bluuebunny/crossref_metadata_2025_split huggingface dataset:
CLCF1 Is a Novel Potential Immune-Related Target With Predictive Value for Prognosis and Immunotherapy Response in Glioma
Authors: Jiang Yuan , Ji Qiankun , Long Xiaoyan , Wang Peng , Tu Zewei , Zhang Xian , Zhu Xingen , Huang Kai , Li Jingying 
Published: February 2022

BackgroundCardiotrophin-like cytokine factor 1 (CLCF1) has been described as an oncogene and a potential therapeutic target in a variety of cancers, but its role in glioma remains unknown.MethodsBased on The Cancer Genome Atlas (TCGA), we conducted a bioinformatics analysis to investigate the clinical significance and biological functions of CLCF1 in glioma at the transcriptional level and predicted the response to immunotherapy of glioma patients with different CLCF1 expression levels. All the results were further verified in Chinese Glioma Genome Altas(CGGA) Data processing and figure generating were performed with R language.ResultsElevated CLCF1 expression was common in cancers and usually predicted poor prognosis, which was also consistent with gliomas. In Univariate Cox Regression analysis and Kaplan-Meier survival analysis, tumor patients with higher CLCF1 expression tended to experience a worse prognosis. In the multivariate Cox proportional hazard model, the expression of CLCF1 was an independent prognostic factor in gliomas. The biological function analysis of CLCF1 in glioma showed that CLCF1 was closely associated with immune signatures, including immune-related pathways, immune cell infiltration, and immune checkpoints. Moreover, glioma patients with low CLCF1 expression showed a greater tendency to respond to anti-PD1/PD-L1 immunotherapy, indicating CLCF1 also had potential clinical significance in guiding immunotherapy. And CLCF1 as a member of the IL6 family had a better predictive value for prognosis and immunotherapy response in glioma than that of IL6 and other IL6 family members.ConclusionCLCF1 expression is an independent prognosticator and a promising therapeutic target correlated with immunotherapy in glioma.
Chronic Inflammation Might Protect Hemodialysis Patients From Severe COVID-19
Authors: Prietl Barbara , Odler Balazs , Kirsch Alexander H. , Artinger Katharina , Eigner Manfred , Schmaldienst Sabine , Pfeifer Verena , Stanzer Stefanie , Eberl Anita , Raml Reingard , Pieber Thomas , Rosenkranz Alexander R. , Brodmann Marianne , Eller Philipp , Eller Kathrin 
Published: February 2022

Hemodialysis patients (HD) are expected to have excess mortality in coronavirus disease 2019 (COVID-19). This was challenged by a recent study reporting HD patients to have comparable mortality and less ICU admissions when hospitalized with COVID-19. An altered immune system due to chronic inflammation might protect HD-patients from severe COVID-19. Therefore, we aimed to describe the peripheral blood immune phenotype in HD-patients and respective controls with COVID-19.MethodsSixty-four patients (31 HD, 33 non-HD) with PCR-confirmed COVID-19 and 16 control patients (10 HD, 6 non-HD) were prospectively included. According to symptoms, COVID-19 patients were categorized as asymptomatic/mild, moderate or severe COVID-19 phenotypes. Cytokine profiling and immune phenotyping was performed.ResultsTh1 and Th17 plasma cytokine levels were highly increased in HD patients without COVID-19 and were not significantly regulated during COVID-19. In non-HD COVID-19 patients these cytokines increased significantly with disease severity. While all patients with moderate or severe COVID-19 showed hallmarks of COVID-19 such as decreased CD3+, CD4+ and CD8+ and CD4+CD25hiFoxP3+ regulatory T cells, significantly increased CD38+CD8+ effector memory and CD38+CD8+ TEMRA T cells were detected in moderate/severe COVID-19 HD patients, which was not observed in non-HD patients with moderate or severe COVID-19. Furthermore, CD161+CD8+ T cells decreased significantly in non-HD COVID-19 patients dependent on disease severity, but not in HD patients. Dynamics of B cells and subtypes were comparable in HD and non-HD COVID-19 patients.ConclusionsHD patients might be protected from severe COVID-19 due to their chronic inflammatory state with increased CD38+CD8+ effector memory and TEMRA T cells as well as CD161+CD8+ T cells.
Association Between Atopic Dermatitis, Asthma, and Serum Lipids: A UK Biobank Based Observational Study and Mendelian Randomization Analysis
Authors: Tang Zhenwei , Shen Minxue , Xiao Yi , Liu Hong , Chen Xiang 
Published: February 2022

