bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ocular surface disease index in Graves’ orbitopathy: a cross-sectional study
Authors: Maglionico Maria Novella , Lanzolla Giulia , Figus Michele , Cosentino Giada , Comi Simone , Marinò Michele , Santini Ferruccio , Posarelli Chiara 
Published: December 2024

IntroductionGraves' Orbitopathy (GO) is an autoimmune disorder characterized by inflammation of orbital tissues, leading to various ocular manifestations, including ocular surface disease. This cross-sectional study aimed to assess the presence of ocular surface disease using the Ocular Surface Disease Index (OSDI) in patients with Graves' disease (GD) and moderate-to-severe active GO compared to those with GD and mild non-active GO. Additionally, we aimed to investigate the correlation between ocular surface disease and the eye features of GO.MethodsConsecutive GD patients with GO referred to the Ophthalmology and Endocrinology Units of the University Hospital of Pisa between June 2022 and February 2023 were enrolled. OSDI scores were obtained from 79 GD patients, categorized into moderate-to-severe active GO and mild non-active GO groups.ResultsOSDI scores were significantly higher in patients with moderate-to-severe active GO compared to those with mild non-active GO (P=0.0006). A cutoff value of 33 for positive tests revealed a higher frequency of pathological OSDI in moderate-to-severe active GO patients compared to mild non-active GO patients (P=0.0221; OR 3.673, CI 1.277-9.531). Within the moderate-to-severe active GO group, a significant positive correlation was found between OSDI and Clinical Activity Score (CAS) (R= 0.3867, 95% CI from 0.1403 to 0.5880; P=0.0030). Using a cutoff value of 55 (the 75th percentile of the study population), patients with CAS ≥ 3 had a significantly higher proportion of pathological OSDI compared to those with CAS &lt;3 (P=0.0039; OR 4.075, CI 1.619-10.39). Proptosis values ≥ 22 mm and the presence of lagophthalmos were identified as significant risk factors for ocular surface disease development (P=0.0406 and P=0.0493, respectively).DiscussionOur study highlights a significantly higher prevalence of ocular surface disease, as measured by OSDI, in patients with moderate-to-severe active GO compared to those with mild non-active disease. The degree of GO activity positively correlates with ocular surface involvement, and proptosis and lagophthalmos increase the risk of its occurrence. These findings emphasise the importance of assessing and managing ocular surface health in GO patients. Early identification and appropriate treatment of ocular surface disease need to be pursued to improve patient management.
Immune-related diagnostic markers for benign prostatic hyperplasia and their potential as drug targets
Authors: Wang YaXuan , Wang Jing , Liu Jibin , Zhu HaiXia 
Published: December 2024

BackgroundBenign prostatic hyperplasia (BPH) is a common issue among older men. Diagnosis of BPH currently relies on imaging tests and assessment of urinary flow rate due to the absence of definitive diagnostic markers. Developing more accurate markers is crucial to improve BPH diagnosis.MethodThe BPH dataset utilized in this study was sourced from the Gene Expression Omnibus (GEO). Initially, differential expression and functional analyses were conducted, followed by the application of multiple machine learning techniques to identify key diagnostic markers. Subsequent investigations have focused on elucidating the functions and mechanisms associated with these markers. The ssGSEA method was employed to evaluate immune cell scores in BPH samples, facilitating the exploration of the relationship between key diagnostic markers and immune cells. Additionally, molecular docking was performed to assess the binding affinity of these key markers to therapeutic drugs for BPH. Tissue samples from BPH patients were collected for experimental validation of the expression differences of the aforementioned genes.ResultA total of 185 differential genes were identified, comprising 67 up-regulated and 118 down-regulated genes. These genes are implicated in pathways that regulate extracellular matrix tissue composition and cellular responses to transforming growth factor beta stimulation, as well as critical signaling pathways such as AMPK and mTOR. Through the application of various machine learning techniques, DACH1, CACNA1D, STARD13, and RUNDC3B were identified as key diagnostic markers. The ssGSEA algorithm further corroborated the association of these diagnostic genes with diverse immune cells. Moreover, molecular docking analysis revealed strong binding affinities of these markers to tamsulosin and finasteride, suggesting their potential as drug targets. Finally, experimental validation confirmed the expression differences of DACH1, CACNA1D, STARD13, and RUNDC3B in BPH tissues.ConclusionThis study introduces novel immune-related diagnostic markers for BPH and highlights their promise as new drug targets, providing a valuable approach for predictive diagnosis and targeted therapy of BPH.
Single-cell transcriptome analysis reveals status changes of immune cells in chronic kidney disease
Authors: Fan Xinhuan , Zhu Yuxin , Kan Hao , Mao Aiqin , Geng Li , Li Changzhu , Zhang Ka 
Published: December 2024

