bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thirty-Day Mortality and Morbidity in COVID-19 Positive vs. COVID-19 Negative Individuals and vs. Individuals Tested for Influenza A/B: A Population-Based Study
Authors: Nersesjan Vardan , Amiri Moshgan , Christensen Hanne K. , Benros Michael E. , Kondziella Daniel 
Published: November 2020

Background: As of October 2020, COVID-19 has caused 1,000,000 deaths worldwide. However, large-scale studies of COVID-19 mortality and new-onset comorbidity compared to individuals tested negative for COVID-19 and individuals tested for influenza A/B are lacking. We investigated COVID-19 30-day mortality and new-onset comorbidity compared to individuals with negative COVID-19 test results and individuals tested for influenza A/B.Methods and findings: This population-based cohort study utilized electronic health records covering roughly half (n = 2,647,229) of Denmark's population, with nationwide linkage of microbiology test results and death records. All individuals ≥18 years tested for COVID-19 and individuals tested for influenza A/B were followed from 11/2017 to 06/2020. Main outcome was 30-day mortality after a test for either COVID-19 or influenza. Secondary outcomes were major comorbidity diagnoses 30-days after the test for either COVID-19 or influenza A/B. In total, 224,639 individuals were tested for COVID-19. To enhance comparability, we stratified the population for in- and outpatient status at the time of testing. Among inpatients positive for COVID-19, 356 of 1,657 (21%) died within 30 days, which was a 3.0 to 3.1-fold increased 30-day mortality rate, when compared to influenza and COVID-19-negative inpatients (all p &lt; 0.001). For outpatients, 128 of 6,263 (2%) COVID-19-positive patients died within 30 days, which was a 5.5 to 6.9-fold increased mortality rate compared to individuals tested negative for COVID-19 or individuals tested positive or negative for influenza, respectively (all p &lt; 0.001). Compared to hospitalized patients with influenza A/B, new-onset ischemic stroke, diabetes and nephropathy occurred more frequently in inpatients with COVID-19 (all p &lt; 0.05).Conclusions: In this population-based study comparing COVID-19 positive with COVID-19 negative individuals and individuals tested for influenza, COVID-19 was associated with increased rates of major systemic and vascular comorbidity and substantially higher mortality. Results should be interpreted with caution because of differences in test strategies for COVID-19 and influenza, use of aggregated data, the limited 30-day follow-up and the possibility for changing mortality rates as the pandemic unfolds. However, the true COVID-19 mortality may even be higher than the stated 3.0 to 5.5-fold increase, owing to more extensive testing for COVID-19.
Relationship Between T-Cell Exosomes and Cellular Subsets in SLE According to Type I IFN-Signaling
Authors: López Patricia , Rodríguez-Carrio Javier , Caminal-Montero Luis , Suárez Ana 
Published: November 2020

Objective: To quantify the levels of circulating exosomes derived from T-cells and monocytes and their possible associations with leukocyte subpopulations and cytokine milieu in Systemic Lupus Erythematosus (SLE).Methods: Total circulating exosomes (CD9+-Ex) and those derived from T-cells (CD3+-Ex) and monocytes (CD14+-Ex) were quantified by flow cytometry in 82 SLE patients and 32 controls. Leukocyte subsets and serum cytokines were analyzed by flow cytometry or by immunoassays. IFN-score was evaluated by real time RT-PCR in whole blood samples from a subgroup of 73 patients and 24 controls.Results: Activation markers (IFNR1 and BLyS) on monocytes, neutrophils and B-cells correlated inversely with circulating exosomes (CD9+-Ex, CD3+-Ex, and CD14+-Ex) in controls but directly with CD3+-Ex in patients (all p &lt; 0.05). Although CD9+-Ex were increased in SLE, no differences were found in CD3+-Ex, supporting that exosome content accounts for this opposite role. Interestingly, CD4+CD28null cells correlated with CD3+-Ex in patients and controls, and displayed similar associations with leukocyte subsets in both groups. Additionally, CD3+-Ex correlated in patients with the expression of CD25 in CD4+CD28null cells. Furthermore, the activated status of this senescent subset was related to IFNα serum levels in controls and to IFN-score in SLE patients. Finally, patients presenting high IFN-score, in addition to elevated CD25+CD28null cells associated with the activation of myeloid cells, displayed higher levels of inflammatory cytokines and chemokines.Conclusion: Our results support a relationship between T-cell exosomes and cellular subsets in SLE according to type I IFN-signaling, which could amplify chronic immune activation and excessive cytokine/chemokine response.
Deep Learning-Based Method to Differentiate Neuromyelitis Optica Spectrum Disorder From Multiple Sclerosis
Authors: Kim Hyunjin , Lee Youngin , Kim Yong-Hwan , Lim Young-Min , Lee Ji Sung , Woo Jincheol , Jang Su-Kyeong , Oh Yeo Jin , Kim Hye Weon , Lee Eun-Jae , Kang Dong-Wha , Kim Kwang-Kuk 
Published: November 2020

