bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Determinants Differentiating the Severity of SARS-CoV-2 Infection in Cancer Patients: Hospital Care or Home Recovery
Authors: Lin Dong D. , Wu Yunhong , Toom Sudhamshi , Sheth Niki , Becker Kevin , Burdette-Radoux Susan , D'Silva James , Huang Yiwu , Lipshitz Jay , Meghal Trishala , Mo Lan , Murthy Pooja , Rubin Philip , Natarajan Vijaya , Donahue Bernadine , Xu Yiqing 
Published: February 2021

Background: Cancer patients may carry a worse prognosis with SARS-CoV-2 infection. Most of the previous studies described the outcomes of hospitalized cancer patients. We aimed to study the clinical factors differentiating patients requiring hospital care vs. home recovery, and the trajectory of their anti-cancer treatment.Methods: This study was conducted in a community cancer center in New York City. Eligible patients were those who had cancer history and were diagnosed of SARS-CoV-2 infection between March 1 and May 30, 2020, with confirmatory SARs-CoV-2 virus test or antibody test. Four groups were constructed: (A) hospitalized and survived, (B) hospitalized requiring intubation and/or deceased, (C) non-hospitalized, asymptomatic, with suspicious CT image findings, close exposure, or positive antibody test, and (D) non-hospitalized and symptomatic.Results: One hundred and six patients were included in the analysis. Thirty-five patients (33.0%) required hospitalization and 13 (12.3%) died. Thirty (28.3%) patients were asymptomatic and 41 (38.7%) were symptomatic and recovered at home. Comparing to patients who recovered at home, hospitalized patients were composed of older patients (median age 71 vs. 63 years old, p = 0.000299), more who received negative impact treatment (62.9 vs. 32.4%, p = 0.0036) that mostly represented myelosuppressive chemotherapy (45.7 vs. 23.9%, p = 0.0275), and more patients with poorer baseline performance status (PS ≥ 2 25.7 vs. 2.8%, p = 0.0007). Hypoxemia (35% in group A vs. 73.3% in group B, p = 0.0271) at presentation was significant to predict mortality in hospitalized patients. The median cumulative hospital stay for discharged patients was 16 days (range 5–60). The median duration of persistent positivity of SARS-CoV-2 RNA was 28 days (range 10–86). About 52.9% of patients who survived hospitalization and required anti-cancer treatment reinitiated therapy. Ninety-two percent of the asymptomatic patients and 51.7% of the symptomatic patients who recovered at home continued treatment on schedule and almost all reinitiated treatment after recovery.Conclusions: Cancer patients may have a more severe status of SARS-CoV-2 infection after receiving myelosuppressive chemotherapy. Avoidance should be considered in older patients with poor performance status. More than two thirds of patients exhibit minimal to moderate symptoms, and many of them can continue or restart their anti-cancer treatment upon recovery.
A Simple-to-Use Web-Based Calculator for Survival Prediction in Acute Respiratory Distress Syndrome
Authors: Liu Yong , Liu Jian , Huang Liang 
Published: February 2021

Background: The aim of this study was to construct and validate a simple-to-use model to predict the survival of patients with acute respiratory distress syndrome.Methods: A total of 197 patients with acute respiratory distress syndrome were selected from the Dryad Digital Repository. All eligible individuals were randomly stratified into the training set (n=133) and the validation set (n=64) as 2: 1 ratio. LASSO regression analysis was used to select the optimal predictors, and receiver operating characteristic and calibration curves were used to evaluate accuracy and discrimination of the model. Clinical usefulness of the model was also assessed using decision curve analysis and Kaplan-Meier analysis.Results: Age, albumin, platelet count, PaO2/FiO2, lactate dehydrogenase, high-resolution computed tomography score, and etiology were identified as independent prognostic factors based on LASSO regression analysis; these factors were integrated for the construction of the nomogram. Results of calibration plots, decision curve analysis, and receiver operating characteristic analysis showed that this model has good predictive ability of patient survival in acute respiratory distress syndrome. Moreover, a significant difference in the 28-day survival was shown between the patients stratified into different risk groups (P &lt; 0.001). For convenient application, we also established a web-based calculator (https://huangl.shinyapps.io/ARDSprognosis/).Conclusions: We satisfactorily constructed a simple-to-use model based on seven relevant factors to predict survival and prognosis of patients with acute respiratory distress syndrome. This model can aid personalized treatment and clinical decision-making.
Dual-Task Exercise to Improve Cognition and Functional Capacity of Healthy Older Adults
Authors: Jardim Naina Yuki Vieira , Bento-Torres Natáli Valim Oliver , Costa Victor Oliveira , Carvalho Josilayne Patricia Ramos , Pontes Helen Tatiane Santos , Tomás Alessandra Mendonça , Sosthenes Marcia Consentino Kronka , Erickson Kirk I. , Bento-Torres João , Diniz Cristovam Wanderley Picanço 
Published: February 2021

