bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stroke-Related Factors Influencing Thrombolysis Eligibility and Outcomes
Authors: Giorelli Maurizio , Aniello Maria Stella , Liuzzi Daniele , De Liso Alfredo , Accavone Donatella , Negri Francesco 
Published: February 2025

Objective:
Intravenous thrombolysis (IVT) improves outcomes of acute ischemic stroke (AIS) when timely administered. The aim of this study was to collect and analyze data of stroke-related factors which may influence the performance of stroke-related rescue chains, the use of IVT, and patients’ outcomes.

Methods:
This study enrolled patients with AIS admitted to our Stroke Unit (SU) between January 1, 2023, and December 31, 2023. We investigated whether age, occurrence of baseline disabling deficits, stroke severity, or stroke location influenced the median Onset-to-Door Time (ODT), the chance of receiving IVT, or the outcomes of AIS in our facility.

Results:
A total of 208 patients were enrolled. Patients who received IVT had higher baseline National Institute of Health Stroke Scale (NIHSS) scores (12.26±1.2) than those who did not (6.77±0.51) (P<0.0001). Patients with IVT further showed a greater strength deficit, less ataxia, and lower median ODT (108±20 min) than patients with NO IVT (720±67) (P<0.0001). Weakness of the lower limbs and higher total NIHSS predicted ODT≤ 3.5 hours and the use of IVT. Ataxia and Posterior Circulation Stroke slowed the rescue chain and were negatively correlated with the use of IVT.

Conclusions:
Stroke-related factors may slow the rescue chain and affect the application of IVT for AIS. New evaluation strategies are warranted to overcome the detrimental effects of these factors and to allow clinicians to effectively manage strokes of any severity and location.
Prophylactic antibiotic use in trauma patients with non-operative facial fractures: A prospective AAST multicenter trial
Authors: Mian Rabiya K. , Grossman Verner Heather M. , Villalta Cynthia I. , Farsakh Dana , Amos Joseph D. , Minoza Karen G. , Kozar Rosemary , Doben Andrew R. , Keric Natasha , Moore Ernest E. , Alvarez Claudia , Murry Jason , Cardenas Tatiana C.P. , Lewis Richard H. , Zebley James A. , Blades Caitlin M. , Tominaga Gail , Charles Michael , Cripps Michael W. , Dultz Linda A. , Bailey Justin , Egodage Tanya , Ra Jin H. ,   the AAST Facial Fracture Study Group
Published: February 2025

BACKGROUND
Craniofacial trauma affects approximately 3 million individuals in the United States annually. Historically, low overall data quality and inadequate sample size have limited the development of clinical practice guidelines for prophylactic antibiotic use in facial fractures. We sought to examine the current use patterns and effects of prophylactic antibiotics in non-operative facial fractures.

METHODS
A prospective analysis of adult patients with nonoperative facial fractures was conducted across 19 centers from January 2022 to December 2023. Kruskal-Wallis H, Mann-Whitney U, Pearson’s χ2, Fisher's exact tests, and logistic regression models were used to evaluate the association between antibiotic duration (no antibiotics, ≤24 hours, and >24 hours) and facial fracture-associated infectious complications.

RESULTS
Among 1,835 patients, 1,168 (63.7%) received no antibiotics and 667 (36.4%) received antibiotics (≤24 hours, n = 264 (14.4%); >24 hours, n = 403 (22.0%). Nineteen (1.0%) patients developed infectious complications (0.7% in the no antibiotic group vs. 1.7% with antibiotics). Most patients (99.0%) did not develop an infection despite the majority (63.7%) receiving no antibiotics. Injuries were predominately closed fractures (86.3%), without mucosal disruption (83.9%) or foreign bodies (97.7%). Antibiotic administration had a statistically significant association with the occurrence of infectious complications (p = 0.050). However, no significant association was seen between antibiotic duration and infectious complications following multivariable logistic regression, adjusting for confounders (≤24 hours: adjusted odds ratio, 1.24; 95% confidence interval, 0.30–5.14; p = 0.766; >24 hours: adjusted odds ratio, 1.32; 95% confidence interval, 0.37–4.69; p = 0.668).