Background and aimsThe immune system plays a crucial role in the development of kidney diseases. Chronic kidney disease (CKD) can lead to various complications, potentially affecting multiple systems throughout the body. Currently, the description of the immune system in human CKD is not comprehensive enough. Constructing a CKD kidney atlas using single-cell RNA sequencing (scRNA-seq) can provide deeper insights into the composition and functional changes of immune cells in CKD, facilitating the discovery of new therapeutic targets.MethodsWe processed and integrated scRNA-seq datasets from healthy and CKD kidneys from three independent cohorts using the same approach (including 42 normal samples and 23 chronic kidney disease samples). Subsequently, we conducted gene enrichment and intercellular communication analysis to construct an immune cell atlas of the kidneys in CKD patients.ResultsWe identified nine major kidney cell clusters. Further clustering analysis of different immune cell clusters revealed that, compared to normal kidneys, CKD patients’ kidneys had decreased CD16+ NK cells while CD4+ naive helper T cells and CCR7+ DC increased. Partial activation of the WNT signaling pathway was observed in T cells and NK cells of CKD patients, while some metabolism-related genes were inhibited. Myeloid cell subgroups also exhibited abnormal signaling pathway alterations. Additionally, we discovered a unique population of SPP1 macrophages in CKD, which are recruited by chemokines released from aPT and aTAL cell subpopulations. These SPP1 macrophages may promote cellular fibrosis through the signaling of SPP1, FN1, and various receptors.ConclusionWe established a human CKD kidney immune cell atlas and identified SPP1 macrophages as a unique cell type in CKD. The interaction between SPP1 macrophages and damaged cells may serve as a potential therapeutic target for treating CKD in the future.
Enhancing D-lactic acid production from non-detoxified corn stover hydrolysate via innovative F127-IEA hydrogel-mediated immobilization of Lactobacillus bulgaricus T15
Authors: Zheng Yuhan , Sun Feiyang , Liu Siyi , Wang Gang , Chen Huan , Guo Yongxin , Wang Xiufeng , Escobar Bonora Maia Lia , Zhang Sitong , Li Yanli , Chen Guang 
Published: December 2024

BackgroundThe production of D-lactic acid (D-LA) from non-detoxified corn stover hydrolysate is hindered by substrate-mediated inhibition and low cell utilization times. In this study, we developed a novel temperature-sensitive hydrogel, F127-IEA, for efficient D-LA production using a cell-recycle batch fermentation process.ResultsF127-IEA exhibited a porous structure with an average pore size of approximately 1 μm, facilitating the formation of stable Lactobacillus bulgaricus clusters within the gel matrix. It also maintains excellent mechanical properties. It also maintains excellent mechanical properties. F127-IEA immobilized Lactobacillus bulgaricus T15 (F127-IEA-T15) can be used in cell-recycle fermentation for over 150 days from glucose and 50 days from corn stover hydrolysate, achieving high production rates of D-LA from glucose (2.71 ± 0.85 g/L h) and corn stover hydrolysate (1.29 ± 0.39 g/L h). F127-IEA-T15 enhanced D-LA production by adsorbing and blocking toxic substances present in corn stover hydrolysate that are detrimental to cellular activity.ConclusionsThe newly developed hydrogels in this study provide a robust platform for large-scale extraction of D-LA from non-detoxified corn stover.
Case report: Ectopic production of intact parathyroid hormone (iPTH) by malignoma mimicking primary hyperparathyroidism
Authors: Wendt Ralph , Heller Marie , Härtwig Daniel , Ullmann Sven Oliver , Bisanz Heike , Geister Daniela , Mantovani Luisa , Hoffmann Ulrike 
Published: December 2024

