bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Accuracy of Early Warning Scores for Clinical Deterioration in Patients With COVID-19
Authors: Su Ying , Ju Min-jie , Xie Rong-cheng , Yu Shen-ji , Zheng Ji-li , Ma Guo-guang , Liu Kai , Ma Jie-fei , Yu Kai-huan , Tu Guo-wei , Luo Zhe 
Published: February 2021

Background: Early Warning Scores (EWS), including the National Early Warning Score 2 (NEWS2) and Modified NEWS (NEWS-C), have been recommended for triage decision in patients with COVID-19. However, the effectiveness of these EWS in COVID-19 has not been fully validated. The study aimed to investigate the predictive value of EWS to detect clinical deterioration in patients with COVID-19.Methods: Between February 7, 2020 and February 17, 2020, patients confirmed with COVID-19 were screened for this study. The outcomes were early deterioration of respiratory function (EDRF) and need for intensive respiratory support (IRS) during the treatment process. The EDRF was defined as changes in the respiratory component of the sequential organ failure assessment (SOFA) score at day 3 (ΔSOFAresp = SOFA resp at day 3–SOFAresp on admission), in which the positive value reflects clinical deterioration. The IRS was defined as the use of high flow nasal cannula oxygen therapy, noninvasive or invasive mechanical ventilation. The performances of EWS including NEWS, NEWS 2, NEWS-C, Modified Early Warning Scores (MEWS), Hamilton Early Warning Scores (HEWS), and quick sepsis-related organ failure assessment (qSOFA) for predicting EDRF and IRS were compared using the area under the receiver operating characteristic curve (AUROC).Results: A total of 116 patients were included in this study. Of them, 27 patients (23.3%) developed EDRF and 24 patients (20.7%) required IRS. Among these EWS, NEWS-C was the most accurate scoring system for predicting EDRF [AUROC 0.79 (95% CI, 0.69–0.89)] and IRS [AUROC 0.89 (95% CI, 0.82–0.96)], while NEWS 2 had the lowest accuracy in predicting EDRF [AUROC 0.59 (95% CI, 0.46–0.720)] and IRS [AUROC 0.69 (95% CI, 0.57–0.81)]. A NEWS-C ≥ 9 had a sensitivity of 59.3% and a specificity of 85.4% for predicting EDRF. For predicting IRS, a NEWS-C ≥ 9 had a sensitivity of 75% and a specificity of 88%.Conclusions: The NEWS-C was the most accurate scoring system among common EWS to identify patients with COVID-19 at risk for EDRF and need for IRS. The NEWS-C could be recommended as an early triage tool for patients with COVID-19.
Circulating MicroRNAs as Promising Diagnostic Biomarkers for Patients With Glioma: A Meta-Analysis
Authors: He Jimin , Jiang Yao , Liu Liang , Zuo Zhihua , Zeng Chun 
Published: February 2021

Backgrounds and Purpose: Currently, circulating microRNAs (miRNAs) are considered to be non-invasive diagnostic biomarkers in a broad range of tumors. Nevertheless, so far, miRNAs have not been fully applied to the clinic for routine screening in glioma patients. Thus, our goal is to evaluate the diagnostic performance of circulating miRNAs for gliomas via a meta-analysis. The present study is registered on the PROSPERO website, with the number CRD42020195883.Methods: Literature retrieval was implemented in the PubMed, Embase, and Web of Science databases using the established search strategy. We pooled the sensitivity, specificity, and its 95% confidence intervals (CIs) for the included studies using the Stata 14.0 software. In addition, the heterogeneity between studies was assessed via the Q statistics and I2 values calculated by a Chi-square test. A bivariate random effects model was selected due to significant heterogeneity. Specifically, for exploring the factors influencing the heterogeneity, we implemented subgroup and meta-regression analyses. Ultimately, a Deek's funnel plot asymmetry test was used to estimate the potential publication bias.Results: A total of 18 articles covering 24 studies were included, containing 2,170 glioma patients and 1,456 healthy participants. The overall pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.84 (95%CI: 0.79–0.87), 0.84 (95%CI: 0.80–0.88), 5.3 (95%CI: 4.1–6.8), 0.19 (95%CI: 0.15–0.25), 27 (95%CI: 18–41), and 0.91 (95%CI: 0.88–0.93), respectively. Additionally, the findings revealed that serum miRNAs and miRNA panels presented superior diagnostic performance.Conclusion: Thus, circulating miRNAs have the potential to serve as diagnostic biomarkers for gliomas, but need to be verified via a large pool of prospective studies. Additionally, specific miRNAs still need to be elucidated in the diagnosis of a glioma, especially in the early screening stage. The findings may provide diagnostic and therapeutic strategies for the glioma population.
Neck Circumference Is Associated With Poor Outcome in Patients With Spontaneous Intracerebral Hemorrhage
Authors: Li Yujian , Zhou Huiqing , Yang Xiang , Zheng Jun , Zhang Fan , Xu Mangmang , Li Hao 
Published: February 2021

