bluuebunny/crossref_metadata_2025_split huggingface dataset:
Information Flow Pattern in Early Mild Cognitive Impairment Patients
Authors: He Haijuan , Ding Shuang , Jiang Chunhui , Wang Yuanyuan , Luo Qiaoya , Wang Yunling ,   Alzheimer's Disease Neuroimaging Initiative
Published: November 2021

Purpose: To investigate the brain information flow pattern in patients with early mild cognitive impairment (EMCI) and explore its potential ability of differentiation and prediction for EMCI.Methods: In this study, 49 patients with EMCI and 40 age- and sex-matched healthy controls (HCs) with available resting-state functional MRI images and neurological measures [including the neuropsychological evaluation and cerebrospinal fluid (CSF) biomarkers] were included from the Alzheimer's Disease Neuroimaging Initiative. Functional MRI measures including preferred information flow direction between brain regions and preferred information flow index of each brain region parcellated by the Atlas of Intrinsic Connectivity of Homotopic Areas (AICHA) were calculated by using non-parametric multiplicative regression-Granger causality analysis (NPMR-GCA). Edge- and node-wise Student's t-test was conducted for between-group comparison. Support vector classification was performed to differentiate EMCI from HC. The least absolute shrinkage and selection operator (lasso) regression were used to evaluate the predictive ability of information flow measures for the neurological state.Results: Compared to HC, disturbed preferred information flow directions between brain regions involving default mode network (DMN), executive control network (ECN), somatomotor network (SMN), and visual network (VN) were observed in patients with EMCI. An altered preferred information flow index in several brain regions (including the thalamus, posterior cingulate, and precentral gyrus) was also observed. Classification accuracy of 80% for differentiating patients with EMCI from HC was achieved by using the preferred information flow directions. The preferred information flow directions have a good ability to predict memory and executive function, level of amyloid β, tau protein, and phosphorylated tau protein with the high Pearson's correlation coefficients (r &gt; 0.7) between predictive and actual neurological measures.Conclusion: Patients with EMCI were presented with a disturbed brain information flow pattern, which could help clinicians to identify patients with EMCI and assess their neurological state.
Serum Albumin and Circulating Metabolites and Risk of Venous Thromboembolism: A Two-Sample Mendelian Randomization Study
Authors: Liu Zhengye , Mi Jiarui 
Published: November 2021

Background and Aim: Previous observational studies indicated that the serum albumin levels and circulating metabolites are associated with a high risk of venous thromboembolism (VTE). However, whether these observations reflect causality remained unclear. Hence, we conducted a two-sample Mendelian randomization (MR) analysis to evaluate the causal associations of serum albumin and circulating metabolites with the risk of VTE.Methods and Results: Summary statistics of genetic instruments proxying serum albumin, total protein, and common circulating metabolites were extracted from genome-wide association studies in the European ancestry. Summary-level results of age- and sex-adjusted estimates for associations of the instruments with VTE were derived from the FinnGen consortium. We used the inverse-variance weighted (IVW) method as the primary analysis for univariable MR. Sensitivity analyses were performed to detect horizontal pleiotropy and outliers. Genetically proxied high-serum albumin and total protein levels were suggestive protective factor of VTE, with odds ratio (OR) = 0.69 (CI 0.54–0.89, p = 4.7 × 10−3) and 0.76 (CI 0.61–0.95, p = 0.015), respectively. Genetically proxied low-monounsaturated fatty acids and the ratio of monounsaturated fatty acid to total fatty acid are causally associated with increased risk of VTE, with ORs = 0.89 (CI 0.80–0.99, p = 0.031) and 0.85 (CI 0.78–0.94, p = 9.92 × 10−4), respectively. There is no indication of causal associations between other circulating metabolites and the risk of VTE.Conclusions: Genetically liability to low-serum albumin and total protein levels, low proxied monounsaturated fatty acids (MUFAs) and the ratio of MUFAs to total fatty acids are associated with the higher risk of VTE.
Microarray Identifies a Key Carcinogenic Circular RNA 0008594 That Is Related to Non-Small-Cell Lung Cancer Development and Lymph Node Metastasis and Promotes NSCLC Progression by Regulating the miR-760-Mediated PI3K/AKT and MEK/ERK Pathways
Authors: Wang Qiushi , Yan Chunhua , Zhang Pengfei , Li Guanghua , Zhu Ruidong , Wang Hanbing , Wu Libo , Xu Guangquan 
Published: November 2021

