bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repeated Intrathecal Administration of Ropivacaine Hydrochloride Induces Apoptosis Via Up-Regulating of Fas/FasL Expression in the Rat Spinal Cord
Authors: Zhang Fuyu , Zeng Lian , Luo Zhao , Sang Ming , Sun Xiaodong , Luo Huiyu 
Published: September 2020

Abstract
Background: Ropivacaine hydrochloride (RH) is a local anesthetic and frequently used for perioperative anesthesia and analgesia; but it has potential neurotoxicity, especially when intrathecally used repeatedly for a long time, although the exact mechanism is unclear.Methods: In this study, the expression of Factor associated suicide receptor (Fas) and its ligand (FasL) in the spinal cord cells was detected in rats receiving repeated intrathecal injection of RH. The paw mechanical withdraw threshold (MWT) was measured before and 3 days after intrathecal cannulation and 24 h after intrathecal administration. Rats received intrathecal injection of 0.5%, 1%, 2% RH at 0.12 ml/kg or saline of equal volume alone. Intrathecal injection was done 8 times with an interval of 1.5h in 12 h. The spinal cord was collected for pathological examination; TUNEL staining was used to assess the apoptosis in the spinal cord and the expression of Fas, FasL, caspase-3, and caspase-8 was detected by qPCR and Western blotting.Results: 1% and 2% RH groups significantly increased the MWT (P<0.05) and more vacuoles or edema was observed in the spinal cord after RH treatment. The apoptosis rates and expression of Fas, FasL, caspase-3, and caspase-8 increased in the RH groups (P<0.05).Conclusions: Repeated intrathecal administration of RH may cause damage to the spinal cord and induce apoptosis in the spinal cord via up-regulating Fas/FasL expression.
Genotype-dependent Response to a Low-energy, Moderate Fiber Diet on Brain-Derived Neurotrophic Factor in Patients who are Obese and Overweight with Type 2 Diabetes
Authors: nazary-vanani ali , Yekaninejad Mir Saeed , Moradi Masoumeh , Clark Cain C. T. , Koohdani Fariba 
Published: September 2020

Abstract
ObjectiveBrain-Derived Neurotrophic Factor (BDNF) plays a key role in the pathway of the hypothalamus by reducing appetite, controlling body weight and maintaining energy balance. The aim of this study was to investigate the effects of a low-energy, moderate fiber diet on BDNF in obese and overweight type 2 diabetic patients with the APOA-II polymorphism.ResultsSerum BDNF levels increased significantly in the total participants following the low-energy, moderate fiber diet intervention (from 177.54 ± 141.54 pg/ml to 253.79 ± 206.34 pg/ml, p value = 0.025). However, the increase of serum BDNF levels did not signifcanty differ between gentyipc sub-types.
4R Tau Modulates Cocaine-Associated Memory Through Adult Hippocampal Neurogenesis
Authors: Li Hongchun , Xu Wei , Wang Denian , Fang Qiyao , Wang Liang , Wan Xuemei , Zhang Jiamei , Hu Yiming , Li Huifang , Zhang Jie , Yang Zhen , Liu Chunqi , Liu Xiaocong , Wang Yonghai , Liu Bin , Zhao Ying , Bu Qian , Wang Hongbo , Tian Jingwei , Zhao Yinglan , Cen Xiaobo 
Published: September 2020

Abstract
Background: Drug memory that generally develops with drug-paired contextual stimuli and drug administration is critical for the development, persistence and relapse of drug addiction. Previous studies have suggested that adult hippocampal neurogenesis (AHN) plays a role in cocaine memory formation; however, the underlying mechanism is not fully understood.Methods: Conditioned place preference (CPP), self-administration and locomotor activity were used to investigate the role of Tau in cocaine-associated memory formation. Virus-mediated gene transfer, western blot, immunohistochemistry, flow cytometry analysis, Tau-interacting proteomics, co-immunoprecipitation, and mutation of 4R Tau were performed. Results: Hippocampal expression of Tau was significantly decreased during the cocaine-associated memory formation. Genetic overexpression of four microtubule-binding repeats Tau (4R Tau) in the hippocampus disrupted cocaine memory by suppressing AHN. Furthermore, 4R Tau directly interacted with phosphoinositide 3-kinase (PI3K)-p85 and impaired its nuclear translocation and PI3K-AKT signaling, processes required for hippocampal neuron proliferation. Conclusions: 4R Tau modulates cocaine memory formation by disrupting AHN, suggesting a novel mechanism underlying cocaine memory formation and provide a new strategy for the treatment of cocaine addiction.
Comparing EQ-5D-3L and EQ-5D-5L in Measuring the HRQoL Burden of 4 Health Conditions in China
Authors: Tan Yani , Zhang Zhen , Hong Yanming , Yang Zhihao , Luo Nan , Jiang Jie , Li Sha 
Published: September 2020