Objective: This study aimed to assess the association between neck circumference (NC) and functional outcome in intracerebral hemorrhage (ICH) patients.Methods: We prospectively analyzed data from ICH patients who received treatment at our institution from January 2018 to November 2019. Patients were categorized into two groups according to 180-day modified Rankin scale (MRS) scores. Univariate and multivariate analyses were performed to assess whether NC was associated with poor outcome in ICH patients. Receiver operating characteristic (ROC) curve analysis was performed to determine the significance of NC in predicting the functional outcome of ICH patients.Results: A total of 312 patients were enrolled in our study. Multivariate logistic regression analysis indicated that NC was an independent predictor of poor 180-day functional outcome [odds ratio (OR) = 1.205, 95% confidence interval (CI): 1.075–1.350, p = 0.001]. ROC analysis revealed that NC could predict poor functional outcome at 6 months.Conclusions: NC is an independent predictor of unfavorable functional outcome at 6 months in ICH patients.
Knowledge, Responsibilities, and Peer Advice From Care Partners of Patients With Parkinson Disease Psychosis
Authors: Mantri Sneha , Edison Briana , Alzyoud Lamees , Albert Steven M. , Daeschler Margaret , Kopil Catherine , Marras Connie , Chahine Lana M. 
Published: February 2021

Introduction:Care partners (CPs) of individuals with Parkinson disease psychosis (PDP) experience increased strain and rely on informal support networks. The objective of this study was to characterize CP responsibilities, sources of support, and peer advice.Methods:This was a mixed-methods cross-sectional study. The sample was recruited from the online Fox Insight study cohort. CPs who indicated their care recipient suffered hallucinations and/or delusions were administered a questionnaire regarding their caregiving experience to person with PDP. A free-text question asked CPs to give advice to a hypothetical peer CP. Responses to multiple-choice questions were tabulated; responses to the free-text question were grouped into advice categories.Results:145 CP of individuals with PDP were included in this analysis, mean age (standard deviation, SD) 66.4 (9.4) years; 110 (75.9%) were women. Most (115, 79.3%) provided caregiving on a daily basis, with a range of responsibilities. Only 16 (11%) learned about PDP from a physician; communication challenges included perceived embarrassment or having to prioritize other issues in a limited appointment time. The most common peer advice was to alert the care recipient's neurologist (n= 38, 30.4%); only 8 (6.4%) suggested medication changes.Conclusion:CPs face challenges with clinician communication and learn about psychosis from a variety of informal sources. Few CPs advocate for medications to control PDP, instead preferring non-pharmacological management strategies. Peer advice favored alerting the care recipient's physician, suggesting that CPs do desire more information from the medical team.
Impact of Clot Shape on Successful M1 Endovascular Reperfusion
Authors: Guenego Adrien , Fahed Robert , Sussman Eric S. , Leipzig Matthew , Albers Gregory W. , Martin Blake W. , Marcellus David G. , Kuraitis Gabriella , Marks Michael P. , Lansberg Maarten G. , Wintermark Max , Heit Jeremy J. 
Published: February 2021

Objectives: The susceptibility-vessel-sign (SVS) allows thrombus visualization, length estimation and composition, and it may impact reperfusion during mechanical thrombectomy (MT). SVS can also describe thrombus shape in the occluded artery: in the straight M1-segment (S-shaped), or in an angulated/traversing a bifurcation segment (A-shaped). We determined whether SVS clot shape influenced reperfusion and outcomes after MT for proximal middle-cerebral-artery (M1) occlusions.Methods: Between May 2015 and March 2018, consecutive patients who underwent MT at one comprehensive stroke center and who had a baseline MRI with a T2* sequence were included. Clinical, procedural and radiographic data, including clot shape on SVS [angulated/bifurcation (A-SVS) vs. straight (S-SVS)] and length were assessed. Primary outcome was successful reperfusion (TICI 2b-3). Secondary outcome were MT complication rates, MT reperfusion time, and clinical outcome at 90-days. Predictors of outcome were assessed with univariate and multivariate analyses.Results: A total of 62 patients were included. 56% (35/62) had an A-SVS. Clots were significantly longer in the A-SVS group (19 mm vs. 8 mm p = 0.0002). Groups were otherwise well-matched with regard to baseline characteristics. There was a significantly lower rate of successful reperfusion in the A-SVS cohort (83%) compared to the S-SVS cohort (96%) in multivariable analysis [OR 0.04 (95% CI, 0.002–0.58), p = 0.02]. There was no significant difference in long term clinical outcome between groups.Conclusion: Clot shape as determined on T2* imaging, in patients presenting with M1 occlusion appears to be a predictor of successful reperfusion after MT. Angulated and bifurcating clots are associated with poorer rates of successful reperfusion.
Aspirin Use and Mortality in Women With Ovarian Cancer: A Meta-Analysis
Authors: Man Xiaxia , Wang Baogang , Tan Yuying , Yang Xiaolin , Zhang Songling 
Published: February 2021

