bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-invasive Liver Fibrosis Scores Are Associated With Recurrence of Postoperative Chronic Subdural Hematoma
Authors: Zhang Peng , Wang Hua , Bao Han , Wang Ning , Chen Zhen , Tu Qi , Lin Xiao , Li Yun , Zheng Zezheng , Chen Yu , Ruan Linhui , Zhuge Qichuan 
Published: June 2022

ObjectiveAlthough liver diseases have already been identified as a risk factor for increased recurrence and mortality in patients with chronic subdural hematoma (CSDH), the association between subclinical liver disease, specifically liver fibrosis (LF), and CSDH remains unknown. In the present study, we aimed to investigate the association between the LF scores and CSDH recurrence.MethodsWe retrospectively analyzed consecutive patients with CSDH who underwent burr-hole irrigation in the First Affiliated Hospital of Wenzhou Medical University between January 2015 and December 2018. The clinical data were collected, and the LF scores were calculated including aspartate aminotransferase–platelet ratio index (APRI), fibrosis-4 (FIB-4), and Forns index. Multivariable logistic regression analysis was applied to identify the association between the LF scores and CSDH recurrence, and Cox regression model and Fine–Gray competing risks model were performed to calculate hazard ratios (HRs) for CSDH recurrence based on time-to-event outcomes. The C-statistic, the integrated discrimination improvement (IDI), and the net reclassification improvement (NRI) evaluated the additive value of the LF scores to predict the recurrence of CSDH.ResultsA total of 419 patients with CSDH were included, hematoma recurrence was observed in 62 patients (14.80%) within 1 year after surgery. The LF scores were significantly higher in those who recurred, whereas the standard hepatic assays were mostly normal. The patients were assigned to groups of high and low LF scores based on the validated cut-offs; compared with the subjects with low scores, those with high score levels had significantly higher recurrence rates. After adjusting for potential confounders, the LF scores were independently associated with CSDH recurrence, multivariable-adjusted HRs (95% CI) for those with higher levels of APRI, FIB-4, and Forns score were 4.32 (1.37–13.60), 2.56 (1.20–5.43), and 2.02 (1.07–3.79) for the recurrence of CSDH, respectively. Moreover, adding the APRI to the conventional model improved the C-statistic from 0.731 to 0.763, with an NRI and IDI of 7.50 and 1.35%, respectively. Two further commonly-used LF score indices (FIB-4 score and Forns index) yielded comparable results.ConclusionsThe data from this study first indicated that the high LF scores were significantly associated with the recurrence of CSDH and that careful follow-up in these patients may be needed.
Association of White Blood Cell Count With Clinical Outcome Independent of Treatment With Alteplase in Acute Ischemic Stroke
Authors: Barow Ewgenia , Quandt Fanny , Cheng Bastian , Gelderblom Mathias , Jensen Märit , Königsberg Alina , Boutitie Florent , Nighoghossian Norbert , Ebinger Martin , Endres Matthias , Fiebach Jochen B. , Thijs Vincent , Lemmens Robin , Muir Keith W. , Pedraza Salvador , Simonsen Claus Z. , Gerloff Christian , Thomalla Götz 
Published: June 2022