Abstract
Background: This study was conducted to compare the measurement properties of both the EQ-5D-3L and EQ-5D-5L in quantifying health related quality of life (HRQoL) burden for 4 different health conditions in China.Methods: A total of 500 participants from China were recruited to complete the 3L and 5L questionnaire via Internet. The 3L and 5L were compared in terms of distribution properties, ceiling effects and relative efficiency. Distributions of responses were also examined. Results: Ceiling effects decreased significantly in the 5L in all domains (P＜0.01), especially in the pain/discomfort dimension (relative difference: 43.10%). Relative efficiency suggested that 5L had a higher absolute discriminatory power than the 3L version between perfectly healthy participant and 4 condition groups, especially for the HIV/AIDS group when the 3L results was not significant. 5L also had smoother and less clustered index value distributions. Conclusions: Both the 3L and 5L are demonstrated to be valid HRQoL instruments for quantifying disease burden in China. The 5L system may be preferable to the 3L, as it demonstrated superior performance with respect to lower ceiling effect, better relative efficiency and distributions.
Preclinical Modeling of Chronic Inhibition of the Parkinson’s Disease Associated Kinase LRRK2 Reveals Altered Function of the Endolysosomal System in Vivo
Authors: KLUSS JILLIAN H. , Mazza Melissa Conti , Li Yan , Manzoni Claudia , Lewis Patrick A. , Cookson Mark R. , Mamais Adamantios 
Published: September 2020

Abstract
BackgroundThe most common mutation in the Leucine-rich repeat kinase 2 gene (LRRK2), G2019S, causes familial Parkinson’s Disease (PD) and renders the encoded protein kinase hyperactive. To date, the molecular effects of chronic LRRK2 inhibition have not yet been examined in vivo. MethodsWe evaluated the utility of newly available phospho-antibodies for Rab substrates pT73 Rab10, pS106 Rab12, pT71 Rab29 and LRRK2 autophosphorylation to examine the pharmacodynamic response to acute treatment paradigms with the potent and specific LRRK2 inhibitor, MLi-2, in brain and peripheral tissue in G2019S LRRK2 knock-in mice to define the relative target engagement between brain and LRRK2-enriched peripheral tissues. The molecular effects of 10 days and 10 weeks of chronic in-diet dosing were also evaluated using TMTpro reagents for LC-MS/MS total and phospho- proteomics in brain and kidney tissues. ResultsWe report higher sensitivity of LRRK2 autophosphorylation to MLi-2 treatment and slower recovery in washout conditions compared to Rab GTPases phosphorylation, and we identify pS106 Rab12 as a robust readout of downstream LRRK2 activity across tissues. The downstream effects of long-term chronic LRRK2 inhibition in vivo were evaluated in G2019S LRRK2 knock-in mice by phospho- and total proteomic analyses following an in-diet administration of MLi-2 for 10 weeks. We observed alterations in endolysosomal and trafficking pathways in the kidney that were sensitive to MLi-2 treatment and that we validated biochemically. Furthermore, a subtle but distinct biochemical signature affecting mitochondrial proteins was observed in brain tissue in the same animals that was reverted by kinase inhibition. ConclusionsThis is the first study to examine the molecular underpinnings of chronic LRRK2 inhibition in a preclinical in vivo PD model and highlights cellular processes that may be influenced by therapeutic strategies aimed at restoring LRRK2 physiological activity in PD patients.
The Novel Biomarkers-Based HALP (Hemoglobin, Albumin, Lymphocyte and Platelet)-Prognostic Model for Acute and Subacute Patients with Cerebral Venous Sinus Thrombosis: A Retrospective Cohort Study
Authors: Li Shen , Liu Kai , Gao Yuan , Zhao Lu , Fang Hui , Zhang Rui , Liu Hongbing , Zhao Jiawei , Xia Zongping , Xu Yuming , Song Bo 
Published: September 2020