Background: Differentiating neuromyelitis optica spectrum disorder (NMOSD) from multiple sclerosis (MS) is crucial in the field of diagnostics because, despite their similarities, the treatments for these two diseases are substantially different, and disease-modifying treatments for MS can worsen NMOSD. As brain magnetic resonance imaging (MRI) is an important tool to distinguish the two diseases, extensive research has been conducted to identify the defining characteristics of MRI images corresponding to these two diseases. However, the application of such research in clinical practice is still limited. In this study, we investigate the applicability of a deep learning-based algorithm for differentiating NMOSD from MS.Methods: In this study, we included 338 participants (213 patients with MS, 125 patients with NMOSD) who visited the Asan medical center between February 2009 and February 2020. A 3D convolutional neural network, which is a deep learning-based algorithm, was trained using fluid-attenuated inversion recovery images and clinical information of the participants. The performance of the final model in differentiating NMOSD from MS was evaluated and compared with that of two neurologists.Results: The deep learning-based model exhibited an area under the receiver operating characteristic curve of 0.82 (95% CI, 0.75–0.89). It differentiated NMOSD from MS with an accuracy of 71.1% (sensitivity = 87.8%, specificity = 61.6%), which is comparable to that exhibited by the neurologists. The intra-rater reliability of the two neurologists was moderate (κ = 0.47, 0.50), which was in contrast with the consistent classification of the deep learning-based model.Conclusion: The proposed model was verified to be capable of differentiating NMOSD from MS with accuracy comparable to that of neurologists, exhibiting the advantage of consistent classification. As a result, it can aid differential diagnosis between two important central nervous system inflammatory diseases in clinical practice.
Impact of COVID-19 on Stroke Admissions and the Medical Care System in the Tokyo Metropolitan Area
Authors: Ota Takahiro , Shiokawa Yoshiaki , Hirano Teruyuki 
Published: November 2020

Aims: This study aimed to assess the number of patients with acute stroke seeking medical emergency care since the declaration of the state of emergency in the COVID-19 pandemic in the Tokyo metropolitan area of Japan.Methods: In this combined retrospective and prospective multicenter survey, data on the numbers of hospital admissions due to acute ischemic stroke, of large vessel occlusion (LVO) cases, and of reperfusion therapies performed from February to July 2020, restrictions of the medical care system, and comprehensive stroke center (CSC) scale scores were collected in 19 stroke centers in Tokyo.Results: In the survey period, 3,456 patients were admitted with acute stroke. There was a decrease in the number of admissions (−22%), LVO (−22%), thrombolysis (−6%), and thrombectomy (−23%) during the state of emergency, but the ratio of thrombectomy to LVO cases was not different. The acceptance of acute stroke cases by emergency transport and emergent operations in the central eastern area of Tokyo, was also significantly decreased to &lt;50% and remains &lt;60%. According to CSC scores, each hospital restricted their infrastructure or educational activities according to their medical resources. There was only one stroke case with COVID-19 (thrombectomy case) in all 3,456 patients in this study.Conclusion: The COVID-19 pandemic had a major impact on stroke care in Tokyo, including stroke admissions and medical care systems, resulting in a significant reduction in thrombolysis and thrombectomy. The extent of the drop may be the result of the number of COVID-19 patients.
Superiority of Epstein-Barr Virus DNA in the Plasma Over Whole Blood for Prognostication of Extranodal NK/T Cell Lymphoma
Authors: Ha Joo Young , Cho Hyungwoo , Sung Heungsup , Jung Ah Ra , Lee Yoon Sei , Lee Sang-Wook , Ryu Jin-Sook , Chae Eun Jin , Kim Kyung Won , Huh Jooryung , Park Chan-Sik , Kim Dong-Joon , Kim Seon-Ok , Yoon Dok Hyun 
Published: November 2020

