bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening of osteoporosis and sarcopenia in individuals aged 50 years and older at different altitudes in Yunnan province: Protocol of a longitudinal cohort study
Authors: Liu Xingli , Ma Cunwen , Wang Shiping , Liang Zhengrong , Yang Juntao , Zhou Jun , Shu Yi , He Zhengying , Zong Jilong , Wu Lizhi , Peng Peiqian , Su Yi , Gao Meng , Shen Kaiming , Zhao Hong , Ruan Jilu , Ji Shaoxuan , Yang Yunhui , Tang Taisong , Yang Zongfa , Luo Guangyin , Zeng Meng , Zhang Weiwan , He Bo , Cheng Xiaoguang , Wang Gang , Wang Ling , Lyu Liang 
Published: November 2022

IntroductionMusculoskeletal system gradually degenerates with aging, and a hypoxia environment at a high altitude may accelerate this process. However, the comprehensive effects of high-altitude environments on bones and muscles remain unclear. This study aims to compare the differences in bones and muscles at different altitudes, and to explore the mechanism and influencing factors of the high-altitude environment on the skeletal muscle system.MethodsThis is a prospective, multicenter, cohort study, which will recruit a total of 4000 participants over 50 years from 12 research centers with different altitudes (50m~3500m). The study will consist of a baseline assessment and a 5-year follow-up. Participants will undergo assessments of demographic information, anthropomorphic measures, self-reported questionnaires, handgrip muscle strength assessment (HGS), short physical performance battery (SPPB), blood sample analysis, and imaging assessments (QCT and/or DXA, US) within a time frame of 3 days after inclusion. A 5-year follow-up will be conducted to evaluate the changes in muscle size, density, and fat infiltration in different muscles; the muscle function impairment; the decrease in BMD; and the osteoporotic fracture incidence. Statistical analyses will be used to compare the research results between different altitudes. Multiple linear, logistic regression and classification tree analyses will be conducted to calculate the effects of various factors (e.g., altitude, age, and physical activity) on the skeletal muscle system in a high-altitude environment. Finally, a provisional cut-off point for the diagnosis of sarcopenia in adults at different altitudes will be calculated.Ethics and disseminationThe study has been approved by the institutional research ethics committee of each study center (main center number: KHLL2021-KY056). Results will be disseminated through scientific conferences and peer-reviewed publications, as well as meetings with stakeholders.Clinical Trial registration numberhttp://www.chictr.org.cn/index.aspx, identifier ChiCTR2100052153.
Genetic regulation of THBS1 methylation in diabetic retinopathy
Authors: Li Yaqi , Gong Chunmei , Xu Yuanfei , Liang Xiongshun , Chen Xiaoping , Hong Wenxu , Yan Junxia 
Published: November 2022

BackgroundDiabetic retinopathy (DR) is a common and serious microvascular complication of diabetes mellitus (DM), but its pathological mechanism, especially the formation mechanism of new blood vessels remains unclear. Thrombospondin-1 (THBS1) is a potent endogenous inhibitor of angiogenesis and it was found over expressed in DR in our previous study. Our study aimed to determine whether overexpression of THBS1 is associated with its promoter methylation level, and whether methylation of THBS1 is regulated by genetic variants in DR.MethodsPatients diagnosed with DR and DM patients without retinal problems were included in the case-control study. DNA methylation detection of THBS1 by bisulfite sequencing and genotyping of specific SNPs by MassARRAY analysis were performed in the patients recruited from 2019-2020. Real time quantitative PCR was performed to obtain mRNA expression of THBS1 in the patients recruited from August to October 2022. The differentially methylated CpG loci of THBS1 were identified by logistic regression, and associations between 13 SNPs and methylation levels of CpG loci were tested by methylation quantitative trait loci (meQTLs) analysis. Mediation analysis was applied to determine whether CpG loci were intermediate factors between meQTLs and DR.Results150 patients diagnosed with DR and 150 DM patients without retinal complications were enrolled in the first recruitment, seven DR patients and seven DM patients were enrolled in the second recruitment. The patients with DR showed promoter hypomethylation of THBS1 (P value = 0.002), and six out of thirty-nine CpG sites within two CpG islands (CGIs) showed hypomethylation(P value &lt; 0.05). THBS1 mRNA expression in peripheral blood was significantly higher in DR patients than in DM patients. Five out of thirteen cis-meQTLs were identified to be associated with CpG sites: rs13329154, rs34973764 and rs5812091 were associated with cis-meQTLs of CpG-4 (P value=0.0145, 0.0095, 0.0158), rs11070177 and rs1847663 were associated with cis-meQTLs of CpG-2 and CpG-3 respectively (P value=0.0201, 0.0275). CpG-4 methylation significantly mediated the effect of the polymorphism rs34973764 on DR (B=0.0535, Boot 95%CI: 0.004~0.1336).ConclusionTHBS1 overexpression is related to THBS1 hypomethylation in patients with DR. DNA methylation may be genetically controlled in DR.
Identification of immune-related signature for the prognosis and benefit of immunotherapy in triple-negative breast cancer
Authors: Sun Xiaorui , Zhang Tiansong 
Published: November 2022