Abstract

Background and purpose: To evaluate the prognosis values of HALP in acute or subacute cerebral venous sinus thrombosis (CVST), to explore the new prognostic model for CVST.Methods: Consecutive patients who were diagnosed as having acute and subacute CVST were retrospectively investigated. We determined the patients' functional outcomes by modified Rankin Scale (mRS). Multivariate logistic regression analysis was used to assess the relationship between factors and poor functional outcomes. The area under the ROC curve (AUC) was estimated to evaluate the ability of markers and models in predicting clinical prognosis. The prognostic model was presented as nomogram. In addition, the decision curve analysis (DCA) was used to analyze the benefit of this model. Furthermore, survival curves were described by the Kaplan‑Meier analysis. Results: A total of 270 patients were included of which 31 had poor outcome. Multivariable logistic regression analysis demonstrated HALP (OR=0.978, 95%CI: 0.958-0.999, P=0.039) was a protective predictor of outcome. The AUC of HALP was 0.749 (95% CI: 0.633-0.865, P=0.044). DCA demonstrated that this model significantly improved risk prediction at threshold probabilities of CVST at 0 to 85%. Patients with higher HALP (P=0.006) presented higher overall survival rates. Conclusions: HALP may be a potential protective marker in acute and subacute CVST patients. The new prognostic model with HALP had potentially better value for Chinese CVST patients.
WITHDRAWN: A Community-based Survey of Household Food Insecurity and Associated Factors Among 2-6 Years Old Children in the Southeast of Iran
Authors: Amaniyan Sara , sotoudeh Mitra , Dadgar Farhad , Jonoush Mona , Vaismoradi Mojtaba 
Published: September 2020

Abstract
Background: To investigate the status of household food security and factors affecting it among 2-6 years old children in an urban area in the southeast of Iran.Methods: A community-based survey was conducted from September to January 2018 on 450 children aged 2-6 years who were selected using stratified cluster random sampling. They lived in six different areas in an urban area in the southeast of Iran. Data was collected using the U.S. Department of Agriculture Food Security questionnaire and anthropometric measurements. Results: The prevalence of food insecurity among children was 81.7% consisting of 2.6% without hunger, 9.2% with moderate hunger and 96.9% with severe hunger. The weight gains of those children who were in the insecurity group without hunger was 2.63 times lower than those children in the food security group. Also, chances of weight gain in the insecurity group without hunger and in the insecurity group with moderate hunger were less as 1.91 and 1.41 times, respectively.Conclusions: Food insecurity in children aged 2-6 years was influenced by various socio-demographic factors. Therefore, policy-makers should plan for improving the quality of life and health of the children through improving their food security.
Feasibility, Effectiveness, and Safety of Endoscopic Vacuum Therapy for Intrathoracic Anastomotic Leakage Following Transthoracic Esophageal Resection: A Prospective Study
Authors: Zhang Chengcheng Christine , Liesenfeld Lukas , Klotz Rosa , Koschny Ronald , Rupp Christian , Schmidt Thomas , Diener Markus K. , Müller-Stich Beat P. , Hackert Thilo , Sauer Peter , Büchler Markus W. , Schaible Anja 
Published: September 2020