IntroductionHigher white blood cell (WBC) count is associated with poor functional outcome in acute ischemic stroke (AIS). However, little is known about whether the association is modified by treatment with intravenous alteplase.MethodsWAKE-UP was a randomized controlled trial of the efficacy and safety of magnetic resonance imaging [MRI]-based thrombolysis in unknown onset stroke. WBC count was measured on admission and again at 22–36 h after randomization to treatment (follow-up). Favorable outcome was defined by a score of 0 or 1 on the modified Rankin scale (mRS) 90 days after stroke. Further outcome were stroke volume and any hemorrhagic transformation (HT) that were assessed on follow-up CT or MRI. Multiple logistic regression analysis was used to assess the association between outcome and WBC count and treatment group.ResultsOf 503 randomized patients, WBC count and baseline parameters were available in 437 patients (μ = 64.7 years, 35.2% women) on admission and 355 patients (μ = 65.1 years, 34.1% women) on follow-up. Median WBC count on admission was 7.6 × 109/L (interquartile range, IQR, 6.1–9.4 × 109/L) and 8.2 × 109/L (IQR, 6.7–9.7 × 109/L) on follow-up. Higher WBC count both on admission and follow-up was associated with lower odds of favorable outcome, adjusted for age, National Institutes of Health (NIH) Stroke Scale Score, temperature, and treatment (alteplase vs. placebo, adjusted odds ratio, aOR 0.85, 95% confidence interval [CI] 0.78–0.94 and aOR 0.88, 95% CI 0.79–0.97). No interaction between WBC count and treatment group was observed (p = 0.11). Furthermore, WBC count on admission and follow-up was significantly associated with HT (aOR 1.14, 95% CI 1.05–1.24 and aOR 1.13, 95% CI 1.00–1.26). Finally, WBC count on follow-up was associated with larger stroke volume (aOR 2.57, 95% CI 1.08–6.07).ConclusionHigher WBC count is associated with unfavorable outcome, an increased risk of HT, and larger stroke volume, independent of treatment with alteplase. Whether immunomodulatory manipulation of WBC count improves stroke outcome needs to be tested.Trial RegistrationClinicalTrials.gov Identifier: NCT01525290.
Alterations of Cerebral Perfusion and Functional Connectivity in Children With Idiopathic Generalized Epilepsy
Authors: Chen Guiqin , Hu Jie , Ran Haifeng , Nie Lei , Tang Wenying , Li Xuhong , Li Qinhui , He Yulun , Liu Junwei , Song Ganjun , Xu Gaoqiang , Liu Heng , Zhang Tijiang 
Published: June 2022

BackgroundStudies have demonstrated that adults with idiopathic generalized epilepsy (IGE) have functional abnormalities; however, the neuropathological pathogenesis differs between adults and children. This study aimed to explore alterations in the cerebral blood flow (CBF) and functional connectivity (FC) to comprehensively elucidate the neuropathological mechanisms of IGE in children.MethodsWe obtained arterial spin labeling (ASL) and resting state functional magnetic resonance imaging data of 28 children with IGE and 35 matched controls. We used ASL to determine differential CBF regions in children with IGE. A seed-based whole-brain FC analysis was performed for regions with significant CBF changes. The mean CBF and FC of brain areas with significant group differences was extracted, then its correlation with clinical variables in IGE group was analyzed by using Pearson correlation analysis.ResultsCompared to controls, children with IGE had CBF abnormalities that were mainly observed in the right middle temporal gyrus, right middle occipital gyrus (MOG), right superior frontal gyrus (SFG), left inferior frontal gyrus (IFG), and triangular part of the left IFG (IFGtriang). We observed that the FC between the left IFGtriang and calcarine fissure (CAL) and that between the right MOG and bilateral CAL were decreased in children with IGE. The CBF in the right SFG was correlated with the age at IGE onset. FC in the left IFGtriang and left CAL was correlated with the IGE duration.ConclusionThis study found that CBF and FC were altered simultaneously in the left IFGtriang and right MOG of children with IGE. The combination of CBF and FC may provide additional information and insight regarding the pathophysiology of IGE from neuronal and vascular integration perspectives.
Knowledge Mapping of Olfactory Dysfunction: A Bibliometric Study
Authors: Hu Wen , Chen Na , Yan Weiheng , Pei Pei , Wei Yongxiang , Zhan Xiaojun 
Published: June 2022

BackgroundOlfaction is one of the five basic senses of human beings. As such, olfactory dysfunction seriously affects patients' quality of life and can even endanger them. In recent years, olfactory dysfunction has attracted greater research interest, and numerous studies have been published on olfactory dysfunction. However, there are few studies on olfactory dysfunction through bibliometric analysis. This study aims to describe the current situation and identify the foci and potential new research directions of olfactory dysfunction using a bibliometric approach.MethodsArticles related to olfactory dysfunction published from 2002 to 2021 were located in the Web of Science Core Collection of Clarivate Analytics (London, UK). Bibliometric analyses were conducted with the CiteSpace (Chaomei Chen, Drexel University, Philadelphia, PA, USA) and VOSviewer (Center for Science and Technology Studies, Leiden University, Leiden, Netherlands) software programs.ResultsThe number of articles published each year showed an upward trend, especially in 2020, where a sharp increase had occurred due to the coronavirus disease 2019 (COVID-19) pandemic. The United States was the country with the most publications and the strongest international cooperation. In terms of institutions, the greatest number of publications from a single institution came from Dresden University of Technology. Thomas Hummel was the author who had contributed the most articles. An analysis of co-citation networks and burst keywords in the field revealed a shift from “gonadotropin-releasing hormone” and “apoptosis” earlier on to “olfactory training,” “COVID-19,” and “Parkinson's disease” more recently. “Outcome,” “COVID-19,” “infection,” and “pathogenesis” are topics of the research frontier and hotspots.ConclusionMore attention has been paid to olfactory dysfunction as the understanding of it has improved in the past 20 years. This study provides researchers with an objective, systematic, and comprehensive analysis of the literature on olfactory dysfunction. The current frontier areas and hotspots in the field focus on the pathological mechanisms of olfactory dysfunction after infection with COVID-19 and its different prognoses. The pathophysiological mechanism of olfactory dysfunction in neurodegenerative diseases and COVID-19 will be a primary future research direction.
Body Mass Index and Prognosis of Patients With Stage II/III Gastric Cancer After Curative Gastrectomy: Completion of Perioperative Adjuvant Chemotherapy May Be a Confounding Factor
Authors: Peng Wei , Dai Jing , Liu Chao-chan , Liu Dian , Xiao Hua 
Published: June 2022

