bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of paediatric injury: an 11-year review of injury trends from the National Trauma Data Bank
Authors: Tomas Carissa , Kallies Kara , Levas Michael , deRoon-Cassini Terri , Cassidy Laura , Flynn-O’Brien Katherine 
Published: February 2025

Background/purposeUnintentional injuries are the leading cause of death among children and adolescents. The objective of this study was to describe temporal trends of paediatric traumatic injury over an 11-year period by mechanism of injury (MOI), age, sex, race and ethnicity, injury severity and hospital discharge disposition.MethodsThe National Trauma Data Bank was queried to identify paediatric patients (1–17 years old) injured from 2012 to 2022. Two-sided non-parametric Mann-Kendall trend tests were used to evaluate temporal trends of MOI for all patients and within demographic groups.Results/outcomesOver the 11-year period, 1 092 308 injury records met study inclusion criteria and had complete demographic and MOI data. Across all patients, there was a significant increase in bites and stings, cut/pierce injuries and firearm injuries, whereas there were decreasing trends in pedestrian and other blunt injuries over time. There was a significant increase in injury over time for Black, Hispanic or Latino, and Pacific Islander patients and those 5–9 years old. The MOIs with the highest injury severity and in-hospital mortality were firearm, pedestrian and motor vehicle transportation occupant injuries.ConclusionsThough a few MOIs increased for all paediatric patients in the study period, disparities persist for several specific populations. As such, injury prevention strategies should be tailored based on age, sex and race or ethnicity, and relevant education and resources should be provided to both children and their adult guardians. Future research should consider additional socioeconomic and community-based characteristics.
Targeted delivery of CCL3 reprograms macrophage antigen presentation and enhances the efficacy of immune checkpoint blockade therapy in hepatocellular carcinoma
Authors: Liu Muqi , Li Linzhe , Cao Lu , Li Wei , Gu Xingshi , Yang Min , Wu Di , Li Yanan , Deng Yao , Zhang Juan , Yang Cejun , Liang Qi , Liu Huaping , Rong Pengfei , Ma Xiaoqian , Wang Wei 
Published: February 2025

BackgroundHepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths worldwide, especially in advanced stages where limited treatment options result in poor prognosis. The immunosuppressive tumor immune microenvironment (TIME), characterized by low immune cell infiltration and exhaustion, limits immunotherapy efficacy. To address this, our study investigates the role of C-C motif chemokine ligand 3 (CCL3) in modulating the HCC TIME.MethodsWe analyzed CCL3 expression in human HCC samples from The Cancer Genome Atlas database, focusing on its correlation with inflammatory gene signatures and immune cell infiltration. High-dimensional single-cell RNA sequencing (scRNA-seq), flow cytometry, and multiplex immunofluorescence were used to investigate CCL3’s effects on macrophage function and T cell activation. The biological impact of CCL3 on macrophages was assessed using co-culture systems, confocal imaging, metabolite detection, and inhibition assays. Preclinical HCC models and ex vivo tumor fragment assays further explored how CCL3 modulates immune responses and enhances immune checkpoint blockade efficacy.ResultsOur study shows that CCL3 is suppressed in the tumor microenvironment and positively correlates with immune infiltration and inflammatory responses. Targeted liver delivery of rAAV-Ccl3 reprograms the immune microenvironment in HCC, promoting immune cell recruitment and tertiary lymphoid structure formation, thus suppressing tumor growth via immune engagement. Through scRNA-seq, flow cytometry, and multiplex immunofluorescence, we found that CCL3 enhances macrophage antigen uptake and activates cytotoxic T cells. In vivo and in vitro experiments confirmed that CCL3 facilitates T cell infiltration and upregulates MHC II expression on macrophages, enhancing antigen presentation. The CCL3-CCR5 pathway also boosts macrophage metabolism, increasing lysosomal activity and antigen uptake, thereby strengthening adaptive immune responses and increasing sensitivity to immune checkpoint blockade therapies in preclinical models.ConclusionsThis study highlights the pivotal role of CCL3 in reshaping the TIME and enhancing antitumor immunity in HCC. By promoting immune cell recruitment and enhancing antigen presentation, CCL3 demonstrates significant potential to improve the efficacy of immunotherapy, particularly in combination with immune checkpoint inhibitors. Targeting CCL3 may help to overcome the immunosuppressive TIME in HCC and improve patient outcomes.
Association of single and multiple cardiometabolic diseases with atrial fibrillation: a prospective cohort study
Authors: Peng Qunyong , Ma Tianqi , Gao Ming , Wang Xuerui , Pan Wei 
Published: February 2025