BackgroundAspirin use has been suggested to reduce the incidence of ovarian cancer (OC) in women. However, previous studies regarding the association between aspirin use and mortality in women with OC showed inconsistent results. We aimed to evaluate the association between aspirin use and mortality in women with OC in a meta-analysis.MethodsRelevant cohort studies were obtained via search of PubMed, Cochrane’s Library, and Embase databases from inception to May 3, 2020. A random-effect model, which incorporates the potential heterogeneity among the included studies, was used to pool the results. Predefined stratified analyses were applied to evaluate the potential study characteristics on the outcome, including the timing of aspirin use, dose of aspirin, age of the women, and the clinical stages of the cancer. Sensitivity analysis by omitting one study at a time was used to assess the stability of the results.ResultsSix cohort studies including 17,981 women with OC were included. Pooled results showed that aspirin use had no statistically significant association with mortality in these patients (adjusted risk ratio [RR]: 0.85, 95% confidence interval [CI]: 0.70 to 1.02, p = 0.08; I2 = 69%). The results were similar for OC-specific mortality (RR: 0.85, 95% CI: 0.57 to 1.26, p = 0.41) and all-cause mortality (RR: 0.78, 95% CI: 0.55 to 1.11, p = 0.17). Stratified analyses suggested that aspirin use had no statistically significant association with mortality risk in OC regardless the timing of aspirin use, dose of aspirin, age of the women, or the clinical stages of the cancer. Funnel plots suggested potential risk of publication bias (p all &gt; 0.05). However, further “trim-and-fill” analysis incorporating hypothesized unpolished studies to achieve symmetrical funnel plots showed similar results of the meta-analysis (RR: 0.91, 95% CI: 0.74 to 1.13, p = 0.39).ConclusionsCurrent evidence from observational studies indicated that aspirin use had no statistically significant association with mortality in women with OC.
Cerebrospinal Fluid Inflammatory Cytokine Levels in Patients With Major Psychiatric Disorders: A Multiplex Immunoassay Study
Authors: Hidese Shinsuke , Hattori Kotaro , Sasayama Daimei , Tsumagari Takuya , Miyakawa Tomoko , Matsumura Ryo , Yokota Yuuki , Ishida Ikki , Matsuo Junko , Yoshida Sumiko , Ota Miho , Kunugi Hiroshi 
Published: February 2021

Aim: Accumulating evidence suggests that neural inflammation plays an important role in psychiatric disorders. We aimed to identify inflammatory cytokines involved in the pathophysiology of such disorders by quantifying them in cerebrospinal fluid (CSF) samples from a large sample of patients with major psychiatric disorders and healthy controls.Methods: The subjects included 94 patients with schizophrenia, 68 with bipolar disorder, 104 with major depressive disorder, and 118 healthy controls, matched for age, sex, and ethnicity (Japanese). Lumbar puncture was performed to collect these CSF samples. A multiplex immunoassay was then performed to measure CSF cytokine levels using magnetic on-bead antibody conjugation for 19 inflammatory cytokines.Results: CSF interferon-β level was significantly higher in total psychiatric patients than in healthy controls (corrected p = 0.000029). In diagnostic group comparisons, CSF interferon-β level was significantly higher in patients with schizophrenia, or bipolar disorder (corrected p = 0.000047 or 0.0034) than in healthy controls.Conclusion: We present novel evidence that CSF IFN-β level showed prominent statistical differences between psychiatric groups and healthy controls. This suggests IFN-β as the most important player among the 19 cytokines tested here in the inflammation-related pathophysiology of major psychiatric disorders.
Synthesis of Paeonol-Ozagrel Conjugate: Structure Characterization and In Vivo Anti-Ischemic Stroke potential
Authors: Zhang Jing , Jiang Miaomiao , Zhao Hui , Han Lan , Jin Yu , Chen Weidong , Wang Jianqing , Zhang Ziyu , Peng Can 
Published: February 2021