BackgroundIt has been suggested that physical inactivity and lack of stimulating cognitive activity are the two most significant modifiable risk factors to impair cognitive function. Although many studies that investigated the cognitive effects of physical exercise and cognitive stimuli in dual-task conditions showed improved cognitive performance, others have not confirmed these findings. The main aim of the present work is to analyze the effects of a dual-task multimodal physical exercise training, at moderate intensity, and cognitive stimulation on cognitive and physical function in healthy older adults.MethodsThis clinical trial was registered on the Brazilian Registry of Clinical Trials (RBR-9zrx3d). Here we tested the effects of a dual-task multimodal physical exercise training, at moderate intensity, on cognitive and physical function and quality of life in community dwelling older adults. The training protocol included 24 group sessions, 2/week, per 75 min. Cognition was assessed using CANTAB automated neuropsychological tests and Functional Capacity to Exercise tests. Performance was compared from baseline to post intervention and to a non-exercise control group using Mixed Linear Model for repeated measures.ResultsControl (CG) and dual-task (DTEx) groups progressed differentially over time on performance of episodic memory, sustained visual attention, functional mobility, cardiorespiratory fitness, lower limbs strength resistance, agility, quality of life and dual-task performance with significant improved DTEx performance. Control group did not show any significant changes on these tests except for showing a reduction in dual-task performance.ConclusionWe suggest that the dual-task combination of multisensory cognitive stimulation and multimodal moderate physical exercise training, twice a week, may be adopted as an effective program to reduce progression of age-related cognitive decline and improve physical fitness and quality of life on healthy older adults.Clinical Trial RegistrationBrazilian Registry of Clinical Trials: https://ensaiosclinicos.gov.br/rg/RBR-9zrx3d -UTN code: U1111-1233-6349.
Dopaminergic and Metabolic Correlations With Cognitive Domains in Non-demented Parkinson’s Disease
Authors: Han Linlin , Lu Jiaying , Tang Yilin , Fan Yun , Chen Qisi , Li Ling , Liu Fengtao , Wang Jian , Zuo Chuantao , Zhao Jue 
Published: February 2021

BackgroundAccruing positron emission tomography (PET) studies have suggested that dopaminergic functioning and metabolic changes are correlated with cognitive dysfunction in Parkinson’s disease (PD). Yet, the relationship between dopaminergic or cerebral metabolism and different cognitive domains in PD is poorly understood. To address this scarcity, we aimed to investigate the interactions among dopaminergic bindings, metabolic network changes, and the cognitive domains in PD patients.MethodsWe recruited 41 PD patients, including PD patients with no cognitive impairment (PD-NC; n = 21) and those with mild cognitive impairment (PD-MCI; n = 20). All patients underwent clinical evaluations and a schedule of neuropsychological tests and underwent both 11C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) PET imaging.Results11C-CFT imaging revealed a significant positive correlation between executive function and striatal dopamine transporter (DAT) binding at both the voxel and regional levels. Metabolic imaging revealed that executive function correlated with 18F-FDG uptake, mainly in inferior frontal gyrus, putamen, and insula. Further analysis indicated that striatal DAT binding correlated strictly with metabolic activity in the temporal gyrus, medial frontal gyrus, and cingulate gyrus.ConclusionOur findings might promote the understanding of the neurobiological mechanisms underlying cognitive impairment in PD.
Comprehensive Analysis of CDCAs Methylation and Immune Infiltrates in Hepatocellular Carcinoma
Authors: Wang Yongkang , Yang Yinfeng , Gao Honglei , Ouyang Ting , Zhang Luyao , Hu Jili , Hu Sheng , Kan Hongxing 
Published: February 2021