BackgroundBoth atopic diseases and dysregulation of serum lipids (SLs) add to significant health burden, but evidences about their association are inconsistent.ObjectiveThis work is to evaluate the association between asthma/atopic dermatitis (AD) and SLs and investigate the potential causal relationship.MethodsA large-scale cross-sectional study based on the UK Biobank (UKB) and then examined the casual relationships between SLs with asthma/AD based on a Mendelian randomization (MR) analysis.ResultsA total of 502,505 participants were included in analysis. After full adjustment, AD was associated with lower TG (β = −0.006; 95%CI, −0.010 to −0.002; P = 0.006), lower LDL (β = −0.004; 95%CI, −0.006 to −0.002, P &lt; 0.001), and lower TC (β = −0.004; 95%CI, −0.005 to −0.002; P &lt; 0.001) but insignificantly correlated to HDL (P = 0.794). Asthma was also inversely correlated to TG (β = −0.005; 95%CI, = −0.007 to −0.003; &lt; 0.001), LDL (β = −0.003; 95%CI, −0.004 to −0.002; P &lt; 0.001), and TC (β = −0.002; 95%CI, −0.003 to −0.002; P &lt; 0.001), but was positively correlated to HDL (β = 0.004; 95%CI, 0.003 to 0.005; P &lt; 0.001), respectively. In subsequent MR analysis, both allergic diseases and asthma showed a protective effect on TC. Allergic diseases, asthma, and AD all showed a negative effect on LDL.ConclusionCollectively, we identify a protective causal effect of allergic diseases on serum lipids, as well as a potentially positive association of HDL with asthma. Owing to the largest sample size and the application of IVs in causal inference, this study will provide a robust evidence for the management of asthma and AD and the prevention of dyslipidemia.
The Efficacy and Safety of Early Renal Replacement Therapy in Critically Ill Patients With Acute Kidney Injury: A Meta-Analysis With Trial Sequential Analysis of Randomized Controlled Trials
Authors: Xiao Chuan , Xiao Jingjing , Cheng Yumei , Li Qing , Li Wei , He Tianhui , Li Shuwen , Gao Daixiu , Shen Feng 
Published: February 2022

The efficacy and safety of early renal replacement therapy (eRRT) for critically ill patients with acute kidney injury (AKI) remain controversial. Therefore, the purpose of our study was to perform an up-to-date meta-analysis with the trial sequential analysis (TSA) of randomized controlled trials (RCTs) to evaluate the therapeutic effect of eRRT on patients in an intensive care unit (ICU). We extensively searched MEDLINE, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov, Gray Literature Report, and Bielefeld Academic Search Engine (BASE), and conducted an updated search on December 27, 2021. The included studies were RCTs, which compared the efficacy and safety of eRRT and delayed renal replacement therapy (dRRT) on critically ill patients with AKI. We adopted TSA and sensitivity analysis to strengthen the robustness of the results. About 12 RCTs with a total of 5,423 participants were included. Patients receiving eRRT and dRRT had the similar rate of all-cause mortality at day 28 (38.7% vs. 38.9%) [risk ratio (RR), 1.00; 95%CI, 0.93–1.07, p = 0.93, I2 = 0%, p = 0.93]. A sensitivity and subgroup analysis produced similar results for the primary outcome. TSA showed that the required information size was 5,034, and the cumulative Z-curve crossed trial sequential monitoring boundaries for futility. Patients receiving eRRT had a higher rate of renal replacement therapy (RRT) (RR, 1.50, 95% CI: 1.28–1.76, p &lt; 0.00001, I2 = 96%), and experienced more adverse events comparing to those receiving dRRT (RR: 1.41, 95% CI: 1.22–1.63, p &lt; 0.0001, heterogeneity not applied). The most remarkable and important experimental finding is that, to our knowledge, the current meta-analysis included the largest sample size from the RCTs, which were published in the past 10 years to date, show that eRRT had no significant survival benefit for ill patients with AKI compared with dRRT and TSA indicating that no more studies were needed to confirm it.Trial RegistrationINPLASY, INPLASY2020120030. Registered 04 December 2020.
Effect of Pulmonary Rehabilitation for Patients With Post-COVID-19: A Systematic Review and Meta-Analysis
Authors: Chen Huan , Shi Hangyu , Liu Xitong , Sun Tianheng , Wu Jiani , Liu Zhishun 
Published: February 2022