Background: There is a lack of biomarkers for predicting the efficacy of immunotherapy in triple-negative breast cancer (TNBC). Hence, we constructed an immune risk score (IRS) model to predict the prognosis of patients with TNBC and evaluate those who are sensitive to immunotherapy.Methods: The ribonucleic acid (RNA) sequencing data, mutation data, and clinical information of TNBC patients were obtained from The Cancer Genome Atlas database. Data of immune-related genes were obtained from the Import and InnateDB databases. The IRS model was constructed using univariate, least absolute shrinkage and selection operator, and multivariate Cox regression analyses, and the predictive ability of the prognostic model was evaluated. Further external validation was performed using the Gene Expression Omnibus (GEO) databases GSE58812 and GSE135565. Data on the clinical characteristics, immune landscape, and immune checkpoint inhibitors used in different risk groups were analyzed. Finally, the drug sensitivity of the patients in the high- and low-risk groups was predicted.Results: The prognostic risk score model comprised six genes: HSPA6, LCN1, ARTN, IL36G, BCL2A1, and CASP12. The area under the curve values at 1 year, 3 years, and 5 years were 0.835, 0.852, and 0.843, respectively, indicating that the model has a good potential for predicting the long-term survival of TNBC patients, which is consistent with the results of the GEO cohort. Compared with the high-risk group, the low-risk group had a better prognosis; more abundant immune-activated cell infiltrates, such as CD8+ T cells and CD4 memory-activated T cells, and a higher enrichment of immune-related signaling pathways, such as the cytokine receptor interaction, nucleotide oligomerization domain-like receptor signal pathway, T-cell receptor signal pathway, and B-cell receptor signaling pathway, were observed. In addition, the immune checkpoint encoding genes, such as CD274, CTLA4, PDCD1, and PDCD1LG2 were highly expressed in the low-risk group, which showed that this group was more likely to benefit from immunotherapy.Conclusion: A new IRS gene feature was established to predict the patients’ prognosis and guide immunotherapy. Moreover, it was revealed that several potential therapeutic drugs can be used in high-risk patients who are unresponsive to immunotherapy.
Dynamics of humoral immune response in SARS-CoV-2 infected individuals with different clinical stages
Authors: Mendez-Cortina Yorjagis , Rodriguez-Perea Ana Lucía , Chvatal-Medina Mateo , Lopera Tulio Jose , Alvarez-Mesa Natalia , Rodas-Marín Jan Karlo , Moncada Diana Carolina , Rugeles Maria Teresa , Velilla Paula Andrea 
Published: November 2022

BackgroundThe COVID-19 pandemic remains a global health problem. As in other viral infections, the humoral immune response against SARS-CoV-2 is thought to be crucial for controlling the infection. However, the dynamic of B cells in the clinical spectrum of this disease is still controversial. This study aimed to characterize B cell subsets and neutralizing responses in COVID-19 patients according to disease severity through a one-month follow-up.MethodsA cohort of 71 individuals with SARS-CoV-2 infection confirmed by RT-PCR were recruited and classified into four groups: i) asymptomatic; ii) symptomatic outpatients; iii) hospitalized in ward, and iv) intensive care unit patients (ICU). Samples were taken at days 0 (inclusion to the study), 7 and 30. B cell subsets and neutralizing antibodies were assessed using multiparametric flow cytometry and plaque reduction neutralization, respectively.ResultsOlder age, male gender and body mass index over 25 were common factors among hospitalized and ICU patients, compared to those with milder clinical presentations. In addition, those requiring hospitalization had more comorbidities. A significant increase in the frequencies of CD19+ cells at day 0 was observed in hospitalized and ICU patients compared to asymptomatic and symptomatic groups. Likewise, the frequency of plasmablasts was significantly increased at the first sample in the ICU group compared to the asymptomatic group, but then waned over time. The frequency of naïve B cells decreased at days 7 and 30 compared to day 0 in hospitalized and ICU patients. The neutralizing antibody titers were higher as the severity of COVID-19 increased; in asymptomatic individuals, it was strongly correlated with the percentage of IgM+ switched memory B cells, and a moderate correlation was found with plasmablasts.ConclusionThe humoral immune response is variable among SARS-CoV-2 infected people depending on the severity and time of clinical evolution. In severe COVID-19 patients, a higher plasmablast frequency and neutralizing antibody response were observed, suggesting that, despite having a robust humoral immunity, this response could be late, having a low impact on disease outcome.
A novel cuproptosis-related lncRNA signature predicts the prognosis and immune landscape in bladder cancer
Authors: Bai Yuchen , Zhang Qi , Liu Feng , Quan Jing 
Published: November 2022