BackgroundAs essential components of cycle growth, the cell division cycle-associated family genes (CDCAs) have crucial roles in tumor development and progression, especially in hepatocellular carcinoma (HCC). However, due to the tumor heterogeneity of HCC, little is known about the methylation variability of CDCAs in mediating phenotypic changes (e.g., immune infiltrates) in HCC. Presently, we aim to comprehensively explore the expression and prognosis of CDCAs methylation with regard to immune infiltrates of HCC.MethodsWe first identified the correlating differentially expressed genes (co-DEGs) among 19 different types of cancer cohorts (a total of 7,783 patients) and then constructed the weighted gene co-expressed and co-methylated networks. Applying the clustering analysis, significant modules of DEGs including CDCAs were selected and their functional bioinformatics analyses were performed. Besides, using DiseaseMeth and TIMER, the correlation between the methylation levels of CDCAs and tumor immune infiltrates was also analyzed. In final, to assess the influence of CDCAs methylation on clinical prognosis, Kaplan-Meier and Cox regression analysis were carried out.ResultA total of 473 co-DEGs are successfully identified, while seven genes of CDCAs (CDCA1–3 and CDCA5–8) have significant over-expression in HCC. Co-expressed and co-methylated networks reveal the strong positive correlations in mRNA expression and methylation levels of CDCAs. Besides, the biological enrichment analysis of CDCAs demonstrates that they are significantly related to the immune function regulation of infiltrating immune cells in HCC. Also, the methylation analysis of CDCAs depicts the strong association with the tumor immunogenicity, i.e., low-methylation of CDCA1, CDCA2, and CDCA8 dramatically reduced the immune infiltrate levels of T cells and cytotoxic lymphocytes. Additionally, CDCA1–6 and CDCA8 with low-methylation levels significantly deteriorate the overall survival of patients in HCC.ConclusionsThe co-expressed and co-methylated gene networks of CDCAs show a powerful association with immune function regulation. And the methylation levels of CDCAs suggesting the prognostic value and infiltrating immune differences could be a novel and predictive biomarker for the response of immunotherapy.
Synthetic TILs: Engineered Tumor-Infiltrating Lymphocytes With Improved Therapeutic Potential
Authors: Jiménez-Reinoso Anaïs , Nehme-Álvarez Daniel , Domínguez-Alonso Carmen , Álvarez-Vallina Luis 
Published: February 2021

Immunotherapy has emerged as an effective and life-changing approach for several types of cancers, both liquid and solid tumors. In combination with traditional treatments such as radiotherapy and/or chemotherapy, immune checkpoints inhibitors have improved prognosis and overall survival of patients with advanced melanoma and many other cancers. Among adoptive cell therapies (ACT), while chimeric antigen receptor T cell therapies have demonstrated remarkable efficacy in some hematologic malignancies, such as B cell leukemias, their success in solid tumors remains scarce due to the characteristics of the tumor microenvironment. On the other hand, ACT using tumor-infiltrating lymphocytes (TILs) is arguably the most effective treatment for metastatic melanoma patients, but even if their isolation has been achieved in epithelial tumors, their success beyond melanoma remains limited. Here, we review several aspects impacting TIL- and gene-modified “synthetic” TIL-based therapies and discuss future challenges that must be addressed with these approaches.
Pretreatment Plasma EBV-DNA Load Guides Induction Chemotherapy Followed by Concurrent Chemoradiotherapy in Locoregionally Advanced Nasopharyngeal Cancer: A Meta-Analysis
Authors: Lai Lin , Chen Xinyu , Zhang Chuxiao , Chen Xishan , Chen Li , Tian Ge , Zhu Xiaodong 
Published: February 2021