Abstract
BackgroundAnastomotic leakage (AL) in the upper gastrointestinal (GI) tract is associated with high morbidity and mortality rates. Especially intrathoracic anastomotic leakage leads to life-threatening adverse events. Endoscopic vacuum therapy (EVT) for anastomotic leakage after transthoracic esophageal resection represents a novel concept. However, sound clinical data are still scarce. This prospective, single-center study aimed to evaluate the feasibility, effectiveness, and safety of EVT for intrathoracic anastomotic leakage following abdomino-thoracic esophageal resection. MethodsFrom March 2014 to September 2019 259 consecutive patients underwent elective transthoracic esophageal resection. 72 patients (27,8 %) suffered from AL. The overall collective in-hospital mortality rate was 3.9% (n=10). Data from those who underwent treatment with EVT were included. ResultsFifty-five patients were treated with EVT. Successful closure was achieved in 89.1% (n=49) by EVT only. The EVT-associated adverse event rate was 5.4% (n=3): bleeding occurred in one patient, while minor sedation-related adverse events were observed in two patients. The median number of EVT procedures per patient was 3. The procedures were performed at intervals of 3-5 days, with a 14-day median duration of therapy. The mortality rate of patients with AL was 7.2% (n=4). Despite successfully terminated EVT, three patients died because of multiple organ failure, acute respiratory distress syndrome, and urosepsis (5.4%). One patient (1.8%) died during EVT due to cardiac arrest. ConclusionsEVT is a safe and effective approach for intrathoracic anastomotic leakages following abdomino-thoracic esophageal resections. It offers a high leakage-closure rate and the potential to lower leakage-related mortalities.
SARS-CoV-2 spike D614G variant exhibits highly efficient replication and transmission in hamsters
Authors: Mok Bobo , Cremin Conor J. , Lau Siu-Ying , Deng Shaofeng , Chen Pin , Zhang Jinxia , Lee Andrew , Liu HOnglian , Liu Siwen , Ng Timothy Ting-Leung , Lao Hiu-Yin , Lee Eddie Lam-Kwong , Leung Kenneth Siu-Sing , Wang Pui , To Kelvin , Chan Jasper , Chan Kwok-Hung , Yuen Kwok-Yung , Siu Gilman Kit-Hang , Chen Honglin 
Published: September 2020

Abstract
SARS-CoV-2 causes disease varying in severity from asymptomatic infections to severe respiratory distress and death in humans. The viral factors which determine transmissibility and pathogenicity are not yet clearly characterized. We used the hamster infection model to compare the replication ability and pathogenicity of five SARS-CoV-2 strains isolated from early cases originating in Wuhan, China, in February, and infected individuals returning from Europe and elsewhere in March 2020. The HK-13 and HK-95 isolates showed distinct pathogenicity in hamsters, with higher virus titers and more severe pathological changes in the lungs observed compared to other isolates. HK-95 contains a D614G substitution in the spike protein and demonstrated higher viral gene expression and transmission efficiency in hamsters. Intra-host diversity analysis revealed that further quasi species were generated during hamster infections, indicating that strain-specific adaptive mutants with advantages in replication and transmission will continue to arise and dominate subsequent waves of SARS-CoV-2 dissemination.
The Interplay Between Oxidative Phosphorylation and Glycolysis as a Potential Marker of Bladder Cancer Progression in Vitro and in Vivo
Authors: Petrella Greta , Ciufolini Giorgia , Burgio Giusy , Salonia Andrea , Montorsi Francesco , Vago Riccardo , Cicero Daniel Oscar 
Published: September 2020

