bluuebunny/crossref_metadata_2025_split huggingface dataset:
Device-Related Complications and Inappropriate Therapies Among Subcutaneous vs. Transvenous Implantable Defibrillator Recipients: Insight Monaldi Rhythm Registry
Authors: Russo Vincenzo , Rago Anna , Ruggiero Vincenzo , Cavaliere Francesca , Bianchi Valter , Ammendola Ernesto , Papa Andrea Antonio , Tavoletta Vincenzo , De Vivo Stefano , Golino Paolo , D'Onofrio Antonio , Nigro Gerardo 
Published: May 2022

IntroductionIn the context of randomized clinical trials, subcutaneous implantable cardiac defibrillators (S-ICDs) are non-inferior to transvenous ICDs (T-ICDs) concerning device-related complications or inappropriate shocks in patients with an indication for defibrillator therapy and not in need of pacing. We aimed at describing the clinical features of patients who underwent S-ICD implantation in our clinical practice, as well as the ICD-related complications and the inappropriate therapies among S-ICD vs. T-ICD recipients during a long-term follow-up.Materials and MethodsAll patients undergoing ICD, both S-ICD and TV-ICD, at Monaldi Hospital from January 1, 2015 to January 1, 2019 and followed up at our institution were included in the present analysis. The clinical variables associated with S-ICD implantation were evaluated by logistic regression analyses. We collected the ICD inappropriate therapies, ICD-related complications (including both pulse generator and lead-related complications), ICD-related infections, appropriate ICD therapies, and overall mortality. Kaplan-Meier (KM) analyses were performed to assess the risk of clinical outcome events between the two subgroups. A time-dependent Cox regression analysis was performed to adjust the results.ResultsTotal 607 consecutive patients (mean age 53.8 ± 16.8, male 77.8%) with both TV-ICD (n: 290, 47.8%) and S-ICD (n: 317, 52.2%), implanted and followed at our center for a mean follow-up of 1614 ± 1018 days, were included in the study. At multivariate logistic regression analysis, an independent association between S-ICD implantation and ionic channel disease [OR: 6.01 (2.26–15.87); p &lt; 0.0001] and ischemic cardiomyopathy [OR: 0.20 (0.12–0.35); p &lt; 0.0001] was shown. The KM analysis did not show a significantly different risk of the inappropriate ICD therapies (log rank p = 0.64) between the two subgroups; conversely, a significant increase in the risk of ICD-related complications (log rank p = 0.02) and infections (log rank p = 0.02) in TV-ICD group was shown. The adjusted risk for ICD-related infections [OR: 0.07 (0.009–0.55), p = 0.01] and complications [0.31 (0.12–0.81), p = 0.01] was significantly lower among patients with S-ICD.ConclusionsThe choice to implant S-ICD was mainly driven by younger age and the presence of ionic channel disease; conversely ischemic cardiomyopathy reduces the probability to use this technology. No significant differences in inappropriate ICD therapies were shown among S-ICD vs. TV-ICD group; moreover, S-ICD is characterized by a lower rate of infectious and non-infectious complications leading to surgical revision or extraction.
