bluuebunny/crossref_metadata_2025_split huggingface dataset:
ATF4-dependent and independent mitokine secretion from OPA1 deficient skeletal muscle in mice is sexually dimorphic
Authors: Streeter Jennifer , Persaud Luis , Gao Jason , Manika Deeraj , Fairman Will , García-Peña Luis Miguel , Marti Alex , Manika Chethan , Gaddi Shreya , Schickling Brandon , Pereira Renata O. , Abel E. Dale 
Published: September 2024

IntroductionReducing Optic Atrophy 1 (OPA1) expression in skeletal muscle in male mice induces Activation Transcription Factor 4 (ATF4) and the integrated stress response (ISR). Additionally, skeletal muscle secretion of Fibroblast Growth Factor 21 (FGF21) is increased, which mediates metabolic adaptations including resistance to diet-induced obesity (DIO) and glucose intolerance in these mice. Although FGF21 induction in this model can be reversed with pharmacological attenuation of ER stress, it remains to be determined if ATF4 is responsible for FGF21 induction and its metabolic benefits in this model.MethodsWe generated mice with homozygous floxed Opa1 and Atf4 alleles and a tamoxifen-inducible Cre transgene controlled by the human skeletal actin promoter to enable simultaneous depletion of OPA1 and ATF4 in skeletal muscle (mAO DKO). Mice were fed high fat (HFD) or control diet and evaluated for ISR activation, body mass, fat mass, glucose tolerance, insulin tolerance and circulating concentrations of FGF21 and growth differentiation factor 15 (GDF15).ResultsIn mAO DKO mice, ATF4 induction is absent. Other indices of ISR activation, including XBP1s, ATF6, and CHOP were induced in mAO DKO males, but not in mOPA1 or mAO DKO females. Resistance to diet-induced obesity was not reversed in mAO DKO mice of both sexes. Circulating FGF21 and GDF15 illustrated sexually dimorphic patterns. Loss of OPA1 in skeletal muscle increases circulating FGF21 in mOPA1 males, but not in mOPA1 females. Additional loss of ATF4 decreased circulating FGF21 in mAO DKO male mice, but increased circulating FGF21 in female mAO DKO mice. Conversely, circulating GDF15 was increased in mAO DKO males and mOPA1 females, but not in mAO DKO females.ConclusionSex differences exist in the transcriptional outputs of the ISR following OPA deletion in skeletal muscle. Deletion of ATF4 in male and female OPA1 KO mice does not reverse the resistance to DIO. Induction of circulating FGF21 is ATF4 dependent in males, whereas induction of circulating GDF15 is ATF4 dependent in females. Elevated GDF15 in males and FGF21 in females could reflect activation by other transcriptional outputs of the ISR, that maintain mitokine-dependent metabolic protection in an ATF4-independent manner.
Assessing the potential of diverse pastures for reducing nitrogen leaching
Authors: Graham Scott L. , Pronger Jack , Laubach Johannes , Hunt John E. , Rogers Graeme N. D. , Carrick Sam , Whitehead David , McLeod Malcolm , Mitchell Grace , Mudge Paul 
Published: September 2024

Mitigation practices for nitrogen leaching losses from livestock agriculture are needed to protect freshwater quality and increase the efficiency of agricultural production. Within New Zealand, the most common pasture type is a two-species mix of perennial ryegrass (Lolium perenne) and white clover (Trifolium repens). Ecological theory suggests that increasing species and functional diversity improves ecosystem function, including nitrogen (N) retention. Use of more diverse pasture types, including a mix of pasture grasses, legumes and other forbs, particularly plantain (Plantago lanceolata), with functional traits, including winter activity, deep-rooting, N fixation, and biological inhibition of nitrification in the soil, is a potential mitigation practice that requires further verification with long-term field measurements. Here we utilize a network of large lysimeters to make field-based measurements of N leaching from 5–8 species diverse pasture, including plantain, under a range of soil, climate and management conditions, for comparison with losses from traditional ryegrass-clover pasture. Over 3 years of measurements, leaching from fully established diverse pasture was 2–80 kg N ha−1 y−1. No differences were observed in dry matter production or N leaching of diverse pasture compared to ryegrass-clover lysimeters. Large losses, up to 120 kg N ha−1, were observed during periods when pasture was not fully established, including cultivation and sowing of new pasture, depending on season. Timing of management activities could be optimized to minimize these losses. These data provide critical assessment of diverse pasture as a mitigation approach for reducing N losses. Further work on diverse pastures should include higher diversity mixes as well as consideration of animal mediated effects of diverse pasture diets on N inputs.
Co-regulation of innate and adaptive immune responses induced by ID93+GLA-SE vaccination in humans
Authors: Fiore-Gartland Andrew , Srivastava Himangi , Seese Aaron , Day Tracey , Penn-Nicholson Adam , Luabeya Angelique Kany Kany , Du Plessis Nelita , Loxton Andre G. , Bekker Linda-Gail , Diacon Andreas , Walzl Gerhard , Sagawa Zachary K. , Reed Steven G. , Scriba Thomas J. , Hatherill Mark , Coler Rhea 
Published: September 2024