BackgroundBladder cancer (BLCA) is one of the deadliest diseases, with over 550,000 new cases and 170,000 deaths globally every year. Cuproptosis is a copper-triggered programmed cell death and is associated with the prognosis and immune response of various cancers. Long non-coding RNA (lncRNA) could serve as a prognostic biomarker and is involved in the progression of BLCA.MethodsThe gene expression profile of cuproptosis-related lncRNAs was analyzed by using data from The Cancer Genome Atlas. Cox regression analysis and least absolute shrinkage and selection operator analysis were performed to construct a cuproptosis-related lncRNA prognostic signature. The predictive performance of this signature was verified by ROC curves and a nomogram. We also explored the difference in immune-related activity, tumor mutation burden (TMB), tumor immune dysfunction and exclusion (TIDE), and drug sensitivity between the high- and low-risk groups.ResultsWe successfully constructed a cuproptosis-related lncRNA prognostic signature for BLCA including eight lncRNAs (RNF139-AS1, LINC00996, NR2F2-AS1, AL590428.1, SEC24B-AS1, AC006566.1, UBE2Q1-AS1, and AL021978.1). Multivariate Cox analysis suggested that age, clinical stage, and risk score were the independent risk factors for predicting prognosis of BLCA. Further analysis revealed that this signature not only had higher diagnostic efficiency compared to other clinical features but also had a good performance in predicting the 1-year, 3-year, and 5-year overall survival rate in BLCA. Notably, BLCA patients with a low risk score seemed to be associated with an inflamed tumor immune microenvironment and had a higher TMB level than those with a high risk score. In addition, patients with a high risk score had a higher TIDE score and a higher half maximal inhibitory concentration value of many therapeutic drugs than those with a low risk score.ConclusionWe identified a novel cuproptosis-related lncRNA signature that could predict the prognosis and immune landscape of BLCA.
Immunomodulatory effects of two recombinant arginine kinases in Sarcoptes Scabiei on host peripheral blood mononuclear cells
Authors: Xu Yanting , Xu Ziyi , Gu Xiaobin , Xie Yue , He Ran , Xu Jing , Jing Bo , Peng Xuerong , Yang Guangyou 
Published: November 2022

BackgroundAs an important zoonotic parasitic disease with global distribution, scabies causes serious public health and economic problems. Arginine kinase (AK) is involved in cell signal transduction, inflammation, and apoptosis. Two AKs were identified in Sarcoptes scabiei, but their functions in the host immune response remain unclear.MethodsrSsAK-1 and rSsAK-2 were expressed, purified, and immunolocalized. The effects of rSsAK-1 and rSsAK-2 on rabbit PBMC proliferation, apoptosis, and migration; Bcl-2, Bcl-xl, Fas, Bax, and NF-κB transcription levels; and IL-2, IFN-γ, IL-4, IL-10, TGF-β1, and IL-17 secretion were detected.ResultsrSsAK-1 and rSsAK-2 were cloned and expressed successfully. Both enzymes were ~57 kDa and contained 17-kDa tagged proteins, and had good catalytic activity and immunoreactivity. The proteins were located in the S. scabiei exoskeleton, chewing mouthparts, legs, stomach, and intestine. SsAK-1 and SsAK-2 were secreted in the pool and epidermis of the skin lesions, which may be involved in S. scabiei–host interaction. rSsAK-1 and rSsAK-2 significantly promoted cell proliferation, induced cell migration, inhibited apoptosis, and increased Bcl-2, Bcl-xl and NF-κB (p65) transcription levels concentration-dependently, and inhibited IL-2, IFN-γ, and IL-10 secretion and promoted IL-4 and IL-17 secretion.ConclusionrSsAK-1 and rSsAK-2 might increase Bcl-2 and Bcl-xl expression by activating the NF-κB signaling pathway to promote cell proliferation and inhibit apoptosis, which induced PBMC survival. By inducing PBMC migration to the infection site, rSsAK-1 and rSsAK-2 shifted the Th1/Th2 balance toward Th2 and changed the Th17/Treg balance, which indicated their immune role in S. scabiei allergic inflammation.
C-Reactive Protein (CRP): A poor prognostic biomarker in COVID-19
Authors: Bouayed Mohamed Zakaria , Laaribi Ilyass , Chatar Charaf Eddine Mohammed , Benaini Iliass , Bouazzaoui Mohammed Amine , Oujidi Younes , Berrichi Samia , El Aidouni Ghizlane , Bkiyar Houssam , Abda Naima , Housni Brahim 
Published: November 2022