Non-alcoholic Fatty Liver Disease Is Associated With Aortic Calcification: A Cohort Study With Propensity Score Matching
Authors: Zhu Rong-Rong , Gao Xu-Ping , Liao Min-Qi , Cui Yun-Feng , Tan Si-Xian , Zeng Fang-Fang , Lou Yan-Mei , Wang Chang-Yi , Xu Shan , Peng Xiao-Lin , Dai Shu-Hong , Zhao Dan , Wang Li , Ping Zhao , Dai Xiao-Yu , Feng Pin-Ning , Han Li-Yuan 
Published: May 2022

ObjectivesNon-alcoholic fatty liver disease (NAFLD) greatly affects cardiovascular disease, but evidence on the associations between NAFLD and markers of aortic calcification is limited. We aim to evaluate the association between NAFLD and aortic calcification in a cohort of Chinese adults using propensity score-matching (PSM) analysis.MethodsThis prospective cohort study involved adults who underwent health-screening examinations from 2009 to 2016. NAFLD was diagnosed by abdominal ultrasonography at baseline, and aortic calcification was identified using a VCT LightSpeed 64 scanner. Analyses included Cox proportional-hazards regression analysis and PSM with predefined covariates (age, gender, marital and smoking status, and use of lipid-lowering drugs) to achieve a 1:1 balanced cohort.ResultsOf the 6,047 eligible participants, 2,729 (45.13%) were diagnosed with NAFLD at baseline, with a median age of 49.0 years [interquartile range, 44.0–55.0]. We selected 2,339 pairs of participants with and without NAFLD at baseline for the PSM subpopulation. Compared with those without NAFLD, patients with NAFLD were at a higher risk of developing aortic calcification during follow-up; significant results were observed before and after matching, with the full-adjusted hazard ratios and corresponding 95% confidence intervals being 1.19 (1.02–1.38) and 1.18 (1.01–1.38), respectively (both p &lt; 0.05). In subgroup analyses, no interaction was detected according to age, gender, smoking status, body mass index, total cholesterol, low-density lipoprotein cholesterol, use of lipid-lowering drugs, hypertension, or type 2 diabetes.ConclusionsNAFLD may be independently associated with aortic calcification. Further studies are warranted to elucidate the possible underlying mechanisms.
The Distribution Characteristics and Human Health Risks of High- Fluorine Groundwater in Coastal Plain: A Case Study in Southern Laizhou Bay, China
Authors: Liu Sen , Liu Yanan , Wang Cong , Dang Xianzhang 
Published: May 2022

High-F groundwater has caused serious human health problems worldwide. In this paper, a typical saline-fresh water mixing zone (SFMZ) in a coastal plain (south of Laizhou Bay, China) was chosen as an example to analyze and summarize the distribution characteristics and enrichment mechanism human health risks of high-fluorine groundwater. Thirty-two groundwater samples have F- concentrations that exceed the drinking water guideline value of the World Health Organization (WHO; 1.5 mg/L), Thirty-two groundwater samples exceeded the drinking water guideline value of the WHO (1.5 mg/L) and 43 groundwater samples exceeded the National Sanitary Standard for drinking water of China (1.0 mg/L), accounting for 68.1 and 91.5% of the total groundwater samples. The groundwater quality is relatively poor in this study area, and the water is unsuitable for human consumption. High-F groundwater is mainly found in the central and northern parts of the study area, and the concentrations increase in the direction of water flow. High-F groundwater is mainly found in the central and northern parts of the study area, and the concentrations increase in the direction of water flow. According to the analysis, the groundwater environment, saline water intrusion (SWI), evaporation and cation exchange are the main factors influencing the enrichment of F in the SFMZ. The neutral and weakly alkaline environment is conducive to the enrichment of F-. Cation exchange and evaporation are the most important factors in the enrichment of F. Human activity is not the main source of groundwater F. Na+ and HCO3− are adequately abundant in the groundwater environment in the study area, creating conditions that are conducive to the dissolution of fluorite and the release of F into the groundwater. An increase in the Na+ concentration and a decrease in the Ca2+ concentration can promote further dissolution of fluorite and other F-containing minerals, thereby releasing F- into the groundwater. Fluorite dissolution is prevalent in the groundwater environment, which can lead to an increase in the F concentration. This study is helpful to the development of strategies for the integrated management of high-F groundwater in coastal plains. The health risk assessment shows that long-term exposure to high-F groundwater can pose a great threat to four age clusters, especially for children and infants. The HQ values for shallow groundwater range from 0.32 to 2.89, 0.39 to 3.61, 0.56 to 5.11, and 0.42 to 3.85 for adults, teenagers, children and infants, respectively. The groundwater in this study area is not for irrigation and animal husbandry, which may indirectly affect human health.