BackgroundMalignant hypercalcemia is usually caused by osteolytic processes of metastases, production of parathormone-related peptide, or secretion of 1,25-dihydroxyvitamin D. Ectopic PTH (parathyroid hormone) production by malignancy is very unusual.MethodsCase report and review of the literature.ResultsWe present a case of a malignant hypercalcemia with a presentation that mimicked primary hyperparathyroidism in a patient with endometrial carcinoma. Finally, ectopic production of PTH by a rapidly progressive neuroendocrine tumor was proven. Systematic literature review revealed ectopic PTH production by malignancies as an extremely rare cause of hypercalcemia and that most cases were initially misdiagnosed as primary hyperparathyroidism and underwent unnecessary surgical neck exploration in almost all cases.ConclusionIn patients even with a suggestive constellation of primary hyperparathyroidism, an ectopic paraneoplastic PTH source should be considered if the localization diagnostics are without abnormalities or if the PTH values are unusually high. Concomitant elevated LDH levels should also raise concern about an ectopic malignant source.
ARMH1 is a novel marker associated with poor pediatric AML outcomes that affect the fatty acid synthesis and cell cycle pathways
Authors: Bakhtiari Mojtaba , Jordan Sean C. , Mumme Hope L. , Sharma Richa , Shanmugam Mala , Bhasin Swati S. , Bhasin Manoj 
Published: December 2024

IntroductionDespite remarkable progress in Pediatric Acute Myeloid Leukemia (pAML) treatments, the relapsed disease remains difficult to treat, making it pertinent to identify novel biomarkers of prognostic/therapeutic significance.Material and methodsBone marrow samples from 21 pAML patients were analyzed using single cell RNA sequencing, functional assays with ARMH1 knockdown and overexpression were performed in leukemia cell lines to evaluate impact on proliferation and migration, and chemotherapy sensitivity. Mitochondrial function was assessed via Seahorse assay, ARMH1 interacting proteins were studied using co-immunoprecipitation. Bulk RNA-seq was performed on ARMH1knockdown and over expressing cell lines to evaluate the pathways and networks impacted by ARMH1.ResultsOur data shows that ARMH1, a novel cancer-associated gene, is highly expressed in the malignant blast cells of multiple pediatric hematologic malignancies, including AML, T/B-ALL, and T/B-MPAL. Notably, ARMH1 expression is significantly elevated in blast cells of patients who relapsed or have a high-risk cytogenetic profile (MLL) compared to standard-risk (RUNX1, inv (16)). ARMH1 expression is also significantly correlated with the pediatric leukemia stem cell score of 6 genes (LSC6) associated with poor outcomes. Perturbation of ARMH1 (knockdown and overexpression) in leukemia cell lines significantly impacted cell proliferation and migration. The RNA-sequencing analysis on multiple ARMH1 knockdown and overexpressing cell lines established an association with mitochondrial fatty acid synthesis and cell cycle pathways.The investigation of the mitochondrial matrix shows that pharmacological inhibition of a key enzyme in fatty acid synthesis regulation, CPT1A, resulted in ARMH1 downregulation. ARMH1 knockdown also led to a significant reduction in CPT1A and ATP production as well as Oxygen Consumption Rate. Our data indicates that downregulating ARMH1 impacts cell proliferation by reducing key cell cycle regulators such as CDCA7 and EZH2. Further, we also established that ARMH1 is a key physical interactant of EZH2, associated with multiple cancers.ConclusionOur findings underscore further evaluation of ARMH1 as a potential candidate for targeted therapies and stratification of aggressive pAML to improve outcomes.
Demographic and clinical characteristics of hospitalized children with suspected and laboratory-confirmed COVID-19 during the six waves of SARS-CoV-2 infection in northern Iran a retrospective cohort study
Authors: Mohammadi Mohsen , Hashemi Erfan , Shirafkan Hoda , Sadeghi Farzin , Yahyapour Yousef 
Published: December 2024

