bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fathers’ perceptions of factors associated with the attainment of paternity leave: a qualitative study
Authors: Mita Naoyuki , Khin Yu Par , Nawa Nobutoshi , Yamaoka Yui , Fujiwara Takeo 
Published: January 2025

BackgroundA systematic review has reported that paternal involvement is beneficial in reducing social, behavioural and psychological problems in children. However, little research has investigated factors associated with the attainment of paternity leave.ObjectiveThe objective of this study was to explore fathers’ perceptions of the factors associated with taking paternity leave.Participants and settingOverall, 21 in-depth interviews were conducted with fathers to obtain information on their perceptions of paternity leave. We also conducted key informant interviews with four supervisors at companies to understand their opinions on paternity leaves and ensure that the implications of this study are relevant at workplaces.MethodsThematic analysis was adopted to analyse the data. Deductive coding was conducted based on previous studies on paternity leave, followed by inductive coding and modification of the initial codes. The final codes were organised based on the social-ecological model.ResultsThemes associated with taking paternity leave included fathers’ career aspirations, fathers’ commitment to supporting infants or mothers, mothers’ or infants’ need for fathers’ involvement, colleagues’ outlook on paternity leaves, fathers’ work schedules or responsibilities, support from relatives, paternity leave policies, and trends toward fathers’ involvement. The supervisors mentioned themes related to paternity leave from the broader perspective of long-term effects and impact on the organisation.ConclusionsThis study revealed fathers’ perceptions regarding the factors associated with taking paternity leave. The results may provide useful information on how to create an environment in which fathers can easily take paternity leave.
Serum and tear autoantibodies from NOD and NOR mice as potential diagnostic indicators of local and systemic inflammation in Sjögren’s disease
Authors: Singh Kakan Shruti , Abdelhamid Sara , Ju Yaping , MacKay J. Andrew , Edman Maria C. , Raman Indu , Zhu Chengsong , Raj Prithvi , Hamm-Alvarez Sarah F. 
Published: January 2025

BackgroundSjögren’s Disease (SjD) is an autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands (LG). The LG produces the protein-rich aqueous component of tears, and SjD-associated autoimmune dacryoadenitis (AD) may thus alter tear autoantibody composition.MethodsThe presence of tertiary lymphoid structures (TLS) in LG from two murine models of SjD-associated AD, male non-obese diabetic (NOD) and male non-obese insulitis resistant (NOR) mice, were evaluated using immunofluorescence. IgG and IgA reactivity in serum and tears from these models were probed in three studies against a panel of 80-120 autoantigens using autoantibody microarrays relative to serum and tears from healthy male BALB/c mice. Sources of Ig in tears were investigated using scRNA-Seq of the LG (GSE132420). Data were analyzed by R package Limma and Seurat.ResultsAnalysis of immunofluorescence in LG sections from both SjD models showed TLS. Only one autoantibody was significantly elevated in tears and serum in both SjD models across all studies. Three autoantibodies were significantly elevated in serum but not in tears in both SjD models across all studies. Conversely, six IgG and thirteen IgA autoantibodies (6 sharing the same autoantigen) were significantly elevated in tears but not serum in both SjD models. Igha and Ighg2b expressing cells were identified in the plasma cell cluster of NOD.H2b LG.ConclusionNOD and NOR mice with SjD-associated AD have distinct autoantibody profiles in tears and serum. Tear IgA isotype autoantibodies showed a greater diversity than tear IgG autoantibodies. TLS observed in LG are a likely source of the tear autoantibodies.
Identification of WDR74 and TNFRSF12A as biomarkers for early osteoarthritis using machine learning and immunohistochemistry
Authors: Chen Yiwei , Lin Jiali , Shi Detong , Miao Yu , Xue Feng , Liu Kexin , Wang Xiaotao , Zhang Changqing 
Published: January 2025