IntroductionThe COVID-19 pandemic continues to be rampant with considerable morbidity and mortality worldwide since its emergence in December 2019. Several studies have focused on identifying different predictive factors of poor prognosis, including biological markers, such as C Reactive Protein among others. The objective of our work was to determine whether the CRP levels on admission to the intensive care unit are predictive of an unfavorable evolution of patients with COVID-19 through the experience of the Anesthesia and Intensive Care Unit of the University Hospital of Oujda and to compare our results with those reported in the literature.MethodsWe conducted a retrospective, monocentric, descriptive and analytical study in the Department of Anesthesia and Intensive Care of the Mohammed VI University Hospital of Oujda, Morocco, between March 2020 and October 2021, including all critically ill patients admitted to the department during this period and meeting the inclusion criteria. The baseline admission CRP value was arbitrarily set at 100mg/d, thus conditioning the division of our patients into two groups (group 1: CRP &lt; 100mg/L, group 2: CRP ≥ 100mg/L).ResultsAmong our 1035 included patients, 291 patients with had a CRP&lt;100mlg/L (group 1) and 744 presented a CRP level equal or superior to 100mg/L (group 2). Lung parenchymal involvement was more severe or even critical (CT involvement &gt; 75%) in group 2 (60.8%) compared to group 1 (39.2%). In group 2, 79.8% of patients were mechanically ventilated, compared to 20.2% of patients in group 1. Finally, the mortality rate in patients with a CRP ≥ 100mg/l was 77.4%, compared with 22.6% for patients with a CRP &lt; 100mg/l. These findings are all statistically highly significant (p&lt;0.001)ConclusionGiven the high contagiousness of the virus and the emergence of several variants, the management of the COVID-19 pandemic has focused more on prevention through vaccination against the virus, but also on an early identification of patients likely to evolve unfavorably for a personalized management.
Association of nutrition knowledge, practice, supplement use, and nutrient intake with strength performance among Taekwondo players in Nepal
Authors: Sunuwar Dev Ram , Singh Devendra Raj , Bohara Man Prasad , Shrestha Vintuna , Karki Kshitij , Pradhan Pranil Man Singh 
Published: November 2022