BackgroundEvidence increasingly suggested that impaired respiratory function remained in about 40% of patients with coronavirus disease 2019 (COVID-19) after discharge, jeopardizing their activities of daily living and quality of life (QoL) in a long term. Pulmonary rehabilitation (PR) can improve exercise capacity and QoL in individuals with chronic lung disease; however, evidence on the effect of PR for patients with post-COIVD-19 was scarce. This study aimed to conduct a systematic review and meta-analysis to evaluate the effect of PR on lung impairment for patients with post-COVID-19.MethodsFive databases were searched for all the published trials of PR for patients with post-COVID-19 from 2019 to October 2021. Data were extracted using a standardized form. The risks of bias of included studies were assessed using the Cochrane risk of the bias assessment tool. Data were synthesized where possible; otherwise, qualitative analysis was done.ResultsAmong 6,000 retrieved studies, 3 studies with 233 patients after COVID-19 were included. The pooled estimate of PR effect on 6-min walk test (6-MWT) (50.41, 95% CI 34.34 to 66.48; p &lt; 0.0001) was in favor of the experiment group with clinical importance. It is found that PR could improve the symptom of dyspnea and QoL; however, its effect on pulmonary function test was inconsistent across studies. The risk of bias of included studies varied, with major concerns on the risk of blinding of participants and interventions performers.ConclusionThe review showed that PR could improve exercise capacity measured by 6-MWT among patients with mild-to-moderate lung impairment after COVID-19. The interpretation of effects on lung function, dyspnea, and QoL should be cautious due to inadequate and conflicting data reported across studies.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021289562, identifier: CRD42021289562.
Comprehensive Characterization of Ageing-Relevant Subtypes Associated With Different Tumorigenesis and Tumor Microenvironment in Prostate Cancer
Authors: Huang Liang , Xu Zhenzhou , Xie Yu , Jiang Shusuan , Han Weiqing , Tang Zhengyan , Zhu Quan 
Published: February 2022

Objective: Accumulated evidence demonstrates that ageing is a robust risk factor of prostate cancer prognosis. Herein, we conducted a systematic analysis about ageing-relevant molecules and relevant tumor microenvironment features in prostate cancer.Methods: Transcriptome data, clinical information, and mutational data of prostate cancer patients were retrospectively collected from the Cancer Genome Atlas cohort. In accordance with the expression of specific ageing-relevant genes, prostate cancer patients were clustered with consensus clustering analyses. WGCNA was adopted for determination of subtype-associated co-expression modules and genes. Thereafter, characteristic genes were further screened with random forest algorithm and a prognostic model was conducted with multivariate cox regression analyses. Tumor microenvironment-infiltrating immune cells were estimated with ssGSEA and ESTIMATE. Activities of the cancer immunity cycle and expressions of HLA and immune checkpoint molecules were then quantified across prostate cancer cases. A serious experiment was conducted to investigate the roles of EIF2S2 in prostate tumorigenesis.Results: This study characterized three ageing-relevant subtypes (C1, C2, and C3) with diverse clinical prognosis. Subtype C1 presented the features of low mutational frequency and immune activation; C2 was characterized by stromal and immune activation; and C3 showed immune suppression. An ageing-derived gene signature was conducted, which independently and robustly predicted patients’ prognosis. Additionally, this signature was in relation to immune inactivation. Among the genes in the signature, EIF2S2 triggered proliferation, invasion, and migration of LNCaP and PC-3 cells.Conclusion: Collectively, ageing-relevant molecular subtypes and gene signature might be of great significance to determine clinical outcomes and tumor microenvironment features and immunotherapeutic responses in prostate cancer.
A Novel U-Shaped Association Between Serum Magnesium on Admission and 28-Day In-hospital All-Cause Mortality in the Pediatric Intensive Care Unit
Authors: Yue Chao Yan , Zhang Chun Yi , Huang Zhen Ling , Ying Chun Mei 
Published: February 2022

