bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of a nomogram for predicting advanced liver fibrosis in patients with chronic hepatitis B
Authors: Han Kexing , Wang Jianfeng , Song Xizhen , Kang Luyang , Lin Junjie , Hu Qinggang , Sun Weijie , Gao Yufeng 
Published: September 2024

BackgroundThe progression of chronic hepatitis B (CHB) to liver fibrosis and even cirrhosis is often unknown to patients, but noninvasive markers capable of effectively identifying advanced liver fibrosis remains absent.ObjectiveBased on the results of liver biopsy, we aimed to construct a new nomogram to validate the stage of liver fibrosis in CHB patients by the basic information of CHB patients and routine laboratory tests.MethodsPatients with CHB diagnosed for the first time in the First Affiliated Hospital of Anhui Medical University from 2010 to 2018 were selected, and their basic information, laboratory tests and liver biopsy information were collected. Eventually, 974 patients were enrolled in the study, while all patients were randomized into a training cohort (n = 732) and an internal validation cohort (n = 242) according to a 3:1 ratio. In the training cohort, least absolute shrinkage and selection operator (Lasso) regression were used for predictor variable screening, and binary logistic regression analysis was used to build the diagnostic model, which was ultimately presented as a nomogram. The predictive accuracy of the nomograms was analyzed by running operating characteristic curve (ROC) to calculate area under curve (AUC), and the calibration was evaluated. Decision curve analysis (DCA) was used to determine patient benefit. In addition, we validated the built models with internal as well as external cohort (n = 771), respectively.ResultsUltimately, the training cohort, the internal validation cohort, and the external validation cohort contained sample sizes of 188, 53, and 149, respectively, for advanced liver fibrosis. Gender, albumin (Alb), globulin (Glb), platelets (PLT), alkaline phosphatase (AKP), glutamyl transpeptidase (GGT), and prothrombin time (PT) were screened as independent predictors. Compared with the aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), and King’s score, the model in the training cohort (AUC = 0.834, 95% CI 0.800–0.868, p &lt; 0.05) and internal validation cohort (AUC = 0.804, 95% CI 0.742–0.866, p &lt; 0.05) showed the best discrimination and the best predictive performance. In addition, DCA showed that the clinical benefit of the nomogram was superior to the APRI, FIB-4 and King’s scores in all cohorts.ConclusionThis study constructed a validated nomogram model with predictors screened from clinical variables which could be easily used for the diagnosis of advanced liver fibrosis in CHB patients.
Association among biomarkers, phenotypes, and motor milestones in Chinese patients with 5q spinal muscular atrophy types 1–3
Authors: Ouyang Shijia , Peng Xiaoyin , Huang Wenchen , Bai Jinli , Wang Hong , Jin Yuwei , Jiao Hui , Wei Maoti , Ge Xiushan , Song Fang , Qu Yujin 
Published: September 2024

BackgroundBiomarkers can be used to assess the severity of spinal muscular atrophy (5q SMA; SMA). Despite their potential, the relationship between biomarkers and clinical outcomes in SMA remains underexplored. This study aimed to assess the association among biomarkers, phenotypes, and motor milestones in Chinese patients diagnosed with SMA.MethodsWe collected retrospective clinical and follow-up data of disease-modifying therapy (DMT)-naïve patients with SMA at our center from 2019 to 2021. Four biomarkers were included: survival motor neuron 2 (SMN2) copies, neuronal apoptosis inhibitory protein (NAIP) copies, full-length SMN2 (fl-SMN2), and F-actin bundling protein plastin 3 (PLS3) transcript levels. Data were analyzed and stratified according to SMA subtype.ResultsOf the 123 patients, 30 were diagnosed with Type 1 (24.3%), 56 with Type 2 (45.5%), and 37 with Type 3 (30.1%). The mortality rate for Type 1 was 50%, with median survival times of 2 and 8 months for types 1a and 1b, respectively. All four biomarkers were correlated with disease severity. Notably, fl-SMN2 transcript levels increased with SMN2 copies and were higher in Type 2b than those in Type 2a (p = 0.028). Motor milestone deterioration was correlated with SMN2 copies, NAIP copies, and fl-SMN2 levels, while PLS3 levels were correlated with standing and walking function.DiscussionOur findings suggest that SMN2 copies contribute to survival and that fl-SMN2 may serve as a valuable biomarker for phenotypic variability in SMA Type 2 subtypes. These insights can guide future research and clinical management of SMA.
Prognostic factors and treatment outcomes in pediatric autoimmune encephalitis: a multicenter study
Authors: Abu Melha Ahlam Ahmed , Aldress Amjad Saad , Alamri Fahad , Aljomah Lama Saleh , Hommady Raid , Al-Rumayyan Ahmed , Albassam Fahad 
Published: September 2024

