bluuebunny/crossref_metadata_2025_split huggingface dataset:
School and student characteristics related to primary and secondary school students’ social–emotional functioning
Authors: de Bruijn Anne G. M. , Ehren Melanie C. M. , Meeter Martijn , Kortekaas-Rijlaarsdam Anne Fleur 
Published: February 2025

IntroductionA healthy social–emotional functioning is vital for students’ general development and wellbeing. The school environment is a major determinant of social–emotional functioning, yet little is known about school-level and student-level characteristics related to healthy social–emotional functioning. In this study, we examined school-level characteristics (school size, school disadvantage score, urbanization level, and school denomination) and student-level characteristics (grade, secondary school track, participation in a COVID-19-related catch-up program, and measurement moment - during or after COVID-19) as predictors of students’ motivation for school, academic self-concept, social acceptance, and school wellbeing.MethodsIn school year 2020–2021, just after the first Covid-19 outbreak, 3,764 parents of primary school students from 242 Dutch primary schools and 2,545 secondary school students from 62 secondary schools filled out online questionnaires, before and after a Covid-19 related catch-up program was implemented at their school. Reliable and validated questionnaires were used to assess students’ motivation (Intrinsic Motivation Inventory), academic self-concept (Harter Self Perception Profile for Children; Self-Description Questionnaire-II), school wellbeing (Dutch School Questionnaire) and social acceptance (PRIMA Social Acceptance Questionnaire). School characteristics were derived from online databases. Student participation in a catch-up program and measurement moment (before or after the program) were taken into account. Data was analyzed via multilevel General Linear Mixed Models, separately for primary and secondary education.ResultsOf the school-level factors, only school disadvantage score was a significant predictor, specifically for primary school students’ motivation. Of the student-level characteristics, grade and catch-up participation were significant predictors of lower motivation, academic self-concept and school-wellbeing in primary school. In secondary school, students in higher grades had significantly lower motivation and school wellbeing; participants in catch-up program had a significantly lower academic self-concept; and perceived social-acceptance and school wellbeing were significantly lower just after COVID-19.ConclusionSchool-level characteristics only played a minor role in explaining differences in students’ social–emotional functioning. In both primary and secondary education, students in higher grades and participating in catch-up programs scored lower on their social–emotional functioning. Schools should be aware of students in higher grades being at risk for more problems in their social–emotional functioning.
Deciphering the role of CNIH4 in pan-cancer landscapes and its significance in breast cancer progression
Authors: Xu Yao , Lai Zengzhen , Li Chaolin 
Published: February 2025

BackgroundThe escalating global cancer burden necessitates the development of biomarkers with enhanced specificity and sensitivity for early diagnosis and therapeutic efficacy monitoring. The CNIH4 gene, an emerging biomarker, is increasingly recognized for its role in the malignant progression across various cancers.MethodsWe conducted a comprehensive multi-omics analysis of CNIH4, including pan-cancer expression profiles, epigenetic alterations, immune microenvironment characteristics, and therapeutic response patterns. Our focus was on clinical features, molecular underpinnings, and drug sensitivity in breast cancer (BRCA) associated with CNIH4. In vitro studies were also performed to assess the effects of CNIH4 knockdown on cell proliferation and cell cycle in the MDA-MB-231 cell line.ResultsCNIH4 upregulation was observed in multiple cancers, significantly correlating with genomic instability. High CNIH4 expression levels were linked to poor prognosis across cancers and associated with key cancer-related pathways, particularly those in cell cycle regulation and DNA repair. Correlation analyses suggest a role for CNIH4 in the tumor immune microenvironment, as evidenced by its association with immune subtypes, immune-related genes, and immune cell infiltration. Single-cell and spatial transcriptome analyses confirmed that CNIH4 expression in BRCA predicts tumor malignancy. Drug sensitivity analysis revealed a significant correlation between CNIH4 and responsiveness to various kinase inhibitors and chemotherapeutic agents. In vitro experiments demonstrated that CNIH4 knockdown significantly impacts the proliferation and cell cycle of MDA-MB-231 cells.ConclusionOur study highlights CNIH4 as a promising pan-cancer biomarker with significant implications for tumor progression and a critical role in cell cycle regulation in BRCA.
Correlation and clinical significance of GSTP1 hypermethylation in hepatocellular carcinoma: a systematic review and meta-analysis
Authors: Li Pengfei , He Lei , Zhang Chunxia , Huang Xinyao , Sun Rong , Zhang Yan , Wang Yan 
Published: February 2025

