverse-variance weighted method served as the primary analytic approach. Robustness checks included the Cochran Q test, Egger intercept test, and leave-one-out analysis. A multivariable MR analysis framework was utilized to assess the direct causal impacts of these traits on migraine risk.

Results:
The univariable MR analysis analysis revealed that genetic predispositions to higher coffee intake (Odds Ratio (OR) = 0.547; 95% CI = 0.359-0.834; P = 0.005), greater oily fish intake (OR = 0.556; 95% CI = 0.394-0.785; P = 0.001), and higher educational attainment (OR = 0.916; 95% CI = 0.884-0.949; P < 0.001) were associated with reduced migraine risk. In contrast, predispositions to higher poultry intake (OR = 4.690; 95% CI = 1.377-15.977; P = 0.013) and longer mobile phone use (OR = 1.526; 95% CI = 1.080-2.157; P = 0.017) correlated with increased risk. These associations remained consistent in the multivariable MR analysis after adjusting for stroke and particulate matter air pollution.

Conclusions:
Our study robustly supports the significant causal roles of specific socioeconomic, behavioral, and dietary factors with physical measurement in the development of migraine. Notably, coffee intake, oily fish intake, and educational attainment appear protective, whereas poultry intake and extensive mobile phone use elevate risk. These insights pave the way for developing targeted preventive strategies for migraine.
Efficacy and Safety of RelabotulinumtoxinA Liquid Botulinum Toxin in the Treatment of Lateral Canthal Lines: Results From the Phase 3 READY-2 Study
Authors: Ablon Glynis , Bank David , Kontis Theda C. , Ibrahim Sherrif F. , Palm Melanie , Cox Sue Ellen , Rivers Jason K. , Grunebaum Lisa , Goldman Mitchel P. , Humphrey Shannon , Coquis-Knezek Sarah 
Published: December 2024

BACKGROUND
RelabotulinumtoxinA (RelaBoNT-A) is a complex-free, ready-to-use, liquid botulinum toxin A.

OBJECTIVE
Efficacy/safety of RelaBoNT-A treatment for lateral canthal lines (LCL).

METHODS
Randomized adults received RelaBoNT-A (30 U/side; n = 230) or placebo (n = 73) during a 6-month, double-blind, Ph3 study (Relabotulinumtoxin Aesthetic Development Study-2 [READY-2]). Primary end points (Month 1, maximum smile) comprised: composite ≥2-grade responder rate using concurrent LCL severity investigator live assessment (LCL-ILA) and subject live assessment (LCL-SLA); LCL-ILA 0 (none)/1 (mild) responder rate. Subject satisfaction and adverse events were also reported.

RESULTS
Month 1 composite ≥2-grade responder rates were 51.8% (RelaBoNT-A) and 1.4% (placebo; (p < .001). Month 1 none/mild LCL-ILA responder rates were 87.2% (RelaBoNT-A) and 11.9% (placebo; p < .001). Onset was reported Day 1 by 34%. At Month 6, LCL-ILA responder rates for RelaBoNT-A remained at 23.3% (none/mild) and 35.9% (≥1-grade improvement). Median return to baseline severity was 24.7 weeks; 64% (RelaBoNT-A group) had not returned to baseline at Month 6. RelaBoNT-A satisfaction was high through Month 6 (71%). Mild/moderate treatment-related adverse events occurred in 6.1% (RelaBoNT-A) and 5.5% (placebo).

CONCLUSION
RelaBoNT-A (60 U) treatment provided statistically significant improvement of moderate-to-severe LCL. One-third of subjects reported onset within 1 day and improvements were maintained through Month 6. Treatment satisfaction was high. RelaBoNT-A was well tolerated.
VITRECTOMY AND COMPLETE DRAINAGE OF SUPRACHOROIDAL FLUID WITHOUT PERIOPERATIVE STEROIDS FOR RHEGMATOGENOUS RETINAL DETACHMENT COMBINED WITH CHOROIDAL DETACHMENT: A RANDOMIZED CLINICAL TRIAL
Authors: Lin Wei , Chen Hao , Ren Minxue , Lin Xiaoyan , Tang Yongping , Wei Yong 
Published: December 2024

Purpose:
To investigate the surgical effect of complete drainage of suprachoroidal fluid (SCF) before vitrectomy to avoid perioperative steroids in rhegmatogenous retinal detachment combined with choroidal detachment (RRD-CD) eyes.