IntroductionThe last few decades have increased our understanding of autoimmune encephalitis (AE). In both the pediatric and adult populations, it proves to be a disease of dramatic acute onset of heterogeneous clinical manifestations, notably encephalopathy with neuropsychiatric symptoms, seizures, and extrapyramidal symptoms. More often, it is triggered by a viral infection in the pediatric age groups, as suggested by the preceding febrile symptoms in over half of cases, and more ostensibly, NMDAR encephalitis post herpes encephalitis. An underlying neoplasm may be present in certain types (i.e., NMDAR encephalitis). The rising rate of antibody detection and subsequent confirmation has been boosted by improved live cellular assay detection methods. The corresponding clinical phenotypes, common underlying malignancies, and histopathological findings have helped improve our management regarding intervention and choice of immunotherapy. New assessment tools such as the Clinical Assessment Scale in Autoimmune Encephalitis (CASE score) have helped improve the objective assessment of impact on cognitive functions (1). Early intervention with immunotherapy (and tumor removal in proven underlying neoplasms) has improved overall outcomes in most presenting patients. But nearly 40% of cases fail to respond to the first tier of treatment (2). The complex interplay between pathogenic autoantibodies, T-cells, B-cells, and cytokines has led to the emergence of additional immunotherapy agents (i.e., tocilizumab and bortezomib).MethodsIn this retrospective observational study of pediatric AE conducted at two tertiary care centers, we observed the clinical characteristics, autoantibody yield, treatment modalities used, and disability scores during presentation and follow-up. Our secondary aim was to delineate prognostic factors for poor outcomes.ResultsNeuropsychiatric symptoms, encephalopathy, and seizures were the predominant manifestations in most of our patients. Younger age groups, refractory seizures, profound encephalopathy, and refractory disease harbored higher disability scores. The group that received combined immunotherapy has shown mitigation of disability score from severe to mild during long-term follow-up, signifying the role of multifaceted immunotherapy in pediatric refractory AE.ConclusionEarly implementation of combined immunotherapy in refractory cases significantly improved longterm disability scores, in spite of lingering residual effects on neurologic functions, notably cognition, behavior, and speech.
Prenatal tobacco and alcohol exposure, white matter microstructure, and early language skills in toddlers from a South African birth cohort
Authors: Scholten Chloe , Ghasoub Mohammad , Geeraert Bryce , Joshi Shantanu , Wedderburn Catherine J. , Roos Annerine , Subramoney Sivenesi , Hoffman Nadia , Narr Katherine , Woods Roger , Zar Heather J. , Stein Dan J. , Donald Kirsten , Lebel Catherine 
Published: September 2024

IntroductionTobacco and alcohol are the two most common substances used during pregnancy, and both can disrupt neurodevelopment, resulting in cognitive and behavioral deficits including language difficulties. Previous studies show that children with prenatal substance exposure exhibit microstructural alterations in major white matter pathways, though few studies have investigated the impact of prenatal substance exposure on white matter microstructure and language skills during the toddler years.MethodsIn this study, 93 children (34 exposed to alcohol and/or tobacco) aged 23 years from the Drakenstein Child Health Study, South Africa, completed Expressive and Receptive Communication assessments from the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and underwent diffusion MRI scans. Diffusion images were preprocessed, and 11 major white matter tracts were isolated. Fractional anisotropy (FA) and mean diffusivity (MD) were extracted for each white matter tract. Linear regression was used to examine differences between the tobacco/alcohol exposed group and unexposed controls for FA, MD, and language scores, as well as relationships between brain metrics and language. There were no significant group differences in language scores or FA.ResultsChildren with alcohol or tobacco exposure had lower average MD in the splenium of the corpus callosum compared to unexposed controls. Significant interactions between prenatal substance exposure and language scores were seen in 7 tracts but did not survive multiple comparisons correction.DiscussionOur findings show that prenatal alcohol and/or tobacco exposure appear to alter the relationship between white matter microstructure and early language skills in this population of toddlers, potentially laying the basis of language deficits observed later in older children with prenatal substance exposure, which may have implications for learning and interventions.
Hesperetin but not ellagic acid increases myosin heavy chain expression and cell fusion in C2C12 myoblasts in the presence of oxidative stress
Authors: Cuijpers Iris , Dohmen Colin G. M. , Bouwman Freek G. , Troost Freddy J. , Sthijns Mireille M. J. P. E. 
Published: September 2024