BackgroundHepatocellular carcinoma (HCC) is one of the most prevalent and fatal cancers globally, with poor prognosis due to late-stage diagnosis and limited early detection methods. GSTP1 gene hypermethylation has been implicated in various cancers, including HCC, as a potential biomarker for diagnosis, prognosis, and therapeutic strategies. This systematic review and meta-analysis aimed to assess the association between GSTP1 hypermethylation and HCC, and its clinical significance.MethodsA comprehensive literature search was conducted across PubMed, Embase, Web of Science, and the Cochrane Library to identify studies examining GSTP1 hypermethylation in HCC. Studies included in the meta-analysis were observational (case-control, cohort) or experimental studies (clinical trials) that reported on the correlation between GSTP1 hypermethylation and clinical outcomes in HCC patients. Pooled odds ratios (ORs) and weighted mean differences (WMDs) were calculated using random or fixed-effects models based on heterogeneity.ResultsA total of 10 case-control studies were included, comprising 1,133 participants. The analysis revealed a significant association between GSTP1 hypermethylation and the presence of HCC (OR = 6.64, 95% CI: 2.17–20.38). GSTP1 hypermethylation was more frequently observed in liver cancer tissue compared to liver tissue from patients with other diseases (P &lt; 0.00001). Additionally, a significant correlation between GSTP1 hypermethylation and poor clinical outcomes, such as advanced tumor stage, recurrence, and reduced overall survival, was observed (OR = 2.56, 95% CI: 1.80–3.64). Subgroup analyses based on study design, sample type, and detection method showed no significant heterogeneity in most comparisons.ConclusionGSTP1 hypermethylation is significantly associated with the presence of HCC and poorer clinical outcomes, making it a promising biomarker for early diagnosis and prognosis. These findings highlight the potential for GSTP1 methylation as a diagnostic and prognostic tool in HCC management. Further large-scale, multicenter studies are required to standardize detection methods and evaluate the therapeutic potential of epigenetic reactivation of GSTP1 in HCC patients.
Short-term fasting before living kidney donation has an immune-modulatory effect
Authors: Oudmaijer Christiaan A. J. , Komninos Daphne S. J. , Ozinga Rutger A. , Smit Kimberly , Rozendaal Nina E. M. , Hoeijmakers Jan H. J. , Vermeij Wilbert P. , Aerts Joachim G. J. V. , IJzermans Jan N. M. , Willemsen Marcella 
Published: February 2025

BackgroundShort-Term Fasting (STF) is an intervention reducing the intake of calories, without causing undernutrition or micronutrient-related malnutrition. It aims to systemically improve resilience against acute stress. Several (pre-)clinical studies have suggested protective effects of STF, marking the systemic effects STF can induce in respect to surgery and ischemia-reperfusion injury. In addition, STF also affects the number of circulating immune cells. We aim to determine the effect of STF on the abundance and phenotype of different immune cell populations.MethodsThirty participants were randomly selected from the FAST clinical trial, including living kidney donors, randomized to an STF-diet or control arm. In an observational cohort sub-study we prospectively included 30 patients who donated blood samples repeatedly during study runtime. Using flow cytometry analyses, immune cell phenotyping was performed on peripheral blood mononuclear cells. Three panels were designed to investigate the presence and activation status of peripheral T cells, B cells, dendritic cells (DCs) and myeloid cells.ResultsEight participants were excluded due to sample constraints. Baseline characteristics showed no significant differences, except for fasting duration. Weight changes were minimal and non-significant across different time intervals, with slight trends toward long-term weight loss pre-surgery. Glucose, insulin, and β-hydroxybutyrate levels differed significantly between groups, reflecting adherence to the fasting diet. Flow cytometry and RNA sequencing analysis revealed no baseline differences between groups, with high variability within each group. STF changes the levels and phenotype of immune cells, reducing the abundance and activation of T cells, including regulatory T cells, increased presence of (naïve) B cells, and elevation of type 1 conventional DCs (cDC1s). In addition, a decrease in central memory T cells was observed.DiscussionIn this study, we observed significant changes due to fasting in B cells, T cells, and DCs, specifically toward less specialized lymphocytes, suggesting an arrest in B and T cell development. Further research should focus on the clinical implications of changes in immune cells and significance of these observed immunological changes.ConclusionSTF results in reduced numbers and activation status of T cells and Tregs, increased presence of (naïve) B cells, and elevation of cDC1s.
Modeling human natural killer cell development and drug response in a microfluidic bone marrow model
Authors: Koenig Leopold , Ben-Eliezer Inbal , Tao Thi Phuong , Winter Annika , Grossman Moran 
Published: February 2025