IntroductionDevelopment of an effective vaccine against tuberculosis is a critical step towards reducing the global burden of disease. A therapeutic vaccine might also reduce the high rate of TB recurrence and help address the challenges of drug-resistant strains. ID93+GLA-SE is a candidate subunit vaccine that will soon be evaluated in a phase 2b efficacy trial for prevention of recurrent TB among patients undergoing TB treatment. ID93+GLA-SE vaccination was shown to elicit robust CD4+ T cell and IgG antibody responses among recently treated TB patients in the TBVPX-203 Phase 2a study (NCT02465216), but the mechanisms underlying these responses are not well understood.MethodsIn this study we used specimens from TBVPX-203 participants to describe the changes in peripheral blood gene expression that occur after ID93+GLA-SE vaccination.ResultsAnalyses revealed several distinct modules of co-varying genes that were either up- or down-regulated after vaccination, including genes associated with innate immune pathways at 3 days post-vaccination and genes associated with lymphocyte expansion and B cell activation at 7 days post-vaccination. Notably, the regulation of these gene modules was affected by the dose schedule and by participant sex, and early innate gene signatures were correlated with the ID93-specific CD4+ T cell response.DiscussionThe results provide insight into the complex interplay of the innate and adaptive arms of the immune system in developing responses to vaccination with ID93+GLA-SE and demonstrate how dosing and schedule can affect vaccine responses.
Trends and research foci in immunoregulatory mechanisms of allergic rhinitis: a bibliometric analysis (2014-2024)
Authors: Wang Yandan , Zhang Liangran , Shi Baoyuan , Luo Junpeng 
Published: September 2024

BackgroundThis study aims to provide a comprehensive bibliometric analysis of research trends, hotspots, and future directions in the immunoregulatory mechanisms of allergic rhinitis (AR) from 2014 to 2024.MethodsData were sourced from the Web of Science Core Collection (WoSCC), covering articles and reviews published between April 1, 2014, and March 31, 2024. The search terms included “Allergic Rhinitis,” “AR,” and related terms along with specific keywords related to immune cells and inflammatory mediators. Bibliometric tools such as CiteSpace, VOSviewer, and SCImago Graphica were used to analyze institutional cooperation networks, keyword co-occurrence, citation bursts, and research topic evolution. Microsoft Excel 2019 was employed to display annual publication trends.ResultsA total of 2200 papers met the inclusion and exclusion criteria. The number of publications showed an upward trend over the past decade, with a significant peak in 2021. China (583 papers) and the United States (454 papers) were the major contributing countries. Imperial College London emerged as the leading institution. Key research frontiers identified include the roles of NF kappa B and air pollution in AR. Keyword burst analysis revealed emerging topics such as respiratory allergy and personalized treatment strategies. Notable limitations include the exclusive use of the WoSCC database and the restriction to English-language publications.ConclusionThe field of immunoregulatory mechanisms in allergic rhinitis has seen significant growth, with China and the United States leading the research. Future research should focus on developing personalized treatment plans and understanding the comprehensive impact of environmental factors. Continued interdisciplinary collaboration and international cooperation will be essential for advancing therapeutic strategies in AR.
Regional diversity in drug-induced lung diseases among the USA, European Union, and Japan
Authors: Sato Jun , Sadachi Ryo , Koyama Takafumi , Katsuya Yuki , Okada Mao , Yamamoto Noboru 
Published: September 2024