Genome-Wide Identification and Characterization of Long Non-Coding RNAs in Longissimus dorsi Skeletal Muscle of Shandong Black Cattle and Luxi Cattle
Authors: Liu Ruili , Han Mingxuan , Liu Xianxun , Yu Kun , Bai Xuejin , Dong Yajuan 
Published: May 2022

There is an increasing understanding of the possible regulatory role of long non-coding RNAs (LncRNA). Studies on livestock have mainly focused on the regulation of cell differentiation, fat synthesis, and embryonic development. However, there has been little study of skeletal muscle of domestic animals and the potential role of lncRNA. In this study, the transcriptome numbers of longissimus muscle of different beef cattle (Shandong black catle and Luxi catlle) were used to construct muscle related lncRNAs-miRNA-mRNA interaction network through bioinformatics analysis. This is helpful to clarify the molecular mechanism of bovine muscle development, and can be used to promote animal husbandry and improve animal husbandry production. According to the screening criteria of |FC|≧2 and q &lt; 0.05, a total of 1,415 transcripts (of which 480 were LncRNAs) were differentially expressed (q &lt; 0.05) in the different breeds. Further, we found that the most differentially expressed LncRNAs were found on chromosome 9, in which the differentially expressed LncRNAs targeted 1,164 protein coding genes (MYORG, Wnt4, PAK1, ADCY7,etc) (upstream and downstream&lt;50 Kb). In addition, Pearson’s correlation coefficients of co-expression levels indicated a potential trans regulatory relationship between the differentially expressed LncRNAs and 43844 mRNAs (r &gt; 0.9). The identified co-expressed mRNAs (MYORG, Dll1, EFNB2, SOX6, MYOCD, and MYLK3) are related to the formation of muscle structure, and enriched in muscle system process, strained muscle cell differentiation, muscle cell development, striated muscle tissue development, calcium signaling, and AMPK signaling. Additionally, we also found that some LncRNAs (LOC112444238, LOC101903367, LOC104975788, LOC112441863, LOC112449549, and LOC101907194) may interact with miRNAs related to cattle muscle growth and development. Based on this, we constructed a LncRNAs-miRNA-mRNA interaction network as the putative basis for biological regulation in cattle skeletal muscle. Interestingly, a candidate differential LncRNA (LOC104975788) and a protein-coding gene (Pax7) contain miR-133a binding sites and binding was confirmed by luciferase reporter assay. LOC104975788 may combined miR-133a competitively with Pax7, thus relieving the inhibitory effect of miR-133a on Pax7 to regulate skeletal muscle development. These results will provide the theoretical basis for further study of LncRNA regulation and activity in different cattle breeds.
