bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cannabinoid Use for Pain Reduction in Spinal Cord Injuries: A Meta-Analysis of Randomized Controlled Trials
Authors: Tsai Sung Huang Laurent , Lin Chun-Ru , Shao Shih-Chieh , Fang Chao-Hua , Fu Tsai-Sheng , Lin Tung-Yi , Hung Yu-Chiang 
Published: April 2022

Background: Spinal cord injury (SCI) often involves multimodal pain control. This study aims to evaluate the efficacy and safety of cannabinoid use for the reduction of pain in SCI patients.Methods and Findings: This study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. We searched PubMed, EMBASE, Scopus, Cochrane, Web of Science, and ClinicalTrials.gov for relevant randomized controlled trials (RCTs) reporting the efficacy (e.g., pain relief) or safety (e.g., adverse events) of cannabinoids in patients with SCI, from inception to 25 December 2021. The study quality and the quality of evidence were evaluated by Cochrane ROB 2.0 and the Grading of Recommendations, Assessment, Development, and Evaluations system (GRADE), respectively. We used the random-effects model to perform the meta-analysis. From a total of 9,500 records, we included five RCTs with 417 SCI patients in the systematic review and meta-analysis. We judged all five of the included RCTs as being at high risk of bias. This meta-analysis indicated no significant difference in pain relief between the cannabinoids and placebo in SCI patients (mean difference of mean differences of pain scores: −5.68; 95% CI: −13.09, 1.73; p = 0.13; quality of evidence: very low), but higher odds of adverse events were found in SCI patients receiving cannabinoids (odds ratio: 3.76; 95% CI: 1.98, 7.13; p &lt; 0.0001; quality of evidence: moderate).Conclusion: The current best evidence suggests that cannabinoids may not be beneficial for pain relief in SCI patients, but they do increase the risks of adverse events, including dizziness, somnolence, and dysgeusia, compared to the placebo. Cannabinoids should not be regularly suggested for pain reduction in SCI patients. Updating the systematic reviews and meta-analyses by integrating future RCTs is necessary to confirm these findings.
Network Pharmacology and Bioinformatics Analyses Identify Intersection Genes of Vitamin D3 and COVID-19 as Potential Therapeutic Targets
Authors: Wang Shanglin , Gao Huayu , Wang Xiaoru , Ma Xiaoli , Zhang Lulu , Xing Yuanxin , Jia Yanfei , Wang Yunshan 
Published: April 2022

Purpose: The persistent pandemic of coronavirus disease 2019 (COVID-19), the discovery of gastrointestinal transmission routes and the possible susceptibility of cancer patients to COVID-19 have forced us to search for effective pathways against stomach adenocarcinoma (STAD)/COVID-19. Vitamin D3 (VD3) is a steroid hormone with antiviral, anti-inflammatory and immunomodulatory properties. This study aimed to evaluate the possible functional role and potential mechanisms of action of VD3 as an anti-COVID-19 and anti- STAD.Methods: Clinicopathological analysis, enrichment analysis and protein interaction analysis using bioinformatics and network pharmacology methods. Validate the binding activity of VD3 to core pharmacological targets and viral crystal structures using molecular docking.Results: We revealed the clinical characteristics of STAD/COVID-19 patients. We also demonstrated that VD3 may be anti- STAD/COVID-19 through antiviral, anti-inflammatory, and immunomodulatory pathways. Molecular docking results showed that VD3 binds well to the relevant targets of COVID-19, including the spike RBD/ACE2 complex and main protease (Mpro, also known as 3CLpro). We also identified five core pharmacological targets of VD3 in anti-STAD/COVID-19 and validated the binding activity of VD3 to PAI1 by molecular docking.Conclusion: This study reveals for the first time that VD3 may act on disease target gene SERPINE1 through inflammatory and viral related signaling pathways and biological functions for the therapy of STAD/COVID-19. This may provide a new idea for the use of VD3 in the treatment of STAD/COVID-19.
Shenling Baizhu Powder Alleviates TNBS-Induced Colitis in Rats by Improving Intestinal Epithelial Permeability and Inhibiting Inflammation Through the TLR5/MyD88/NF-κB Pathway
Authors: Rao Kehan , Qin Shumin , Yang Yuanming , Zhan Kai , Wu Haomeng , Zheng Huan , Huang Shaogang 
Published: April 2022