IntroductionSkeletal muscle regeneration is impaired in elderly. An oxidative stress-induced decrease in differentiation capacity of muscle satellite cells is a key factor in this process. The aim of this study is to investigate whether orange polyphenol hesperetin and pomegranate polyphenol ellagic acid enhance myoblast differentiation in the presence and absence of oxidative stress, and to explore underlying mechanisms.MethodsC2C12 myoblasts were proliferated for 24 h and differentiated for 120 h while exposed to hesperetin (5, 20, 50 μM), ellagic acid (0.05, 0.1 μM) or a combination (20 μM hesperetin, 0.05 μM ellagic acid) with and without oxidative stress-inducing compound menadione (9 μM) during 24 h of proliferation and during the first 5 h of differentiation. The number of proliferating cells was assessed using fluorescent labeling of incorporated 5-ethynyl-2′-deoxyuridine. Myosin heavy chain expression was assessed by fluorescence microscopy and cell fusion index was calculated. Furthermore, protein expression of phosphorylated p38 and myomixer were assessed using Western blot.ResultsNone of the compounds induced effects on cell proliferation. Without menadione, 50 μM hesperetin increased fusion index by 12.6% compared to control (p &lt; 0.01), while ellagic acid did not affect measured parameters of differentiation. Menadione treatment did not change myosin heavy chain expression and fusion index. In combination with menadione, 20 μM hesperetin increased myosin heavy chain expression by 35% (p &lt; 0.01) and fusion index by 7% (p = 0.04) compared to menadione. Furthermore, the combination of menadione with hesperetin and ellagic acid increased myosin heavy chain expression by 35% compared to menadione (p = 0.02). Hesperetin and ellagic acid did not change p38 phosphorylation and myomixer expression compared to control, while treatment with menadione increased p38 phosphorylation (p &lt; 0.01) after 5 h and decreased myomixer expression (p = 0.04) after 72 h of differentiation.Conclusion and discussionHesperetin increased myosin heavy chain expression in the presence of oxidative stress induced by menadione, and increased cell fusion both in the presence and absence of menadione. Ellagic acid did not affect the measured parameters of myoblast differentiation. Therefore, hesperetin should be considered as nutritional prevention or treatment strategy to maintain muscle function in age-related diseases such as sarcopenia. Future research should focus on underlying mechanisms and translation of these results to clinical practice.
Dietary patterns and association with Iron deficiency among children and adolescents aged 9–17 years in rural Guangzhou, China: a cross-sectional study
Authors: Fu Jinhan , Zeng Chunzi , Huang Jie , Guo Jiaying , Su Zheng , Luo Shiyun , Zhang Weiwei , Zhang Zhoubin , Zhu Huilian , Li Yan 
Published: September 2024

