bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triglyceride and Glucose Index and Sex Differences in Relation to Major Adverse Cardiovascular Events in Hypertensive Patients Without Diabetes
Authors: Yang Kun , Liu Wenxian 
Published: November 2021

IntroductionStudies from recent decades have suggested that women have a lower risk of cardiovascular disease than men due to their characteristics, but hyperglycemia and hyperinsulinemia caused by IR (insulin resistance) might reverse this gender-protective effect. This study examined whether there were sex differences in the relationship between IR [evaluated by triglyceride and glucose index (TyG index)] and major adverse cardiovascular events (MACEs) in hypertensive patients without diabetes.MethodsThis was a post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT). We explored the relationship between TyG index and MACEs by multivariate Cox proportional hazard regressions and two-piecewise linear regression models. The primary endpoint was MACEs, same as SPRINT, defined as a composite of myocardial infarction, stroke, heart failure, and/or death from cardiovascular causes. We used multiple adjustment models for all regressions.ResultsA total of 9,323 patients from the SPRINT were included in our analysis. TyG index was significantly related to the risk of MACEs in every adjusted model. Each 1 unit increase in TyG index increased the risk of MACEs in total participants (HR, 1.40; 95% CI, 1.20–1.64; P&lt;0.01) and men (HR, 1.42; 95% CI, 1.18–1.71; P=0.02). However, TyG index was not associated with MACEs among female hypertensive patients (HR, 1.33; 95% CI, 0.97–1.82; P=0.0776). There was no interaction between the sex and TyG index (P for interaction= 0.73). We also used the two-stage linear regression model and did not find any threshold effect. There was no significant interaction in other confounders.ConclusionWe found the TyG index was associated with MACEs in the hypertensive patients, and there was no gender difference between the TyG index and MACEs.
Sensitivity to Thyroid Hormone Indices Are Closely Associated With NAFLD
Authors: Lai Shuiqing , Li Jiarong , Wang Zixiao , Wang Wei , Guan Haixia 
Published: November 2021

BackgroundPrevious studies on the association between thyroid function and non‐alcoholic fatty liver disease (NAFLD) have contradicted. Acquired resistance to thyroid hormone theory might provide a reasonable explanation for these contradictions. We aimed to analyze the association between sensitivity to thyroid hormone indices with NAFLD.MethodsA total of 4,610 individuals from the health medical center of the First Hospital of China Medical University were included in this study. The previously used thyroid feedback quantile-based index (TFQIFT4) was calculated. Also, we substituted free triiodothyronine (FT3) into the TFQI formulas to get the TFQIFT3 index. NAFLD was defined using abdominal ultrasound.ResultsStudy results showed that FT3/FT4 and TFQIFT3 were positively correlated with the triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels (P&lt;0.05) and negatively correlated with high-density lipoprotein cholesterol (HDL-C) level (P&lt;0.05). In contrast, TFQIFT4 was positively correlated with HDL-C level (P &lt; 0.05). After adjustment for multiple confounders, FT3, FT3/FT4, and TFQIFT3 were positively associated with the risks of dyslipidemia and NAFLD (P &lt; 0.05). TFQIFT3 and FT3/FT4 performed better than TFQIFT4 on ROC analyses for NAFLD prediction, although the diagnostic sensitivity and specificity at the optimal cut-points were low. However, no association was observed between TFQIFT4 with the risks of dyslipidemia and NAFLD.ConclusionTFQIFT3 and FT3/FT4 can be used as new indicators for predicting dyslipidemia and NAFLD, although with low sensitivity and specificity at the optimal cut-points, while TFQIFT4 has insufficient evidence in predicting dyslipidemia and NAFLD.
A Role for Drylands in a Carbon Neutral World?
Authors: Hanan Niall P. , Milne Eleanor , Aynekulu Ermias , Yu Qiuyan , Anchang Julius 
Published: November 2021