Aim of the study: To evaluate the protective effect and mechanism of shenling baizhu powder (SBP) on TNBS-induced colitis.Methods: Rats were given TNBS to establish the model of colitis and subsequently treated with different doses of SBP or mesalamine (MES). In addition, the expression of the TLR5/MyD88/NF-κB signaling pathway and critical targets of the intestinal mucosal barrier was detected by immunochemical analysis techniques.Results: SBP significantly ameliorated the symptoms of TNBS-induced colitis in rats and reduced the secretion of pro-inflammatory cytokines. SBP could effectively strengthen epithelial barrier integrity in TNBS-induced colitis by increasing the secretion of mucin and tight junction and inhibiting apoptosis. Furthermore, we identified the crucial role of the TLR5/MyD88/NF-κB signaling pathway in exerting the therapeutic effect of SBP.Conclusion: The results of our study suggest that SBP has therapeutic effects on TNBS-induced colitis and potential value in treating and maintaining remission of colitis.
Efficacy and Safety of Qili Qiangxin Capsule on Dilated Cardiomyopathy: A Systematic Review and Meta-Analysis of 35 Randomized Controlled Trials
Authors: Wei Jingjing , Li Bin , Wang Xinlu , Li Xingyuan , Hu Yucai , Qiao Lijie , Zhou Cheng , Yu Peng , Sang Tianqing , Zhu Mingjun , Wang Yongxia 
Published: April 2022

Objective: Qili Qiangxin Capsule (QQC), a Chinese patent medicine, is clinically effective in treating dilated cardiomyopathy (DCM). However, the meta-analysis of QCC combined with conventional western medicine (CWM) on DCM remains unexplored. This study aimed to systematically evaluate the efficacy and safety of QCC in the treatment of DCM.Methods: Searched the studies of the combination of QQC and CWM in the treatment of DCM, from databases like PubMed, Cochrane Library, Web of Science, Wan Fang Databases, Chinese Biomedical Literature Database, China Science and Technology Journal Database, China National Knowledge Infrastructure, prior to 15 January 2022. Two reviewers respectively regulated research selection, data extraction, and risk of bias assessment. Review Manager Software 5.4 was used for meta-analysis. Furthermore, GRADE pro3.6.1 software was selected to grade the current evidence in our findings. This meta-analysis has been registered in PROSPERO (CRD42022297906).Results: There were 35 studies pertaining to 3,334 patients included. The meta-analysis showed compared with CWM alone, the combination therapy had significant advantages in improving the clinical efficiency rate (RR = 1.24, 95% CI: 1.19 to 1.29, p &lt; 0.00001), 6 min walking distance (6MWD) (MD = 41.93, 95%CI: 39.82 to 44.04, p &lt; 0.00001), superior in ameliorating the left ventricular ejection fraction (LVEF) (MD = 5.73, 95%CI: 4.70 to 6.77, p &lt; 0.00001), left ventricular end-diastolic dimension (LVEDD) (MD = −4.09, 95%CI: −4.91 to −3.27), p &lt; 0.00001), left ventricular end-systolic diameter (LVESD) (MD = −4.73, 95%CI: −5.63 to −3.84), p &lt; 0.00001) and BNP (MD = −101.09, 95%CI: -132.99 to −69.18), p &lt; 0.00001), and also superior in reducing hypersensitive-C-Reactive Protein (hs-CRP) (MD = −3.78, 95%CI: −4.35 to −3.21), p &lt; 0.00001), Interleukin- 6 (IL-6) (MD = −25.92, 95%CI: −31.35 to -20.50), p &lt; 0.00001), tumor necrosis factor-α (TNF-α) (MD = -5.04, 95%CI: −6.13 to −3.95), p &lt; 0.00001), high mobility group protein B1 (HMGB1) (MD = −4.34, 95%CI: −5.22 to −3.46), p &lt; 0.00001), and adverse reactions (ARs) (RR = 0.70, 95%CI: 0.51–0.97), p = 0.03). The GRADE evidence quality rating presented with moderate or low quality of evidence for the available data.Conclusion: Compared with the control group, QQC combined with CWM may be effective in treating DCM. However, the conclusion of this study must be interpreted carefully due to the inferior quality and ambiguity of bias in the included trials.Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier [CRD42022297906].
Increased Serum Levels of Proinflammatory Cytokines Are Accompanied by Fatigue in Military T-6A Texan II Instructor Pilots
Authors: Damato Elizabeth G. , Fillioe Seth J. , Margevicius Seunghee P. , Mayes Ryan S. , Somogyi Jonathan E. , Vannix Ian S. , Abdollahifar Alireza , Turner Anthony M. , Ilcus Lidia S. , Decker Michael J. 
Published: April 2022