Methods:
It was a prospective, randomized controlled trial. 58 eyes were randomly divided into the no steroids (NS) group and local steroids (LS) group, 29 eyes each, respectively. Patients in the LS group received a single preoperative periocular injection of methylprednisolone, while SCF drainage was performed before vitrectomy in eyes of the NS group. Follow-up assessments were performed at 1 week, 1 month, 3 months, 6 months postoperatively.

Results:
The postoperative retinal reattachment rate was similar in the NS and LS groups (96.6% vs 93.1%, p = 1.00). Best-corrected visual acuity was improved in 72.4% and 75.9% in the NS and LS groups, respectively. Inflammation occurred in 5 eyes (17.2%) in the NS group and 6 eyes (20.7%) in the LS group (p = 0.74). Hypotony occurred in 11 (37.9%) and 14 (48.3%) eyes in the LS and NS groups (p = 0.43), respectively. Macular chorioretinal folds were found in 21 (72.4%) and 22 (75.9%) eyes in the LS and NS groups (p = 0.76), respectively. Hypotony and chorioretinal folds disappeared after 1 week postoperatively.

Conclusions:
Preoperative steroids may not be necessary for RRD-CD patients if the SCF is completely drained before vitrectomy. Postoperative retinal reattachment does not depend on the use of preoperative steroids; instead, surgeons should focus on improving surgical techniques in RRD-CD to improve the retinal reattachment rate.
Adipose stem cells prevent esophageal strictures after extensive endoscopic submucosal dissection – experimental research
Authors: Liu Jie , Jiang Yuting , Chen Xianzeng , Wei Xujin , Wang Xiangyu , Yang Zeliang , Yang Jie , Zhang Jianhui , Peng Yunyi , Lin Caihao , Chen Qilin , Yu Genmiao , Chen Yangyang , Wei Qingqing , Zheng Xiaoling , Zheng Shengwu 
Published: December 2024

Background and aims:
Endoscopic submucosal dissection (ESD) is a pivotal technique for excision of early-stage esophageal tumors. However, its primary complication, postoperative esophageal stricture, is a significant challenge owing to the absence of effective preventive measures. Adipose-derived stem cells (ADSCs) have emerged as a promising treatment modality to address this concern. In this study, we aimed to investigate, for the first time, the efficacy of allogenic ADSC injections in preventing esophageal stenosis after ESD.

Methods:
We administered allogeneic ADSC injections (same-species but different individual) to a porcine model of ESD as a way to observe the role of ADSC in preventing esophageal stricture. We also co-cultured rats’ ADSCs with rats’ esophageal fibroblasts and esophageal mucosal epithelial cells to investigate the mechanism.

Results:
ADSCs notably facilitated epithelial–mesenchymal transition of epithelial cells. Furthermore, ADSC-conditioned medium exhibited a substantial inhibitory effect on fibroblast proliferation and migration, which was mediated by the transforming growth factor-beta pathway.

Conclusions:
Our findings underscore the potential of ADSC injections as a promising therapeutic intervention to enhance recovery and prevent post-ESD complications.
Comparison of outcomes of Impella-assisted high-risk percutaneous coronary intervention in patients with and without prior coronary artery bypass graft
Authors: Murthi Mukunthan , Prasath Naveen , Memdani Anisha , Sivasubramanian Dhiran , Attanasio Steve , Dhar Gaurav , Jolly Neeraj , Vij Aviral 
Published: December 2024

Background
Limited data is available regarding in-hospital outcomes of patients undergoing high-risk percutaneous coronary intervention (HR-PCI) with Impella with and without a prior history of coronary artery bypass grafting (CABG).