Identification of Novel Characteristics in TP53-Mutant Hepatocellular Carcinoma Using Bioinformatics
Authors: Yang Yang , Qu Yajuan , Li Zhaopeng , Tan Zhiyong , Lei Youming , Bai Song 
Published: May 2022

Background: TP53 mutations are the most frequent mutations in hepatocellular carcinoma (HCC) and affect the occurrence and development of this cancer type. Therefore, it is essential to clarify the function and mechanism of TP53 mutations in HCC.Methods: We performed a sequence of bioinformatic analyses to elucidate the characteristics of TP53 mutations in HCC. We downloaded the data of hepatocellular carcinoma from The Cancer Genome Atlas database and used different R packages for serial analyses, including gene mutation analysis, copy number variation analysis, analysis of the tumor mutational burden and microsatellite instability, differential gene expression analysis, and functional enrichment analysis of TP53 mutations, and performed gene set enrichment analysis. We established a protein-protein interaction network using the STRING online database and used the Cytoscape software for network visualization, and hub gene screening. In addition, we performed anticancer drug sensitivity analysis using data from the Genomics of Drug Sensitivity in Cancer. Immune infiltration and prognosis analyses were also performed.Results: Missense mutations accounted for a great proportion of HCC mutations, the frequency of single nucleotide polymorphisms was high, and C &gt; T was the most common form of single nucleotide variations. TP53 had a mutation rate of 30% and was the most commonly mutated gene in HCC. In the TP53 mutant group, the tumor mutational burden (p &lt; 0.001), drug sensitivity (p &lt; 0.05), ESTIMATE score (p = 0.038), and stromal score (p &lt; 0.001) dramatically decreased. The Cytoscape software screened ten hub genes, including CT45A1, XAGE1B, CT55, GAGE2A, PASD1, MAGEA4, CTAG2, MAGEA10, MAGEC1, and SAGE1. The prognostic model showed a poor prognosis in the TP53 mutation group compared with that in the wild-type group (overall survival, p = 0.023). Univariate and multivariate cox regression analyses revealed that TP53 mutation was an independent risk factor for the prognosis of HCC patients (p &lt;0.05). The constructed prognostic model had a favorable forecast value for the prognosis of HCC patients at 1 and 3 years (1-year AUC = 0.752, 3-years AUC = 0.702).Conclusion: This study further deepened our understanding of TP53-mutated HCC, provided new insights into a precise individualized therapy for HCC, and has particular significance for prognosis prediction.
Integrated Analysis Reveals Critical Ferroptosis Regulators and FTL Contribute to Cancer Progression in Hepatocellular Carcinoma
Authors: Ke Shaoying , Wang Congren , Su Zijian , Lin Shaoze , Wu Gongle 
Published: May 2022

Background: The carcinogenesis and prognosis of hepatocellular carcinoma (HCC) involve complex molecular mechanisms, and ferroptosis is related to the development and therapeutic efficacy of HCC, but the specific mechanism and prognostic role of ferroptosis-related genes in HCC have not been elucidated.Methods: Differentially expressed gene analysis, Cox regression, and unsupervised consensus clustering were applied to identify crucial ferroptosis regulators and establish ferroptosis-related subtypes in HCC. Random forest analysis and survival analysis were adopted to confirm FTL as the hub prognostic and diagnostic ferroptosis regulator in HCC.Results: The ferroptosis-related subtypes based on the crucial prognostic ferroptosis regulators showed that patients in fescluster A had a higher survival probability (p &lt; 0.001) and better clinical characteristics than patients in fescluster B in the TCGA-LIHC cohort. Patients with a high tumor mutation burden (TMB) in fescluster B presented a significantly poorer prognosis. FTL was the core ferroptosis regulator, and its low expression revealed a significant survival advantage compared with its high expression (p = 0.03). The expression and predictive value of FTL were both closely related to the clinical features (p &lt; 0.05). Expression of FTL accurately distinguished HCC from normal tissues in the TCGA-LIHC cohort, ICGC cohort, and GSE14520 dataset. In addition, higher infiltrating fractions of immune cells, such as activated CD8+ T cells and Gamma delta T cells, mainly enriched immune-related signaling pathways, including the IL2-STAT3 signaling pathway and interferon-gamma response signaling pathway, and higher expression of immune checkpoints, including PDCD1, CTLA4, TIGIT, and CD83, were presented in patients with high FTL expression (p &lt; 0.05). Patients with high FTL were more sensitive to some targeted drugs, such as cisplatin, dasatinib, and sorafenib, than those with low FTL (p &lt; 0.05). A nomogram based on FTL accurately predicted the prognosis of HCC. Further knockdown of FTL was determined to significantly inhibit cell proliferation and migration in HCC.Conclusion: Our study validated ferroptosis-related subtypes and FTL with effective prognostic value in HCC and was beneficial for identifying candidates suitable for targeted drug therapy and immunotherapy, thereby offering further insight into individual treatment strategies to improve disease outcomes in HCC patients.