Tactical aviation imposes unprecedented physical challenges including repetitive exposure to hypergravity, hyperoxia, increased work of breathing, and profound cognitive workloads. Each stressor evokes outcomes ranging from musculoskeletal duress and atelectasis to physical and cognitive fatigue, the latter among the foremost threats to aviators. Whereas sleep loss is traditionally considered the primary cause of fatigue in aviators, converging experimental, observational, and medical studies have identified biochemical mechanisms promoting onset of fatigue. Those mechanisms, which fundamentally differ from sleep loss, revolve around increased proinflammatory cytokines, produced and released in response to tissue injury, chronic inflammatory disorders, allergens, or physical duress. This study’s objective was to inform our understanding of potential relationships between serum levels of proinflammatory cytokines and onset of fatigue within a cohort of aviators who experience multiple high-performance sorties on a daily basis.Methods:Active duty and reservist T-6A Texan II instructor pilots were studied on three separate days across their week-long flying schedule. Data collected included a physical assessment, subjective fatigue levels, venous blood samples for measures of chemistry and serum analytes, and urine samples for specific gravity.Results:Twenty-three persons were studied, of which 22 fulfilled minimum study requirements of completing two sorties. The study cohort was comprised of primarily males, age 37.95 ± 4.73 years with a BMI of 26.63 ± 3.15 kg/m2. Of 37 measurable serum analytes, 20 differed significantly (p&lt; 0.05) between baseline values with those measured at the study endpoint. Thirteen of the aviators reported increased fatigue scores across their flying schedule whereas nine did not. Eleven blood serum analytes were associated with increasing levels of fatigue.Discussion:Fatigue in aviators has been attributed almost solely to sleep loss, nocturnal sorties, or disrupted circadian rhythmicity. In contrast, our study findings suggest an alternative mechanism that can promote onset of fatigue: increased blood levels of proinflammatory cytokines. Specific mechanisms triggering synthesis and release of those cytokines and other analytes are yet to be determined. However, their expression patterns suggest responses to both chronic and acute inflammation, hyperoxia, or bronchopulmonary responses to inspiration of dry gas, positive airway pressure, or perhaps atelectasis.
Basal Vascular Smooth Muscle Cell Tone in eNOS Knockout Mice Can Be Reversed by Cyclic Stretch and Is Independent of Age
Authors: De Moudt Sofie , Hendrickx Jhana O. , De Meyer Guido R. Y. , Martinet Wim , Fransen Paul 
Published: April 2022

Introduction and Aims: Endothelial nitric oxide synthase (eNOS) knockout mice develop pronounced cardiovascular disease. In the present study, we describe the alterations in aortic physiology and biomechanics of eNOS knockout and C57Bl/6 control mice at 2–12 months of age, including a thorough physiological investigation of age and cyclic stretch-dependent VSMC contractility and aortic stiffness.Methods and Results: Peripheral blood pressure and aortic pulse wave velocity were measured in vivo, and aortic biomechanical studies and isometric contractions were investigated ex vivo. Age-dependent progression of aortic stiffness, peripheral hypertension, and aortic contractility in eNOS knockout mice was absent, attenuated, or similar to C57Bl/6 control mice. Voltage-gated calcium channel (VGCC)-dependent calcium influx inversely affected isometric contraction and aortic stiffening by α1-adrenergic stimulation in eNOS knockout mice. Baseline aortic stiffness was selectively reduced in eNOS knockout mice after ex vivo cyclic stretch exposure in an amplitude-dependent manner, which prompted us to investigate cyclic stretch dependent regulation of aortic contractility and stiffness. Aortic stiffness, both in baseline conditions and after activation of vascular smooth muscle cell (VSMC) contraction, was reduced with increasing cyclic stretch amplitude. This cyclic stretch dependency was attenuated with age, although aged eNOS knockout mice displayed better preservation of cyclic stretch-dependency compared to C57Bl/6 control mice. Store operated calcium entry-medicated aortic stiffening as induced by inhibiting sarcoplasmic reticulum calcium ATPase pumps with 10 µM CPA was most pronounced in the aorta of aged mice and at low cyclic stretch amplitude, but independent of eNOS. Basal aortic tonus and VSMC depolarization were highly dependent on eNOS, and were most pronounced at low cyclic stretch, with attenuation at increasing cyclic stretch amplitude.Conclusion: eNOS knockout mice display attenuated progression of arterial disease as compared to C57Bl/6 control mice. Basal VSMC tone in eNOS knockout mice could be reduced by ex vivo exposure to cyclic stretch through stretch-dependent regulation of cytosolic calcium. Both baseline and active aortic stiffness were highly dependent on cyclic stretch regulation, which was more pronounced in young versus aged mice. Other mediators of VSMC contraction and calcium handling were dependent on cyclic stretch mechanotransduction, but independent of eNOS.
Muc5b Contributes to Mucus Abnormality in Rat Models of Cystic Fibrosis
Authors: Keith Johnathan D. , Henderson Alexander G. , Fernandez-Petty Courtney M. , Davis Joy M. , Oden Ashley M. , Birket Susan E. 
Published: April 2022