Methods
We performed a retrospective study from the Nationwide Inpatient Sample from year 2016 to 2020. We identified patients who underwent Impella and percutaneous coronary intervention on the same day and excluded those with cardiogenic shock. Subsequently, we stratified them into those with and without prior CABG.

Results
During the study period, 18 925 patients underwent HR-PCI. Among these, 2043 (10.8%) patients had prior CABG. Patients without prior CABG had a higher percentage of acute coronary syndrome at presentation (62.7 vs 56.1%, P = 0.008). The proportion of females was significantly higher in those without prior CABG (32.4 vs 21.7%, P < 0.001). On multivariate analysis, there was no statistically significant difference in the in-hospital mortality (5.8% in CABG vs 8.5% in non-CABG, P = 0.52). Patients without prior CABG had higher rates of acute kidney injury, major bleeding, and blood transfusions. There were no significant differences in rates of cardiac arrest, ventricular arrhythmias, acute stroke, coronary dissections, and coronary perforations. Those without prior CABG had a longer duration of hospitalization (6.8 vs 9.3 days, P < 0.001) and higher hospital charges ($292 267 vs $322 206, P < 0.035).

Conclusion
Our study highlights that a history of previous CABG does not increase the risk of in-hospital mortality in patients undergoing Impella-assisted HR-PCI but is associated with reduced rates of complications.
Use of water in dialysis and its impact on the environment
Authors: Watnick Suzanne 
Published: December 2024

Purpose of review
The climate crisis poses significant challenges across various sectors, including healthcare, where resource consumption often exacerbates environmental issues. This review addresses concerns over current levels of water use for dialysis treatment, a critical procedure for patients with kidney failure. Despite its life-saving importance, the dialysis process consumes large quantities of water, contributing to water scarcity and increased carbon emissions associated with water treatment and distribution.

Recent findings
Through a comprehensive analysis of current practices, we identify inefficiencies and propose sustainable alternatives aimed at reducing water usage in dialysis.

Summary
Findings indicate that optimizing treatment protocols and considering innovative technologies can significantly mitigate the environmental impact while maintaining patient care standards. This review underscores the urgent need for the healthcare sector to adopt sustainable practices in response to the climate crisis.
Increasing Adherence to Societal Recommendations in Radiology Reporting
Authors: Mugu Vamshi K. , Carr Brendan M. , Olson Mike C. , Schupbach John C. , Eguia Francisco A. , Schmitz John J. , Khandelwal Ashish 
Published: December 2024

Abstract
Incidental findings in diagnostic imaging are common, but follow-up recommendations often lack consistency. The Society of Radiologists in Ultrasound (SRU) issued guidelines in 2021 for managing incidentally detected gallbladder polyps, aiming to balance follow-up with avoiding overtreatment. There is variable adherence to these guidelines in radiology reports, however, which makes it difficult for the clinician to pursue appropriate follow-up for the patient. The purpose of this project is to test the feasibility of a Large Language Model (LLM)–based tool to incorporate SRU guidelines into radiology reports. Additionally, we propose a framework for closely integrating societal follow-up recommendations into radiology reports, using this tool as an example.
Following institutional review board approval, we retrospectively reviewed gallbladder ultrasound examinations performed on adult ED patients in 2022. Data on patient demographics and radiology report content were collected. Using the 2021 SRU guidelines, we developed an interactive tool employing a retriever-augmented generator (RAG) and prompt engineering. A board-certified radiologist tested the accuracy, whereas a board-certified emergency medicine physician assessed the clarity and consistency of the recommendations.
The interactive tool, GB-PRL, outperformed leading closed-source and open-source LLMs, achieving 100% accuracy in risk categorization and follow-up recommendations on hypothetical user queries (P < 0.001). The tool also showed superior accuracy compared to radiology reports on retrospective data (P = 0.04). Although GB-PRL demonstrated greater clarity and consistency, the improvement from the radiology reports was not statistically significant (P = 0.22). Further work is needed for prospective testing of GB-PRL before integrating it into clinical practice.
Sox15is a novel retinal developmental gene that promotes cone photoreceptor differentiation through inhibition of alternative rod photoreceptor fates
Authors: Belair-Hickey Justin J. , Khalili Saeed , Coles Brenda L.K. , Ballios Brian G. , Liu Jeff C. , Bader Gary D. , van der Kooy Derek 
Published: December 2024