PurposeThis study aimed to explore the circular RNA (circRNA/circ) profile engaged in non-small cell lung cancer (NSCLC) development and metastasis and to investigate potentially key carcinogenic circRNAs related to NSCLC.MethodsCircRNA profiles between 10 NSCLC tissues and 10 adjacent tissues and between five NSCLC tissues with lymph node metastasis (LNM) and five NSCLC tissues without LNM were detected by Arraystar Human circRNA Array followed by bioinformatics. Circ_0008594 knockdown, circ_0004293 overexpression, and circ_0003832 overexpression plasmids were transfected into H23 and H460 cells to sort potential oncogenic circRNA. Then circ_0008594 overexpression and knockdown plasmids were transfected, followed by that circ_0008594 knockdown plus miR-760 knockdown plasmids were transfected into these cells. Cell proliferation, apoptosis, invasion, stemness, and pathways were detected. In addition, xenograft mice models were constructed via injecting H23 cells with circ_0008594 overexpression or knockdown to validate the findings.ResultsA total of 455 dysregulated circRNAs in NSCLC tissues versus adjacent tissues and 353 dysregulated circRNAs in NSCLC tissues with LNM versus those without LNM were discovered. Via cross-analysis, 19 accordant circRNAs were uncovered, among which three candidate circRNAs (circ_0008594, circ_0004293, circ_0003832) were chosen for functional experiments, during which it was observed that circ_0008549 affected H23 and H460 cell proliferation and apoptosis more obviously than circ_0004293 and circ_0003832. Subsequent experiments showed that circ_0008594 promoted H23 and H460 cell proliferation and invasion but affected stemness less and negatively regulated miR-760 via direct binding. Furthermore, miR-760 attenuated the effect of circ_0008549 on regulating H23 and H460 cell functions and the PI3K/AKT and MEK/ERK pathways. In vivo experiments further confirmed that circ_0008549 increased tumor volume, epithelial-mesenchymal transition, and the PI3K/AKT and MEK/ERK pathways while reducing tumor apoptosis and miR-760 NSCLC xenograft models.ConclusionOur study identifies several valuable circRNAs related to NSCLC development and LNM. Furthermore, as a key functional circRNA, circ_0008594 was observed to promote NSCLC progression by regulating the miR-760-mediated PI3K/AKT and MEK/ERK pathways.
Herb-Drug Interaction Between Xiyanping Injection and Lopinavir/Ritonavir, Two Agents Used in COVID-19 Pharmacotherapy
Authors: Ye Linhu , Cheng Lei , Deng Yan , Liu Hong , Wu Xinyu , Wang Tingting , Chang Qi , Zhang Yan , Wang Dan , Li Zongze , Yang Xixiao 
Published: November 2021

The global epidemic outbreak of the coronavirus disease 2019 (COVID-19), which exhibits high infectivity, resulted in thousands of deaths due to the lack of specific drugs. Certain traditional Chinese medicines (TCMs), such as Xiyanping injection (XYPI), have exhibited remarkable benefits against COVID-19. Although TCM combined with Western medicine is considered an effective approach for the treatment of COVID-19, the combination may result in potential herb-drug interactions in the clinical setting. The present study aims to verify the effect of XYPI on the oral pharmacokinetics of lopinavir (LPV)/ritonavir (RTV) using an in vivo rat model and in vitro incubation model of human liver microsomes. After being pretreated with an intravenous dose of XYPI (52.5 mg/kg) for one day and for seven consecutive days, the rats received an oral dose of LPV/RTV (42:10.5 mg/kg). Except for the t1/2 of LPV is significantly prolonged from 4.66 to 7.18 h (p &lt; 0.05) after seven consecutive days pretreatment, the pretreatment resulted in only a slight change in the other pharmacokinetic parameters of LPV. However, the pharmacokinetic parameters of RTV were significantly changed after pretreatment with XYPI, particularly in treatment for seven consecutive days, the AUC0-∞ of RTV was significantly shifted from 0.69 to 2.72 h μg/mL (p &lt; 0.05) and the CL exhibited a tendency to decrease from 2.71 L/h to 0.94 L/h (p &lt; 0.05), and the t1/2 of RTV prolonged from 3.70 to 5.51 h (p &lt; 0.05), in comparison with the corresponding parameters in untreated rats. After administration of XYPI, the expression of Cyp3a1 protein was no significant changed in rats. The in vitro incubation study showed XYPI noncompetitively inhibited human CYP3A4 with an apparent Ki value of 0.54 mg/ml in a time-dependent manner. Our study demonstrated that XYPI affects the pharmacokinetics of LPV/RTV by inhibiting CYP3A4 activity. On the basis of this data, patients and clinicians can take precautions to avoid potential drug-interaction risks in COVID-19 treatment.
Elevated Serum Uric Acid is Associated With Poor Survival in Advanced HCC Patients and Febuxostat Improves Prognosis in HCC Rats
Authors: Wu Le , Yang Wenlong , Zhang Yu , Du Xiaoyue , Jin Nan , Chen Wen , Li Huangbao , Zhang Shouhua , Xie Baogang 
Published: November 2021