Abstract
BackgroundUrothelial bladder cancer (UBC) is the most common tumor of the urinary system, the ninth most common cancer worldwide and the one with the most expensive treatment from diagnosis to death. One of the biggest problems related to this disease is the lack of sufficiently accurate markers that can anticipate the progression of the cancer from a low-grade non-muscle invasive to a high-grade muscle invasive UBC. Genomics and transcriptomics have recently added a number of molecular markers to traditional observations based on pathological parameters, which have greatly improved the prediction of risk of recurrence and progression. The inclusion of information from other omics sciences, such as metabolomics, could significantly improve this scenario.MethodsIn this study, we present the metabolic characterization using 1H-NMR of three UBC cell lines representing tumors with low-risk of progression, RT4, high-risk, 5637, and a cell line that shares characteristics with both, RT112. The metabolic profiles were classified by multivariate analysis. To validate the in vitro results, concentrations of two metabolites were measured in vivo in the urine of 91 patients with non-invasive and invasive tumors.ResultsRT4 cells mainly use oxidative phosphorylation to produce ATP and biomass, 5637 cells depend mainly on glycolysis, while RT112 cells show a mixed state with both metabolisms partially activated. The lactate/alanine ratio proved to be the most sensitive marker to the different type of metabolism active in the cells in vitro. By measuring its value in vivo in urine, we have found a two-fold increase among patients with high-grade tumors compared to low-grade ones.ConclusionsOur results reveal for the first time the relative importance of glycolysis and oxidative phosphorylation in the growth and maintenance of different UBC cell lines, and the relationship with their genomic signatures. They suggest that oxidative and non-oxidative metabolic states are primarily related to cell lines with low and high risk of progression, respectively. From this observation and our preliminary in vivo results, it appears that the lactate/alanine ratio in patients' urine is a good candidate to become a new marker to predict the conversion of low-grade tumors into more malignant forms.
m5C regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in papillary thyroid carcinoma
Authors: Li Fei , Deng Qingmei , Pang Xiaoxi , Huang Shan , Zhang Jingmiao , Zhu Xiaxia , Chen Hong , Liu Xiuxia 
Published: September 2020

Abstract
BackgroundRecently, immune response modulation at epigenetic level is illustrated in studies, but it is still unclear about the possible function of RNA 5-methylcytosine (m5C) modification in the cell infiltration within tumor microenvironment (TME).MethodsIn this study, the m5C modification patterns from altogether 493 papillary thyroid carcinoma (PTC) samples were assessed completely according to 9 m5C regulators. Afterwards, the modification patterns were correlated with the cell infiltration features in TME. The m5C modification patterns in tumor samples were quantified through the principal component analysis (PCA) algorithms to establish the m5C-score. Moreover, this study mined the signature genes related to the m5C-score, constructed the PTC diagnostic model by the support vector machine (SVM) method, and verified its accuracy based on samples in TCGA and GEO databases. The effects of 5 potential drugs based on the PTC m5C-score model in PTC cells were investigated through in vitro and in vivo assays (i.e., cell counting kit 8 and xenograft model). ResultsA total of 3 different m5C modification patterns were identified, and high differentiation degree was observed in the cell infiltration features within TME under the above 3 identified patterns. It was revealed that, evaluating m5C modification patterns in single tumor samples helped to estimate the stromal activity in TME, expression of immune checkpoint genes, and prognosis for patients. Typically, a low m5C-score, which was reflected in the activated immunity, predicted the relatively favorable prognostic outcome. Few effective immune infiltration was seen in high m5C-score subtype, indicating the dismal patient survival. Finally, this study constructed a diagnostic model using the 10 signature genes highly related to the m5C-score, discovered that the model exhibited high diagnostic accuracy for PTC, and screened out 5 potential drugs for PTC based on this m5C-score model. ConclusionsAccording to findings in the present study, m5C modification exerts an important part in forming the TME complexity and diversity. It is valuable to evaluate the m5C modification patterns in single tumors, so as to enhance our understanding towards the infiltration characterization in TME and to better guide clinical diagnosis as well as immunotherapies.
COVID-19 Impact on Neurology Training Program in Italy
Authors: Francesco Di Lorenzo , Tommaso Ercoli , Luca Cuffaro , Francesco Barbato , Francesco Iodice , Gioacchino Tedeschi , Alessandro Bombaci 
Published: September 2020

Abstract
The ongoing COVID-19 pandemic is having a huge impact on clinical activity of all hospitals, including the ones involved in training of residents. In addition, neurology residents underwent substantial modifications of their training program.Aim of our investigation was to evaluate the impact of COVID-19 pandemic on the educational activities of Italian neurology residents through an online questionnaire delivered to neurology residents.The results obtained showed that almost 30% of the respondents were redistributed to COVID-19 units. Neurology departments underwent substantial modifications of their organization influencing clinical educational activities; lessons and seminars were rescheduled online and research protocols were stopped and transferred to remote working, when feasible. There was a relevant use of telemedicine approach even if most of the respondents had never been trained before. Some of the changes had a North-South gradient, following the epidemiology of the pandemic.The data obtained from our survey highlight those points to address to be prepared for possible future emergencies.