IntroductionThe human bone marrow is a complex organ that is critical for self-renewal and differentiation of hematopoietic progenitor cells into various lineages of blood cells. Perturbations of the hematopoietic system have been reported to cause numerous diseases. Yet, understanding the fundamental biology of the human bone marrow in health and disease and during the preclinical stages of drug development is challenging due to the complexity of studying or manipulating the human bone marrow. Human cell-based microfluidic bone marrow models are promising research tools to explore multi-lineage differentiation of human stem and progenitor cells over long periods of time.MethodsHuman hematopoietic stem and progenitor cells were cultured with mesenchymal stromal cells on a zirconium oxide ceramic scaffold in a microfluidic device recapitulating the human bone marrow. NK cell differentiation was induced by the application of a lymphoid cultivation medium containing IL-15. The kinetics of differentiation into mature NK cells was traced by flow cytometry over a period of up to seven weeks, and functionality was measured by stimulation with phorbol myristate acetate (PMA) and ionomycin. The effect of an anti-IL-15 monoclonal antibody (TEV-53408) on different NK cell subtypes was tested at different time points.ResultsOur data shows that within 28 days of culture, differentiation into all developmental stages of NK cells was accomplished in this system. Alongside with the NK cells, myeloid cells developed in the system including granulocytes, monocytes and dendritic cells. The differentiated NK cells could be activated after stimulation with PMA and ionomycin indicating the functionality of the cells. Treatment with an anti-IL-15 antibody induced a reduction in proliferation of late-stage NK cells as shown by EdU staining. This led to significantly dose dependent reduction in the number of circulating stage 4 - 6 NK cells in the system after one week of treatment. This effect was partially reversible after a two-week treatment-free period.DiscussionIn summary, the presented model enables investigation of human NK cell development in the bone marrow and provides a basis to study related diseases and drug response effects in a microenvironment that is designed mimic human physiology.
Programmed cell death markers in COVID-19 survivors with and without sepsis
Authors: Mallarpu Chandra Shekar , Chelluri Srinivasa Ikswaja , Katragadda Tapaswi Krishna , Singarapu Maneendra , Chelluri Lakshmi Kiran , Madiraju Charitha 
Published: February 2025

