bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonlinear associations between sleep duration and the risks of all-cause and cardiovascular mortality among the general adult population: a long-term cohort study
Authors: Li Jie , Wu Qiyong , Fan Li , Yan Zining , Shen Dan , Zhang Ming 
Published: June 2023

ObjectiveThis study aims to investigate the correlation between sleep duration and all-cause and cardiovascular mortality in the general population.MethodsA total of 26,977 participants aged ≥18 years were included in the analysis from the National Health and Nutrition Examination Survey (NHANES) database covering the period from 2005 to 2014. Data on cardiovascular and all-cause deaths were collected until December 2019. Sleep duration was assessed using a structured questionnaire, and participants were categorized into five groups based on their reported sleep duration (≤5, 6, 7, 8, or ≥9 h). Kaplan-Meier survival curves were employed to examine the mortality rates across different sleep duration groups. Multivariate Cox regression models were utilized to explore the association between sleep duration and mortality. Additionally, a restricted cubic spline regression model was employed to identify the non-linear relationship between sleep duration and all-cause and cardiovascular mortality.ResultsThe average age of participants was 46.23 ± 18.48 years, with 49.9% of the subjects being male. Over a median follow-up period of 9.42 years, 3,153 (11.7%) participants died from all-cause mortality, among which 819 (3.0%) were attributed to cardiovascular causes. The groups with sleep durations of ≥9 and ≤5 h exhibited the lowest cumulative survival rates for all-cause mortality and cardiovascular mortality, respectively. When using a sleep duration of 7 h as the reference, the hazard ratios (with 95% confidence intervals) for all-cause mortality were 1.28 (1.14–1.44) for ≤5 h, 1.10 (0.98–1.23) for 6 h, 1.21 (1.10–1.34) for 8 h, and 1.53 (1.35–1.73) for ≥9 h. The hazard ratios (with 95% confidence intervals) for cardiovascular mortality were 1.32 (1.04–1.67) for ≤5 h, 1.22 (0.97–1.53) for 6 h, 1.29 (1.05–1.59) for 8 h, and 1.74 (1.37–2.21) for ≥9 h. A U-shaped non-linear relationship between sleep duration and all-cause and cardiovascular mortality was observed, with inflection point thresholds at 7.32 and 7.04 h, respectively.ConclusionThe findings suggest that the risk of all-cause and cardiovascular mortality is minimized when sleep duration is approximately 7 h.
Association between systemic immune-inflammation index and risk of lower extremity deep venous thrombosis in hospitalized patients: a 10-year retrospective analysis
Authors: Chen Xi , Ou Yili , Wang Zhicong , Liu Hailong , Liu Yuehong , Liu Mozhen 
Published: June 2023

BackgroundThe systemic immune-inflammation index (SII), as a novel inflammatory biomarker, has recently attracted attention in cardiovascular disease research. However, the relationship between SII and risk of lower extremity deep venous thrombosis (LEDVT) remains unclear to date. Thus, this study aimed to explore the association in a large sample over a 10-year period (2012–2022).MethodsAll hospitalized patients undergoing lower extremity compression ultrasonography (CUS) examination were consecutively screened by searching our hospital information system database. The receiver operating characteristic (ROC) curve analysis was used to identify the optimal cut-off value for high and low SII group. Multivariate logistic regression analyses were performed to investigate the relationship between SII and LEDVT risk. Propensity score matching (PSM), subgroup and sensitivity analyses were also conducted. Moreover, restricted cubic spline (RCS) regression and two-piecewise linear regression models were used to assess the dose-response relationship between natural log transformed SII [ln(SII)] and risk of LEDVT.ResultsA total of 16,725 consecutive hospitalized patients were included, and 1,962 LEDVT events occurred. After adjusting for confounding factors, patients in the high SII group (≥ 574.2 × 109/L) showed a 1.740-fold risk of LEDVT (95% CI: 1.546–1.959, P &lt; 0.001), and elevated ln(SII) was associated with a 36.1% increased risk of LEDVT (95% CI: 1.278–1.449, P &lt; 0.001). PSM, subgroup and sensitivity analyses confirmed the robustness of the association. A non-linear relationship was observed (Pnon−linear &lt; 0.001), with a threshold value of 5.6 × 109/L for all LEDVT events. Above the threshold, each unit increase in ln(SII) had a 1.369-fold higher risk of LEDVT (95% CI: 1.271–1.475, P &lt; 0.001). The association also existed in both distal and proximal LEDVT.ConclusionElevated SII is significantly associated with an increased risk of LEDVT in hospitalized patients. Additionally, the association is non-linear and exhibit a threshold effect.
First-year seminars through the lens of Vincent Tinto's theories of student departure. A systematic review
Authors: Samoila Magda Elena , Vrabie Tina 
Published: June 2023