Cystic fibrosis (CF) airway disease is characterized by excessive and accumulative mucus in the airways. Mucociliary clearance becomes defective as mucus secretions become hyperconcentrated and viscosity increases. The CFTR-knockout (KO) rat has been previously shown to progressively develop delayed mucociliary transport, secondary to increased viscoelasticity of airway secretions. The humanized-G551D CFTR rat model has demonstrated that abnormal mucociliary clearance and hyperviscosity is reversed by ivacaftor treatment. In this study, we sought to identify the components of mucus that changes as the rat ages to contribute to these abnormalities. We found that Muc5b concentrations, and to a lesser extent Muc5ac, in the airway were increased in the KO rat compared to WT, and that Muc5b concentration was directly related to the viscosity of the mucus. Additionally, we found that methacholine administration to the airway exacerbates these characteristics of disease in the KO, but not WT rat trachea. Lastly we determined that at 6 months of age, CF rats had mucus that was adherent to the airway epithelium, a process that is reversed by ivacaftor therapy in the hG551D rat. Overall, these data indicate that accumulation of Muc5b initiates the muco-obstructive process in the CF lung prior to infection.
The Mobile Phone Addiction and Depression Among High School Students: The Roles of Cyberbullying Victimization, Perpetration, and Gender
Authors: Wu Wenzhi , Chen Yongchuan , Shi Xiuying , Lv Hua , Bai Rui , Guo Zhichao , Yu Lei , Liu Yilin , Liu Jianping , Chen Yatang , Zeng Yong 
Published: April 2022

ObjectiveTo examine the relation between mobile phone addiction and high school students’ depression, and its inner mechanism—the sequential mediating roles of the cyberbullying victimization and the cyberbullying perpetration in this relationship.Methods1297 high school students were recruited to complete the Smartphone Addiction Scale, European Cyberbullying Intervention Project Questionnaire and the Center for Epidemiological Studies Depression Scale.Results(1) Mobile phone addiction was positively correlated with and high school students’ depression; (2) cyberbullying victimization and the cyberbullying perpetration significantly mediated the relation between mobile phone addiction and high school students’ depression, which contained tow mediating paths—the independent mediating effects of cyberbullying victimization and the sequential mediating effect of cyberbullying victimization and the cyberbullying perpetration; (3) there are gender differences in the sequential mediation model, and boys who are victims of cyberbullying are more likely to develop into cyberbullying perpetrators than girls.ConclusionThe results of this study indicate that depression among high school students with mobile phone addiction can be eliminated through the development of cyberbullying victimization and the cyberbullying perpetration.
Impact of Depression, Resilience, and Locus of Control on Adjustment of Health-Related Expectations in Aging Individuals With Chronic Illness
Authors: Schönenberg Aline , Zipprich Hannah M. , Teschner Ulrike , Prell Tino 
Published: April 2022