Drylands are a critical part of the earth system in terms of total area, socioeconomic and ecological importance. However, while drylands are known for their contribution to inter-annual atmospheric CO2 variability, they are sometimes overlooked in discussions of global carbon stocks. Here, in preparation for the November 2021 UN Climate Change Conference (COP26), we review dryland systems with emphasis on their role in current and future carbon storage, response to climate change and potential to contribute to a carbon neutral future. Current estimates of carbon in dryland soils and vegetation suggest they are significant at global scale, containing approximately 30% of global carbon in above and below-ground biomass, and surface-layer soil carbon (top 30 cm). As ecosystems that are limited by water, the drylands are vulnerable to climate change. Climate change impacts are, however, dependent on future trends in rainfall that include both drying and wetting trends at regional scales. Regional rainfall trends will initiate trends in dryland productivity, vegetation structure and soil carbon storage. However, while management of fire and herbivory can contribute to increased carbon sequestration, impacts are dependent on locally unique ecosystem responses and climate-soil-plant interactions. Similarly, while community based agroforestry initiatives have been successful in some areas, large-scale afforestation programs are logistically infeasible and sometimes ecologically inappropriate at larger scales. As climate changes, top-down prescriptive measures designed to increase carbon storage should be avoided in favour of locally-adapted approaches that balance carbon management priorities with local livelihoods, ecosystem function, biodiversity and cultural, social and economic priorities.
Efficacy and Treatment-Related Adverse Events of Romidepsin in PTCL Clinical Studies: A Systematic Review and Meta-Analysis
Authors: Du Jun , Han Xinle , Lin Suwen , Qiu Chen , Zhu Lijun , Huang Zoufang , Hou Jian 
Published: November 2021

Background: Peripheral T-cell lymphoma (PTCL) is an extensive class of biologically and clinically heterogeneous diseases with dismal outcomes. The histone deacetylase inhibitor (HDACi) romidepsin was approved for relapsed and refractory (R/R-PTCL) in 2011. This meta-analysis was performed to assess the efficacy and safety of romidepsin in PTCL.Methods: We searched for articles on the HDAC inhibitor romidepsin in the treatment of PTCL in Embase, Web of Science, and PubMed. The methodology is further detailed in PROSPERO (CRD42020213651, CRD42020213553). The 2-year overall survival (OS), 2-year progression-free survival (PFS), and their corresponding to 95% confidence intervals (CIs) were measured. Besides, corresponding 95% CIs were pooled for the complete response (CR), partial response (PR), duration of response (DoR), and risk of adverse events (AEs).Results: Eleven studies containing 388 patients were incorporated into the quantitative synthesis, of which R/R-PTCL patients were the dominant portion, accounting for 94.3% (366/388). For all studies, the CR rate was 20% (95% CI, 13–27%, random effects model), and the PR rate was 18% (95% CI, 12–25%, random effects model). The 2-year OS was 48% (95% CI, 38–59%, fixed effects model), and the 2-year PFS was 17% (95% CI, 13–21%, fixed effects model). There were no significant differences between romidepsin monotherapy and romidepsin plus additional drugs. Hematological toxicities, such as lymphopenia and granulocytopenia, remained the most continually happening grade 3 or higher AEs, accounting for 46 and 28%, respectively. None of the studies reported any drug-related mortality.Conclusions: Considering that most of the included patients had R/R-PTCL, the addition of romidepsin significantly enhance the efficacy. And AEs were tolerable as the grade 3/4 AEs in romidepsin monotherapy was 7% (95% CI, 6–8%). It is imperative to further expand the first-line application of romidepsin and carry out personalized therapy based on epigenomics, which will improve the survival of PTCL patients.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020213651 and https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020213553.
The Availability and Safety Study of Remimazolam Besylate for Injection on Sedation of ERAS Patients Under Mechanical Ventilation in ICU: Protocol for a Randomized, Open-Label, Controlled Trial
Authors: Liu Shengjun , Su Longxiang , Zhang Bo , He Huaiwu , Li Zunzhu , Li Qi , Wang Qianlin , Smith Fang , Long Yun 
Published: November 2021

Introduction: The most common physiological and psychological disorders associated with critical care patients are pain and anxiety. Sedatives and analgesics are commonly used to relieve these symptoms. However, the adverse effects of sedatives and analgesics are common and inevitable. As a new type of sedative drug, limited number of trials are available to evaluate Remimazolam Besylate's availability and safety compared with propofol.Methods: This study is a single center, randomized, open-label, controlled trial. A total of 84 patients who meet ERAS criteria and receive mechanical ventilation in ICU, aged ≥18 years old will be included. Patients will be randomized (1:1) into two groups: Remimazolam Besylate group and Propofol group. The Primary outcomes includes satisfaction rate of sedation and incidence rate of major clinical events. Secondary outcomes including incidence of delirium, time to weaning and extubation, Difficulty of nursing RASS, BIS and PI, 28-days survival, side-effect and vital signs during medications, total dose and dose per kilogram body weight of analgesic and sedatives and incidence of rescue therapy in experimental group.Ethics and Dissemination: This trial has been approved by the ethics boards of Peking Union Medical College Hospital. Recruitment began in January 2022 and will continue until June 2022. Dissemination plans include presentations at scientific conferences, scientific publications, stakeholder engagement efforts and presentation to the public via lay media outlets.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04947345
Change in Anemia by Carnitine Supplementation in Patients Undergoing Peritoneal Dialysis: A Retrospective Observational Study
Authors: Kaneko Shohei , Yanai Katsunori , Kitano Taisuke , Miyazawa Haruhisa , Hirai Keiji , Ookawara Susumu , Morishita Yoshiyuki 
Published: November 2021