BackgroundDrug-induced lung disease (DILD) is a considerable and potentially fatal adverse event with poorly understood risk factors. Large-scale, data-driven analyses investigating regional discrepancies in DILD incidence are lacking. The aim of this study was to investigate the potential association among DILD prevalence, regional differences and other factors based on large-scale data base.MethodsThis retrospective observational study analyzed spontaneous adverse event reports from the FDA Adverse Event Reporting System (FAERS) database between January 2010 and December 2020. Regional disparities in DILD incidence were assessed among reports from the United States of America (USA), the European Union (EU), and Japan (JP). Using multivariate logistic regression accounting for age, sex, and reporting years, we calculated the reporting odds ratios (RORs) with 95% confidence intervals. Subgroup analyses were performed for different types of anticancer agents, including tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), antibody–drug conjugates (ADCs), and cytotoxic agents.ResultsRegional differences in RORs were observed for anticancer drugs in reports from JP and the EU compared with those from the USA (JP, ROR 4.432; EU, ROR 1.291) and for non-anticancer drugs (JP, ROR 3.481; EU, ROR 1.086). Significantly higher RORs were observed for all anticancer drug regimens reported in JP than in the USA (TKIs, ROR 3.274; ICIs, ROR 2.170; ADCs, ROR 2.335; cytotoxic agents, ROR 3.989). The EU reports exhibited higher RORs for TKIs and cytotoxic agents than the USA reports, with no significant differences in ICIs or ADCs (TKIs, ROR 1.679; ICIs, ROR 1.041; ADCs, ROR 1.046; cytotoxic agents, ROR 1.418).ConclusionThe prevalence of DILD in JP, the EU, and the USA differed. These findings have important implications in evaluating the safety profiles of drugs and patient safety in drug development and clinical practice. This study is the first to identify regional differences in DILDs using a large global database.
Radiomics in distinguishing between lung adenocarcinoma and lung squamous cell carcinoma: a systematic review and meta-analysis
Authors: Shi Lili , Zhao Jinli , Wei Zhichao , Wu Huiqun , Sheng Meihong 
Published: September 2024

ObjectivesThe aim of this study was to systematically review the studies on radiomics models in distinguishing between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) and evaluate the classification performance of radiomics models using images from various imaging techniques.Materials and methodsPubMed, Embase and Web of Science Core Collection were utilized to search for radiomics studies that differentiate between LUAD and LUSC. The assessment of the quality of studies included utilized the improved Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Radiomics Quality Score (RQS). Meta-analysis was conducted to assess the classification performance of radiomics models using various imaging techniques.ResultsThe qualitative analysis included 40 studies, while the quantitative synthesis included 21 studies. Median RQS for 40 studies was 12 (range -5~19). Sixteen studies were deemed to have a low risk of bias and low concerns regarding applicability. The radiomics model based on CT images had a pooled sensitivity of 0.78 (95%CI: 0.71~0.83), specificity of 0.85 (95%CI:0.73~0.92), and the area under summary receiver operating characteristic curve (SROC-AUC) of 0.86 (95%CI:0.82~0.89). As for PET images, the pooled sensitivity was 0.80 (95%CI: 0.61~0.91), specificity was 0.77 (95%CI: 0.60~0.88), and the SROC-AUC was 0.85 (95%CI: 0.82~0.88). PET/CT images had a pooled sensitivity of 0.87 (95%CI: 0.72~0.94), specificity of 0.88 (95%CI: 0.80~0.93), and an SROC-AUC of 0.93 (95%CI: 0.91~0.95). MRI images had a pooled sensitivity of 0.73 (95%CI: 0.61~0.82), specificity of 0.80 (95%CI: 0.65~0.90), and an SROC-AUC of 0.79 (95%CI: 0.75~0.82).ConclusionRadiomics models demonstrate potential in distinguishing between LUAD and LUSC. Nevertheless, it is crucial to conduct a well-designed and powered prospective radiomics studies to establish their credibility in clinical application.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=412851, identifier CRD42023412851.
A complete benchmark for polyp detection, segmentation and classification in colonoscopy images
Authors: Tudela Yael , Majó Mireia , de la Fuente Neil , Galdran Adrian , Krenzer Adrian , Puppe Frank , Yamlahi Amine , Tran Thuy Nuong , Matuszewski Bogdan J. , Fitzgerald Kerr , Bian Cheng , Pan Junwen , Liu Shijle , Fernández-Esparrach Gloria , Histace Aymeric , Bernal Jorge 
Published: September 2024