BackgroundIron deficiency and iron deficiency anemia cause a huge disease burden worldwide. Diet is an important factor affecting the iron levels. This study aims to explore the dietary patterns of school-aged children in rural areas of Guangzhou and their association with iron deficiency.MethodsData on dietary surveys, lifestyle, demographic and laboratory tests were gathered from rural school-age children in Guangzhou. Factor analysis was applied to derive dietary patterns. Robust Poisson regression and subgroup analysis were used to analyze the association between dietary patterns and iron deficiency.ResultsA total of 2,530 children and adolescents aged 9–17 years were enrolled. The prevalence of iron deficiency was 13.36%. Four dietary patterns were identified including snack and fast-food pattern, fruit and vegetable pattern, cereal and tuber pattern and meat and offal pattern. Both children and adolescents in the Q4 group (the highest propensity) of snack and fast-food pattern and cereal and tuber pattern had a higher risk of iron deficiency than the Q1 group (the lowest propensity). Both children and adolescents in the Q4 group of meat and offal pattern and fruit and vegetable pattern had a lower risk of iron deficiency than the Q1 group. The results of stratified analysis showed the negative effect of snack and fast-food pattern and the protective benefits of meat and offal pattern are more obvious for boys, and the negative effect of cereal and tuber pattern were obvious for girls. The negative effect or protective benefits of the four dietary patterns were obvious for children aged 9–13.ConclusionFemales, older children, and those with shorter sleep duration are at higher risk of iron deficiency. Snack and fast-food pattern and cereal and tuber pattern are risk factors for iron deficiency, and fruit and vegetable pattern and meat and offal pattern are protective factors for iron deficiency. The impact of diet on body iron levels is more obvious in boys and younger children. The findings of this study can provide evidence for formulating prevention and control measures on children and adolescents iron deficiency and iron deficiency anemia.
Clinicopathological and molecular differences between stage IV screen-detected and interval colorectal cancers in the Flemish screening program
Authors: Neefs Isabelle , Tran Thuy Ngan , Ferrari Allegra , Janssens Sharon , Van Herck Koen , Op de Beeck Ken , Van Camp Guy , Peeters Marc , Fransen Erik , Hoeck Sarah , Van Hal Guido 
Published: September 2024

IntroductionInterval cancer (IC) is an important quality indicator in colorectal cancer (CRC) screening. Previously, we found that fecal immunochemical test (FIT) ICs are more common in women, older age, right-sided tumors, and advanced stage. Here, we extended our existing stage IV patient cohort with clinicopathological and molecular characteristics, to identify factors associated with FIT-IC.MethodsLogistic regression models were fit to identify variables associated with the odds of having a stage IV FIT-IC. Multivariate models were corrected for gender, age, and location.ResultsA total of 292 screen-detected (SD) CRCs and 215 FIT-IC CRCs were included. FIT-IC CRC had 5 fold higher odds to be a neuroendocrine (NET) tumor and 2.5 fold higher odds to have lymphovascular invasion. Interestingly, some variables lost significance upon accounting for location. Thus, tumor location is a critical covariate that should always be included when evaluating factors related to FIT-IC.ConclusionsWe identified NETs and lymphovascular invasion as factors associated with increased odds of having a stage IV FIT-IC. Moreover, we highlight the importance of tumor location as a covariate in evaluating FIT-IC related factors. More research across all stages is needed to clarify how these insights might help to optimize the Flemish CRC screening program.
Epidemiology of injuries among children and adolescents from the Xinglin District in Xiamen, 2016–2019
Authors: Lin Gangxi , Zeng Qiyi 
Published: September 2024

ObjectiveTo investigate the epidemiology of injuries among children and adolescents in the Xinglin District of Xiamen from 2016 to 2019.MethodsThis study collected data from patients who attended the outpatient and emergency departments of the Xinglin District at the First Affiliated Hospital of Xiamen University between January 2016 and December 2019, diagnosed with injuries.ResultsA total of 13,123 patients were included, categorized into age groups 0–4 (n = 4,834), 5–9 (n = 3,924), 10–14 (n = 2,671), and 15–18 (n = 1,694). The rates of unintentional injuries were 97.00%, 96.94%, 94.50%, and 90.08% in the 0–4, 5–9, 10–14, and 15–18 age groups, respectively (P &lt; 0.001). The proportion of head injuries decreased with age (from 41.13% in the 0–4 age group to 18.00% in the 15–18 age group), compensated by an increase in rates of injuries to upper and lower extremities and multisite injuries (P &lt; 0.001). The most common causes of injuries were fall-related injuries (30.46%–52.05%), followed by mechanical injuries (18.35%–36.42%), with the rates of fall-related injuries decreasing with age and rates of mechanical injuries increasing with age (P &lt; 0.001). Age-period-cohort models revealed that the time factor was not significant for fall-related injuries and mechanical injuries (all P &gt; 0.05) despite apparent increases in incidence over time.ConclusionInjuries in children and adolescents continue to be a significant public health concern in the Xinglin District (China), predominantly driven by fall-related injuries and mechanical injuries.
Antihypertensive drug-associated adverse events in osteoarthritis: a study of a large real-world sample based on the FAERS database
Authors: Guo Zijian , Di Jingkai , Zhang Zhibo , Chen Shuai , Mao Xingjia , Wang Zehua , Yan Zehui , Li Xiaoke , Tian Zui , Mu Changjiang , Xiang Changxin , Xiang Chuan 
Published: September 2024