Ischemic stroke is a common neurological disease that can lead to mortality and disability. The current curative effect remains unsatisfactory because drug accumulation in the diseased areas is insufficient as a result of the unique blood–brain barrier. Therefore, much attention has been paid to develop a novel therapeutic compound, paeonol-ozagrel conjugate (POC), for ischemic stroke. Then, POC was successfully synthesized by conjugating of paeonol and ozagrel as mutual prodrug. A series of in vitro characterizations and evaluations, including high - resolution mass spectroscopy, nuclear magnetic resonance spectroscopy, partition coefficient, and assessment of cytotoxicity against PC12 cells, were performed. Pharmacokinetic study demonstrated POC is eliminated quickly (t1/2 = 53.46 ± 19.64 min), which supported a short dosing interval. The neurological score, infarct volume, histopathological changes, oxidative stress, inflammatory cytokines levels, and TXA2 levels also were evaluated in vivo in middle cerebral artery occlusion (MCAO) rats. All results showed that POC had a significant curative and therapeutic effect on ischemic stroke, as evaluated by the middle cerebral artery occlusion. Overall, POC can be expected to become a new drug candidate for the treatment of ischemic stroke.
Analgesic and Anti-Inflammatory Effects of Perampanel in Acute and Chronic Pain Models in Mice: Interaction With the Cannabinergic System
Authors: De Caro Carmen , Cristiano Claudia , Avagliano Carmen , Cuozzo Mariarosaria , La Rana Giovanna , Aviello Gabriella , De Sarro Giovambattista , Calignano Antonio , Russo Emilio , Russo Roberto 
Published: February 2021

Pain conditions, such as neuropathic pain (NP) and persistent inflammatory pain are therapeutically difficult to manage. Previous studies have shown the involvement of glutamate receptor in pain modulation and in particular same of these showed the key role of the AMPA ionotropic glutamate receptor subtype. Antiseizure medications (ASMs) are often used to treat this symptom, however the effect of perampanel (PER), an ASM acting as selective, non-competitive inhibitor of the AMPA receptor on the management of pain has not well been investigated yet. Here we tested the potential analgesic and anti-inflammatory effects of PER, in acute and chronic pain models. PER was given orally either in acute (5 mg/kg) or repeated administration (3 mg/kg/d for 4 days). Pain response was assessed using models of nociceptive sensitivity, visceral and inflammatory pain, and mechanical allodynia and hyperalgesia induced by chronic constriction injury to the sciatic nerve. PER significantly reduced pain perception in all behavioral tests as well as CCI-induced mechanical allodynia and hyperalgesia in acute regimen (5 mg/kg). This effect was also observed after repeated treatment using the dose of 3 mg/kg/d. The antinociceptive, antiallodynic and antihyperalgesic effects of PER were attenuated when the CB1 antagonist AM251 (1 mg/kg/i.p.) was administered before PER treatment, suggesting the involvement of the cannabinergic system. Moreover, Ex vivo analyses showed that PER significantly increased CB1 receptor expression and reduced inflammatory cytokines (i.e. TNFα, IL-1β, and IL-6) in the spinal cord. In conclusion, these results extend our knowledge on PER antinociceptive and antiallodynic effects and support the involvement of cannabinergic system on its mode of action.
Specific TLR4 Blocking Effect of a Novel 3,4-Dihydropyrimidinone Derivative
Authors: Zhou Mingqian , Wang Yiqi , Lin Xiaoying , Wan Jieping , Wen Chengping 
Published: February 2021