CONCLUSION
Despite most patients not receiving antibiotics, infection rates remained low. This indicates prophylactic antibiotic use does not reduce the risk of fracture-associated infections for most injury patterns. While a randomized trial is optimal to validate these data, at this time, there is no evidence to support presumptive antibiotics for closed non-operative facial fractures.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level II.
Examining Geographic Disparity: Variation in Cancer Outcomes within Appalachia
Authors: Burus Todd , Hull Pamela C , Lang Kuhs Krystle A , Gao Tianyan , Brainson Christine F , Evers B Mark 
Published: February 2025

Background:
The Appalachian region of the United States (US) extends from the Mississippi delta to southern New York. Although disparities in Appalachian cancer outcomes have long been observed, recent rates and trends have not been assessed.

Study Design:
We calculated 5-year age-adjusted US cancer incidence and mortality rates for 2017–2021, stratified into Appalachian and non-Appalachian populations, as well as Appalachian subregions, using the US Cancer Statistics Incidence Analytics Database and National Center for Health Statistics mortality files. Annual rates for 2004–2021 were also calculated.

Results:
In 2017–2021, all-site cancer incidence (466.6; 95% confidence interval (CI), 465.5–467.6) and mortality rates (165.5; 95% CI, 164.9–166.1) among Appalachian residents were significantly higher (5.6% and 12.8%, respectively) than among non-Appalachian residents. Within Appalachia, the Central subregion—predominantly eastern Kentucky—had the highest rates of all-site cancer incidence (495.9) and mortality (201.9). In addition, the Central subregion had the highest rates of lung and colorectal cancer incidence, and the highest rates of lung, colorectal, and cervical cancer mortality. All-site cancer incidence and mortality rates among Appalachian individuals have decreased significantly since 2004 (-0.33%/year and -1.39%/year, respectively), with site-specific incidence rate decreases for late-stage lung (-2.19%/year), late-stage colorectal (-0.75%/year) and late-stage female breast (-0.35%/year) cancers in Appalachia.

Conclusion:
While cancer incidence and mortality rates are declining in Appalachia, they remain substantially higher and demonstrate slower progress than elsewhere in the US—particularly in the Central Appalachian subregion—indicating the need for targeted research to delineate and address the factors driving these cancer health disparities.
Multimodal AI-Based Risk Stratification for Distant Metastasis in Nasopharyngeal Carcinoma
Authors: Zhou Jiayu , Wibawa Made Satria , Wang Ruoyu , Deng Ying , Huang Haoyang , Luo Zhuoying , Xia Yue , Guo Xiang , Young Lawrence S. , Lo Kwok-Wai , Rajpoot Nasir , Lv Xing 
Published: February 2025

AbstractBackgroundThe TNM staging system is the primary tool for treatment decisions in nasopharyngeal carcinoma (NPC). However, therapeutic outcomes vary considerably between patients, and guidelines for the management of distant metastasis treatment remain limited. This study aimed to develop and validate a deep learning-based risk score to predict NPC survival.MethodsWe developed graph for nasopharyngeal carcinoma (GNPC) risk score, a multimodal deep learning based digital score incorporating signals from both Haematoxylin and Eosin (H&E)-stained tissue slides and clinical information. Digitised images of NPC tissue slides were represented as graphs to capture spatial context and tumour heterogeneity. The proposed GNPC score was developed and validated on 1,949 patients from two independent cohorts.ResultsThe GNPC score successfully stratified patients in both cohorts, achieving statistically significant results for distant metastasis (p < 0.001), overall survival (p < 0.01) and local recurrence (p < 0.05). Further downstream analyses of morphological characteristics, molecular features, and genomic profiles identified several factors associated with GNPC score-based risk groups.ConclusionThe proposed digital score demonstrates robust predictive performance for distant metastasis, overall survival, and local recurrence in NPC. These findings highlight its potential to assist with personalised treatment strategies and improve clinical management for NPC.
Early Imaging Identification of Osteoradionecrosis and Classification Using the Novel ClinRad System: Results from A Retrospective Observational Cohort
Authors:   MD Anderson Head and Neck Cancer Symptom Working Group; Collaborators, Rigert Jillian , Kaffey Zaphanlene , Belal Zayne , Tripuraneni Lavanya , Humbert-Vidan Laia , Sahli Ariana , Attia Serageldin , Hutcheson Katherine A. , Watson Erin , Hope Andrew , Dede Cem , Kiat-amnuay Sudarat , Walji Muhammad , Mohamed Abdallah S.R. , Sandulache Vlad C. , Fuller Clifton David , Lai Stephen Y. , Moreno Amy 
Published: February 2025