Background: Carnitine supplementation improves various dialysis-related symptoms including erythropoietin-resistant anemia in patients who are undergoing hemodialysis. However, the utility of carnitine supplementation in patients who are undergoing peritoneal dialysis (PD) is not fully understood.Methods: Thirteen patients undergoing PD [mean age: 54.2 ± 14.8 years, males: 9/13 (69%)] administered oral carnitine supplementation (mean dose: 9.1 ± 3.3 mg/kg/day) for 4–6 months were retrospectively investigated. Changes in serum carnitine levels and other clinical variables including the erythropoietin resistance index (ERI) were analyzed after carnitine supplementation.Results: Carnitine supplementation increased serum total carnitine (48.5 ± 10.2 vs. 130.1 ± 37.2 μmol/L, P &lt; 0.01), free carnitine (31.1 ± 8.3 vs. 83.1 ± 24.6 μmol/L, P &lt; 0.01), and acyl carnitine (17.4 ± 2.8 vs. 46.9 ± 13.8, P &lt; 0.01) levels. The acyl carnitine/free carnitine ratio was not affected (0.6 ± 0.1 vs. 0.6 ± 0.1, P = 0.75). Although the mean ERI was not affected by carnitine supplementation [13.7 ± 4.7 vs. 11.6 ± 3.4 IU/kg/(g/dL)/week, P = 0.28], the ERI change rate was significantly decreased (1.00 ± 0.00 vs. 0.87 ± 0.11, P &lt; 0.01).Conclusion: Carnitine supplementation may improve erythropoietin resistance in patients who are undergoing PD.
Analysis and Construction of a Molecular Diagnosis Model of Drug-Resistant Epilepsy Based on Bioinformatics
Authors: Han Tenghui , Wu Zhenyu , Zhu Jun , Kou Yao , Li Jipeng , Deng Yanchun 
Published: November 2021

Background: Epilepsy is a complex chronic disease of the nervous system which influences the health of approximately 70 million patients worldwide. In the past few decades, despite the development of novel antiepileptic drugs, around one-third of patients with epilepsy have developed drug-resistant epilepsy. We performed a bioinformatic analysis to explore the underlying diagnostic markers and mechanisms of drug-resistant epilepsy.Methods: Weighted correlation network analysis (WGCNA) was applied to genes in epilepsy samples downloaded from the Gene Expression Omnibus database to determine key modules. The least absolute shrinkage and selection operator (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE) algorithms were used to screen the genes resistant to carbamazepine, phenytoin, and valproate, and sensitivity of the three-class classification SVM model was verified through the receiver operator characteristic (ROC) curve. A protein–protein interaction (PPI) network was utilized to analyze the protein interaction relationship. Finally, ingenuity pathway analysis (IPA) was adopted to conduct disease and function pathway and network analysis.Results: Through WGCNA, 72 genes stood out from the key modules related to drug resistance and were identified as candidate resistance genes. Intersection analysis of the results of the LASSO and SVM-RFE algorithms selected 11, 4, and 5 drug-resistant genes for carbamazepine, phenytoin, and valproate, respectively. Subsequent union analysis obtained 17 hub resistance genes to construct a three-class classification SVM model. ROC showed that the model could accurately predict patient resistance. Expression of 17 hub resistance genes in healthy subjects and patients was significantly different. The PPI showed that there are six resistance genes (CD247, CTSW, IL2RB, MATK, NKG7, and PRF1) that may play a central role in the resistance of epilepsy patients. Finally, IPA revealed that resistance genes (PRKCH and S1PR5) were involved in “CREB signaling in Neurons.”Conclusion: We obtained a three-class SVM model that can accurately predict the drug resistance of patients with epilepsy, which provides a new theoretical basis for research and treatment in the field of drug-resistant epilepsy. Moreover, resistance genes PRKCH and S1PR5 may cooperate with other resistance genes to exhibit resistance effects by regulation of the cAMP-response element-binding protein (CREB) signaling pathway.
Association Between the Rate of Treatment Response and Short-Term Outcomes in Childhood Guillain-Barré Syndrome
Authors: Jin Mei , Zhao Libo , Liu Jing , Geng Weijin , Zhao Ziwei , Li Chunzhen , Xue Jingru , Sun Suzhen 
Published: November 2021