Hyper-IgE and Carcinoma in CADINS Disease
Authors: Pietzsch Leonora , Körholz Julia , Boschann Felix , Sergon Mildred , Dorjbal Batsukh , Yee Debra , Gilly Vanessa , Kämmerer Eva , Paul Diana , Kastl Clemens , Laass Martin W. , Berner Reinhard , Jacobsen Eva Maria , Roesler Joachim , Aust Daniela , Lee-Kirsch Min A. , Snow Andrew L. , Schuetz Catharina 
Published: May 2022

BackgroundAtopic dermatitis (AD) affects up to 25% of children and 10% of adults in Western countries. When severe or recurrent infections and exceedingly elevated serum IgE levels occur in AD patients, an inborn error of immunity (IEI) may be suspected. The International Union of Immunological Societies classification lists variants in different genes responsible for so-called Hyper-IgE syndromes. Diagnosing an underlying IEI may influence treatment strategies.MethodsClinical and diagnostic workup of family members are presented including a detailed immunological description and histology of the carcinoma. Functional testing of the novel variant in CARD11 underlying ‘CARD11-associated atopy with dominant interference of NF-kB signaling’ (CADINS) was performed.ResultsWe report on an 18-year-old patient with a long-standing history of infections, accompanied by hypogammaglobulinemia, intermittent agranulocytosis, atopy, eosinophilia and colitis. The working diagnosis of common variable immunodeficiency was revised when a novel heterozygous CARD11 variant [c.223C&gt;T; p.(Arg75Trp)] was identified. Functional studies confirmed this variant to have a dominant negative (DN) effect, as previously described in patients with CADINS. Five other family members were affected by severe atopy associated with the above variant, but not hypogammaglobulinemia. Malignancies occurred in two generations: an HPV-positive squamous cell carcinoma and a cutaneous T-cell lymphoma. So far, one patient is under treatment with dupilumab, which has shown marked benefit in controlling severe eczema.ConclusionThe phenotypic spectrum associated with heterozygous CARD11 DN mutations is broad. Partial T-cell deficiency, diminished IFN-γ cytokine and increased IL-4 production, were identified as disease-causing mechanisms. Malignant disease associated with germline CARD11 DN variants has only been reported sporadically. HPV vaccination in teenage years, and cytology screening analogous with routine cervical swabs may be recommended. Treatment with dupilumab, a monoclonal antibody blocking interleukin-4- and interleukin-13 signaling, may be of benefit in controlling severe and extended AD for some patients as reported for STAT3 loss-of-function.
Granulocyte Colony-Stimulating Factor Accelerates the Recovery of Hepatitis B Virus-Related Acute-on-Chronic Liver Failure by Promoting M2-Like Transition of Monocytes
Authors: Tong Jingjing , Wang Hongmin , Xu Xiang , Wan Zhihong , Fang Hongbin , Chen Jing , Mu Xiuying , Liu Zifeng , Chen Jing , Su Haibin , Liu Xiaoyan , Li Chen , Huang Xiaowen , Hu Jinhua 
Published: May 2022

Background and AimAcute-on-chronic liver failure (ACLF) has a high mortality rate. The role of granulocyte colony-stimulating factor (G-CSF) in ACLF remains controversial. Monocytes/macrophages are core immune cells, which are involved in the initiation and progression of liver failure; however, the effect of G-CSF on monocytes/macrophages is unclear. The study aimed to verify the clinical efficacy of G-CSF and explore the effect of it on monocytes in hepatitis B virus (HBV)-related ACLF (HBV-ACLF) paitents.MethodsWe performed a large randomized controlled clinical trial for the treatment of HBV-ACLF using G-CSF. A total of 111 patients with HBV-ACLF were prospectively randomized into the G-CSF group (5 μg/kg G-CSF every day for 6 days, then