BackgroundExtranodal natural killer T cell lymphoma (ENKTL) is a rare subtype of non-Hodgkin lymphoma with invariable infection of lymphoma cells with Epstein-Barr virus (EBV), and the presence of EBV-DNA in the blood is a well-known prognosticator. However, there is no consensus on which blood compartment is more optimal for predicting survival outcomes.MethodsWe analyzed 60 patients who were newly diagnosed with ENKTL from a prospectively collected database. EBV-DNA was measured in the whole-blood (WB) and plasma at the time of diagnosis and after treatment completion.ResultsEBV-DNA was detected in pre-treatment WB and plasma in 37 (61.7%) and 23 (38.3%) patients, respectively. The presence of pre-treatment plasma EBV-DNA was significantly associated with advanced stage while presence of WB EBV-DNA did not. Positivity of pre-treatment plasma-EBV, but not WB EBV-DNA, was independently associated with poor PFS (HR, 4.22;95% CI, 1.79–9.97; P=0.001) and OS (HR, 8.38; 95% CI, 3.03–23.19; P&lt;0.001) in the multivariate analysis. After treatment completion, positivity of plasma-EBV was independently associated with poor PFS (HR, 9.41; 95% CI, 2.27–39.02; P=0.002) and OS (HR, 32.38; 95% CI, 3.25–322.56; P=0.003), whereas no significant association was observed between WB-EBV status and survival outcomes.ConclusionsOur results suggest that EBV-DNA in the plasma has better prognostic values than WB in patients with ENKTL.
Inulin Exerts Beneficial Effects on Non-Alcoholic Fatty Liver Disease via Modulating gut Microbiome and Suppressing the Lipopolysaccharide-Toll-Like Receptor 4-Mψ-Nuclear Factor-κB-Nod-Like Receptor Protein 3 Pathway via gut-Liver Axis in Mice
Authors: Bao Ting , He Fang , Zhang Xiaoxia , Zhu Lili , Wang Zhen , Lu Haixia , Wang Ting , Li Yiwei , Yang Shaoqi , Wang Hao 
Published: November 2020

Background:Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disease worldwide with chronic low-grade inflammation and alteration of gut microbiota. Inulin (INU) has been confirmed to exhibit benefit for metabolic diseases. The aim of this study was to clarify the effects and mechanism of INU on NAFLD inflammation via gut-liver axis.Methods:C57BL/6 mice were randomly divided into four groups: normal diet group (ND); high-fat diet group (HFD); ND with INU group (ND-INU); HFD with INU group (HFD-INU). After 14 weeks of feeding, mice were sacrificed and associated indications were investigated.Results:Significant increases of body weight, liver weight, liver biochemical aspartate aminotransferase, alanine aminotransferase, triglyceride, total cholesterol and pro-inflammatory indicators (Lipopolysaccharide, interleukin (IL)-18, IL-1β, TNF-α and IL-6), as well as a reduction of plasma IL-10 were observed in HFD group, while INU treatment restored these abnormal indicators. The ratio of hepatic macrophages (Mψs) and Toll-like receptor 4+Mψs were both reduced with INU intervention. Nuclear factor-κB, nod-like receptor protein 3, apoptosis-associated speck-like protein and caspase-1 were decreased in HFD-INU group. Additionally, the results of 16S rRNA sequencing and analysis showed that INU administration modulated the composition of gut microbial community in NAFLD mice by up-regulating the abundances ofAkkermansiaandBifidobacteriumas well as down-regulating the abundances ofBlautiaand the ratio ofFirmicutes/Bacteroidetes. Short-chain fatty acids including acetic acid, propionic acid and butyric acid, were increased with INU treatment. Correlation analysis revealed close relationships among inflammatory indicators, metabolic indicators as well as gut microbiota/its metabolite short-chain fatty acids.Conclusion:INU prevents NAFLD via modulating gut microbiota and suppressing Lipopolysaccharide-Toll-like receptor 4-Mψ-Nuclear factor-κB-nod-like receptor protein 3 inflammatory pathway via the gut-liver axis.
Efficacy of Intravenous Tranexamic Acid in Reducing Perioperative Blood Loss and Blood Product Transfusion Requirements in Patients Undergoing Multilevel Thoracic and Lumbar Spinal Surgeries: A Retrospective Study
Authors: Todeschini Alexandre B. , Uribe Alberto A. , Echeverria-Villalobos Marco , Fiorda-Diaz Juan , Abdel-Rasoul Mahmoud , McGahan Benjamin G. , Grossbach Andrew J. , Viljoen Stephanus , Bergese Sergio D. 
Published: November 2020