BackgroundIndividual cardiometabolic diseases (CMDs) increase atrial fibrillation (AF) risk; however, whether multiple CMDs exert a cumulative effect on AF risk remains unclear. Our objective was to examine the link between coexisting CMDs and AF, as well as their cumulative impact.MethodsThis UK Biobank-based prospective cohort study included data from participants with information related to CMDs and AF. The assessment of CMDs and AF was based on participants’ self-reported medical histories and electronic health records. Cox proportional hazard regression models were employed to analyse the link between the number of CMDs and AF and to determine the cumulative effect of multiple CMDs. Further, we performed stratified analyses and adjusted for confounding factors.ResultsThe study included 308 916 participants. The risk of AF was substantially associated with varying numbers of CMDs after multivariable adjustment in comparison to the reference group (all p<0.001). In the fully adjusted model, participants with 1, 2 and ≥3 CMDs exhibited elevated risks of 54% (HR: 1.54, 95% CI 1.48 to 1.59), 104% (HR: 2.04, 95% CI 1.94 to 2.15) and 212% (HR: 3.12, 95% CI 2.87 to 3.38), respectively. A significant cumulative dose-response relationship was noted between the number of CMDs and AF risk (HR: 1.45, 95% CI 1.42 to 1.48, p<0.001). A consistent dose-dependent cumulative relationship was observed in both stratified and sensitivity analyses.ConclusionsMultiple CMDs increased AF risk and exhibited a significant cumulative effect based on the number of CMDs.
Efficacy of cardiac myosin inhibitors mavacamten and aficamten in hypertrophic cardiomyopathy: a systematic review and meta-analysis of randomised controlled trials
Authors: Aman Ayesha , Akram Arfa , Akram Bisma , Maham Momina , Bokhari Masooma Zainab , Akram Aleena , Akram Sania , Yaqub Furqan 
Published: February 2025

BackgroundUnlike other suggested therapies, myosin inhibitors have been shown to change the course of hypertrophic cardiomyopathy by altering the contractile mechanics of cardiomyocytes. This meta-analysis sought to determine the efficacy of mavacamten and aficamten in hypertrophic cardiomyopathy.MethodsThe online databases were searched from inception to July 2024, including the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, ClinicalTrials.gov. The meta-analytical data were pooled using risk ratios (RRs) with 95% CI, standard mean difference (SMD) and SE.ResultsA total of 6 randomised controlled trials with 826 hypertrophic cardiomyopathy patients (mean age±SD up to 59.8±14.2 years in intervention vs 60.9±10.5 years in placebo) were included in our study. Of these, 443 received a cardiac myosin inhibitor and 383 received a placebo. The resting left ventricular outflow tract (LVOT) gradient between the two groups was considerably improved by cardiac myosin inhibitors (MD −57.27; 95% CI −63.05 to −51.49). Significant differences were also observed in the post-Valsalva LVOT gradient between the two groups (MD −55.86; 95% CI −65.55 to −46.18). Significantly decreased left ventricle ejection fraction (LVEF) was also seen (MD −4.74; 95% CI −7.22 to −2.26). The New York Health Association (NYHA) class improvement between the two groups also changed significantly (RR 2.21; 95% CI 1.75 to 2.80). Cardiac myosin inhibitors also caused significant improvement in the Kansas City Cardiomyopathy Questionnaire in a Clinical Summary Score between the two groups (MD 7.71; 95% CI 5.37 to 10.05) and significant reduction in the N-terminal pro-B-type natriuretic peptide (SMD −13.27; 95% CI −17.51 to −9.03) and the cardiac troponin I (SMD −11.90; 95% CI −15.07 to −8.72).ConclusionAccording to our meta-analysis, cardiac myosin inhibitors significantly improve the resting and post-Valsalva LVOT gradient, reduce the LVEF and improve the NYHA class and cardiac biomarkers when compared with the placebo.PROSPERO registration numberCRD52024586161.
Targeting the IL-17A pathway for therapy in early-stage tendinopathy
Authors: Millar Neal L , McInnes Iain B , Kolbinger Frank , Raulf Friedrich , Akbar Moeed , Li Yufei , Beckmann Nicolau , Accart Nathalie , Leupin Olivier , Calonder Claudio , Schieker Matthias , Kneissel Michaela , Bruns Christian , Siegel Richard M , Weber Eckhard 
Published: February 2025