BackgroundThe efficacy of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal cancer (LA-NPC) is controversial. In this paper, we conduct a meta-analysis based on relevant studies to provide strong evidence for clinical strategies.Materials and MethodsWe searched the MEDLINE, Embase, Cochrane, PubMed, and Web of Science databases for studies that stratified patients based on a high or low plasma Epstein–Barr virus deoxyribonucleic acid (EBV-DNA) load before treatment and compared the clinical efficacy of IC+CCRT vs. CCRT alone in LA-NPC. We tested for heterogeneity of studies and conducted sensitivity analysis. Subgroup analysis was performed for overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS).ResultsSeven studies with a total of 5289 cases were finally included in the meta-analysis. The heterogeneity test revealed the homogeneity of OS (I2 = 0.0%, p=0.794), PFS (I2 = 0.0%, p=0.778), DMFS (I2 = 0.0%, p=0.997), and LRFS (I2 = 0.0%, p=0.697) in patients with EBV-DNA loads of ≥4000 copies/ml in both the IC+CCRT and CCRT groups. The results reveal that IC+CCRT significantly extended the OS (HR 0.70 [95% CI 0.58-0.83], p=0.000), PFS (HR 0.83 [95% CI 0.70-0.99], p=0.033), and DMFS (HR 0.79 [95% CI 0.69-0.9], p=0.000) of patients compared with the CCRT group, but there were no beneficial effects on LRFS (HR 1.07 [95% CI 0.80-1.42], p=0.647). The heterogeneity test found that there was no significant heterogeneity of PFS (I2 = 0.0%, p=0.564), DMFS (I2 = 0.0%, p=0.648), LRFS (I2 = 22.3%, p=0.257), and OS (I2 = 44.6%, p=0.164) in patients with EBV-DNA loads of &lt;4000 copies/ml. The results show that IC+CCRT prolonged DMFS (HR 0.57 [95% CI 0.39-0.85], p=0.006) of patients without significant improvements in OS (HR 0.88 [95% CI 0.55-1.26], p=0.240), PFS (HR 0.98 [95% CI 0.74-1.31], p=0.908), and LRFS (HR 0.98 [95% CI 0.54-1.77], p=0.943).ConclusionsPretreatment plasma EBV-DNA can be considered a promising effective marker for the use of IC in LA-NPC patients. The addition of IC could improve the OS and PFS of patients with EBV-DNA load ≥4000 copies/ml, but we saw no efficacy in patients with EBV-DNA load &lt;4000 copies/ml. Moreover, regardless of the EBV-DNA load, IC could improve DMFS, but there was no effect on LRFS.
Mindset Moderates Healthcare Providers' Longitudinal Performance in a Digital Neonatal Resuscitation Simulator
Authors: Lu Chang , Ghoman Simran K. , Cutumisu Maria , Schmölzer Georg M. 
Published: February 2021

Background: Simulation education can benefit healthcare providers (HCPs) by providing opportunities to practice complex neonatal-resuscitation tasks in low-stake environments. To our knowledge, no study investigated the role of growth mindset on longitudinal performance on neonatal resuscitation before and after simulation-based training.Objectives: This study examines whether 1) the RETAIN digital/table-top simulators facilitate HCPs' neonatal resuscitation knowledge gain, retention, and transfer and 2) growth mindset moderates HCPs' longitudinal performance in neonatal resuscitation.Methods: Participants were n = 50 HCPs in a tertiary perinatal center in Edmonton, Canada. This longitudinal study was conducted in three stages including 1) a pretest and a mindset survey, immediately followed by a posttest using the RETAIN digital simulator from April to August 2019; 2) a 2-month delayed posttest using the same RETAIN neonatal resuscitation digital simulator from June to October 2019; and 3) a 5-month delayed posttest using the low-fidelity table-top neonatal resuscitation digital simulator from September 2019 to January 2020. Three General Linear Mixed Model (GLMM) repeated-measure analyses investigated HCPs' performance on neonatal resuscitation over time and the moderating effect of growth mindset on the association between test time points and task performance.Results: Compared with their pretest performance, HCPs effectively improved their neonatal resuscitation knowledge after the RETAIN digital simulation-based training on the immediate posttest (Est = 1.88, p &lt; 0.05), retained their knowledge on the 2-month delayed posttest (Est = 1.36, p &lt; 0.05), and transferred their knowledge to the table-top simulator after 5 months (Est = 2.01, p &lt; 0.05). Although growth mindset did not moderate the performance gain from the pretest to the immediate posttest, it moderated the relationship between HCPs' pretest and long-term knowledge retention (i.e., the interaction effect of mindset and the 2-month posttest was significant: Est = 0.97, p &lt; 0.05). The more they endorsed a growth mindset, the better the HCPs performed on the posttest, but only when they were tested after 2 months.Conclusions: Digital simulators for neonatal resuscitation training can effectively facilitate HCPs' knowledge gain, maintenance, and transfer. Besides, growth mindset shows a positive moderating effect on the longitudinal performance improvement in simulation-based training. Future research can be conducted to implement growth-mindset interventions promoting more effective delivery of technology-enhanced, simulation-based training and assessment.
Liver Enzymes Correlate With Metabolic Syndrome, Inflammation, and Endothelial Dysfunction in Prepubertal Children With Obesity
Authors: Valle-Martos Rosario , Valle Miguel , Martos Rosario , Cañete Ramón , Jiménez-Reina Luis , Cañete María Dolores 
Published: February 2021