ObjectiveOur purpose is to evaluate whether serum magnesium when entering the ICU is related to 28-day in-hospital all-cause mortality in the pediatric ICU.MethodsWe used the PIC database to conduct a retrospective analysis to investigate the first-time serum magnesium levels of 10,033 critically ill children admitted to the pediatric ICU, and analyzed association between serum magnesium and all-cause mortality. Smoothing spline plots, subgroup analysis and segmented multivariate logistic regression analysis were conducted to estimate the relative risk between serum magnesium and all-cause mortality. The shape of the curve was used to describe the relationship between magnesium and 28-day in-hospital mortality.ResultsThere is a non-linear relationship between serum magnesium and 28-day in-hospital all-cause mortality. The U-type relationship between serum magnesium and all-cause mortality was observed. The optimal range of serum magnesium with the lowest risk of mortality was 0.74–0.93 mmol/L. As the serum magnesium level reaches the turning point (0.74 mmol/L), the risk of death decreases by 60% for every 0.1 mmol/L increase in serum magnesium; when the serum magnesium level exceeds 0.93, an increase of 0.1 mmol/L increases the risk of death by 38 %.ConclusionSerum magnesium has a U-shaped relationship with 28-day in-hospital all-cause mortality. Both low and high serum magnesium can increase the risk of death. The best serum magnesium range when the risk of death is the lowest is 0.74–0.93 mmol/L.
Discovery of Novel and Highly Potent Inhibitors of SARS CoV-2 Papain-Like Protease Through Structure-Based Pharmacophore Modeling, Virtual Screening, Molecular Docking, Molecular Dynamics Simulations, and Biological Evaluation
Authors: Tian Xiaoyan , Zhao Quanfeng , Chen Xiaohong , Peng Zhe , Tan Xiaodan , Wang Qin , Chen Lin , Yang Yang 
Published: February 2022

Background and Objective: COVID-19 has struck our society as a great calamity, and the need for effective anti-viral drugs is more urgent than ever. Papain-like protease (PLpro) of SARS CoV-2 plays important roles in virus maturation, dysregulation of host inflammation, and antiviral immune responses, which is being regarded as a promising druggable target for the treatment of COVID-19. Here, we carried out a combined screening approach to identify novel and highly potent PLpro inhibitors for the treatment of COVID-19.Methods: We used a combined screening approach of structure-based pharmacophore modeling and molecular docking to screen an in-house database containing 35,000 compounds. SARS CoV-2 PLpro inhibition assay was used to carry out the biological evaluation of hit compounds. Molecular dynamics (MD) simulations were conducted to check the stability of the PLpro-hit complexes predicted by molecular docking.Results: We found that four hit compounds showed excellent inhibitory activities against PLpro with IC50 values ranging from 0.6 to 2.4 μM. Among them, the most promising compound, hit 2 is the best PLpro inhibitor and its inhibitory activity was about 4 times higher than that of the positive control (GRL0617). The study of MD simulations indicated that four hits could bind stably to the active site of PLpro. Further study of interaction analysis indicated that hit 2 could form hydrogen-bond interactions with the key amino acids such as Gln269 and Asp164 in the PLpro-active site.Conclusion: Hit 2 is a novel and highly potent PLpro inhibitor, which will open the way for the development of clinical PLpro inhibitors for the treatment of COVID-19.
The Bioflavonoids Rutin and Rutin Succinate Neutralize the Toxins of B. jararaca Venom and Inhibit its Lethality
Authors: Sachetto Ana Teresa Azevedo , Miyamoto Jackson Gabriel , Tashima Alexandre Keiji , de Souza Ana Olívia , Santoro Marcelo Larami 
Published: February 2022

The venom of the Brazilian pit viper Bothrops jararaca (BjV) is a complex mixture of molecules, and snake venom metalloproteinases (SVMP) and serine proteinases (SVSP) are the most abundant protein families found therein. Toxins present in BjV trigger most of the deleterious disturbances in hemostasis observed in snakebites, i.e., thrombocytopenia, hypofibrinogenemia and bleedings. The treatment of patients bitten by snakes still poses challenges and the bioflavonoid rutin has already been shown to improve hemostasis in an experimental model of snakebite envenomation. However, rutin is poorly soluble in water; in this study, it was succinylated to generate its water-soluble form, rutin succinate (RS), which was analyzed comparatively regarding the chemical structure and characteristic features of rutin. Biological activities of rutin and RS were compared on hemostatic parameters, and against toxic activities of crude BjV in vitro. In vivo, C57BL/6 mice were injected i.p. with either BjV alone or pre-incubated with rutin, RS or 1,10-phenanthroline (o-phe, an SVMP inhibitor), and the survival rates and hemostatic parameters were analyzed 48 h after envenomation. RS showed the characteristic activities described for rutin – i.e., antioxidant and inhibitor of protein disulfide isomerase – but also prolonged the clotting time of fibrinogen and plasma in vitro. Differently from rutin, RS inhibited typical proteolytic activities of SVMP, as well as the coagulant activity of BjV. Importantly, both rutin and RS completely abrogated the lethal activity of BjV, in the same degree as o-phe. BjV induced hemorrhages, falls in RBC counts, thrombocytopenia and hypofibrinogenemia in mice. Rutin and RS also improved the recovery of platelet counts and fibrinogen levels, and the development of hemorrhages was totally blocked in mice injected with BjV incubated with RS. In conclusion, RS has anticoagulant properties and is a novel SVMP inhibitor. Rutin and RS showed different mechanisms of action on hemostasis. Only RS inhibited directly BjV biological activities, even though both flavonoids neutralized B. jararaca toxicity in vivo. Our results showed clearly that rutin and RS show a great potential to be used as therapeutic compounds for snakebite envenomation.
Effects of Three Different Modes of Resistance Training on Appetite Hormones in Males With Obesity
Authors: Ataeinosrat Ali , Haghighi Marjan Mosalman , Abednatanzi Hossein , Soltani Mohammad , Ghanbari-Niaki Abbass , Nouri-Habashi Akbar , Amani-Shalamzari Sadegh , Mossayebi Ali , Khademosharie Mitra , Johnson Kelly E. , VanDusseldorp Trisha A. , Saeidi Ayoub , Zouhal Hassane 
Published: February 2022