BackgroundOsteoarthritis (OA) is a chronic joint condition that causes pain, limited mobility, and reduced quality of life, posing a threat to healthy aging. Early detection is crucial for improving prognosis. Recent research has focused on the role of ubiquitination-related genes (URGs) in early OA prediction. This study aims to integrate URG expression data with machine learning (ML) to identify biomarkers that improve diagnosis and prognosis in the early stages of OA.MethodsOA single-cell RNA sequencing datasets were collected from the GEO database. Single-cell analysis was performed to investigate the composition and relationships of chondrocytes in OA. The potential intercellular communication mechanisms were explored using the CellChat R package. URGs were retrieved from GeneCards, and ubiquitination scores were calculated using the AUCell package. Gene module analysis based on co-expression network analysis was conducted to identify core genes. Additionally, ML analysis was performed to identify core URGs and construct a diagnostic model. We employed XGBoost, a gradient-boosting ML algorithm, to identify core URGs and construct a diagnostic model. The model’s performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. In addition, we explored the relationship between core URGs and immune processes. The ChEA3 database was utilized to predict the transcription factors regulated by core ubiquitination-related genes. The expression of select URGs was validated using qRT-PCR and immunohistochemistry (IHC).ResultsWe identified WDR74 and TNFRSF12A as pivotal ubiquitination-related genes associated with OA, exhibiting considerable differential expression. The diagnostic model constructed with URGs exhibited remarkable accuracy, with area under the curve (AUC) values consistently exceeding 0.9. The expression levels of WDR74 and TNFRSF12A were significantly higher in the IL-1β-induced group in an in vitro qPCR experiment. The IHC validation on human knee joint specimens confirmed the upregulation of WDR74 and TNFRSF12A in OA tissues, corroborating their potential as diagnostic biomarkers.ConclusionsWDR74 and TNFRSF12A as principal biomarkers highlighted their attractiveness as therapeutic targets. The identification of core biomarkers might facilitate early intervention options, potentially modifying the illness trajectory and enhancing patient outcomes.
Age influences the circulating immune profile in pediatric sepsis
Authors: Fisler Grace , Brewer Mariana R. , Yaipen Omar , Deutschman Clifford S. , Taylor Matthew D. 
Published: January 2025

BackgroundThe immune response changes as patients age, yet studies on the immune dysregulation of sepsis often do not consider age as a key variable.ObjectiveWe hypothesized that age would influence the immune response in septic children and that there would be a distinct variation in the immune profile in healthy children and children with either sepsis, uncomplicated infection, or acute organ dysfunction without infection. We characterized the circulating immune profile of children presenting to our tertiary care children’s hospital.MethodsThis investigation was a prospective, observational cohort study that enrolled patients from July 2020 – September 2022. Patients were included if they were &lt; 21 years, admitted to the PICU, and received fluid resuscitation and antibiotics. Peripheral blood mononuclear cells were isolated from samples collected on PICU day 1.ResultsEighty patients were enrolled. Children with sepsis had more regulatory CD4+ T cells and memory CD4+ T cells and less CD4+IL-10+ and CD8+T-bet+ T cells than healthy children. After ex vivo stimulation, sepsis samples had less of a reduction in CD4+ T cells producing IL-10 than healthy controls. Memory CD4+ T cells and regulatory CD4+ T cells were positively associated with age in sepsis alone.ConclusionA regulatory T cell failure may contribute to pediatric sepsis pathogenesis. Age is an important variable affecting sepsis-associated immune dysregulation and memory T cells in peripheral circulation correlate with age in sepsis alone.
Comprehensive analysis of Pan-Immune Inflammation and all-cause mortality in rheumatoid arthritis: a database-driven approach, 1999-2018
Authors: Mardan Muradil· , Zheng Huoliang , Xu Qingyin , Song Shaokuan , Lu Zeyu , Deng Hui , Cai Hao , Chen Qizhu , Yang Bingyi , Abuduwufuer Kudelaiti· , Chen Pengbo , Li Bo , Jiang Shengdan , Jiang Leisheng , Zheng Xin-feng 
Published: January 2025