Objective: Serum uric acid is associated with tumor progression and hepatocarcinogenesis. Here, we aimed to determine whether serum uric acid is related to the survival time of patients with hepatocellular carcinoma (HCC) and whether the inhibition of uric acid production affects the progression and survival of rats with HCC.Methods: The follow-up data of 288 patients with advanced HCC were analyzed. Ten purine metabolites in serum and liver samples of diethylnitrosamine (DEN)-induced HCC rats were quantitatively determined by an established UPLC-MS/MS method. On this basis, febuxostat, a specific inhibitor of xanthine oxidase (XOD), was used to interfere with HCC rats.Results: The serum uric acid level of HCC patients was significantly negatively correlated with survival days (r = -0.155). The median survival time was 133.5 days in the high uric acid group (&gt;360 μmol/L, n = 80) and 176.0 days in the normal serum uric acid group (&lt;360 μmol/L, n = 208, p = 0.0013). The levels of hypoxanthine, guanine, and uric acid; XOD activity; and xanthine dehydrogenase mRNA expression in the serum or liver samples of HCC rats were significantly upregulated compared with those in the control group. After febuxostat intervention in DEN-induced HCC rats, the number of atypical cells and inflammatory cells decreased significantly; the serum alpha fetoprotein level and Fisher’s ratio tended to return to normal; the median survival time increased from 36 to 96 days (p = 0.08). In addition, serum malondialdehyde, superoxide dismutase, and glutathione activity nearly returned to the level of the healthy control group.Conclusion: The elevation of serum uric acid implies a risk of poor survival in advanced HCC patients and Febuxostat can reduce the generation of reactive oxygen species, thereby playing a role in delaying the progression of liver cancer.
Exercise Enhanced Cardiac Function in Mice With Radiation-Induced Heart Disease via the FNDC5/Irisin-Dependent Mitochondrial Turnover Pathway
Authors: He Wuyang , Tang Yinghong , Li Chunqiu , Zhang Xiaoyue , Huang Shunping , Tan Benxu , Yang Zhenzhou 
Published: November 2021

Background: Despite the development of radiation therapy (RT) techniques, concern regarding the serious and irreversible heart injury induced by RT has grown due to the lack of early intervention measures. Although exercise can act as an effective and economic nonpharmacologic strategy to combat fatigue and improve quality of life for cancer survivors, limited data on its application in radiation-induced heart disease (RIHD) and the underlying molecular mechanism are available.Methods: Fifteen young adult male mice were enrolled in this study and divided into 3 groups (including exercised RIHD group, sedentary RIHD group, and controls; n =5 samples/group). While the mice in the control group were kept in cages without irradiation, those in the exercised RIHD group underwent 3weeks of aerobic exercise on the treadmill after radiotherapy. At the end of the 3rd week following RT, FNDC5/irisin expression, cardiac function, aerobic fitness, cardiomyocyte apoptosis, mitochondrial function, and mitochondrial turnover in the myocardium were assessed to identify the protective role of exercise in RIHD and investigate the potential mechanism.Results: While sedentary RIHD group had impaired cardiac function and aerobic fitness than controls, the exercised RIHD mice had improved cardiac function and aerobic fitness, elevated ATP production and the mitochondrial protein content, decreased mitochondrial length, and increased formation of mitophagosomes compared with sedentary RIHD mice. These changes were accompanied by the elevated expression of FNDC5/irisin, a fission marker (DRP1) and mitophagy markers (PINK1 and LC3B) in exercised RIHD group than that of sedentary RIHD group, but the expression of biogenesis (TFAM) and fusion (MFN2) markers was not significantly changed.Conclusion: Exercise could enhance cardiac function and aerobic fitness in RIHD mice partly through an autocrine mechanism via FNDC5/irisin, in which autophagy was selectively activated, suggesting that FNDC5/irisin may act as an intervening target to prevent the development of RIHD.
Perceived Parenting Styles of Individuals With Gender Dysphoria
Authors: Garcia Cláudia C. , Schwarz Karine , Costa Angelo B. , Bridi Filho Cesar A. , Lobato Maria Inês R. 
Published: November 2021