AbstractObjectiveOsteoradionecrosis of the jaw (ORNJ) is a chronic radiation-associated toxicity that lacks standardized classification criteria and treatment guidelines. Understanding early signs of tissue injury could help us better predict, prevent, and conservatively manage ORN. Our primary aims were to identify initial clinically-detected signs of ORN, determine the frequency of imaging-detected ORNJ, and validate the ability to classify cases using the novel system, ClinRad.Study DesignA retrospective electronic health record review of 91 patients treated for head and neck cancer at The University of Texas MD Anderson Cancer Center with suspected ORN was performed by an Oral Medicine specialist to identify initial signs of ORN. Patients who received reirradiation to the head and neck or did not have enough evidence of ORN were excluded. A descriptive analysis was performed.Results51 patients met the inclusion criteria. Half (53%) presented with imaging findings and exposed bone. Imaging findings in the absence of bone exposure were identified in 37%, of which disease progression was observed in 26%. All cases were classifiable using ClinRad.ConclusionSubclinical signs of bony changes consistent with ORN may be evident on imaging without exposed bone, supporting the use of imaging surveillance. ClinRad provided a mechanism to classify all cases at early onset.Data availability statementAnonymized data for the reported analyses is made publicly available on figshare at 10.6084/m9.figshare.28292186.Reporting guideline compliance statementIn accordance with the EQUATOR Network (Enhancing the QUAlity and Transparency Of health Research) guidance, we have utilized the RECORD checklist, a guideline for the “REporting of studies Conducted using Observational Routinely-collected health data” (Benchimool El at al., 2015) The RECORD checklist is provided as a Supplementary file and available via 10.6084/m9.figshare.28292219.Data was anonymized in accordance with the EQUATOR guideline “Preparing raw clinical data for publication: guidance for journal editors, authors, and peer reviewers” (Hrynaszkiewicz I et al., 2010).
Fatty Acid Transport Protein-2 (FATP2) Inhibition Enhances Glucose Tolerance through α-Cell-mediated GLP-1 Secretion
Authors: Khan Shenaz , Gaivin Robert J. , Liu Zhiyu , Li Vincent , Samuels Ivy , Son Jinsook , Osei-Owusu Patrick , Garvin Jeffrey L. , Accili Domenico , Schelling Jeffrey R. 
Published: February 2025

ABSTRACTType 2 diabetes affects more than 30 million people in the US, and a major complication is kidney disease. During the analysis of lipotoxicity in diabetic kidney disease, global fatty acid transport protein-2 (FATP2) gene deletion was noted to markedly reduce plasma glucose in db/db mice due to sustained insulin secretion. To identify the mechanism, we observed that islet FATP2 expression was restricted to α-cells, and α-cell FATP2 was functional. Direct evidence of FATP2KO-induced α-cell-mediated GLP-1 secretion included increased GLP-1-positive α-cell mass in FATP2KO db/db mice, small molecule FATP2 inhibitor enhancement of GLP-1 secretion in αTC1-6 cells and human islets, and exendin[9-39]-inhibitable insulin secretion in FATP2 inhibitor-treated human islets. FATP2-dependent enteroendocrine GLP-1 secretion was excluded by demonstration of similar glucose tolerance and plasma GLP-1 concentrations in db/db FATP2KO mice following oral versus intraperitoneal glucose loading, non-overlapping FATP2 and preproglucagon mRNA expression, and lack of FATP2/GLP-1 co-immunolocalization in intestine. We conclude that FATP2 deletion or inhibition exerts glucose-lowering effects through α-cell-mediated GLP-1 secretion and paracrine β-cell insulin release.Graphical abstract
Ancient human extinction risk: Implications from high-precision computation and fossil evidence
Authors: Zhou Sumei , Zhou Yiwen , Di Vincenzo Fabio , Manzi Giorgio , Hu Wangjie , Hao Ziqian , Pan Yi-Hsuan , Li Haipeng 
Published: February 2025

AbstractReconstructing ancient population size dynamics is essential for understanding human evolution. Using the fast infinitesimal time coalescent process (FitCoal), we identified a severe population bottleneck approximately 930,000 years ago, which pushed human ancestors to near extinction but left only subtle genomic traces in present-day humans. Detecting this signal requires precise computational methods. Compared withmushiand ten billion simulations performed usingmsprime, FitCoal provides the fastest and most accurate inference of expected branch lengths across site frequency spectrum categories. Independent fossil and paleoclimate records corroborate the timing and evolutionary impact of this bottleneck, highlighting the need to integrate genetic, paleontological, and environmental evidence. These findings refine our understanding of hominin evolution and the demographic events that shaped modern human ancestry.
A systematic review of the factors affecting sperm binding and release from the oviduct using in vitro experimental animal models
Authors: Sitali Muloongo C. , Chelenga Madalitso 
Published: February 2025