ObjectivesTendinopathy is a frequent clinical problem and represents an extraordinary health economic and socioeconomic burden with high unmet medical needs. Recent clinical evidence suggests blockade of interleukin 17A (IL-17A) for tendinopathy therapy. The present preclinical study elucidates the biological mechanisms of IL-17A pathway stimulation and blockade in tendinopathy.MethodsWe explored whether IL-17A and other IL-17 family members are differentially expressed in biopsies of healthy, early-stage and late-stage tendinopathic human rotator cuff tendons using RT-qPCR. IL-17 pathway signature genes in healthy human tendon-derived cells were identified following IL-17A stimulation using AmpliSeq RNA. The molecular, structural and functional consequences of IL-17A pathway stimulation were explored in healthy human tendon-derived cells and in a rat tendon fascicle model ex vivo. The effects of IL-17A pathway blockade were investigated in a rat model of rotator cuff tendinopathy in vivo.ResultsWe provide evidence of differential expression of IL-17A mRNA (IL17A) versus other IL-17 family members in human rotator cuff early-stage tendinopathy. In human tendon-derived cells, stimulation with IL-17A induced the expression of the selected IL-17A pathway signature genesNFKBIZ, ZC3H12A, CXCL1, IL6, MMP3. Expression was inhibited by IL-17A blockade. In the rat ex vivo and in vivo models, IL-17A blockade alleviated inflammatory immune effector release, tendon structural degeneration, tendon inflammation and impaired tendon function.ConclusionOur data provide evidence that IL-17A is a key contributor to the pathogenesis of tendinopathy by promoting tendon inflammation and degeneration and that IL-17A blockade may represent a potential therapy in early-stage tendinopathy.
Continued nintedanib in patients with systemic sclerosis-associated interstitial lung disease: 3-year data from SENSCIS-ON
Authors: Allanore Yannick , Vonk Madelon C , Distler Oliver , Azuma Arata , Mayes Maureen D , James Alexandra , Kohlbrenner Veronika , Alves Margarida , Khanna Dinesh , Highland Kristin B 
Published: February 2025

ObjectiveWe assessed adverse events and changes in forced vital capacity (FVC) in patients treated with open-label nintedanib over 148 weeks of SENSCIS-ON, the extension of the SENSCIS trial.MethodsAdverse events and changes in FVC over 148 weeks of SENSCIS-ON were assessed in patients who received nintedanib in SENSCIS and continued nintedanib in SENSCIS-ON (‘continued nintedanib’ group) and in patients who received placebo in SENSCIS or received nintedanib for ≤28 days in a drug–drug interaction study and then received nintedanib in SENSCIS-ON (‘initiated nintedanib’ group).ResultsThe continued nintedanib group comprised 197 patients, and the initiated nintedanib group comprised 247 patients (231 from SENSCIS). Diarrhoea was the most frequent adverse event, reported in 152 (77.2%) and 183 (74.1%) patients in the continued nintedanib and initiated nintedanib groups, respectively. Among patients in the continued and initiated nintedanib groups, respectively, 53 (26.9%) and 148 (59.9%) had ≥1 dose reduction, 72 (36.5%) and 131 (53.0%) had ≥1 treatment interruption and 29 (14.7%) and 72 (29.1%) had adverse events that led to treatment discontinuation. Mean (SE) changes in FVC (mL) at week 148 were −189.1 (29.5) in the continued nintedanib group and −126.4 (26.4) in the initiated nintedanib group.ConclusionThe safety profile of nintedanib over 148 weeks of SENSCIS-ON was consistent with that reported in SENSCIS. Changes in FVC during SENSCIS and SENSCIS-ON supported a continued effect of nintedanib on slowing the decline in lung function, but showed continued progression of SSc-ILD.
Incidence of rheumatoid arthritis in Austria: a prospective population-based cohort study in a federal province
Authors: Puchner Rudolf , Sautner Judith , Ritschl Valentin , Pieringer Herwig , Alkin Alois , Balcar Lorenz , Rammer Yvonne , Schumacher Sabine , Stamm Tanja A 
Published: February 2025