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease marked by systemic inflammation and immune dysregulation, leading to a higher risk of all-cause mortality. The Pan-Immune Inflammation Value (PIV), a novel biomarker capturing immune-inflammatory activity, has shown prognostic value in various diseases. However, its role in predicting outcomes in RA patients remains largely unexplored.ObjectivesThis study aimed to evaluate the association between PIV and all-cause mortality in RA patients, investigate nonlinear relationships, and identify threshold effects.MethodsData from the 1999–2018 National Health and Nutrition Examination Survey (NHANES) were used, including 1,882 RA patients. PIV was calculated as (neutrophil count×platelet count×monocyte count)/lymphocyte count and categorized into quartiles (Q1–Q4). Multivariable Cox proportional hazards models were applied to assess the relationship between PIV and mortality, with results expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic splines (RCS) explored nonlinear trends, and segmented Cox regression identified threshold effects. Kaplan-Meier survival curves and subgroup analyses validated the findings and assessed potential modifiers.ResultsElevated PIV levels were strongly associated with increased all-cause mortality. Compared to Q1, adjusted HRs for Q2, Q3, and Q4 were 1.60 (95% CI: 1.01–2.53, P = 0.047), 1.70 (95% CI: 1.10–2.63, P = 0.016), and 2.12 (95% CI: 1.33–3.37, P = 0.002), respectively (P for trend &lt; 0.001). RCS analysis revealed a nonlinear relationship with a threshold at PIV = 302. Below this threshold, increasing PIV was associated with higher mortality risk (HR = 1.67, 95% CI: 1.07–2.61, P = 0.024). Conversely, above the threshold, further increases in PIV were linked to reduced mortality risk (HR = 0.98, 95% CI: 0.97–0.99, P = 0.026). Kaplan-Meier survival curves showed a clear decline in survival probability with increasing PIV quartiles (P &lt; 0.001). Subgroup analyses confirmed consistent findings, with a notable interaction observed in diabetic patients (P for interaction = 0.002).ConclusionsPIV is a significant and independent predictor of all-cause mortality in RA patients, characterized by a nonlinear association and a distinct threshold effect. These findings highlight the potential of PIV as a pragmatic biomarker for stratifying mortality risk and informing personalized treatment strategies in RA.
Postnatal health of infants born to mothers with autoimmune diseases when treated with hydroxychloroquine
Authors: Matys Viviana , Rizzo Francesca , De Carolis Maria Pia , Barresi Salvatore , Serio Anna Maria , Lanzone Antonio , Garufi Ester , De Carolis Sara , Garufi Cristina 
Published: January 2025

IntroductionThis retrospective cohort study aimed to observe the postnatal health of infants born to mothers with systemic autoimmune rheumatic diseases treated with hydroxychloroquine (HCQ) during pregnancy.MethodsA total of 312 pregnancies of patients who suffered from different systemic autoimmune rheumatic diseases were considered. Pregnancy data were collected; a telephone follow-up questionnaire was successfully completed in 182 infants to detect the long-term pediatric outcome. The women who took hydroxychloroquine during pregnancy were defined as “HCQ group” and were compared to women who did not take hydroxychloroquine, “non-HCQ group”.ResultsA higher prevalence of women with multiple maternal diseases was detected in the HCQ group, in comparison to that of non-HCQ group (p = 0.0015). Despite HCQ group consisting of more complicated maternal conditions, the obstetrical and neonatal outcomes were similar between the two groups. Regarding postnatal health, 40% of infants in HCQ group revealed no pathologies versus 25% of the children in non-HCQ group (p = 0.0368).DiscussionThe protective role of HCQ on infants should be further evaluated in prospective multicenter long-term studies.
The mechanism of endoplasmic reticulum (ER) stress in cell apoptosis and ROS (reactive oxygen species) of CNE2 cell line induced by single wall carbon nanohorn (SWCNH)
Authors: Cao Xianbao , Gong Shunmin , Chen Shujin , Hu Shuang , Li Tianshu , Guan Yanfei , Feng Chun , Zhang Jinqian 
Published: January 2025