BackgroundHypertension is a common complication in patients with osteoarthritis (OA). There is increasing interest in the relationship between hypertension and OA. However, hypertension has been reported to negatively affect symptoms and quality of life in patients with OA. Therefore, treating hypertension is crucial for patients with OA. However, there is a lack of real-world studies on the effects of medications for treating hypertension on OA.MethodsData from the FAERS database from January 2004 to December 2023 were extracted for disproportionality analyses, and proportional reporting ratios (PRRs) were used to assess the association between medications for hypertension and all types of arthritis. Adverse event signals were identified and determined using reporting odds ratios (RORs) Adverse event signals were considered to have occurred if a drug-induced adverse event was recorded more than or equal to 3 and the lower limit of the ROR confidence interval was more than 1. We selected five classes of drugs including, calcium channel blockers (CCBs), angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), thiazide diuretics and β-blockers and representative drugs were analysed for osteoarthritis-related adverse reactions, and age and gender subgroups were analysed for drugs of significance. We also analysed the occurrence of AEs in relation to time using the Weibull distribution.ResultsIn terms of overall data, we found significant OA adverse reaction signals only for ARBs among the five drug classes.ARB AEs for spinal osteoarthritis (ROR 4.64, 95% CI 3.62–5.94), osteoarthritis (ROR 3.24 95% CI 2.82–3.72) and gouty arthritis (ROR 3.27 95% CI 1.22–8.75) were the three adverse reactions with the loudest signals. Next, we found that valsartan had strong osteoarthritis adverse reaction signals among the three ARBs, namely, irbesartan, cloxartan, and valsartan. We also analysed age and gender subgroups and found that osteoarthritis signals were strongest in the 18–65 and 65+ population, while females seem to be more prone to valsartan-related OA AEs.ConclusionARBs, especially valsartan, have significant positive signals for OA AEs. Therefore, ARB drugs, especially valsartan, should be used with caution when treating patients with OA combined with hypertension.
A cheminformatics and network pharmacology approach to elucidate the mechanism of action of Mycobacterium tuberculosis γ-carbonic anhydrase inhibitors
Authors: Manaithiya Ajay , Bhowmik Ratul , Bhattacharya Kunal , Ray Rajarshi , Shyamal Sagar Singh , Carta Fabrizio , Supuran Claudiu T. , Parkkila Seppo , Aspatwar Ashok 
Published: September 2024

BackgroundMycobacterium tuberculosis (Mtb) carbonic anhydrases (CAs) are critical enzymes that regulate pH by converting CO2 to HCO3−, essential for Mtb’s survival in acidic environments. Inhibiting γ-CAs presents a potential target for novel antituberculosis drugs with unique mechanisms of action.ObjectiveThis study aimed to explore the biological connections underlying Mtb pathogenesis and investigate the mechanistic actions of antituberculosis compounds targeting the Cas9 protein.MethodsWe employed homology modeling and virtual screening to identify compounds with high binding affinities for Cas9 protein. This study used the homology modeling approach employing high-quality AlphaFold DB models for γ-CA. Furthermore, the systems biology approach was used for analyzing the integrated modelling of compounds, integrating data on genes, pathways, phenotypes, and molecular descriptors. Single-cell RNA sequencing was also conducted to profile gene expression.ResultsThree compounds, F10921405, F08060425, and F14437079, potentially binding to Cas9 protein, have been identified. F10921405 and F08060425 showed significant overlap in their effects on pathways related to the immune response, while F14437079 displayed distinct mechanistic pathways. Expression profiling revealed high levels of genes such as PDE4D, ROCK2, ITK, MAPK10, and SYK in response to F1092–1405 and F0806-0425, and MMP2 and CALCRL in response to F1443-7079. These genes, which play a role in immune modulation and lung tissue integrity, are essential to fight against Mtb.ConclusionThe molecular relationship and pathways linked to the mentioned compounds give the study a holistic perspective of targeting Mtb, which is essential in designing specific therapeutic approaches. Subsequent research will involve experimental validation to demonstrate the efficacy of the promising candidates in Mtb infections.