IntroductionVincent Tinto is a towering figure in the study of dropout in higher education whose theory regarding student departure is a widely accepted contribution that explains how students become involved in the academic community and how their level of engagement impacts their decision to persist or to drop out. The aim of this study is to advance understanding of how Vincent Tinto's theories influence the current practices and support services offered by higher education institutions to freshman students through first-year seminars (FYS).MethodsA systematic review was conducted based on peer-reviewed articles published between 2020 and 2022, selected through a multi-stage process. With reference to Tinto's contribution, this systematic review aims at providing answers to the following research questions: What are the methodological approaches identified in the studies under analysis? What knowledge can be identified in recent studies related to the categories of students attending FYS? What knowledge about students' personal and psychological characteristics with relevance for FYS can be found in recent studies? What knowledge about academic pedagogical and counseling factors with relevance for FYS can be found in recent studies? What knowledge about social and relational factors integration with relevance for FYS can be found in recent studies?ResultsThe findings indicate three categories of studies that capitalize on Tinto's theories with regard to the design, conduct and evaluation of first-year seminars: a. studies that assess the role of students' personal and psychological variables, considered within FYS; b. studies that analyze the pedagogical and counseling interventions destined to students within FYS; c. studies that analyze the role of the social and relational dimension within FYS.DiscussionThe literature on the topic capitalizes on Vincent Tinto's contributions in relation to a student corpus which is extremely diverse in terms of age, socio-economic status, racial and cultural characteristics, attended specialization (a significant number of studies are destined to students who attend STEM specializations), generational characteristics (the example of first-generation students). Therefore, the interventions aimed at facilitating the integration of first-year students are carefully tailored and customized according to the needs of these categories of beneficiaries.
Validation of a targeted gene panel sequencing for the diagnosis of hereditary chronic liver diseases
Authors: Ronzoni Luisa , Marini Ilaria , Passignani Giulia , Malvestiti Francesco , Marchelli Daniele , Bianco Cristiana , Pelusi Serena , Prati Daniele , Valenti Luca 
Published: June 2023

Background: The cause of chronic liver diseases (CLD) remains undiagnosed in up to 30% of adult patients. Whole-Exome Sequencing (WES) can improve the diagnostic rate of genetic conditions, but it is not yet widely available, due to the costs and the difficulties in results interpretation. Targeted panel sequencing (TS) represents an alternative more focused diagnostic approach.Aims: To validate a customized TS for hereditary CLD diagnosis.Methods: We designed a customized panel including 82 CLD-associated genes (iron overload, lipid metabolism, cholestatic diseases, storage diseases, specific hereditary CLD and susceptibility to liver diseases). DNA samples from 19 unrelated adult patients with undiagnosed CLD were analyzed by both TS (HaloPlex) and WES (SureSelect Human All Exon kit v5) and the diagnostic performances were compared.Results: The mean depth of coverage of TS-targeted regions was higher with TS than WES (300x vs. 102x; p &lt; 0.0001). Moreover, TS yielded a higher average coverage per gene and lower fraction of exons with low coverage (p &lt; 0.0001). Overall, 374 unique variants were identified across all samples, 98 of which were classified as “Pathogenic” or “Likely Pathogenic” with a high functional impact (HFI). The majority of HFI variants (91%) were detected by both methods; 6 were uniquely identified by TS and 3 by WES. Discrepancies in variant calling were mainly due to variability in read depth and insufficient coverage in the corresponding target regions. All variants were confirmed by Sanger sequencing except two uniquely detected by TS. Detection rate and specificity for variants in TS-targeted regions of TS were 96.9% and 97.9% respectively, whereas those of WES were 95.8% and 100%, respectively.Conclusion: TS was confirmed to be a valid first-tier genetic test, with an average mean depth per gene higher than WES and a comparable detection rate and specificity.
Discordant renal progression of Fabry disease in male monozygotic twins: a case report
Authors: Lee Do-Yun , Jeong Jun-Yeong , Lee Seung-Eun , Lee Jae-Hun , Moon Ju-Young , Jung Su Woong , Lee Sang-Ho , Kim Yang Gyun 
Published: June 2023