BackgroundOptimum dietary intake and adequate nutritional knowledge have been recognized as the key factors that play a critical role in improving the athlete's health and nutrition status. This study aimed to measure the association of nutritional knowledge, practice, supplement use, and nutrient intake with strength performance among Nepalese Taekwondo players.MethodsBetween August 2019 and January 2020, a cross-sectional study was conducted among 293 Taekwondo players in Kathmandu Metropolitan City (mean age, 18 years; 63.1% male, 36.9% female). Face-to-face interviews were conducted using semi-structured questionnaires. Anthropometric measures, nutritional intake, nutrition knowledge, and practice were all recorded. The handgrip strength was measured using a handgrip dynamometer as a proxy for strength performance. Univariate and bivariate analyses were used to find out the association between predictor and outcome variables.ResultsMore than half of the participants had poor nutrition knowledge [54.3% (159/293)], and poor nutrition practice [55.3% (162/293)] scores. Daily mean energy, carbohydrate, protein and fat intake were 48.0 kcal.kg−1.d−1, 8.6, 1.6, and 1.5 g.kg−1.d−1, respectively among Taekwondo players. Daily total energy and carbohydrate intake were 48.2 kcal.kg−1.d−1 and 8.7 g.kg−1.d−1, respectively among male players which is higher than female players. However, daily protein and fat intake were higher in female players (1.7 and 1.6 g.kg−1.d−1, respectively). Both calcium (375.3 mg) and iron (9 mg) intake among Taekwondo players were significantly lower than current sports nutrition guidelines. Nutritional knowledge score (r = 0.117), height (r = 0.538), weight (r = 0.651), body mass index (r = 0.347), fat (r = 0.075), and energy (r = 0.127) intake showed significant positive correlation with strength performance of athletes. The strength performance was positively associated with training hours per day (β = 0.41, 95% CI: 0.09–0.91), body mass index (β = 0.35, 95% CI: 0.09–0.61), nutrition knowledge score (β = 0.13, 95% CI: 0.01–0.25), and energy intake (β = 0.13, 95% CI: 0.12–0.14).ConclusionsThe nutritional knowledge and practice both were suboptimal among Taekwondo athletes. Height, weight, body mass index, nutritional knowledge, energy, and fat intake showed a positive correlation with strength performance. Future studies can build on the premise of this study to identify the robust relationship between nutritional knowledge, practice, different supplement use, and nutrient intake among other athletes too.
Optimizing margin status for improving prognosis in patients with oral cavity squamous cell carcinoma: A retrospective study from the two highest-volume Taiwanese hospitals
Authors: Liao Chun-Ta , Lee Li-Yu , Lee Shu-Ru , Ng Shu-Hang , Liu Tsang-Wu , Chien Chih-Yen , Lin Jin-Ching , Wang Cheng Ping , Terng Shyuang-Der , Hua Chun-Hung , Chen Tsung-Ming , Chen Wen-Cheng , Tsai Yao-Te , Kang Chung-Jan , Tsai Chi-Ying , Chu Ying-Hsia , Lin Chien-Yu , Fan Kang-Hsing , Wang Hung-Ming , Hsieh Chia-Hsun , Yeh Chih-Hua , Lin Chih-Hung , Tsao Chung-Kan , Yen Tzu-Chen , Cheng Nai-Ming , Fang Tuan-Jen , Huang Shiang-Fu , Lee Li-Ang , Fang Ku-Hao , Wang Yu-Chien , Lin Wan-Ni , Hsin Li-Jen , Wen Yu-Wen 
Published: November 2022

BackgroundIn the treatment of oral cavity squamous cell carcinoma (OCSCC), surgical quality measures which are expected to affect outcomes, including the achievement of a clear margin, are surgeon-dependent but might not be invariably associated with hospital volume. Our objective was to explore surgical margin variations and survival differences of OCSCC between two highest-volume hospitals in Taiwan.Materials and methodsA total of 2009 and 1019 patients with OCSCC who were treated at the two highest-volume Taiwanese hospitals (termed Hospital 1 and Hospital 2, respectively) were included. We examined how a pathological margin &lt;5 mm impacted patient outcomes before and after propensity score (PS) matching.ResultsThe prevalence of margins &lt;5 mm was markedly lower in Hospital 1 than in Hospital 2 (34.5%/65.2%, p&lt;0.0001). Compared with Hospital 2, tumor severity was higher in Hospital 1. On univariable analysis, being treated in Hospital 2 (versus Hospital 1; hazard ratio [HR] for 5-year disease-specific survival [DSS] = 1.34, p=0.0002; HR for 5-year overall survival [OS] = 1.17, p=0.0271) and margins &lt;5 mm (versus ≥5 mm; HR for 5-year DSS = 1.63, p&lt;0.0001; HR for 5-year OS = 1.48, p&lt;0.0001) were identified as adverse factors. The associations of treatment in Hospital 2 and margins &lt;5 mm with less favorable outcomes remained significant after adjustment for potential confounders in multivariable analyses, as well as in the PS-matched cohort. The 5-year survival differences between patients operated in Hospital 1 and Hospital 2 were even more pronounced in the PS-matched cohort (before PS matching: DSS, 79%/74%, p=0.0002; OS, 71%/68%, p=0.0269; after PS matching: DSS, 84%/72%, p&lt;0.0001; OS, 75%/66%, p&lt;0.0001). In the entire cohort, the rate of adjuvant therapy was found to be lower in patients with margins ≥5 mm than in those with margins &lt;5 mm (42.7%/57.0%, p&lt;0.0001).ConclusionsWithin the two highest-volume hospitals in Taiwan, patients with OCSCC with a clear margin status (≥5 mm) achieved more favorable outcomes. These results have clinical implications and show how initiatives aimed at improving the margin quality can translate in better outcomes. A clear margin status can reduce the need for adjuvant therapy, ultimately improving quality of life.