ObjectiveTo investigate the association between body mass index (BMI) and overall survival (OS) of patients with stage II/III gastric cancer (GC) after radical gastrectomy, and evaluate the potential influence of perioperative adjuvant chemotherapy (PAC).MethodsMedical records of 2,510 consecutive stage II/III GC patients who underwent curative resection between November 2010 and December 2020 were retrospectively reviewed. The optimal cutoff value of BMI for OS was determined by X-tile. The independent predictive factors for completeness of PAC were identified using univariate and multivariate logistic regression analyses. Cox regression analyses assessed the association among BMI, completeness of PAC, and OS.ResultsOf the 2,510 patients, 813 cases with BMI &lt; 20.3 kg/m2 were classified as belonging in the low BMI group. Further analyses confirmed that low BMI was an independent predictor for incomplete PAC (&lt; 6 cycles, n = 920) and poorer OS (hazard ratio: 1.317, 95% confidence interval: 1.162-1.494, P &lt; 0.001), but neo-adjuvant chemotherapy (NAC) was a protective factor. An additive effect was found in those with both low BMI and incomplete PAC, as they had even worse OS. However, in patients with low BMI, completion of PAC (≥ 6 cycles) significantly improved OS, which became comparable to that in the high BMI group (P = 0.143).ConclusionsLow preoperative BMI independently affects completion of PAC and prognosis of patients with stage II/III GC, but completing PAC can compensate for the adverse influence of low BMI on OS. Thus, strategies designed to ensure the completion of PAC, such as NAC and nutritional support, should be further investigated.
Endothelial Activin Receptor-Like Kinase 1 (ALK1) Regulates Myofibroblast Emergence and Peritubular Capillary Stability in the Early Stages of Kidney Fibrosis
Authors: Martínez-Salgado Carlos , Sánchez-Juanes Fernando , López-Hernández Francisco J. , Muñoz-Félix José M. 
Published: June 2022

Renal tubulo-interstitial fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) in the tubular interstitium during chronic kidney disease. The main source of ECM proteins are emerging and proliferating myofibroblasts. The sources of myofibroblasts in the renal tubular interstitium have been studied during decades, in which the epithelial contribution of the myofibroblast population through the epithelial-to-mesenchymal (EMT) process was assumed to be the major mechanism. However, it is now accepted that the EMT contribution is very limited and other mechanisms such as the proliferation of local resident fibroblasts or the transdifferentiation of endothelial cells seem to be more relevant. Activin receptor-like kinase 1 (ALK1) is a type I receptor which belongs to the transforming growth factor beta (TGF-β) superfamily, with a key role in tissue fibrosis and production of ECM by myofibroblast. Predominantly expressed in endothelial cells, ALK1 also plays an important role in angiogenesis and vessel maturation, but the relation of these processes with kidney fibrosis is not fully understood. We show that after 3 days of unilateral ureteral obstruction (UUO), ALK1 heterozygous mice (Alk1+/−) display lower levels of kidney fibrosis associated to a lower number of myofibroblasts. Moreover, Alk1+/− mice have a lower degree of vascular rarefaction, showing improved peritubular microvasculature after UUO. All these data suggest an important role of ALK1 in regulating vascular rarefaction and emergence of myofibroblasts.
Isolation and Quantification of the Hepatoprotective Flavonoids From Scleromitron diffusum (Willd.) R. J. Wang With Bio-Enzymatic Method Against NAFLD by UPLC–MS/MS
Authors: Qin Yuxi , Zhao Baojin , Deng Huifang , Zhang Mengjiao , Qiao Yanan , Liu Qiling , Shi Chuandao , Li Yunlan 
Published: June 2022