Introduction: Acute perioperative blood loss is a common and potentially major complication of multilevel spinal surgery, usually worsened by the number of levels fused and of osteotomies performed. Pharmacological approaches to blood conservation during spinal surgery include the use of intravenous tranexamic acid (TXA), an anti-fibrinolytic that has been widely used to reduce blood loss in cardiac and orthopedic surgery. The primary objective of this study was to assess the efficacy of intraoperative TXA in reducing estimated blood loss (EBL) and red blood cell (RBC) transfusion requirements in patients undergoing multilevel spinal fusion.Materials and Methods: This a single-center, retrospective study of subjects who underwent multilevel (≥7) spinal fusion surgery who received (TXA group) or did not receive (control group) IV TXA at The Ohio State University Wexner Medical Center between January 1st, 2016 and November 30th, 2018. Patient demographics, EBL, TXA doses, blood product requirements and postoperative complications were recorded.Results: A total of 76 adult subjects were included, of whom 34 received TXA during surgery (TXA group). The mean fusion length was 12 levels. The mean total loading, maintenance surgery and total dose of IV TXA was 1.5, 2.1 mg per kilo (mg/kg) per hour and 33.8 mg/kg, respectively. The mean EBL in the control was higher than the TXA group, 3,594.1 [2,689.7, 4,298.5] vs. 2,184.2 [1,290.2, 3,078.3] ml. Among all subjects, the mean number of intraoperative RBC and FFP units transfused was significantly higher in the control than in the TXA group. The total mean number of RBC and FFP units transfused in the control group was 8.1 [6.6, 9.7] and 7.7 [6.1, 9.4] compared with 5.1 [3.4, 6.8] and 4.6 [2.8, 6.4], respectively. There were no statistically significant differences in postoperative blood product transfusion rates between both groups. Additionally, there were no significant differences in the incidence of 30-days postoperative complications between both groups.Conclusion: Our results suggest that the prophylactic use of TXA may reduce intraoperative EBL and RBC unit transfusion requirements in patients undergoing multilevel spinal fusion procedures ≥7 levels.
Chemical Fingerprint Analysis and Ultra-Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry-Based Metabolomics Study of the Protective Effect of Buxue Yimu Granule in Medical-Induced Incomplete Abortion Rats
Authors: Zhang Yan , Li Wei , Chen Ting-Ting , Yang Yong , Wu Meng-Yao , Luo Jie-Ying , Gong Yun , Zou Liang 
Published: November 2020

Medical abortion is a common method to terminate an early pregnancy and often causes serious complications such as abnormal uterine bleeding and endometritis. Buxue Yimu granule (BYG) is a well-known traditional Chinese medicine prescription composed of five kinds of drugs and is widely used in gynecology and obstetrics. The aim of the present study was to establish the quality standard of BYG and investigate its protective effect on incomplete abortion. The chemical fingerprint of BYG was established by high performance liquid chromatography (HPLC). The major compounds of BYG were determined by ultra-performance liquid chromatography with triple quadrupole mass spectrometry. An incomplete abortion rat model was induced by intragastric administration of mifepristone (8.3 mg·kg−1) combined with misoprostol (100.0 μg·kg−1) during early pregnancy. The serum levels of human chorionic gonadotrophin (HCG), estradiol (E2), and progesterone (PG) were determined. The serum endogenous metabolites were analyzed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Multivariate analysis, including partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA), was employed to analyze the metabolic profiles, and MetaboAnalyst was used to investigate the metabolic pathways. Furthermore, hematoxylin-eosin staining (HE) was used to evaluate the histopathological changes in uterine tissue. The expression levels of VEGFA and NF-κB were detected by immunohistochemistry. The results indicated that HPLC fingerprint analysis can be successfully used to assess the quality of BYG. The medical-induced incomplete abortion rats were clearly separated from control rats, and the biochemical changes were gradually restored to normal after administration of BYG. Moreover, 19 potential biomarkers, including N-lactoylleucine, 2-piperidinone, isobutyryl-l-carnitine, eicosapentaenoylcholine, LysoPC(14:0), LysoPC(20:5), physagulin C, LysoPC(18:3), leukotriene D5, deoxycholic acid 3-glucuronide, glycine, pregnanediol 3-O-glucuronide, LysoPC(18:2), LysoPC(17:0/0:0), N-acetyl-leukotriene E4, LysoPC(18:0), platelet-activating factor, LysoPA(24:1), and LysoPC(18:1), which were mainly related to the amino acids metabolism, lipids metabolism, and bile acid biosynthesis, were identified. Consequently, BYG exerts a potential protective role in the intervention of incomplete abortion by anti-inflammatory, promote endometrial repair, and regulate the metabolic disorders.
Semi-Mechanistic Modeling of HY-021068 Based on Irreversible Inhibition of Thromboxane Synthetase
Authors: Li Ping , Huang Jie , Geng Donghao , Liu Peihua , Chu Zhaoxing , Zou Jianjun , Yang Guoping , Liu Li 
Published: November 2020