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disease caused by mutations in the GLA gene that encodes α-galactosidase A (α-GAL). Clinical phenotypes tend to vary in monozygotic female twins because mutations are located on the X-chromosome, whereas similar phenotypes are found in male monozygotic twins. Here we report the case of male monozygotic twins with FD presenting with distinguishable renal phenotypes.Case: A 49-year-old male patient who visited the hospital with proteinuria 14 years prior was readmitted for the same issue. His monozygotic twin brother had started hemodialysis 6 months prior due to renal failure of unknown origin. The patient’s renal function was within the normal range, while his spot urine protein-to-creatinine ratio was 557 mg/g. Echocardiography revealed left ventricular hypertrophy (LVH). The findings of a renal biopsy were consistent with FD. Genetic testing identified a c.656T&gt;C mutation in the GLA gene, and α-GAL activity was significantly decreased. Genetic screening of his family clarified that his mother, older sister, twin brother, and his daughter had the same genetic mutations. The patient received enzyme replacement therapy 34 times. Subsequently, migalastat was initiated that continues today. Renal function and proteinuria remain stable, and the LVH has mildly improved.Conclusion: This is the first case of male monozygotic twins expressing different progressions of FD. Our findings demonstrate the possibility that environmental or epigenetic factors may critically influence genotype–phenotype discordance.
Merosin-deficient congenital muscular dystrophy type 1a: detection of LAMA2 variants in Vietnamese patients
Authors: Tran Van Khanh , Nguyen Ngoc-Lan , Tran Lan Ngoc Thi , Le Phuong Thi , Tran Anh Hai , Pham Tuan L. A. , Lien Nguyen Thi Kim , Xuan Nguyen Thi , Thanh Le Tat , Ta Thanh Van , Tran Thinh Huy , Nguyen Huy-Hoang 
Published: June 2023

Background: Merosin-deficient congenital muscular dystrophy type 1A (MDC1A), also known as laminin-α2 chain-deficient congenital muscular dystrophy (LAMA2-MD), is an autosomal recessive disease caused by biallelic variants in the LAMA2 gene. In MDC1A, laminin- α2 chain expression is absent or significantly reduced, leading to some early-onset clinical symptoms including severe hypotonia, muscle weakness, skeletal deformity, non-ambulation, and respiratory insufficiency.Methods: Six patients from five unrelated Vietnamese families presenting with congenital muscular dystrophy were investigated. Targeted sequencing was performed in the five probands. Sanger sequencing was carried out in their families. Multiplex ligation-dependent probe amplification was performed in one family to examine an exon deletion.Results: Seven variants of the LAMA2 (NM_000426) gene were identified and classified as pathogenic/likely pathogenic variants using American College of Medical Genetics and Genomics criteria. Two of these variants were not reported in the literature, including c.7156-5_7157delinsT and c.8974_8975insTGAT. Sanger sequencing indicated their parents as carriers. The mothers of family 4 and family 5 were pregnant and a prenatal testing was performed. The results showed that the fetus of the family 4 only carries c.4717 + 5G&gt;A in the heterozygous form, while the fetus of the family 5 carries compound heterozygous variants, including a deletion of exon 3 and c.4644C&gt;A.Conclusion: Our findings not only identified the underlying genetic etiology for the patients, but also provided genetic counseling for the parents whenever they have an offspring.
Identification of immunity-related lncRNAs and construction of a ceRNA network of potential prognostic biomarkers in acute myeloid leukemia
Authors: Xue Jia , Chen Haoran , Lu Jinqi , Zhang Haojun , Geng Jie , He Peifeng , Lu Xuechun 
Published: June 2023