ObjectivesQuality of Life (QoL) depends on the discrepancy between desired and current experiences (referred to as the Calman gap), thus in chronic illness, adjustment of expectations and interpretation of the current situation are crucial. Depression is known to influence this gap, and the present study aims to further assess the role of resilience and health locus of control (HLC).MethodsA total of 94 patients (age M = 71.8, SD = 7.7 years) with neurological disorders were screened via telephone regarding depression, resilience and HLC. Current and desired state of several life domains were assessed, such as Fitness, General Health, Pain, Daily Activities, Finances, Leisure, and Family. Elastic net regularization and analyses of variance were used to disentangle the impact of depression, resilience, HLC, and sociodemographic factors on the perception of current and desired state, and the gap between both.ResultsA gap was present for all domains but largest for pain. Interpretation of the current state was linked to desired state, HLC, and age. All gaps were related to depression; certain domains were in addition influenced by resilience, HLC and sociodemographic factors. Of note, for most domains, patients did not select the highest possible desired state.ConclusionOlder patients with neurological disorders report a gap between current and desired state for many aspects of life. Adjusting expectations is beneficial in the face of declining health, but a reasonably increased desired state may positively influence the perception of the current situation. Depression negatively influences the interpretation of the Calman gap.
Experiences of Siblings of Children With Neurodevelopmental Disorders: Comparing Qualitative Analysis and Machine Learning to Study Narratives
Authors: Bastiaansen Jort. A. J. , Veldhuizen Elien E. , De Schepper Kees , Scheepers Floortje E. 
Published: April 2022

IntroductionRelatively few studies have focused on the wellbeing, experiences and needs of the siblings of children with a psychiatric diagnosis. However, the studies that have been conducted suggest that the impact of such circumstances on these siblings is significant. Studying narratives of diagnosed children or relatives has proven to be a successful approach to gain insights that could help improve care. Only a few attempts have been made to study narratives in psychiatry utilizing a machine learning approach.MethodIn this current study, 13 narratives of the experiences of siblings of children with a neurodevelopmental disorders were collected through largely unstructured interviews. The interviews were analyzed using the traditional qualitative, hermeneutic phenomenology method as well as latent Dirichlet allocation (LDA), an unsupervised machine learning method clustering words from documents into topics. One aim of this study was to evaluate the experiences of the siblings in order to find leads to improve care and support for these siblings. Furthermore, the outcomes of both analyses were compared to evaluate the role of machine learning in analyzing narratives.ResultsQualitative analysis of the interviews led to the formulation of nine main themes: confrontation with conflicts, coping strategies siblings, need for rest and time for myself, need for support and attention from personal circle, wish for normality, influence on personal choices and possibilities for development, doing things together, recommendations and advices, ambivalence and loyalty. Using unsupervised machine learning (LDA) 24 topics were formed that mostly overlapped with the qualitative themes found. Both the qualitative analysis and the LDA analysis detected themes that were unique to the respective analysis.ConclusionThe present study found that studying narratives of siblings of children with a neurodevelopmental disorder contributes to a better understanding of the subjects' experiences. Siblings cope with ambivalent feelings toward their brother or sister and this emotional conflict often leads to adapted behavior. Several coping strategies are developed to deal with the behavior of their brother or sister like seeking support or ignoring. Devoted support, time and attention from close relatives, especially parents, is needed. The LDA analysis didn't appear useful to distract meaning and context from the narratives, but it was proposed that machine learning could be a valuable and quick addition to the traditional qualitative methods by finding overlooked topics and giving a rudimental overview of topics in narratives.
Evaluation of the Relationship Between BDNF Val66Met Gene Polymorphism and Attention Deficit Hyperactivity Disorder: A Meta-Analysis
Authors: Mei Shufang , Chen Wencai , Chen Sijing , Hu Yani , Dai Xiaoyan , Liu Xiujun 
Published: April 2022

BackgroundAttention deficit hyperactivity disorder (ADHD) is a common neurobehavioral disorder in childhood. Brain-derived neurotrophic factor (BDNF) is widely distributed in the central nervous system and plays an important role in neural development. Despite several previous studies have examined the association between the Val66Met polymorphism BDNF and ADHD, the results are conflicting.ObjectiveThis study aimed to evaluate the association between Val66Met polymorphism and ADHD in case-control and transmission disequilibrium test (TDT) studies using a meta-analysis.MethodsKeywords “rs6265” or “Val66Met” and “Attention deficit hyperactivity disorder” were used to search in the PubMed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure databases before April 2021. Genotype data were extracted to calculate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsFifteen studies, comprising of 8,692 samples (containing 4,364 cases, 4,328 controls) and 1,578 families were included and results demonstrated that rs6265 was not associated with susceptibility to ADHD (OR = 0.95, 95% CI: 0.87–1.04, P = 0.291). Stratified analyses by study design, ethnicity, and sample size further supported that rs6265 was not associated with ADHD.ConclusionThe present study shows that the polymorphism of the BDNF Val66Met gene is not associated with susceptibility to ADHD.