Introduction: Few studies have examined the association between the rate of treatment response and the outcome of pediatric Guillain-Barré syndrome (GBS). Therefore, our study aimed to identify treatment response in relation to the short-term outcomes of GBS. Further, we investigated its potential predictive value for prognosis.Methods: Our retrospective study included children diagnosed with GBS in the Pediatric Neurology Department of the Children's Hospital of Hebei Province from 2016 to 2020. According to the rate of response from the standard intravenous immunoglobulin (IVIg) treatment, patients were divided into two groups: rapid-response GBS (initial response within 7 days) and slow-response (initial response within 8–30 days). The GBS disability score (Hughes Functional Grading Scale) was used to assess the children's functional disability at nadir, 1 month, and 6 months after onset.Results: Among the 36 children included in the study, 18 (50%) and 18 (50%) were rapid and slow responders, respectively. Time from IVIg treatment to the initial response was significantly shorter in the rapid-response group (5 [3–6.25] days vs. 10.5[8.75–15] days in slow-response GBS, p &lt; 0.001). Hughes score at 1 month was worse than the rapid responders (Fisher's exact test, p = 0.006). Survival analysis (Kaplan–Meier) with respect to regaining the ability to walk independently (Hughes Functional Grading Scale of 2) within 1 month after onset was significantly different among the two groups (log-rank test for trend, p = 0.024). The abnormal levels of cerebral spinal fluid proteins and autonomic dysfunction were more frequent in the slow-response group than those in the rapid group (p &lt; 0.05).Conclusion: The rate of response to IVIg treatment was correlated with short-term outcomes in children with GBS and had predictive value for prognosis. The role of patient's initial responses to treatment could be significantly valuable in developing more effective and efficient treatment options.
Conditional Deletion of Activating Rearranged During Transfection Receptor Tyrosine Kinase Leads to Impairment of Photoreceptor Ribbon Synapses and Disrupted Visual Function in Mice
Authors: Peng Wei-Hao , Liao Meng-Lin , Huang Wan-Chun , Liu Pei-Kang , Levi Sarah R. , Tseng Yun-Ju , Lee Chia-Ying , Yeh Lung-Kun , Chen Kuan-Jen , Chien Chung-Liang , Wang Nan-Kai 
Published: November 2021

Purpose: The rearranged during transfection (RET) receptor tyrosine kinase plays a key role in transducing signals related to cell growth and differentiation. Ret mutant mice show abnormal retinal activity and abnormal levels and morphology of bipolar cells, yet die on the 21st day after birth as a result of renal underdevelopment. To extend the observation period, we generated the Ret conditional knockout Chx10-Cre;C-Retlx/lx mouse model and analyzed the retinal function and morphological changes in mature and aging Chx10-Cre;C-Retlx/lx mice.Methods: Retina-specific depletion of Ret was achieved using mice with floxed alleles of the Ret gene with CHX10-driven Cre recombinase; floxed mice without Cre expression were used as controls. Retinal function was examined using electroretinography (ERG), and 2-, 4-, 12-, and 24-month-old mice were analyzed by hematoxylin staining and immunohistochemistry to evaluate retinal morphological alterations. The ultrastructure of photoreceptor synapses was evaluated using electron microscopy.Results: The results of the ERG testing showed that b-wave amplitudes were reduced in Chx10-Cre;C-Retlx/lx mice, whereas a-waves were not affected. A histopathological analysis revealed a thinner and disorganized outer plexiform layer at the ages of 12 and 24 months in Chx10-Cre;C-Retlx/lx mice. Moreover, the data provided by immunohistochemistry showed defects in the synapses of photoreceptor cells. This result was confirmed at the ultrastructural level, thus supporting the participation of Ret in the morphological changes of the synaptic ribbon.Conclusion: Our results provide evidence of the role of Ret in maintaining the function of the retina, which was essential for preserving the structure of the synaptic ribbon and supporting the integrity of the outer plexiform layer.
Establishment of a prognosis Prediction Model Based on Pyroptosis-Related Signatures Associated With the Immune Microenvironment and Molecular Heterogeneity in Clear Cell Renal Cell Carcinoma
Authors: Jiang Aimin , Meng Jialin , Bao Yewei , Wang Anbang , Gong Wenliang , Gan Xinxin , Wang Jie , Bao Yi , Wu Zhenjie , Lu Juan , Liu Bing , Wang Linhui 
Published: November 2021