IntroductionSepsis remains a leading cause of mortality, especially in COVID-19 patients, due to delayed diagnosis and limited therapeutic options. While the mechanisms of programmed cell death (PCD) in COVID-19 and sepsis are complex, understanding the molecular markers involved in these processes may aid in assessing disease severity. This study aimed to investigate the roles of PCD markers, inflammatory cytokines, and MHC molecules in distinguishing disease severity in COVID-19 patients with and without sepsis.MethodsThe study involved adult patients (≥18 years) who survived COVID-19, grouped into four cohorts: COVID-19 with sepsis (C19wSepsis), COVID-19 without sepsis (C19NoSepsis), sepsis alone, and healthy controls. Serum and peripheral blood mononuclear cells (PBMCs) from each cohort were analyzed using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. PCD markers (caspase-3, caspase-1, MLKL, LC3B, p62/SQSTM1), inflammatory cytokines (IL-1-beta, IFN-gamma), and MHC molecules (MHC I-A, MHC II-DRB1) were assessed. Statistical analyses were performed to evaluate differences in marker levels between and within cohorts.ResultsThe analysis identified two distinct molecular signatures associated with disease severity. The first signature, characterized by elevated levels of secreted markers of PCD, IL-1-beta, IFN-gamma, MHC I-A and MHC II-DRB1, was common to the C19wSepsis and C19NoSepsis cohorts. The second signature, which was more prominent in the cellular markers of PCD (caspase-1, caspase-3, MLKL, p62/SQSTM1), was uniquely associated with the C19wSepsis cohort.ConclusionThese findings provide insight into the molecular signatures distinguishing immune responses in COVID-19-related sepsis and may serve as valuable biomarkers for assessing disease severity, while guiding therapeutic interventions in critical care settings.
Impact of hyperhydration on fluid overload and hematopoietic cell transplant after post-transplant cyclophosphamide-based graft-versus-host-disease prophylaxis
Authors: Samuels Diana T. , Yao Janny M. , Samara Yazeed , Yang Dongyun , Mokhtari Sally , Tiemann Katrin , Otoukesh Salman , Arslan Shukaib , Pourhassan Hoda , Wu Stephanie , Blackmon Amanda , Agrawal Vaibhav , Amanam Idoroenyi , Ali Haris , Salhotra Amandeep , Aldoss Ibrahim , Ball Brian , Koller Paul , Aribi Ahmed , Sandhu Karamjeet , Pullarkat Vinod , Artz Andrew , Smith Eileen , Stewart Forrest , Becker Pamela , Stein Anthony , Marcucci Guido , Forman Stephen J. , Nakamura Ryotaro , Al Malki Monzr M. 
Published: February 2025

IntroductionHemorrhagic cystitis (HC) is an early complication after hematopoietic cell transplant (HCT) with post-transplant cyclophosphamide (PTCy). Hyperhydration can reduce HC, but may lead to fluid overload (FO), which has been associated with higher non-relapse mortality (NRM) after HCT.MethodsThe objectives of this study were to grade FO between days 3 and 8 based on weight gain, diuretic therapy, and FO-related organ dysfunction and analyze the impact of FO on non-relapse mortality (NRM) and subsequently on overall survival (OS) of patients undergoing HCT with PTCy-based GvHD prophylaxis.ResultsTwo hundred seventy-five patients who received PTCy at City of Hope from 2009 to 2018 were included. A majority, 270 (98%) patients were diagnosed with early FO from day 3-8 post HCT, of whom 248 (92%) experienced mild to moderate (grade 1-2) FO, and 22 (8%) experienced severe (grade 3-4) FO. Day 100 NRM was significantly higher in patients with grade 3-4 FO compared to patients with grade 0-1 (59.1 vs 1.7%, CI: 0.006-0.053p&lt;0.001) and grade 2 (59.1 vs 8.8%, CI: 0.043-0.178, p&lt;0.001) FO. At 2 years, OS and DFS were significantly lower in patients who experienced grade 3-4 FO compared to patients who had grade 0-1 FO (31.8% vs 68.2%, CI: 0.616-0.755, p&lt;0.001) and grade 2 FO (31.8% vs 62.5%; CI: 0.527-0.741, p&lt;0.001). Additionally, each 5% weight gain from baseline was associated with higher NRM (HR=1.91, 95%CI: 1.64-2.23, p&lt;0.001).ConclusionAlmost all patients undergoing hyperhydration for PTCy-induced HC will present with FO. Grade 3-4 FO is uncommon and associated with poor clinical outcomes. Weight gain could be used as an early and possibly modifiable indicator of FO.
Serum HDL-C levels in children with epilepsy: a single-center retrospective study
Authors: Guo Hong-Li , Dong Na , Hu Ya-Hui , Qiu Jin-Chun , Jiang Zhen-Zhou , Liu Qian-Qi , Lu Xiao-Peng , Chen Feng 
Published: February 2025