Objective: To map patterns of behavior of parents and/or caregivers as perceived by their adult children, transgender patients seen through the Programa Transdisciplinar de Identidade de Gênero, and to determine if one parenting style was more prevalent.Design: 82 patients were interviewed by the Parenting Style Inventory.Results: The 82 patients (32 transgender men and 50 transgender women) completed a total of 145 protocols, being 65 concerning their fathers, and 80 concerning their mothers. The transgender women’s perceptions of their mothers were significantly different from those concerning their fathers. The transgender men and women had a positive mean perception of their relationship with their mothers and a negative mean perception of their fathers. The transgender women had on average a positive perception of their relationship with their mothers and a negative perception of their relationship with their fathers. This difference in perception was primarily in positive practices; the women felt that their mothers exhibited more positive practices of Positive Monitoring (A) and Moral Behavior (B) than their fathers. When we compared negative practices, negligence alone was considered the worst parental pattern by both transgender men and women.Conclusion: Our study shows that fathers, more so than mothers, need to be encouraged to participate in the process of understanding the transgender condition and that in general, families need to be supported by mental health professionals to provide a more welcoming environment for individuals with Gender Dysphoria.
Comorbidities in Obsessive-Compulsive Disorder Across the Lifespan: A Systematic Review and Meta-Analysis
Authors: Sharma Eesha , Sharma Lavanya P. , Balachander Srinivas , Lin Boyee , Manohar Harshini , Khanna Puneet , Lu Cynthia , Garg Kabir , Thomas Tony Lazar , Au Anthony Chun Lam , Selles Robert R. , Højgaard Davíð R. M. A. , Skarphedinsson Gudmundur , Stewart S. Evelyn 
Published: November 2021

Comorbidities are seen with obsessive-compulsive disorder (OCD) across the lifespan. Neurodevelopmental comorbidities are common in young children, followed by mood, anxiety, and obsessive-compulsive related disorders (OCRDs) in children, adolescents and adults, and neurological and degenerative disorders in the elderly. Understanding comorbidity prevalence and patterns has clinical and research implications. We conducted a systematic review and meta-analysis on comorbidities in OCD across the lifespan, with the objective to, first, estimate age-wise pattern and prevalence of comorbidities with OCD and, second, to examine associations of demographic (age at assessment, gender distribution) and clinical characteristics (age of onset, illness severity) with comorbidities. Four electronic databases (PubMed, EMBASE, SCOPUS, and PsycINFO) were searched using predefined search terms for articles published between 1979 and 2020. Eligible studies, across age, reported original findings on comorbidities and had an OCD sample size of ≥100. We excluded studies that did not use standardised diagnostic assessments, or that excluded patients on the basis of comorbidity. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The review protocol has been registered on the International Prospective Register of Systematic Reviews. A comorbidity rate of 69% was found in a pooled sample of more than 15,000 individuals. Mood disorders (major depressive disorder), anxiety disorders (generalised anxiety disorder), neurodevelopmental disorders (NDDs) and OCRDs were the commonest comorbidities. Anxiety disorders prevailed in children, mood disorders in adults, whereas NDDs were similarly prevalent. Higher comorbidity with any psychiatric illness, NDDs, and severe mental disorders was seen in males, vs. females. Illness severity was inversely associated with rates for panic disorder, tic disorders, OCRDs, obsessive compulsive personality disorder, and anorexia nervosa. This systematic review and meta-analysis provides base rates for comorbidities in OCD across the lifespan. This has implications for comprehensive clinical evaluation and management planning. The high variability in comorbidity rates suggests the need for quality, multi-centric, large studies, using prospective designs.Systematic Review Registration:Unique Identifier:CRD42020215904.
Mental Health in Children in the Context of COVID-19: Focus on Discharged Children
Authors: Zhang Anyi , Shi Le , Yan Wei , Xiao Han , Bao Yanping , Wang Zhe , Deng Jiahui , Ravindran Arun , Yuan Kai , Mei Hong , Shi Jie , Liu Zhisheng , Liu Jiajia , Lu Lin 
Published: November 2021