IntroductionThe interaction between the materials themselves and cancer cells are rarely explored. Therefore, the biological roles of raw single wall carbon nanohorn (SWCNH) on endoplasmic reticulum (ER) stress in the apoptosis of CNE2 were explored.MethodsTherefore, ERS of CNE2 cells was induced by SWCNH, and 4-phenylbutyrate (4-PBA) was selected as a inhibitor of ERS. CNE2 cells were co-cultured with SWCNH, 4-PBA and SWCNH+4-PBA, respectively. Furthermore, the apoptotic status of CNE2 cells and its ROS (Reactive oxygen species) levels were determined. Moreover, the apoptotic protein expression of caspase 3 (cysteinyl aspartate specific proteinase 3), the expression levels of ER pathway protein eIF2α, ATF4 and CHOP, or the OS (Oxidative stress)-related proteins NQO1, GCLC, HO-1, and Nrf2 was detected, respectively.ResultsCNE2 apoptotic rate, ROS levels, the caspase 3 or ER pathway proteins ATF4 and CHOP expression, even the NQO1, GCLC, HO-1, and Nrf2 levels of oxidative stress-related proteins in the groups of SWCNH and SWCNH+4-PBA were higher compared to the control group. Moreover, these indicators were higher compared to the group of SWCNH+4-PBA (p &lt; 0.05).DiscussionER stress is the key possible mechanism of CNE2 apoptosis induced by SWCNH. After injury of ERS, SWCNH causes oxidative stress injury, which may eventually lead to apoptosis of CNE2 cells.
Hypertension moderates the relationship between plasma beta-amyloid and cognitive impairment: a cross-sectional study in Xi’an, China
Authors: Liu Ziyu , He Yaoli , Cui Simeng , Dang Liangjun , Zhang Binyan , Wang Jin , Lu Wenhui , Huo Kang , Jiang Yu , Chen Chen , Gao Ling , Wei Shan , Zhao Yi , Hu Ningwei , Wang Jingyi , Lv Hong , Qu Qiumin , Shang Suhang 
Published: January 2025

BackgroundPlasma beta-amyloid (Aβ) are important biomarkers for Alzheimer’s disease and cognitive impairment (CI), but results are controversial. It remains unclear whether hypertension modulates their relationship. This cross-sectional study investigates whether hypertension moderates the relationship between plasma Aβ and cognitive impairment (CI).MethodsThis cross-sectional study included 1488 subjects ≥ 40 years from rural areas of northwestern China. CI was defined as a Mini-Mental State Examination score lower than the cutoff. Firstly, plasma Aβ40, Aβ42, Aβ42/Aβ40 were analyzed as restricted cubic spline. Then, categories of combined plasma Aβ were created by making bisection of plasma Aβ according to average and combining them as L-Aβ40 and L-Aβ42, H-Aβ40 and L-Aβ42, L-Aβ40 and H-Aβ42, H-Aβ40 and H-Aβ42. Decreased plasma Aβ40 was defined as &lt; 25th percentile. Multivariate logistic regression examined the relationship between plasma Aβ and CI in total population, the hypertension subgroup and the non-hypertension subgroup.Results737 participants (49.5%) had hypertension and 189 participants (12.7%) had CI. Simultaneously elevated plasma Aβ40 and Aβ42 was associated with CI in hypertension (H-Aβ40 and H-Aβ42 vs. L-Aβ40 and L-Aβ42, 21.1% vs.10.7%, P = 0.033; OR = 1.984 [95% CI, 1.067–3.691], P = 0.030) but not in the non-hypertension. Decreased plasma Aβ40 was associated with CI in the non-hypertension (14.9% vs. 9.2%, P = 0.026; OR = 1.728 [95% CI, 1.018–2.931], P = 0.043) but not in the hypertension.ConclusionHypertension is an important modulator in the relationship between plasma Aβ and CI. Simultaneously elevated plasma Aβ40 and Aβ42 in the hypertension, and decreased plasma Aβ40 in the non-hypertension, may be risk factors for CI. These findings emphasize the need to consider hypertension in CI detection.
Altered brain functional network connectivity and topology in type 2 diabetes mellitus
Authors: Ni Weiwei , Liu Weiyin Vivian , Li Mingrui , Wei Shouchao , Xu Xuanzi , Huang Shutong , Zhu Lanhui , Wang Jieru , Wen Fengling , Zhou Hailing 
Published: January 2025