Flavonoids were the major phytochemicals against hepatic peroxidative injury in Scleromitron diffusum (Willd.) R. J. Wang with an inventive bio-enzymatic method by our group (LU500041). Firstly, the total flavonoids from Scleromitron diffusum (Willd.) R. J. Wang were extracted by reflux, ultrasonic, ultrasound-assisted enzymatic methods (TFH), and the bio-enzymatic method (Ey-TFH). Then 24 flavonoid compounds were isolated and quantified in the extracts by UPLC-MS/MS. Next, six representative differential compounds in Ey-TFH were further screened out by multivariate statistical analysis compared with those in TFH. In a further step, Ey-TFH presented a higher protective rate (59.30 ± 0.81%) against H2O2-damaged HL-02 hepatocytes than TFH. And six representative differential compounds at 8 and 16 μmol/L all exerted significant hepatoprotective effects (p &lt; 0.05 or p &lt; 0.01). Finally, the therapeutic action of Ey-TFH for nonalcoholic fatty liver disease (NAFLD) was processed by a rat’s model induced with a high-fat diet. Ey-TFH (90, 120 mg/kg) significantly ameliorated the lipid accumulation in the rat model (p &lt; 0.05). Meanwhile, Ey-TFH relieved liver damage. The levels of ALT, ALP, AST, LDH, and γ-GT in rats’ serum were also significantly reduced (p &lt; 0.05 or p &lt; 0.01). In addition to this, the body’s antioxidant capacity was improved with elevated SOD and GSH levels (p &lt; 0.05) and down-regulated MDA content (p &lt; 0.01) after Ey-TFH administration. Histopathological observations of staining confirmed the hepatic-protective effect of Ey-TFH.
Drug-Related Hospital Admissions via the Department of Emergency Medicine: A Cross-Sectional Study From the Czech Republic
Authors: Očovská Zuzana , Maříková Martina , Kočí Jaromír , Vlček Jiří 
Published: June 2022

Background: Drug-related hospital admissions (DRAs) represent a significant problem affecting all countries worldwide. This study aimed to determine the prevalence and preventability of DRAs, identify the most common medications involved in DRAs, the most common clinical manifestations of DRAs and describe the preventability aspects of DRAs.Methods: This cross-sectional study examined unplanned hospital admissions to the University Hospital Hradec Králové via the department of emergency medicine in August–November 2018. Data were obtained from electronic medical records. The methodology of DRA identification was adapted from the OPERAM DRA adjudication guide.Results: Out of 1252 hospital admissions, 195 DRAs have been identified (145 related to treatment safety, 50 related to treatment effectiveness). The prevalence of DRAs was 15.6% (95% CI 13.6–17.6). The most common medication classes involved in DRAs related to treatment safety were Antithrombotic agents, Antineoplastic agents, Diuretics, Corticosteroids for systemic use, and Beta blocking agents. The most common medication classes involved in DRAs related to treatment effectiveness included Diuretics, Antithrombotic agents, Drugs used in diabetes, Agents acting on the renin-angiotensin system, and Lipid modifying agents. Gastrointestinal disorders were the leading causes of DRAs related to treatment safety, while Cardiac disorders were the leading causes of DRAs related to treatment effectiveness. The potential preventability of DRAs was 51%. The highest share of potential preventability in medication classes repeatedly involved in DRAs related to treatment safety was observed for Anti-inflammatory and antirheumatic products, Psycholeptics, and Drugs used in diabetes. Potentially preventable DRAs related to treatment safety were most commonly associated with inappropriate drug selection, inappropriate monitoring, inappropriate dose selection, and inappropriate lifestyle measures. On the contrary, DRAs related to treatment effectiveness were more commonly associated with medication nonadherence.Conclusion: It should be emphasized that in most DRAs, medications were only a contributory reason of hospital admissions and that benefits and risks have to be carefully balanced. It is highlighted by the finding that the same medication classes (Antithrombotic agents and Diuretics) were among the most common medication classes involved in DRAs related to treatment safety and simultaneously in DRAs related to treatment effectiveness. The study highlighted that apart from problems related to prescribing, problems related to monitoring and patient-related problems represent significant preventability aspects.
Effect of Bufalin-PLGA Microspheres in the Alleviation of Neuropathic Pain via the CCI Model
Authors: Long Lina , Zhong Wenwei , Guo Liwei , Ji Jing , Nie Hong 
Published: June 2022