Background: HY-021068 [4-(2-(1H-imidazol-1-yl) ethoxy)-3-methoxybenzoate], developed by Hefei Industrial Pharmaceutical Institute Co., Ltd. (Anhui, China), is a potential thromboxane synthetase inhibitor under development as an anti-platelet agent for the treatment of stroke. A semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model was developed to characterize the PK of HY-021068 and its platelet aggregation inhibitory effect in beagle dogs.Method: Beagle dogs received single oral administration of 2.5 mg/kg HY-021068 or consecutively oral administration of 5 mg/kg HY-021068 once daily for 7 days. The plasma concentration of HY-021068 and the platelet aggregation rate (PAR) were determined by liquid chromatography tandem-mass spectrometry (LC‐MS/MS) assay and a photometric method, respectively. The PK/PD data was sequentially fitted by Phoenix NLME. The PK/PD parameters of HY-021068 in beagle dogs were estimated by 2.5 and 5 mg/kg dosing on the 1st day, and then used to simulate the PAR of HY-021068 on the 7th day after 5 mg/kg dosing daily.Result: A one-compartment model with saturable Michaelis-Menten elimination was best fitted to the PK of HY-021068. A mechanistic PD model based on irreversible inhibition of thromboxane synthetase was constructed to describe the relationship between plasma concentration of HY-021068 and PAR. Diagnostic plots showed no obvious bias. Visual predictive check confirmed the stability and reliability of the model. Most of PK/PD observed data on the 7th day after 5 mg/kg dosing fell in the 90% prediction interval.Conclusion: We established a semi-mechanistic PK/PD model for characterizing the PK of HY-021068 and its anti-platelet effect in beagle dogs. The model can be used to predict the concentration and PAR under different dosage regimen of HY-021068, and might be served as a reference for dose design in the future clinical studies.
Corticosterone as a Potential Confounding Factor in Delineating Mechanisms Underlying Ketamine’s Rapid Antidepressant Actions
Authors: Wegman-Points Lauren , Pope Brock , Zobel-Mask Allison , Winter Lori , Wauson Eric , Duric Vanja , Yuan Li-Lian 
Published: November 2020

Recent research into the rapid antidepressant effect of subanesthetic doses of ketamine have identified a series of relevant protein cascades activated within hours of administration. Prior to, or concurrent with, these activation cascades, ketamine treatment generates dissociative and psychotomimetic side effects along with an increase in circulating glucocorticoids. In rats, we observed an over 3-fold increase in corticosterone levels in both serum and brain tissue, within an hour of administration of low dose ketamine (10 mg/kg), but not with (2R, 6R)-hydroxynorketamine (HNK) (10 mg/kg), a ketamine metabolite shown to produce antidepressant-like action in rodents without inducing immediate side-effects. Hippocampal tissue from ketamine, but not HNK, injected animals displayed a significant increase in the expression of sgk1, a downstream effector of glucocorticoid receptor signaling. To examine the role conscious sensation of ketamine’s side effects plays in the release of corticosterone, we assessed serum corticosterone levels after ketamine administration while under isoflurane anesthesia. Under anesthesia, ketamine failed to increase circulating corticosterone levels relative to saline controls. Concurrent with its antidepressant effects, ketamine generates a release of glucocorticoids potentially linked to disturbing cognitive side effects and the activation of distinct molecular pathways which should be considered when attempting to delineate the molecular mechanisms of its antidepressant function.