IntroductionType 2 diabetes mellitus (T2DM) accelerates brain aging and disrupts brain functional network connectivity, though the specific mechanisms remain unclear. This study aimed to investigate T2DM-driven alterations in brain functional network connectivity and topology.MethodsEighty-five T2DM patients and 67 healthy controls (HCs) were included. All participants underwent clinical, neuropsychological, and laboratory tests, followed by MRI examinations, including resting-state functional magnetic resonance imaging (rs-fMRI) and three-dimensional high-resolution T1-weighted imaging (3D-T1WI) on a 3.0 T MRI scanner. Post-image preprocessing, brain functional networks were constructed using the Dosenbach atlas and analyzed with the DPABI-NET toolkit through graph theory.ResultsIn T2DM patients, functional connectivity within and between the default mode network (DMN), frontal parietal network (FPN), subcortical network (SCN), ventral attention network (VAN), somatosensory network (SMN), and visual network (VN) was significantly reduced compared to HCs. Conversely, two functional connections within the VN and between the DMN and SMN were significantly increased. Global network topology analysis showed an increased shortest path length and decreased clustering coefficient, global efficiency, and local efficiency in the T2DM group. MoCA scores were negatively correlated with the shortest path length and positively correlated with global and local efficiency in the T2DM group. Node network topology analysis indicated reduced clustering coefficient, degree centrality, eigenvector centrality, and nodal efficiency in multiple nodes in the T2DM group. MoCA scores positively correlated with clustering coefficient and nodal efficiency in the bilateral precentral gyrus in the T2DM group.DiscussionThis study demonstrated significant abnormalities in connectivity and topology of large-scale brain functional networks in T2DM patients. These findings suggest that brain functional network connectivity and topology could serve as imaging biomarkers, providing insights into the underlying neuropathological processes associated with T2DM-related cognitive impairment.
Optimal channel and feature selection for automatic prediction of functional brain age of preterm infant based on EEG
Authors: Li Ling , Li Jiahui , Wu Hui , Zhao Yanping , Liu Qinmei , Zhang Hairong , Xu Wei 
Published: January 2025

IntroductionApproximately 15 million premature infants are born each year, many of whom face risks of neurological impairments. Accurate assessment of brain maturity is crucial for timely intervention and treatment planning. Electroencephalography (EEG) is a noninvasive method commonly used for this purpose. However, using all channels and features for brain maturity assessment can lead to high computational burden and overfitting, which can decrease the performance of the prediction system.MethodsIn this study, we propose an automatic prediction framework based on EEG to predict functional brain age (FBA) for assessing brain maturity in preterm infants. To optimize channel selection, we combine Binary Particle Swarm Optimization (BPSO) with Forward Addition (FA) and Backward Elimination (BE) methods. For feature selection, we combine the Pearson Correlation Coefficient (PCC), Recursive Feature Elimination (RFE), and Support Vector Regression (SVR) model.ResultsThe proposed framework achieved a prediction accuracy of 76.71% within ±1 week and 94.52% within ±2 weeks. Effective channel and feature selection significantly improved model performance while reducing computational costs.DiscussionThese results demonstrate that optimizing channel and feature selection can enhance the performance of FBA prediction in preterm infants, offering a more efficient and accurate tool for brain maturity assessment.
Association of oxidative balance score with all-cause and cardiovascular mortality in overweight and obese
Authors: Ying Shuxin , Ding Hongyan , Chen Yanjin , Zheng Su 
Published: January 2025

BackgroundThe oxidative balance score (OBS) combines diverse dietary components with lifestyle factors to comprehensively evaluate oxidative stress. The investigation focuses on the link between the OBS and mortality outcomes, including cardiovascular and all-cause deaths, in overweight and obese individuals.MethodsThe analysis utilized data from the National Health and Nutrition Examination Survey (NHANES), covering the period from 1999 to 2018. Mortality information, categorized into all-cause and cardiovascular deaths, was gathered from the National Death Index (NDI). Kaplan–Meier survival analysis, along with multivariate Cox regression and restricted cubic spline (RCS) modeling, were utilized to explore the link between OBS and mortality risks. Subgroup analysis and sensitivity analysis were used to assess the robustness of the results and possible effect modifiers. Mediation analysis identifies pathways through which the independent variable affects the dependent variable.ResultsIn this study, 26,219 participants with overweight or obesity were enrolled, with an average age of 49.8 ± 17.4 years. During a median follow-up duration of 115 months, 2,239 participants (8.5%) died, including 837 (3.2%) from cardiovascular disease. According to Kaplan–Meier analysis, mortality was highest among participants in the lowest OBS quartile (Q1) and lowest among those in the highest quartile (Q4). Participants in the fourth OBS quartile experienced a 21.7% decrease in the risk of mortality from all causes and a 29.5% decrease in cardiovascular mortality risk, according to fully adjusted results, compared to those in the first quartile. These results were validated through subgroup analyses. The analysis of RCS revealed a notable inverse association between OBS and mortality outcomes. Mediation analysis indicates that white blood cell count (WBC) and gamma-glutamyl transferase (GGT) serve as significant mediators in the association between OBS and mortality risk.ConclusionElevated levels of OBS were strongly linked to reduced potential for both cardiovascular and all-cause mortality among individuals who are overweight or obese.