PurposeThis study explored the effect of three different modes of resistance training on appetite hormones [leptin, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide tyrosine–tyrosine (PYY)], cardiometabolic and anthropometric measures in males with obesity.MethodsForty-four males with obesity (age: 27.5 ± 9.4 yrs.; mean weight: 93.2 ± 2.2 kg, body mass index: 32.9 ± 1.2 kg/m2) were randomized to traditional resistance training (TRT, n = 11), circuit resistance training (CRT, n = 11), interval resistance training (IRT, n = 11) or control (C, n = 11) groups. All resistance training groups received 50 min of supervised training per session, three days per week, for 12 weeks. Measurements were taken at baseline and after 12 weeks of training.ResultsPlasma levels of leptin, ghrelin, CCK, and PYY decreased significantly in all three different modalities of resistance training groups when compared to the control group (p &lt; 0.05). GLP-1 increased significantly in both CRT and IRT groups compared to TRT and C groups (p &lt; 0.05). Glucose-dependent insulinotropic polypeptide decreased significantly in CRT and IRT groups compared to the C group (p &lt; 0.05). Adiponectin levels increased significantly in all resistance training groups compared to the C group (p &lt; 0.05).ConclusionOverall, CRT and IRT protocols had the greatest impact on appetite hormones compared to individuals who engaged in TRT or did not exercise (C).
Sex Difference in Global Burden of Major Depressive Disorder: Findings From the Global Burden of Disease Study 2019
Authors: Li Sangzi , Xu Yufeng , Zheng Leilei , Pang Hu , Zhang Qianni , Lou Lixia , Huang Xingru 
Published: February 2022

ObjectivesGlobally, major depressive disorder (MDD) is considered to be a leading cause of disability. In this article, we aim to investigate the sex difference in global burden of MDD by year, age, and socioeconomic development, utilizing disability-adjusted life-years (DALYs).MethodsGlobal and national sex-specific DALY estimates caused by MDD from 1990 to 2019 and in different age groups were obtained from the Global Burden of Disease (GBD) Study 2019. Human development index (HDI) was used as an indicator of national socioeconomic development. Spearman correlation and linear regression analyses were performed to explore the relationship between national socioeconomic development and sex difference in MDD burden.ResultsSex difference in global burden of MDD persisted between 1990 and 2019, with age-standardized DALY rates being 352 among males vs. 593 among females in 1990 and 354 vs. 564 in 2019. Females had higher burden of MDD than males at the same age. Disability-adjusted life-years numbers and rates among both sexes rapidly increased with age for those aged 10–24 years, along with gradually enlarging sex difference. Age-standardized DALY rates among females were higher than that among males for each HDI-based country group (P &lt; 0.001). National age-standardized DALY rates among both sexes were negatively related to HDI. However, female-to-male age-standardized DALY rate ratios were positively associated with HDI (Spearman r = 0.383, P &lt; 0.001; standardized β = 0.300, P &lt; 0.001).ConclusionAlthough some improvement in sex difference in global burden of MDD has been achieved, it still persists in the past three decades, with females bearing more burden than males. To reduce sex difference in global MDD burden, more attention should be paid to young people and people in developed countries. The findings highlight the importance of making sex-specific health policy to manage mental impairment caused by MDD.