IntroductionColorectal cancer (CRC) is one of the main causes of deaths worldwide. Early detection and diagnosis of its precursor lesion, the polyp, is key to reduce its mortality and to improve procedure efficiency. During the last two decades, several computational methods have been proposed to assist clinicians in detection, segmentation and classification tasks but the lack of a common public validation framework makes it difficult to determine which of them is ready to be deployed in the exploration room.MethodsThis study presents a complete validation framework and we compare several methodologies for each of the polyp characterization tasks.ResultsResults show that the majority of the approaches are able to provide good performance for the detection and segmentation task, but that there is room for improvement regarding polyp classification.DiscussionWhile studied show promising results in the assistance of polyp detection and segmentation tasks, further research should be done in classification task to obtain reliable results to assist the clinicians during the procedure. The presented framework provides a standarized method for evaluating and comparing different approaches, which could facilitate the identification of clinically prepared assisting methods.
Epidemiological investigation of allergic rhinitis in children aged 6–12 years in Bayannur City, China
Authors: Yan Xiaobo , Li Limin 
Published: September 2024

BackgroundAllergic rhinitis (AR) is an inflammatory condition of the nasal mucosa triggered by exposure to non-harmful substances. Over the past decade, the prevalence of AR in Chinese children has been steadily increasing. However, detailed epidemiological data on AR in children from Bayannur City are lacking.MethodsThis study randomly selected six primary schools in Bayannur City. Electronic questionnaires were distributed via the web, and parents and children completed the questionnaires by scanning the two-dimensional code within a designated timeframe. Statistical analysis was performed on the collected data.ResultsA total of 4,754 valid responses were obtained. The self-reported prevalence of AR among children in Bayannur city was 39.79%. Multivariate analysis revealed that male gender, belonging to an ethnic minority, a history of food or drug allergies, frequent antibiotic use (≥3 times per year in the past two years, with each course lasting ≥3 days), and residence in urban or pastoral areas was associated with an increased prevalence of AR in children. The proportion of children experiencing moderate to severe AR hat impacted their studies or daily life was 48.78%. Chronic AR was reported in 56.71% of cases. Among AR patients with other allergic conditions, the incidence rates were as follows: bronchial asthma 35.99%, upper airway cough syndrome (UACS) 64.32%, secretory otitis media (SOM) 22.41%, obstructive sleep apnea hypopnea-syndrome (OSAHS) 49.58%, allergic dermatitis (AD) 48.72%, and allergic conjunctivitis (AC) 85.20%. The prevalence of AR was 50.30% in urban areas, 13.733% in rural areas and 20.90% in pastoral areas. Seasonal effects on AR prevalence were notably significant in urban and pastoral regions.ConclusionsThe prevalence of AR among children in Bayannur city was 39.80%. Of those with AR, 48.72% experienced significant impacts on their learning or daily life, while only 14.80% had no other allergic conditions. There were significant variations in the prevalence and onset of AR among children between urban, agricultural and pastoral areas.
Potential mechanisms underlying podophyllotoxin-induced cardiotoxicity in male rats: toxicological evidence chain (TEC) concept
Authors: Ma Kaiyue , Sun Lu , Jia Chunxue , Kui Hongqian , Xie Jiaqi , Zang Shidan , Huang Shixin , Que Jinfeng , Liu Chuanxin , Huang Jianmei 
Published: September 2024

IntroductionPodophyllotoxin (PPT) is a high-content and high-activity compound extracted from the traditional Chinese medicinal plant Dysosma versipellis (DV) which exhibits various biological activities. However, its severe toxicity limits its use. In clinical settings, patients with DV poisoning often experience adverse reactions when taking large doses in a short period. The heart is an important toxic target organ, so it is necessary to conduct 24-h acute cardiac toxicity studies on PPT to understand its underlying toxicity mechanism.MethodsBased on the concept of the toxicological evidence chain (TEC), we utilized targeted metabolomic and transcriptomic analyses to reveal the mechanism of the acute cardiotoxicity of PPT. The manifestation of toxicity in Sprague-Dawley rats, including changes in weight and behavior, served as Injury Phenotype Evidence (IPE). To determine Adverse Outcomes Evidence (AOE), the hearts of the rats were evaluated through histopathological examination and by measuring myocardial enzyme and cardiac injury markers levels. Additionally, transcriptome analysis, metabolome analysis, myocardial enzymes, and cardiac injury markers were integrated to obtain Toxic Event Evidence (TEE) using correlation analysis.ResultsThe experiment showed significant epistaxis, hypokinesia, and hunched posture in PPT group rats within 24 h after exposure to 120 mg/kg PPT. It is found that PPT induced cardiac injury in rats within 24 h, as evidenced by increased serum myocardial enzyme levels, elevated concentrations of cardiac injury biomarkers, and altered cardiac cell morphology, all indicating some degree of cardiac toxicity. Transcriptome analysis revealed that primary altered metabolic pathway was arachidonic acid metabolism after PPT exposure. Cyp2e1, Aldob were positively correlated with differential metabolites, while DHA showed positive correlation with differential genes Fmo2 and Timd2, as well as with heart injury markers BNP and Mb.ConclusionThis study comprehensively evaluated cardiac toxicity of PPT and initially revealed the mechanism of PPT-induced acute cardiotoxicity, which involved oxidative stress, apoptosis, inflammatory response, and energy metabolism disorder.
Mining and evaluation of adverse event signals for capmatinib based on the FAERS database
Authors: Chen Xinnan , Jiang Ying , Zhu Haohao , Tian Man 
Published: September 2024