IntroductionNorthern Iran is one of the regions of the country most affected by COVID-19. The aim of the current study was to examine the demographics, clinical characteristics, and outcomes of suspected and laboratory-confirmed patients &lt;18 years of age hospitalized over two years (during six waves of SARS-CoV-2).MethodsThis retrospective cohort study examined hospitalized patients with suspected SARS-CoV-2 infection in Babol, northern Iran. The study included patients &lt;18 years of age admitted to a pediatric referral hospital from March 7, 2020 to March 20, 2022. Epidemiological and demographic characteristics, real-time PCR cycle threshold (Ct), clinical data and COVID-19 results were analyzed in the hospitalized patients.ResultsTotally, 2,731 patients with suspected COVID-19 were examined from March 2020 to 2022, with a mean age of 4.6 years, and were male (54.3%). Most suspected cases occurred during the fifth (Delta) and sixth (Omicron) relapse (30% and 20%, respectively). Among them, 461 patients had comorbidities, with brain and neurological diseases (BND), malignancies and hematopoietic and blood disorders (HBDs) being the most common (6.7%, 2.6% and 2.1%, respectively). Real-time RT- PCR showed that 391 patients were positive. The mean age of the positive patients was 5.2 years. Most positive cases were in the fifth wave (30.9%), male (53.7%) and 1–5 years old (49.1%). BND (9.5%) and cardiovascular diseases (CVD) (4.3%) were common underlying conditions. A higher viral load (Ct score = 9–20) was most common in the fifth wave. Moreover, 8.7% of ICU admissions and 2.4% of deaths were due to a Ct score of 9–20. Most deaths occurred in the 1–5 age group and were associated with BND. More deaths occurred in women (73.9% overall, 71.4% real-time RT- PCR -positive), and the highest mortality was in the fifth wave. The risk ratio of mortality was higher in children with kidney disease (KD) and BND.ConclusionThere were 27 ICU admissions (6.9%) and seven deaths (1.8%). The current study also revealed that children of any age can be susceptible to SARS-CoV-2 infection, while children aged 1–5 years are more susceptible to COVID-19. The Delta variant is associated with higher rates of hospitalization and ICU admission, and the presence of BND is associated with higher mortality rates.
Interventions for prevention and treatment of trastuzumab-induced cardiotoxicity: an umbrella review of systematic reviews and meta-analyses
Authors: Wang Yunfang , Xu Jianguo , Xie Yafei , Zhou Dan , Guo Mingyue , Qin Yu , Yi Kang , Tian Jinhui , You Tao 
Published: December 2024

BackgroundTrastuzumab therapy for HER2-positive cancers is associated with cardiotoxicity. This umbrella review synthesizes evidence from systematic reviews and meta-analyses on cardioprotective interventions during trastuzumab treatment.MethodsA comprehensive search was conducted in PubMed, Embase, Cochrane Library, and Web of Science. Systematic reviews and meta-analyses examining cardioprotective interventions in patients receiving trastuzumab were included. The methodological quality was assessed using the AMSTAR-2 tool. Data on cardiac events, treatment interruptions, left ventricular ejection fraction (LVEF) changes, and exercise interventions were synthesized.ResultsTen systematic reviews met the inclusion criteria. Statins demonstrated the strongest cardioprotective effect (RR = 0.47, 95% CI: 0.26–0.84), potentially preventing more than half of cardiac events during trastuzumab therapy, followed by beta-blockers (RR = 0.61, 95% CI: 0.39–0.93). Beta-blockers and ACEIs effectively reduced treatment interruptions, enabling approximately 40% more patients to maintain treatment continuity (RR = 0.63, 95% CI: 0.47–0.86). Among non-pharmacological interventions, structured exercise programs showed significant benefits in preserving cardiac function, demonstrating meaningful improvements in resting LVEF (WMD = −3.27%, 95% CI: −5.86 to −0.68).DiscussionThis review demonstrates that cardioprotective interventions, particularly statins and beta-blockers, significantly reduce the risk of cardiac complications during trastuzumab therapy. The positive impact on cardiac events and treatment interruptions suggests these interventions may enhance overall treatment efficacy by allowing more patients to complete their prescribed course.ConclusionEvidence strongly supports the systematic implementation of cardioprotective strategies in clinical practice, particularly statins and beta-blockers, as part of routine care protocols for patients receiving trastuzumab therapy. These interventions demonstrate significant potential in preventing cardiac complications and maintaining treatment continuity. Further research should focus on optimizing personalized approaches and evaluating long-term outcomes.
Predicting the diabetic foot in the population of type 2 diabetes mellitus from tongue images and clinical information using multi-modal deep learning
Authors: Tian Zhikui , Wang Dongjun , Sun Xuan , Cui Chuan , Wang Hongwu 
Published: December 2024