Background: Toll-like receptor 4 (TLR4) initiates both innate and adaptive immune responses, which plays an important protective role in self-defense mechanisms. Excessive or inappropriate TLR4 activation causes the development of many autoimmune diseases. Dihydropyrimidinone derivatives are medicinally important molecules with diverse pharmacological activities, including anti-inflammatory activity. The present study focused on novel synthesized 3,4-dihydropyrimidinone derivatives and evaluated their inhibitory effects on TLR4.Methods: A series of 3,4-dihydropyrimidinone derivatives were recently synthesized and evaluated for their TLR4 inhibition activities and cytotoxic on HEK-BlueTM hTLR4 cells with the help of QUANTI-Blue assay and MTS assay. Selected compound 3 was analyzed for its molecular docking with TLR4 by using Autodock vina 1.1.2. Its effect on the TLR4 pathway related cytokines was also evaluated in THP-1 cells and human peripheral blood mononuclear cells by using real-time PCR, ELISA and western blot.Results: Five compounds were synthesized and characterized for effectiveness based on 3,4-dihydropyrimidinone. Compound 3 was found to be the potent hybrid among the synthesized compounds, with high TLR4 inhibition activities and low cytotoxic activities against HEK-BlueTM hTLR4 cells. Molecular docking analysis showed that two hydrogen bonds between compound 3 and residues Asp209(TLR4) and Asp99(MD-2) mainly contribute to the TLR4 inhibition. In addition, compound 3 suppressed LPS-induced of the mRNA expression of TLR4, IP-10, TNF-α, IL-6, IL-12A, and IL-12B, the protein expression of pIRF3 and pNFκB and the secretion of IP-10, TNF-α in THP-1 cell line. Compound 3 also inhibited LPS-induced expression of TNF-α, IL-6, and IL-1β but increased IP-10 at mRNA levels in human peripheral blood mononuclear cells.Conclusion: Our study reveals compound 3, a novel 3,4-dihydropyrimidinone derivative, is a potential TLR4 antagonist, which opens up new research avenues for the development of promising therapeutic agents for inflammatory and autoimmune diseases.
Curcumin Regulated the Homeostasis of Memory T Cell and Ameliorated Dextran Sulfate Sodium-Induced Experimental Colitis
Authors: Zhong You-Bao , Kang Zeng-Ping , Zhou Bu-Gao , Wang Hai-Yan , Long Jian , Zhou Wen , Zhao Hai-Mei , Liu Duan-Yong 
Published: February 2021

Immune memory is protective against reinvasion by pathogens in the homeostatic state, while immune memory disorders can cause autoimmune disease, including inflammatory bowel disease. Curcumin is a natural compound shown to be effective against human inflammatory bowel disease and experimental colitis, but the underlying mechanism is unclear. Here, experimental colitis was induced by dextran sulfate sodium (DSS) in this study. Significant changes in the percentages of naïve, central memory T (TCM), and effector memory (TEM) cells and their CD4+ and CD8+ subsets were found in the peripheral blood of mice with colitis using flow cytometry. After 7 days of continuous curcumin (100 mg/kg/day) administration, the DSS-induced experimental colitis was effectively relieved, with significant decreases in the ratio of day weight to initial body weight, colonic weight, pathological injury score, levels of proinflammatory cytokines IL-7, IL-15, and IL-21, colonic mucosal ulceration, and amount of inflammatory infiltrate. Importantly, curcumin significantly restored the percentages of naïve, TCM, and TEM cells and their CD4+ and CD8+ subpopulations. In addition, curcumin significantly inhibited the activation of the JAK1/STAT5 signaling pathway, downregulation of JAK1, STAT5, and p-STAT5 proteins in colon tissue, and upregulation of PIAS1 proteins. These results suggested that curcumin effectively regulated the differentiation of naïve, TCM, and TEM cells in the peripheral blood to alleviate DSS-induced experimental colitis, which might be related to the inhibition of JAK1/STAT5 signaling activity.
Strong Associations Between Childhood Victimization and Community Violence in Male Forensic Mental Health Patients
Authors: Fosse Roar , Eidhammer Gunnar , Selmer Lars Erik , Knutzen Maria , Bjørkly Stål 
Published: February 2021

Background: Childhood abuse and neglect increase the risk of both mental disorders and violent behavior. Associations between child relational adversities and violent behavior have not been extensively investigated in forensic mental health settings. We asked whether the extent of child adversities predicts the extent of violence in the community in forensic mental health patients.Methods: We included 52 male patients at a medium security forensic mental health ward, with diagnoses of predominantly paranoid schizophrenia and other schizophrenia and psychotic disorders. Seventy-five percent had comorbid substance abuse. We extracted information on six types of child adversities based on clinicians' administrations of the Historical Clinical Risk Management 20 version 3 (HCR 20) scale and summary notes in electronic patient journals. These same sources were used to extract information on war trauma and interpersonal violence in the community. We established cumulative scales for exposure to number of types of child adversities and number of incidents of community violence.Results: Physical and emotional abuse, emotional and physical neglect, and bullying were associated with higher levels of community violence. We observed a linear, significant increase in the frequency of community violence with cumulative numbers of child adversity types.Conclusions: Cumulative exposure to child adversities may be associated with higher degrees of violence in forensic mental health patients, with the most violent patients having the most extensive exposures to adversities. An enhanced focus on child adversities in risk assessment and management of violence may be considered in forensic inpatient settings.