ObjectiveTo conduct a comprehensive data analysis based on the FDA’s Adverse Event Reporting System (FAERS) to mine possible adverse event (AE) signals of Capmatinib, providing valuable references for its clinical application.MethodsCapmatinib was the primary suspected drug in the search of FAERS database from the second quarter of 2020 to the fourth quarter of 2023. Data processing, screening, and classification were performed using methods such as the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS).ResultsA total of 1,991 AE reports directly related to Capmatinib were screened, identifying 269 Preferred Terms (PTs) involving 26 System Organ Classes (SOCs). Besides the AEs recorded in the drug label (such as edema, nausea, fatigue, and dyspnea), the study unearthed other high-risk AEs not listed in the label, including Renal and urinary disorders, Vocal cord paralysis, and Ear and labyrinth disorders. Among these, renal and urinary disorders, and ear and labyrinth disorders had a higher frequency and intensity of signals, suggesting that their mechanisms of occurrence could be a future research direction.ConclusionThis study uncovered new potential AEs of Capmatinib based on the FAERS database, providing reference for its safe clinical use. Special attention should be given to the occurrence of ear and labyrinth disorders and renal and urinary disorders, primarily presenting as pseudo-acute kidney injury, during treatment.
Population pharmacokinetic study in children with vascular anomalies: body weight as a key variable in predicting the initial dose and dosing frequency of sirolimus
Authors: Fan Lin , Guo Hong-Li , Zhao Yue-Tao , Li Yue , Wang Wei-Jun , Huang Jian , Hu Ya-Hui , Zou Ji-Jun , Chen Feng 
Published: September 2024

BackgroundThe main challenges faced when using sirolimus in children with vascular anomalies (VAs) still include significant pharmacokinetic (PK) variability, uncertainty in the target concentration range, as well as inconsistencies in initial dosing and dosing frequency. The aim of this study is to establish a new population pharmacokinetic (PPK) model for children with VAs to guide the individualized use of sirolimus.MethodsA PPK study was performed using data from children with VAs who received sirolimus between July 2017 and April 2022. A nonlinear mixed-effect modeling with a one-compartment model structure was applied. Monte Carlo simulation was employed to propose specific dosing recommendations to achieve the target trough concentrations (Ctrough) of 5–15 ng/mL.ResultsIn total, 134 blood concentrations from 49 pediatric patients were used to characterize the sirolimus pharmacokinetics. Covariate analysis identified body weight (BW) as a significant factor affecting clearance (CL) in the final PPK model. The typical clearance rate and distribution volume, standardized to a BW of 16 kg, were 4.06 L/h (4% relative standard error, RSE) and 155 L (26% RSE), respectively. Optimal dosing regimens were simulated for different BWs. For a twice-daily regimen, the recommended doses were 0.05, 0.06, 0.07, and 0.08 mg/kg/day for BW of &lt;10, 10–20, 20–40, and ≥40 kg, respectively; for a once-daily regimen, the recommended doses were 0.06, 0.07, 0.08, and 0.09 mg/kg/day for BW of &lt;10, 10–30, 30–50, and ≥50 kg, respectively. Notably, sirolimus Ctrough could be maintained between 5–15 ng/mL across various dosing frequencies based on the recommended dosing regimen.ConclusionWe established a PPK model of sirolimus for children with VAs and proposed an initial dosing strategy. Integrating initial dose and medication frequency recommendations into sirolimus’ guidelines will broaden its clinical options and simplify the clinical management for childhood VAs.