Introduction: To date, the mental health consequences of children hospitalized with COVID-19 remain unclear. We aimed to assess mental health status in children in the context of COVID-19, with a focus on discharged children.Methods: We recruited discharged children who recovered from COVID-19 and healthy controls between July and September 2020 in Wuhan Children's Hospital. Post-traumatic stress disorder (PTSD), anxiety, depression, and sleep problems were assessed in these children using questionnaires. Univariable and multivariable logistic and linear regressions were conducted to identify risk factors.Results: Totally, there were 152 children (61 discharged children and 91 healthy controls) aged 7–18 years old in our study. An increasing trend in the prevalence of PTSD, anxiety, and depression was observed in the discharged children compared with healthy controls (PTSD: 8.20 vs. 2.20%, anxiety: 22.95 vs. 13.19%; depression: 47.54 vs. 32.97%). Discharged children tended to report more depressive symptoms (β = 0.39) and less sleep problems (β = −0.37). Discharged children who lived in nuclear families and had longer hospital stays were more likely to report depression [odds ratio (OR) = 3.68 and 1.14, respectively]. Anxiety symptoms and the severity of sleep problems of discharged children were positively associated with caregivers' depression and PTSD symptoms (OR = 21.88 and 31.09, respectively).Conclusion: In conclusion, PTSD, anxiety, and depression symptoms were common among recovered children 4 months after COVID-19 hospitalization. Children from nuclear family and those had longer hospital stays need special attention. In addition, parental mental health had a significant impact on their children's mental resilience and recovery.
Use of Technology and Its Association With Academic Performance and Life Satisfaction Among Children and Adolescents
Authors: Ramírez Saray , Gana Sofía , Garcés Soledad , Zúñiga Teresa , Araya Ricardo , Gaete Jorge 
Published: November 2021

Introduction: In the last years, there has been a rise in the use of technology among children and adolescents, which has led to a greater concern about its impact on their socioemotional and cognitive development.Aims: To explore the time spent using technology, the risk perception of its use by students, and the association between frequency of technology use and life satisfaction and academic performance among children and adolescents in Chile. Additionally, we explored the mediating effect of sleep deprivation on these outcomes.Methods: This is a cross-sectional study, where 2,440 students (9-12 years old) from 13 schools participated. Data was collected using an online survey answered by students during school hours. The association analyses were performed using multivariable regression models considering life satisfaction and academic performance as dependent variables. Additionally, mediating analyses were conducted using structural equation modeling.Results: Time watching television and using cellphones were similar on weekdays, and playing video games was the most frequent activity during weekends. A 42.1% of students reported playing online video games with strangers, and 12.7% had sleep deprivation. Lower self-reported academic performance was associated with cyberbullying victimization, sleep deprivation, being hacked, exposure to violent content, time spent using cell phones during weekdays and weekends, and playing video games during weekdays. Students who perceived that playing video games after 9 pm affected their sleep had a higher academic performance. There was a clear mediating effect of sleep deprivation in the relationship between time spent using a cellphone during weekdays and weekends and playing video games during weekdays and GPA.Conclusions: Time spent using technological devices was not associated with life satisfaction; however, the time spent using cell phones and playing video games was related to lower self-reported academic performance, mediated by sleep deprivation. Future research may focus on a better understanding of the mechanisms involved in the effect of technology use on sleep routines among adolescents and potential interventions to reduce its impact on academic performance.