AbstractBackgroundAfter insemination, spermatozoa bind to epithelial cells of the isthmic part of the oviduct to form a functional sperm reservoir responsible for regulating sperm viability and capacitation prior to the ovulation signal that triggers its release. Understanding this information is essential for improving outcomes of in-vitro fertilization programs and semen-sorting process.ObjectiveThis review aims to provide a comprehensive systematic assessment of the literature on the non-steroid hormone factors involved in sperm binding and release from the sperm reservoir in animal species in in-vitro experiments.MethodsPubMed, Web of Science, and Google Scholar databases were searched, and eligible studies included articles published between 1stJanuary 1990 and 31stJuly 2024 reporting molecules involved in sperm binding and release from the oviduct, as well as the impact of released sperm on in-vitro fertilization.ResultsSperm and oviducts from bovine, porcine, canine, camelid, equine, hamster and ovine were used and different culture systems such as epithelial explants, monolayers, and ex-vivo oviducts were established. The behaviour of sperm in the oviductal epithelium was influenced by several factors such as carbohydrates and their derivatives, seminal plasma proteins, glycoproteins, tyrosine phosphorylation of sperm, endocannabinoids, sex-sorting and glycosaminoglycans. Further, the seminal plasma proteins increased the binding ability of epididymal sperm to the oviductal explants.ConclusionsFuture studies should focus on designing comparative research across various species. This may aid in identifying species-specific adaptations and conserved mechanisms in sperm-oviduct interactions, which may be helpful for conservation and breeding efforts.Summary SentenceHerein we review factors that affect sperm binding and release from the oviductal epithelial cells in-vitro that has a direct effect on the fertilizing potential of sperm
Genome-wide associations spanning 194 in-hospital drug dosage change phenotypes highlight diverse genetic backgrounds in concurrent drug therapy
Authors: Henriksen Alexander Pil , Leal Rodríguez Cristina , Currant Hannah , Louloudis Ioannis , Biel Jorge Hernansanz , Herrero-Zazo Maria , Birney Ewan , Hansen Thomas Folkmann , Mazzoni Gianluca , Haue Amalie Dahl , Bundgaard Henning , Erikstrup Christian , Dinh Khoa Manh , Quinn Liam , Bruun Mie Topholm , Hjalgrim Henrik , Sørensen Erik , Mikkelsen Christina , Schwinn Michael , Vestager Pedersen Ole Birger , Ullum Henrik , Ostrowski Sisse Rye ,   DBDS Genomic Consortium, Banasik Karina , Brunak Søren 
Published: February 2025

AbstractAs populations get older and medicine consumption rises, the rate of concurrent drug use and polypharmacy among patients is increasing. Polypharmacy is known to complicate therapy and increase the risk of drug-drug interactions, the individuality of which remain largely unexplored. Here, we perform a series of genome-wide association studies to identify variants associated with dosage changes during episodes of concurrent drug therapy. We extracted in-hospital drug prescription records from 847,537 patients in a population-wide Danish hospital cohort. Using imputed genotype data from the Copenhagen Hospital Biobank and the Danish Blood Donor Study we then performed a series of genome-wide association analyses across 194 drug pair phenotypes fulfilling selection criteria. We identified 51 genome-wide significant (p < 5e-08) loci, 49 so far unreported in any genome-wide association studies, associated with dosage changes across 42 different drug pair phenotypes. 49 of the identified loci were unique to the respective drug pairs. Through annotation of the identified loci, expression quantitative trait loci analyses, and gene-based tests we found links to 57 distinct genes, several of which have previously been associated with disease.This study identifies genes that may modulate response to drug therapy in the context of polypharmacy. Our findings reveal distinct patterns of genetic variation across different drug pairs, suggesting a diverse set of genes involved in drug efficacy and drug response. This study may give a better understanding of the individuality of such mechanisms and may aid the development personalized treatment approaches.
Echocardiography can accurately estimate pulmonary artery wedge pressure without left atrial volume information – diagnostic and prognostic performance
Authors: Lindow Thomas , Manouras Aristomenis , Strange Geoff , Lindqvist Per , Playford David , Bech-Hanssen Odd , Ugander Martin 
Published: February 2025