AimsBased on the quantitative and qualitative fusion data of traditional Chinese medicine (TCM) and Western medicine, a diabetic foot (DF) prediction model was established through combining the objectified parameters of TCM and Western medicine.MethodsThe ResNet-50 deep neural network (DNN) was used to extract depth features of tongue demonstration, and then a fully connected layer (FCL) was used for feature extraction to obtain aggregate features. Finally, a non-invasive DF prediction model based on tongue features was realized.ResultsAmong the 391 patients included, there were 267 DF patients, with their BMI (25.2 vs. 24.2) and waist-to-hip ratio (0.953 vs. 0.941) higher than those of type 2 diabetes mellitus (T2DM) group. The diabetes (15 years vs. 8 years) and hypertension durations (10 years vs. 7.5 years) in DF patients were significantly higher than those in T2DM group. Moreover, the plantar hardness in DF patients was higher than that in T2DM patients. The accuracy and sensitivity of the multi-mode DF prediction model reached 0.95 and 0.9286, respectively.ConclusionWe established a DF prediction model based on clinical features and objectified tongue color, which showed the unique advantages and important role of objectified tongue demonstration in the DF risk prediction, thus further proving the scientific nature of TCM tongue diagnosis. Based on the qualitative and quantitative fusion data, we combined tongue images with DF indicators to establish a multi-mode DF prediction model, in which tongue demonstration and objectified foot data can correct the subjectivity of prior knowledge. The successful establishment of the feature fusion diagnosis model can demonstrate the clinical practical value of objectified tongue demonstration. According to the results, the model had better performance to distinguish between T2DM and DF, and by comparing the performance of the model with and without tongue images, it was found that the model with tongue images performed better.
Factors predicting the mathematics anxiety of adolescents: a structural equation modeling approach
Authors: Ahmmed Suman , Saha Jashodhan , Tamal Maruf Ahmed , Abdullah Al Mamun Khondaker , Islam Sajani 
Published: December 2024

IntroductionMathematics anxiety (MA) is a distinct negative emotional state or trait that individuals experience when confronted with mathematical problems in everyday life and academic contexts. This study aims to identify the key predictors of MA among secondary-level students in Bangladesh.MethodsUtilizing a quantitative cross-sectional research design, data were collected from 486 students across 89 institutions. Later, the data were analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM).ResultsThe findings revealed that math related negative past experiences (β = 0.241, t = 4.914, p &lt; 0.001) and a perceived lack of teacher support (β = 0.234, t = 5.440, p &lt; 0.001) significantly contribute to students’ low self-efficacy in mathematics. This low self-efficacy is further influenced by negative attitudes and test anxiety, ultimately leading to increased MA (β = 0.694, t = 22.695, p &lt; 0.001). Additionally, cognitive challenges, particularly working memory difficulties, directly affect MA (β = 0.110, t = 2.659, p = 0.008). The study also found that negative attitudes (β = 0.347, t = 9.063, p &lt; 0.001) and test anxiety (β = 0.251, t = 5.913, p &lt; 0.001) independently exacerbate MA. Moreover, a lack of motivation in learning mathematics is directly influenced by this elevated level of MA (β = 0.384, t = 9.939, p &lt; 0.001).DiscussionTaken together, the study proposes several key recommendations and policy implications to inform the development of synchronized policies by educational authorities aimed at combatting, reducing MA among secondary-level students in Bangladesh and similar contexts.
Linking adolescents’ phubbing to depression: the serial mediating effects of peer relationship quality and psychological need frustration
Authors: Yue Heng , Gao Shiwen , Feng Fei , Wu Feiteng , Bao Hugejiletu , Zhang Xuemin 
Published: December 2024

IntroductionPhubbing is defined as a phenomenon in which individuals use their smartphones during conversations with others, focusing on the smartphones and escaping from interpersonal interactions. This phenomenon has been extensively studied in the literature. However, most studies concerning phubbing have focused on understanding its impact on the receivers; few have investigated the consequences of phubbing on the actors themselves. The present study aimed to explore the link between adolescents’ phubbing behavior and depression, focusing on the underlying psychological mechanisms.MethodsA total of 441 Chinese high school students participated in this study in September 2023. SPSS 25.0 and AMOS 24.0 were used to analyze the data. A hierarchical linear regression analysis was used to test the effect of phubbing on depression. A serial mediation model was applied to assess the roles of peer relationship quality and psychological need frustration in the link between phubbing and depression.ResultsThis study found that among adolescents, (1) phubbing had a significant direct association with depression; (2) phubbing had two significant indirect associations with depression, separately mediated via peer relationship quality and psychological need frustration; (3) the direct effect of phubbing on depression was sequentially mediated through peer relationship quality and psychological need frustration; (4) these results were applicable to both male and female adolescents.DiscussionThese findings suggested that interventions aimed at improving peer relationships and addressing psychological need frustration might reduce depressive symptoms associated with phubbing in adolescents.