ObjectiveWhen it comes to prospective studies on the incidence of rheumatoid arthritis (RA), the Norfolk study from 1994 is still frequently cited as prospective incidence data by many countries lacking comprehensive RA registries, including Austria. The aim of this study was, therefore, to gather robust data on the incidence of RA among Austrian adults for the first time.MethodsAll Upper Austrian rheumatologists reported newly diagnosed RA patients with symptom onset between 2016 and 2018, together with demographic data, laboratory and radiographic results. Cases still unclear at the end of 2018 were tracked in an extended observation period until 2023.ResultsIn total, 701 RA cases were reported. 583 complete patient datasets were analysed. In all 551 individuals with a mean age of 60.2 (±14.2) years, 359 (65.2%) being females, the diagnosis of RA was ascertained clinically by a rheumatologist, optionally applying RA-classification criteria. Across all 3 years, the annual RA incidence rate was 14.9/100 000 (95% CI 12.9 to 17.3), ranging from 20.0/100 000 (95% CI 17.6 to 22.7) in 2016 to 13.5/100 000 (95% CI 11.5 to 15.7) in 2017 and 11.3/100 000 (95% CI 9.5 to 13.3) in 2018. The incidence was highest in individuals >65 years (21.6/100 000, 95% CI 16.4 to 27.9). Women had a higher RA incidence (18.1/100 000, 95% CI 14.9 to 21.7) than men (10.4/100 000, 95% CI 8.0 to 13.3).ConclusionsThis study provided prospective population-based data on the incidence of RA in Austrian adults for the first time. Incidence rates were comparable with other European countries. Compared with the Norfolk study, we found lower rates in both genders, more pronounced in females, however.
Religious practices and quality of life in palliative care: insights from Tanzania
Authors: Sokoine Sonia Nada Edward , Kilonzo Gad , Ahmed Nadia , Sawe Kelvin Furanaeli 
Published: February 2025

ObjectiveTo explore the role of religious practices in palliative care and their impact on the quality of life among inpatients at Ocean Road Cancer Institute.MethodsA quantitative cross-sectional study was conducted, using structured surveys to gather data from 150 inpatients receiving palliative care. The WHO Quality of Life-BREF (WHOQOL-BREF) tool was used to measure quality of life, alongside data on the usage of religious practices.ResultsThe findings reveal that most of the participants (90%) expressed a need for religious practices, predominantly prayer. Notably, access to these practices positively correlated with improved perceptions of well-being, despite a considerable portion of patients reporting a poor quality of life (84.7%).ConclusionThe study’s findings highlight the importance of incorporating religious practices into palliative care, particularly in low-resource settings like Tanzania, to provide culturally sensitive, holistic support for patients with cancer.
Thermal fluctuation effects on shear viscosity to entropy ratio in five-dimensional Kerr–Newman black holes
Authors: Pourhassan Behnam , Sakallı İzzet , Brzo Aram Bahroz 
Published: February 2025

Abstract
We investigate how thermal fluctuations affect the properties of five-dimensional Kerr–Newman black holes, focusing particularly on the shear viscosity to entropy ratio. Our analysis incorporates logarithmic corrections to the Bekenstein–Hawking entropy and examines their impact on black hole thermodynamics. We explore three approaches to studying the shear viscosity-entropy ratio in the presence of thermal fluctuations: considering independent shear viscosity, thermally corrected shear viscosity, and an independent ratio assumption. Notably, we find that the lower bound of

$$\eta /S \ge 1/4\pi $$

η
/
S
≥
1
/
4
π

remains valid even with thermal fluctuations, though the specific behavior depends on the black hole mass and correction parameter. Our results suggest that thermal fluctuations generally decrease the ratio for massive black holes while maintaining the universal lower bound. This work extends our understanding of quantum corrections to black hole transport properties.
Cosmic ray sources and detectors
Authors: Mohanty Pravata Kumar 
Published: February 2025

Abstract
The origin of cosmic rays has remained an enduring mystery in astrophysics since their discovery by Victor Hess in 1912. However, extensive studies on the energy spectrum, mass composition, and angular distributions of cosmic rays have been conducted through both space-based and ground-based experiments. Although space-based experiments are limited to measuring cosmic rays with energies below about 10

$$^{14}$$

14

eV, their high precision has led to the discovery of several new features in the cosmic ray spectrum. However, ground-based detector arrays have provided valuable insights into cosmic rays at higher energies, offering new information on their spectrum, composition, and angular distributions. This paper reviews the major cosmic ray detectors currently in operation, both in space and on the ground, followed by an in-depth look at the GRAPES-3 experiment, which operates in Ooty, India, and focuses on the TeV-PeV energy range. Recent findings from GRAPES-3 on the cosmic ray spectrum and anisotropy are discussed, along with an update on the ongoing upgrade of the experiment.
Prevalence of Obstructive Sleep Apnea Among Lebanese Patients With Chronic Kidney Disease: Its Repercussion on Disease Trajectory and Its Effect on Patients’ Quality of Life
Authors: Yakdan Salim , Rahhal Nazih , Al Chaar Soltan , Alhaddad Juliano , Al Akoum Monifa , Chahine Yaacoub , Najem Robert , Chahine Mirna N. 
Published: February 2025