BackgroundA quantitative estimate of pulmonary artery wedge pressures (PAWP) can be obtained using echocardiography, but including left atrial (LA) volume (ePAWP-LA) in the estimation may be misleading. We aimed to derive and validate a new estimate without LA volume information (ePAWP-NOLA) and compare its performance to the ASE/EACVI algorithms for diastolic dysfunction.MethodsePAWP-NOLA was derived and validated in separate datasets of patients who had undergone right heart catheterization and echocardiography. Prognosis was assessed in the validation cohort and the National Echocardiography Database Australia (NEDA) using Cox regression adjusted for age, sex and left ventricular ejection fraction (LVEF).ResultsIn the derivation cohort (60±15 years, 40% males, 31% with LVEF<50%), ePAWP-NOLA was derived from mitral (E), and pulmonary vein systolic (S) and diastolic (D) Doppler velocities (n=134, mean difference±SD vs PAWP: 0.0±5.5 mmHg). In the validation cohort (n=116, 51±14 years, 69% males, 89% with LVEF<50%), PAWP agreed with both ePAWP-NOLA and ePAWP-LA (difference 1.3±6.1, 3.2±6.3 mmHg). PAWP>15 mmHg was accurately detected by both ePAWP-NOLA and ePAWP-LA (area under the curve (AUC): 0.84 [0.76–0.92], 0.80 [0.72–0.88]). AUC for the ASE/EACVI algorithm was lower ([0.69 [0.61–0.77]). ePAWP-NOLA and ePAWP-LA correlated with right ventricular afterload, associated with death or implantation of left ventricular assist device (hazard ratio: 1.09 [1.02–1.16], 1.07 [1.02–1.14]), and with cardiovascular death in NEDA (n=38,844, hazard ratio: 1.08 [1.07–1.09], 1.08 [1.07–1.09]).ConclusionsePAWP-NOLA has diagnostic and prognostic performance comparable to ePAWP-LA, and improved diagnostic performance compared to the ASE/EACVI diastolic dysfunction algorithm.
Nectriatides with no antifungal activity bind to ergosterol and potentiate the antifungal activity of amphotericin B againstCandida albicans
Authors: Kobayashi Keisuke , Miyake Ryosuke , Nagai Kenichiro , Sato Yukino , Seki Reiko , Sakai-Kato Kumiko , Nishimura Shinichi , Ohshiro Taichi , Tomoda Hiroshi 
Published: February 2025

AbstractFungal cyclotetrapeptide nectriatide and its synthetic linear derivatives (nectriatide-based compounds, NCTs), having no antifungal activity, potentiated antifungal activity of amphotericin B (AmB) againstCandida albicans. The mechanism of action was investigated using fluorescein-conjugated and biotin-tagged probes. Microscopy revealed fluorescent-probe localization at theC. albicanscell membrane. The biotinyl probe binding assay towards membrane lipids showed the highest affinity for ergosterol but no affinity for cholesterol. Ergosterol binding was confirmed by a liposome disruption assay. LC-MS quantification of AmB inC. albicansrevealed that NCTs increased AmB binding toC. albicans. These results indicate that NCTs bind to ergosterol on the fungal plasma membrane, subsequently localizing AmB, explaining the observed potentiation of AmB fungicidal activity.
Information Shielding Through Neural Deactivation: A Fundamental Mechanism of Human Information Processing
Authors: He Zhenhong , Du Yifan , Fu Ziqi , Zheng Youcun , Muhlert Nils , Sahakian Barbara , Elliott Rebecca 
Published: February 2025

AbstractInformation processing is a core issue in cognitive neuroscience. The brain can either accept or shield information. However, information shielding has traditionally been regarded as a byproduct of other cognitive processes that prepare brain areas for activation, with the accompanying brain deactivation seen as merely supportive. Here, we offer an alternative perspective, demonstrating that people can directly perform information shielding without engaging other cognitive processes. Using information shielding as a novel investigative lens, we provide direct evidence that deactivation serves as a primary mechanism in its own right. We found that information shielding was characterized by a deactivation-dominant neural dynamic, with initial executive control region activation giving way to increased sensory region deactivation, especially after a 3-second boundary. Neural decoding results further confirmed this deactivation trend. This deactivation pattern was consistent across both auditory and visual modalities. Furthermore, non-invasive brain stimulation demonstrated a causal relationship between the deactivation pattern and information shielding, and we found that this deactivation mechanism extended to general unnecessary information processing, regardless of whether the necessity was determined objectively or subjectively. This challenges the conventional emphasis on activation as the primary mode of information processing and opens new fundamental avenues for understanding inhibitory cognitive processes.