Objective: Using bioinformatics analyses, this study aimed to identify lncRNAs related to the immune status of acute myeloid leukemia (AML) patients and ascertain the potential impact in immunity-related competing endogenous RNA (ceRNA) networks on AML prognosis.Methods: AML-related RNA-seq FPKM data, AML-related miRNA expression microarray data, and gene sets associated with immunity-related pathways were, respectively, obtained from the TCGA, GEO, and ImmReg databases. An immunity-related ceRNA network was then constructed according to the predicted interactions between AML-related mRNAs, lncRNAs, and miRNAs. After performing LASSO and multivariate Cox regression analyses, lncRNAs in the ceRNA network were used to establish an AML prognostic model. According to mutual regulatory relationships and consistent trends of expression among candidate ceRNAs, two ceRNA subnetworks related to the AML prognostic model were determined. Finally, the correlation between the expression levels of mRNAs, lncRNAs, and miRNAs in each ceRNA subnetwork and immune cell infiltration (assessed by combining the ESTIMATE and CIBERSORT methods and ssGSEA) was analyzed.Results: A total of 424 immunity-related differentially expressed (IR-DE) mRNAs (IR-DEmRNAs), 191 IR-DElncRNAs, and 69 IR-DEmiRNAs were obtained, and a ceRNA network of 20 IR-DElncRNAs, 6 IR-DEmRNAs, and 3 IR-DEmiRNAs was established. Univariate Cox regression analysis was conducted on 20 IR-DElncRNAs, and 7 of these were identified to be significantly correlated with the overall survival (OS) time in AML patients. Then, two IR-DElncRNAs (MEG3 and HCP5) were screened as independent OS-related factors by LASSO and multivariable Cox regression analyses, and a prognostic model was constructed to evaluate the survival risk in AML patients. Survival analyses indicated that the OS of patients was often poor in the high-risk group. Additionally, from this model, two ceRNA regulatory pathways, namely, MEG3/miR-125a-5p/SEMA4C and HCP5/miR-125b-5p/IL6R, which were potentially involved in the immune regulation of AML prognosis were identified.Conclusion: lncRNAs HCP5 and MEG3 may act as key ceRNAs in the pathogenesis in AML by regulating immune cell representation as part of the regulatory lncRNA-miRNA-mRNA axes. The candidate mRNAs, lncRNAs, and miRNAs included in the ceRNA network identified here may serve as useful prognostic biomarkers and immunotherapeutic targets for AML.
The therapeutic mechanism of transcranial iTBS on nerve regeneration and functional recovery in rats with complete spinal cord transection
Authors: Liu Jia-Lin , Wang Shuai , Chen Zheng-Hong , Wu Rong-Jie , Yu Hai-Yang , Yang Shang-Bin , Xu Jing , Guo Yi-Nan , Ding Ying , Li Ge , Zeng Xiang , Ma Yuan-Huan , Gong Yu-Lai , Wu Chuang-Ran , Zhang Li-Xin , Zeng Yuan-Shan , Lai Bi-Qin 
Published: June 2023