The treatment of neuropathic pain (NPP) is considered challenging, while the search for alternative medication is striving. NPP pathology is related with the expression of both the purinergic 2X7 (P2X7) receptor and the transient receptor potential vanilloid 1 receptor (TRPV1). Bufalin is a traditional Chinese medication derived from toad venom with pronounced antitumor, analgesic, and anti-inflammatory properties. However, poor solubility, rapid metabolism, and the knowledge gap on its pain alleviation mechanism have limited the clinical application of bufalin. Hence, the purpose of this study is to illustrate the NPP alleviation mechanism of bufalin via chronic constriction injury (CCI). To address the concern on fast metabolism, bufalin-PLGA microspheres (MS) were prepared via membrane emulsification to achieve prolonged pain-relieving effects. Western blot, real-time PCR, immunofluorescence, and molecular docking were employed to demonstrate the therapeutic action of bufalin on NPP. The results showed enhanced thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) after the administration of both bufalin and bufalin-PLGA MS in the CCI rats. Prolonged pain-relieving effects for up to 3 days with reduced dose frequency was achieved via bufalin-PLGA MS. In the CCI rats treated with bufalin-PLGA MS, the expression levels of protein and mRNA in TRPV1 and P2X7, both localized in the dorsal root ganglion (DRG), were reduced. Moreover, bufalin-PLGA MS effectively reduced the levels of IL-1β, IL-18, IL-6, and TNF-α in the CCI group. The results from molecular docking suggested a possible mechanism of NPP alleviation of bufalin through binding to P2X7 receptors directly. The administration of bufalin-PLGA MS prepared by membrane emulsification demonstrated promising applications for sustained effect on the alleviation of NPP.
Comparative Lipidomic and Metabolomic Analyses Reveal the Mystery of Lacquer Oil from Toxicodendron vernicifluum for the Treatment of “Yuezi” Disease in Nujiang, China: From Anti-Inflammation and Anti-Postpartum Depression Perspective
Authors: Liu Liya , Cai Fei , Lu Yitong , Xie Yuting , Li Hao , Long Chunlin 
Published: June 2022

Background: In southwest China, especially in Nujiang, lacquer oil from the drupes of Toxicodendron vernicifluum (Stokes) F. A. Barkley, including black lacquer oil (BLO) and white lacquer oil (WLO), is one of the most important edible oils for the local people. Through the field investigation, the locals believe that lacquer oil has benefits for parturient women and for the treatment of “Yuezi” disease. However, studies on bioactivities and the chemical compositions of lacquer oil are limited.Purpose: This study was designed to reveal the mystery of lacquer oil for the treatment of “Yuezi” disease by testing its anti-inflammatory and anti-postpartum depressant activities and related bioactive compounds.Methods: The anti-inflammatory effects of lacquer oil were examined by establishing a lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model and detecting the level of pro-inflammatory factors such as NO, IL-6 and TNF-α. The antidepressant effects of lacquer oil were studied by building a mouse model of postpartum depression (PPD), and the animal behavior changes of PPD model mice were assessed by open field test (OFT), forced swimming test (FST) and tail suspension test (TST). The chemical profiles of BLO and WLO were detected by lipidomic and the untargeted metabolomic research methods based on UPLC-MS/MS.Results: The results showed that BLO and WLO exerted anti-inflammatory effects by reducing the release of pro-inflammatory factors and BLO had better anti-inflammatory effects than WLO. While only BLO had anti-postpartum depressant activities, as evidenced by the significantly reduced the immobility time of the BLO-treated PPD mice in TST and FST compared to the PPD model mice. The comparative lipidomic analysis revealed that BLO contained high levels of Diacylglycerols (DAG) and Diacylglyceryl trimethylhomoserines (DGTS) but low level of ceramides (Cer), sphingomyelines (SM), phosphatidylcholines (PC) and phosphatidylethanolamines (PE) compared with WLO. Metabolomics analysis showed that there were 57 chemical markers between BLO and WLO, of which 17 potential biomarkers have been declared to possess anti-inflammatory and/or antidepressant activities.Conclusion: The findings of this study furnish a scientific support for the traditional uses of lacquer oil for the treatment of “Yuezi” disease from anti-inflammation and anti-postpartum depression perspective.