AbstractThe type of cell fate decisions a progenitor can make in the developing nervous system are dependent on a combination of cell intrinsic gene expression programs and cell extrinsic signaling molecules that influence expression programs. Moreover, both the progenitor’s spatial location in the tissue and time at which it exists during development can, to varying degrees, influence the competency of differentiation. Here, we use the developing mouse retina to understand how signaling factors in the retinal niche can influence a progenitor to become unipotentially-restricted to differentiate into cone photoreceptors, and how this competency changes over the course of retinal development. We show that the secreted inhibitory protein COCO causes progenitors to become cone-restricted, and that the competency for this restricted differentiation is maintained throughout retinal development. Using RNA-sequencing, we identify the transcription factorSox15as a potential novel marker of restricted progenitors in the developing retina, and that it acts in response to COCO’s effects. Knockdown experiments indicate that this novel retinal transcription factor promotes cone differentiation by inhibiting differentiation into alternative photoreceptor types.
Exposure to low doses ofBatrachochytrium dendrobatidisreveals variation in resistance in the Critically Endangered southern corroboree frog
Authors: Davidson Mikaeylah J. , Berger Lee , Aquilina Amy , Poveda Melissa Hernandez , Guinto Daniel , McFadden Michael , Gilbert Deon , Goodall Damian , Zenger Kyall R. , Skerratt Lee F. , Kosch Tiffany A. 
Published: December 2024

AbstractChytridiomycosis poses a significant extinction threat to many amphibians, including the critically endangered southern corroboree frog (Pseudophryne corroboree). Captive breeding programs have become essential to maintain populations while effective long-term conservation strategies are developed. Understanding the variation in susceptibility to chytridiomycosis within this species is essential in exploring the potential for selective breeding to enhance disease resistance. In this study, we conducted a large-scaleBatrachochytrium dendrobatidis(Bd) exposure experiment involving 972 juvenileP. corroboreeselected to ensure a broad genetic representation of the species. Three replicate experiments were conducted under uniform conditions, to assess individual susceptibility and compare results across replicate experiments. Significant variation was observed within and between experiments, with individual survival rates ranging from 44-74% across experiments, influenced notably by the zoo in which frogs were bred. Remarkably, 21-47% of exposed frogs remainedBd-negative, suggesting potential innate resistance. Infection intensity correlated positively with body condition, in one experiment, while age and size showed inconsistent effects on survival and infection rates across experiments, but younger and smaller frogs were more susceptible to infection and had lower survival. Among frogs that became infected, none cleared infection, with most progressing to terminal stages within an average of 69 days (ranging from 33 to 97 days). However, a few individuals maintained stable infection loads without displaying clinical signs of chytridiomycosis. This observed phenotypic variation inP. corroboreeresponses toBdhighlights the potential for selective breeding to improve survival outcomes in this species. The dataset generated from this study will be instrumental in guiding breeding strategies that strengthen conservation efforts for this critically endangered species.
Comparative effectiveness of Mirror Therapy and Music Therapy on psychomotor rehabilitation of ischemic stroke: A Systematic Review and Meta-Analysis
Authors: Estévez Aída , Pérez-Nieto Miguel Ángel , Herrero Laura 
Published: December 2024