BackgroundAfter spinal cord transection injury, the inflammatory microenvironment formed at the injury site, and the cascade of effects generated by secondary injury, results in limited regeneration of injured axons and the apoptosis of neurons in the sensorimotor cortex (SMC). It is crucial to reverse these adverse processes for the recovery of voluntary movement. The mechanism of transcranial intermittent theta-burst stimulation (iTBS) as a new non-invasive neural regulation paradigm in promoting axonal regeneration and motor function repair was explored by means of a severe spinal cord transection.MethodsRats underwent spinal cord transection and 2 mm resection of spinal cord at T10 level. Four groups were studied: Normal (no lesion), Control (lesion with no treatment), sham iTBS (lesion and no functional treatment) and experimental, exposed to transcranial iTBS, 72 h after spinal lesion. Each rat received treatment once a day for 5 days a week; behavioral tests were administered one a week. Inflammation, neuronal apoptosis, neuroprotective effects, regeneration and synaptic plasticity after spinal cord injury (SCI) were determined by immunofluorescence staining, western blotting and mRNA sequencing. For each rat, anterograde tracings were acquired from the SMC or the long descending propriospinal neurons and tested for cortical motor evoked potentials (CMEPs). Regeneration of the corticospinal tract (CST) and 5-hydroxytryptamine (5-HT) nerve fibers were analyzed 10 weeks after SCI.ResultsWhen compared to the Control group, the iTBS group showed a reduced inflammatory response and reduced levels of neuronal apoptosis in the SMC when tested 2 weeks after treatment. Four weeks after SCI, the neuroimmune microenvironment at the injury site had improved in the iTBS group, and neuroprotective effects were evident, including the promotion of axonal regeneration and synaptic plasticity. After 8 weeks of iTBS treatment, there was a significant increase in CST regeneration in the region rostral to the site of injury. Furthermore, there was a significant increase in the number of 5-HT nerve fibers at the center of the injury site and the long descending propriospinal tract (LDPT) fibers in the region caudal to the site of injury. Moreover, CMEPs and hindlimb motor function were significantly improved.ConclusionNeuronal activation and neural tracing further verified that iTBS had the potential to provide neuroprotective effects during the early stages of SCI and induce regeneration effects related to the descending motor pathways (CST, 5-HT and LDPT). Furthermore, our results revealed key relationships between neural pathway activation, neuroimmune regulation, neuroprotection and axonal regeneration, as well as the interaction network of key genes.
Ferroptosis-related gene HIC1 in the prediction of the prognosis and immunotherapeutic efficacy with immunological activity
Authors: Wu Yanlin , Lin Zhengjun , Tang Xianzhe , Tong Zhongyi , Ji Yuqiao , Xu Yingting , Zhou Ziting , Yang Jing , Li Zhihong , Liu Tang 
Published: June 2023

BackgroundHypermethylated in Cancer 1 (HIC1) was originally confirmed as a tumor suppressor and has been found to be hypermethylated in human cancers. Although growing evidence has supported the critical roles of HIC1 in cancer initiation and development, its roles in tumor immune microenvironment and immunotherapy are still unclear, and no comprehensive pan-cancer analysis of HIC1 has been conducted.MethodsHIC1 expression in pan-cancer, and differential HIC1 expression between tumor and normal samples were investigated. Immunohistochemistry (IHC) was employed to validate HIC1 expression in different cancers by our clinical cohorts, including lung cancer, sarcoma (SARC), breast cancer, and kidney renal clear cell carcinoma (KIRC). The prognostic value of HIC1 was illustrated by Kaplan-Meier curves and univariate Cox analysis, followed by the genetic alteration analysis of HIC1 in pan-cancer. Gene Set Enrichment Analysis (GSEA) was conducted to illustrate the signaling pathways and biological functions of HIC1. The correlations between HIC1 and tumor mutation burden (TMB), microsatellite instability (MSI), and the immunotherapy efficacy of PD-1/PD-L1 inhibitors were analyzed by Spearman correlation analysis. Drug sensitivity analysis of HIC1 was performed by extracting data from the CellMiner™ database.ResultsHIC1 expression was abnormally expressed in most cancers, and remarkable associations between HIC1 expression and prognostic outcomes of patients in pan-cancer were detected. HIC1 was significantly correlated with T cells, macrophages, and mast cell infiltration in different cancers. Moreover, GSEA revealed that HIC1 was significantly involved in immune-related biological functions and signaling pathways. There was a close relationship of HIC1 with TMB and MSI in different cancers. Furthermore, the most exciting finding was that HIC1 expression was significantly correlated with the response to PD-1/PD-L1 inhibitors in cancer treatment. We also found that HIC1 was significantly correlated with the sensitivity of several anti-cancer drugs, such as axitinib, batracylin, and nelarabine. Finally, our clinical cohorts further validated the expression pattern of HIC1 in cancers.ConclusionsOur investigation provided an integrative understanding of the clinicopathological significance and functional roles of HIC1 in pan-cancer. Our findings suggested that HIC1 can function as a potential biomarker for predicting the prognosis, immunotherapy efficacy, and drug sensitivity with immunological activity in cancers.