every other day until day 18) or the control group (standard therapy). All participants were followed up for at least 180 days. The relationship between monocyte count and mortality risk was analyzed. The effect of G-CSF on the phenotype and function of monocytes from patients with HBV-ACLF was evaluated using flow cytometry in vivo and in vitro experiments.ResultsThe survival probability of the G-CSF group at 180 days was higher than that of the control group (72.2% vs. 53.8%, P = 0.0142). In the G-CSF-treated group, the monocyte counts on days 0 and 7 were independently associated with an evaluated mortality risk in the fully adjusted model (Model 3) [at day 0: hazard ratio (HR) 95% confidence interval (CI): 15.48 (3.60, 66.66), P = 0.0002; at day 7: HR (95% CI): 1.10 (0.50, 2.43), P=0.8080]. Further analysis showed that after treatment with G-CSF in HBV-ACLF patients, the expression of M1-like markers (HLA-DR and CD86) in monocytes decreased (HLA-DR: P = 0.0148; CD86: P = 0.0764). The expression of MerTK (M2-like marker) increased (P = 0.0002). The secretion of TNF-α, IL-6, and IL-10 from monocytes decreased without lipopolysaccharide (LPS) stimulation (TNF-α: P &lt; 0.0001; IL-6: P= 0.0025; IL-10: P = 0.0004) or with LPS stimulation (TNF-α: P = 0.0439; P = 0.0611; IL-10: P = 0.0099). Similar effects were observed in vitro experiments.ConclusionG-CSF therapy confers a survival benefit to patients with HBV-ACLF. G-CSF can promote the anti-inflammatory/pro-restorative phenotype (M2-like) transition of monocytes, which may contribute to the recovery of ACLF.Clinical Trial Registration NumberClinicalTrials.gov, identifier (NCT02331745).
Safety and Efficacy of PD-1/PD-L1 Inhibitors in Cancer Patients With Preexisting Autoantibodies
Authors: Tang Hui , Geng Ruixuan , Xu Xiuxiu , Wang Yingyi , Zhou Jiaxin , Zhang Shulan , Zhao Lin , Guan Mei , Bai Chunmei 
Published: May 2022

BackgroundProgrammed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors therapy is now a routine scheme in cancers. However, the effect of preexisting autoantibodies on the safety and efficacy of PD-1/PD-L1 inhibitors in cancer patients is not well understood.MethodsThe present retrospective cohort study evaluated the safety and efficacy of PD-1/PD-L1 inhibitors in patients with preexisting autoantibodies. Patients who received PD-1/PD-L1 inhibitors in the Department of Medical Oncology, Peking Union Medical College Hospital between November 2017 and August 2021 were reviewed.Results67 (37.9%) of the 177 patients, 27 (20.3%) of the 133 patients, and 16 (11.0%) of 146 patients who received PD-1/PD-L1 inhibitors were positive for ANA, anti-Ro52, and antithyroid antibodies, respectively. Preexisting ANA and anti-Ro52 antibody were not associated with the increased risk of immune-related adverse events (irAEs), while thyroid dysfunction was more frequent in patients with positive antithyroid antibody (75.0% versus 13.8%, p &lt; 0.001). The median progression-free survival (PFS, 13.1 versus 7.0 months, p = 0.015) was significantly longer in the ANA-positive patients, while the median overall survival (OS, 14.5 versus 21.8 months, p = 0.67) did not differ significantly between the ANA-positive and ANA-negative groups. Moreover, the preexisting anti-Ro52 and antithyroid antibodies were not significantly associated with PFS and OS.ConclusionsThe presence of ANA and anti-Ro52 antibody were not associated with a higher risk of irAEs, whereas patients positive for antithyroid antibody should monitor closely immune-related thyroid dysfunction. Preexisting ANA might be a predictor of longer PFS, while anti-Ro52 and antithyroid antibodies had no significant effect on survival outcomes in patients receiving PD-1/PD-L1 inhibitors therapy.