BackgroundPyroptosis is essential for tumorigenesis and progression of neoplasm. However, the heterogeneity of pyroptosis and its relationship with the tumor microenvironment (TME) in clear cell renal cell carcinoma (ccRCC) remain unclear. The purpose of the present study was to identify pyroptosis-related subtypes and construct a prognosis prediction model based on pyroptosis signatures.MethodsFirst, heterogenous pyroptosis subgroups were explored based on 33 pyroptosis-related genes and ccRCC samples from TCGA, and the model established by LASSO regression was verified by the ICGC database. Then, the clinical significance, functional status, immune infiltration, cell–cell communication, genomic alteration, and drug sensitivity of different subgroups were further analyzed. Finally, the LASSO-Cox algorithm was applied to narrow down the candidate genes to develop a robust and concise prognostic model.ResultsTwo heterogenous pyroptosis subgroups were identified: pyroptosis-low immunity-low C1 subtype and pyroptosis-high immunity-high C2 subtype. Compared with C1, C2 was associated with a higher clinical stage or grade and a worse prognosis. More immune cell infiltration was observed in C2 than that in C1, while the response rate in the C2 subgroup was lower than that in the C1 subgroup. Pyroptosis-related genes were mainly expressed in myeloid cells, and T cells and epithelial cells might influence other cell clusters via the pyroptosis-related pathway. In addition, C1 was characterized by MTOR and ATM mutation, while the characteristics of C2 were alterations in SPEN and ROS1 mutation. Finally, a robust and promising pyroptosis-related prediction model for ccRCC was constructed and validated.ConclusionTwo heterogeneous pyroptosis subtypes were identified and compared in multiple omics levels, and five pyroptosis-related signatures were applied to establish a prognosis prediction model. Our findings may help better understand the role of pyroptosis in ccRCC progression and provide a new perspective in the management of ccRCC patients.
Dosimetric Comparison of Helical Tomotherapy, Volume-Modulated Arc Therapy, and Fixed-Field Intensity-Modulated Radiation Therapy in Locally Advanced Nasopharyngeal Carcinoma
Authors: Lu Shan , Fan Huiqi , Hu Xueyuan , Li Xin , Kuang Yingying , Yu Deyang , Yang Shanshan 
Published: November 2021

ObjectiveTo compare the dosimetric parameters of different radiotherapy plans [helical tomotherapy (HT), volume-modulated arc therapy (VMAT), and fixed-field intensity-modulated radiation therapy (FF-IMRT)] for locally advanced nasopharyngeal carcinoma (NPC).MethodsA total of 15 patients with locally advanced NPC were chosen for this retrospective analysis and replanned for HT, VMAT, and FF-IMRT. The prescribed planning target volume (PTV) dose for the primary tumor and metastatic lymph nodes was 70 Gy (2.12 Gy/fraction, delivered over 33 fractions). The prescribed PTV dose for the high-risk subclinical region was 59.4 Gy (1.8 Gy/fraction, delivered over 33 fractions). The dosimetric parameters of the PTV and organs at risk (OARs) and the efficiency of radiation delivery were assessed and compared using the paired-samples t-test.ResultsCompared with VMAT and FF-IMRT plans, HT plans significantly improved the mean conformity index (CI) and homogeneity index (HI). The HT plans reduced the maximum doses delivered to OARs, such as the brainstem, spinal cord, and optic nerves, and significantly reduced the volume delivered to the high-dose region, especially when examining the V30 value of the parotid glands. However, VMAT reduced the treatment time and improved the efficiency of radiation delivery compared with HT.ConclusionsFor locally advanced NPC, the results showed that HT and VMAT possessed better target homogeneity and conformity, reducing the dose delivered to OARs compared with conventional FF-IMRT, with HT achieving the best effect. Among the techniques studied, VMAT had the shortest radiation delivery time. The results of this study can provide guidance for the selection of appropriate radiation technologies used to treat patients with locally advanced NPC who are undergoing concurrent chemoradiotherapy.