AbstractThe blockage of cerebral vessels is one of the most common strokes. The consequences may vary according to the location of the lesion, but psychomotor abilities are usually affected. Together with specific neurorehabilitation programs and pharmacological treatments some novel non-pharmacological therapies are emerging in recent years. In this context, the impact of both Mirror and Music therapies has been separately analyzed in different studies. However, it is not clear at a what point their true effects are similar or not. The main aim of this study was to carry out a systematic review and meta-analysis to analyze the effects of MiT and MuT over matched controls on the psychomotor recovery of ischemic stroke patients as well as to explore whether the benefits of one of them may outpace the other by using network meta-analytical technics. A total of 28 observations (Mirror therapy, N = 15; Music therapy, N = 13), from 11 randomized trials’ studies we included in the network approach analysis which includes both direct and indirect comparisons. The systematic review revealed interesting similarities in the implementation of the therapies. The results of the meta- analysis showed small to moderate significant effect sizes of both Mirror and Music therapies over paired controls and non-significant differences between them.
Temperature-driven biogeography of marine giant viruses infecting the picoeukaryoteMicromonas
Authors: Demory David , Endo Hisashi , Baudoux Anne-Claire , Bigeard Estelle , Grimsley Nigel , Simon Nathalie , Ogata Hiroyuki , Weitz Joshua S. 
Published: December 2024

AbstractClimate shapes the biogeography of microbial and viral communities in the ocean. Among abiotic factors, temperature is one of the main drivers of microbial community distribution. However, we lack knowledge on how temperature shapes the life history traits, population dynamics, and the biogeography of marine viruses. This study integrates mathematical modeling with in situ observations to investigate the temperature-driven biogeography of marine viruses. We focused on prasinoviruses, a group of giant viruses that infect the picoeukaryoteMicromonas, a widespread phytoplankton with thermotypes adapted from poles to tropics. Analyzing the Tara Oceans and Polar Circle databases, we found that temperature is the primary determinant ofMicromonasvirus (MicV) distribution in the surface ocean. Phylogenetic reconstruction of MicV-s revealed that these viruses form several groups with cryophile or cryo-mesophile preferences. We applied a mechanistic model to describe temperature-driven population dynamics, allowing us to predict the global presence and absence of MicV-s. Lysis and infection emerged as reliable predictors of MicV distribution, indicating that temperature-driven cellular mechanisms significantly shape viral community structure and distribution. This study provides new insights into the role of temperature in regulating viral populations, emphasizing the importance of integrating modeling with observations to understand marine viral ecology.
Incomplete lineage sorting of segmental duplications defines the human chromosome 2 fusion site early during African great ape speciation
Authors: Jiang Xinrui , Zhang Lu , Yang Zikun , Yang Xiangyu , Ma Kaiyue , Yoo DongAhn , Lu Yong , Zhang Shilong , Chen Jieyi , Nie Yanhong , Bian Xinyan , Han Junmin , Fu Lianting , Zhang Juan , Zhang Guojie , Sun Qiang , Eichler Evan E. , Mao Yafei 
Published: December 2024

ABSTRACTAll great apes differ karyotypically from humans due to the fusion of chromosomes 2a and 2b, resulting in human chromosome 2. Yet, the structure, function, and evolutionary history of the genomic regions associated with this fusion remain poorly understood. Here, we analyze finished telomere-to-telomere chromosomes in great apes and macaques to show that the fusion was associated with multiple pericentric inversions, segmental duplications (SDs), and the rapid turnover of subterminal repetitive DNA. We characterized the fusion site at single-base-pair resolution and identified three distinct SDs that originated more than 5 million years ago. These three distinct SDs were differentially distributed among African great apes as a result of incomplete lineage sorting (ILS) and lineage-specific duplication. Most conspicuously, one of these SDs shares homology to a hypomethylated SD spacer sequence present in hundreds of copies in the subterminal heterochromatin of chimpanzees and bonobos. The fusion in human was accompanied by a systematic degradation of the three divergent α-satellite arrays representing the ancestral centromere creating five distinct structural haplotypes in humans. CRISPR/Cas9-mediated depletion of the fusion site in human cell lines significantly alters the expression of 108 genes, indicating a potential regulatory consequence to this human-specific karyotypic change.