PurposeThis study aims to compare the difference in serum high-density lipoprotein cholesterol (HDL-C) levels between children with epilepsy and healthy children and to assess its potential influencing factors.MethodsFor comparison, we retrospectively collected data on 1,002 children with epilepsy who visited the Department of Neurology at the Children’s Hospital of Nanjing Medical University. Additionally, we included 127 healthy children who underwent routine health examinations at our hospital’s Health Examination Center. This study also incorporated 98 recently diagnosed epilepsy patients who had not yet received treatment with anti-seizure medications (ASMs) as a source of baseline data. Demographic information and laboratory test results were retrieved from the hospital information system. The Kolmogorov–Smirnov test, the Mann–Whitney test, the Fisher’s exact test, odds ratios (OR), Spearman or Pearson correlation coefficients, and post-hoc analysis were used to conduct statistical analysis.ResultsHealthy children exhibited significantly higher serum levels of HDL-C compared to children with epilepsy and the baseline values. Notably, a higher percentage of children with epilepsy exhibited a low HDL-C levels (&lt;1.0 mmol/L) compared to healthy children, showing an increased risk of dyslipidemia (OR, 2.773; 95% CI, 0.9879–7.457). The type of ASMs had a notable effect on serum HDL-C levels, particularly with hepatic enzyme-inducing ASMs like oxcarbazepine, which significantly raised the serum HDL-C levels. The serum HDL-C levels were also associated with factors such as age, epilepsy history, and brain magnetic resonance imaging findings. Additionally, there was a weak negative association between serum vitamin D levels and serum HDL-C levels (R = -0.37, p = 0.0014). Moreover, children who received vitamin D supplementation demonstrated a higher level of HDL-C than those without such supplementation.ConclusionSerum HDL-C levels are notably lower in children with epilepsy than in healthy children. Treatment with ASMs can partially increase the serum HDL-C levels, potentially approaching those found in healthy children. Therefore, the decrease in serum HDL-C levels in children with epilepsy irrespective of receiving ASMs treatment should warrant ongoing attention.
Impacts of sarcopenia on adverse events and prognosis in Chinese patients with esophageal cancer undergoing chemoradiotherapy
Authors: Qu Jiaoyue , Liu Yang , Yuan Yin , Yu Zhao , Ding Jianming , He Zelai , Wang Gengming 
Published: February 2025

BackgroundSarcopenia is a common indicator of systemic nutritional status in patients with cancer progression. This study investigated the impacts of sarcopenia on adverse effects and prognosis of sarcopenia on patients with esophageal cancer receiving chemoradiotherapy.MethodsThe clinical data of 158 patients with initially diagnosed esophageal cancer who received chemoradiotherapy were collected, and nutritional indexes and inflammatory markers were calculated. The cross-sectional areas of the skeletal muscle, subcutaneous fat and visceral fat were calculated using computed tomography (CT) images of the midpoint of the third lumbar (L3) vertebra. The incidence of adverse events, response evaluation, 1-year and 3-year overall survival (OS) and progression-free survival (PFS) were compared between sarcopenia group and non-sarcopenia groups.ResultsThis study included 158 patients, 103 (71.5%) in the sarcopenia group and 45 (28.5%) in the non-sarcopenia group. The last follow-up date was January 31, 2024. The median follow-up time was 36 months for all patients. The chi-square test revealed no significant difference in the incidence of serious adverse events between the two groups. The complete response rates (CR) of patients in the sarcopenia and non-sarcopenia groups 1 month after chemoradiotherapy were 2.7 and 13.3%, respectively, p = 0.017, and the difference was statistically significant. Moreover, the objective response rates (ORR) were 38.9 and 60.0%, respectively (χ2 = 5.770, p = 0.016). The median survival time for all patients was 36 months [95% Confidence Interval CI 24–48]. Univariate analysis (Cox proportional risk model) showed that sarcopenia, KPS score, albumin level, T stage, and N stage were correlated with patients’ OS. Multivariate analysis showed that sarcopenia (Hazard Ratio HR 2.84, 95%CI [1.45–5.57], p = 0.002), KPS score, albumin level and N stage were independent prognostic factors for OS.ConclusionSarcopenia reduced OS in patients with EC treated with chemoradiotherapy. It can be used as an independent indicator to predict the OS of such patients, which may help in developing optimal treatment strategies.