Background: Metabolic syndrome (MetS) can start in children with obesity at very young ages. Non-alcoholic fatty liver disease (NAFLD) is considered to be the hepatic component of metabolic syndrome. If left untreated, the clinical course of NAFLD can be progressive and can become chronic if not detected at an early stage.Objective: We aimed to quantify the differences in liver enzymes between prepubertal children with obesity and children with normal weight to determine any associations between them and parameters related to MetS, adipokines, or markers of endothelial dysfunction and inflammation.Methods: This cross-sectional study included 54 prepuberal children with obesity (aged 6–9 years) and 54 children with normal weight, matched by age and sex. Liver enzymes, C-reactive protein (CRP), interleukin-6, soluble intercellular adhesion molecule-1 (sICAM-1), adipokines, and parameters related to metabolic syndrome (MetS) were all measured.Results: Alanine aminotransferase (ALT) levels, serum butyryl cholinesterase (BChE), leptin, CRP, sICAM-1, triglycerides, blood pressure, and homeostasis model assessment for insulin resistance were significantly higher in children with obesity, while Apolipoprotein A-1, HDL-cholesterol, and adiponectin were significantly lower. In the children with obesity group, ALT and BChE levels correlated with anthropometric measurements, insulin resistance, and lipid parameters, leptin, interleukin-6, CRP, and sICAM-1 while BChE levels negatively correlated with adiponectin.Conclusions: Compared to children with normal weight, prepubertal children with obesity had elevated values for liver enzymes, leptin, markers of insulin resistance, inflammation, and endothelial dysfunction, and variables associated with MetS. There was also a correlation between these disorders and liver enzyme levels.
LncRNA-H19 Drives Cardiomyocyte Senescence by Targeting miR-19a/socs1/p53 Axis
Authors: Zhuang Yuting , Li Tingting , Xiao Hongwen , Wu Jiaxu , Su Shuang , Dong Xue , Hu Xiaoxi , Hua Qi , Liu Junwu , Shang Wendi , Ju Jiaming , Sun Fei , Pan Zhenwei , Lu Yanjie , Zhang Mingyu 
Published: February 2021

Purpose: Cardiomyocyte senescence is associated with a progressive decline in cardiac physiological function and the risk of cardiovascular events. lncRNA H19 (H19), a well-known long noncoding RNA (lncRNA), is involved in the pathophysiological process of multiple cardiovascular disease such as heart failure, cardiac ischemia and fibrosis. However, the role of H19 in cardiomyocyte senescence remains to be further explored.Methods: Senescence-associated β-galactosidases (SA-β-gal) staining was used to detect cardiomyocyte senescence. Western blot, qRT-PCR and luciferase reporter assay were employed to evaluate the role of H19 in cardiomyocyte senescence and its underling molecular mechanism.Results: H19 level was significantly increased in high glucose-induced senescence cardiomyocytes and aged mouse hearts. Overexpression of H19 enhanced the number of SA-β-gal-positive cells, and the expression of senescence-related proteins p53 and p21, whereas H19 knockdown exerted the opposite effects. Mechanistically, H19 was demonstrated as a competing endogenous RNA (ceRNA) for microRNA-19a (miR-19a): H19 overexpression downregulated miR-19a level, while H19 knockdown upregulated miR-19a. The expression of SOSC1 was dramatically increased in senescence cardiomyocytes and aged mouse hearts. Further experiments identified SOCS1 as a downstream target of miR-19a. H19 upregulated SOCS1 expression and activated the p53/p21 pathway by targeting miR-19a, thus promoting the cardiomyocytes senescence.Conclusion: Our results show that H19 is a pro-senescence lncRNA in cardiomyocytes acting as a ceRNA to target the miR-19a/SOCS1/p53/p21 pathway. Our research reveals a molecular mechanism of cardiomyocyte senescence regulation and provides a novel target of the therapy for senescence-associated cardiac diseases.