Background and Objectives: Chronic kidney disease (CKD) remains a public health threat and a major cause of morbidity and mortality worldwide. A bidirectional relationship is found between sleep disorders and CKD worldwide. However, to our knowledge, this study is the first to assess the prevalence of obstructive sleep apnea (OSA) and to evaluate its impact on the progression of other comorbidities among Lebanese patients with CKD.Materials and Methods: The study is an observational cross‐sectional study, carried out between September and November 2021. Lebanese patients with any stage of CKD were included. Patients’ characteristics were collected via electronic health record and baseline questionnaires. We screened for obstructive sleep apnea using the STOP‐Bang questionnaire.Results: We included 168 patients. The prevalence of OSA among our patients was 47.6%. The prevalence of OSA is higher in males compared with females (81.2% vs. 18.8%, p = 0.002). Obesity was more prevalent in patients with OSA compared with patients without OSA (42.5% vs. 19.3%, p = 0.002). Among the 168 patients, 69.6% had hypertension, with a significantly higher prevalence among those with OSA compared with those without OSA (81.2% vs. 59.1%, p = 0.003). Patients with OSA reported significantly lower scores compared with those without OSA in several domains of physical and emotional health, including physical functioning (54.06 vs. 66.88, p = 0.002), role limitations due to physical health (42.19 vs. 63.07, p = 0.001), role limitations due to emotional problems (49.17 vs. 69.32, p = 0.004), pain (61.31 vs. 70.45, p = 0.019), and physical component score (52.53 vs. 69.53, p = 0.002). All the abovementioned parameters were also examined in two subpopulations: patients with CKD and ESRD. Similarly, some comorbidities and a lower physical QOL score were observed more in patients with OSA in these two subpopulations.Conclusion: Patients with OSA in our study have higher probability of being male, obese, and hypertensive as well as poorer QOL compared with their counterparts without OSA. Implementing more effective screening and treatment of OSA in CKD patients is necessary.
Intratumoral Fusobacterium nucleatum Recruits Tumor-Associated Neutrophils to Promote Gastric Cancer Progression and Immune Evasion
Authors: Zhang Tianhao , Li Ying , Zhai Ertao , Zhao Risheng , Qian Yan , Huang Zhixin , Liu Yinan , Zhao Zeyu , Xu Xiang , Liu Jianqiu , Li Zikang , Liang Zhi , Wei Ran , Ye Linying , Ma Jinping , Wu Qingping , Chen Jianhui , Cai Shirong 
Published: February 2025

Abstract
Intratumoral microbiota can impact the development and progression of many types of cancer, including gastric cancer (GC). A better understanding of the precise mechanisms by which microbiota support GC could lead to improved therapeutic approaches. Here, we investigated the effect of intratumoral microbiota on the tumor immune microenvironment (TIME) during GC malignant progression. Analysis of human GC tissues with 16S rRNA amplicon sequencing revealed that Fusobacterium nucleatum (F. nucleatum) was significantly enriched in GC tissues with lymph node metastasis and correlated with a poor prognosis. F. nucleatum infection spontaneously induced chronic gastritis and promoted gastric mucosa dysplasia in mice. Furthermore, GC cells infected with F. nucleatum showed accelerated growth in immunocompetent mice compared to immunodeficient mice. Single-cell RNA sequencing uncovered that F. nucleatum recruited tumor-associated neutrophils (TANs) to reshape the tumor immune microenvironment. Mechanistically, F. nucleatum invaded GC cells and activated IL-17/NF-κB/RelB signaling, inducing TAN recruitment. F. nucleatum also stimulated TAN differentiation into the pro-tumoral subtype and subsequent promotion of PD-L1 expression, further facilitating GC immune evasion while also enhancing the efficacy of anti-PD-L1 antibody therapy. Together, this data uncovers mechanisms by which F. nucleatum affects GC immune evasion and immunotherapy efficacy, providing insights for developing effective treatment strategies.