bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transduction of inflammation from peripheral immune cells to the hippocampus induces neuronal hyperexcitability mediated by Caspase-1 activation
Authors: Shaker Tarek , Chattopadhyaya Bidisha , Amilhon Bénédicte , Cristo Graziella Di , Weil Alexander G. 
Published: November 2020

Abstract
1.1. Background Recent studies report infiltration of peripheral blood mononuclear cells (PBMCs) into the central nervous system (CNS) in epileptic disorders, suggestive of a potential contribution of PBMC extravasation to the generation of seizures. Nevertheless, the underlying mechanisms involved in PBMC infiltrates promoting neuronal predisposition to ictogenesis remain unclear. Therefore, we developed an in vitro model mimicking infiltration of activated PBMCs into the brain in order to investigate potential transduction of inflammatory signals from PBMCs to the CNS.1.2. Methods To establish our model, we first extracted PBMCs from rat spleen, then, immunologically primed PBMCs with lipopolysaccharide (LPS), followed by further activation with nigericin. Thereafter, we co-cultured these activated PBMCs with organotypic cortico-hippocampal brain slice cultures (OCHSCs) derived from the same rat, and compared PBMC-OCHSC co-cultures to OCHSCs exposed to PBMCs in the culture media. We further targeted a potential molecular pathway underlying transduction of peripheral inflammation to OCHSCs by incubating OCHSCs with the Caspase-1 inhibitor VX-765 prior to co-culturing PBMCs with OCHSCs. After 24 hours, we analyzed inflammation markers in the cortex and the hippocampus using semiquantitative immunofluorescence. In addition, we analyzed neuronal activity by whole-cell patch-clamp recordings in cortical layer II/III and hippocampal CA1 pyramidal neurons.1.3. Results In the cortex, co-culturing immunoreactive PBMCs treated with LPS + nigericin on top of OCHSCs upregulated inflammatory markers and enhanced neuronal excitation. In contrast, no excitability changes were detected after adding primed PBMCs (i.e. treated with LPS only), to OCHSCs. Strikingly, in the hippocampus, both immunoreactive and primed PBMCs elicited similar pro-inflammatory and pro-excitatory effects. However, when immunoreactive and primed PBMCs were cultured in the media separately from OCHSCs, only immunoreactive PBMCs gave rise to neuroinflammation and hyperexcitability in the hippocampus, whereas primed PBMCs failed to produce any significant changes. Finally, VX-765 application to OCHSCs, co-cultured with either immunoreactive or primed PBMCs, protected them from neuroinflammation and hippocampal hyperexcitability.1.4. Conclusions Our study shows a higher susceptibility of the hippocampus to peripheral inflammation as compared to the cortex, mediated via Caspase-1-dependent signaling pathways. Thus, our findings suggest that Caspase-1 inhibition may potentially provide therapeutic benefits during hippocampal neuroinflammation and hyperexcitability secondary to peripheral innate immunity.
Clinical Manifestations, Laboratory Markers, and Renal Ultrasonographic Examinationsin 1-month to12-year-old Iranian Children with Pyelonephritis: A Six-year Cross-sectional Retrospectivestudy
Authors: Fahimi Daryoosh , Khedmat Leila , Afshin Azadeh , Noparast Zahra , Jafaripor Maryam , Beigi Effat Hosseinali , Ghodsi Maryam , Izadi Anahita , MOJTAHEDI SAYED YUSEF 
Published: November 2020

Abstract
Background: Upper urinary tract infection (UTI) or pyelonephritismay increase the pathogenesis rate and risk of severe complications in children due to the atrophy of the kidneys.Objective: A set of clinical symptoms, laboratory markers, and ultrasound findings were assessed to reach early diagnosis and prognosis of pyelonephritis in hospitalized pediatrics.Methods: A cross-sectional study was conducted on 104 Iranian children (95 girls and 9 boys) aged 1 month to 12 years with acute pyelonephritis during 2012-2018. The ultrasound examination of kidneys and urinary tract during the hospitalization period, the incidence of clinical symptoms, and the monitoring of laboratory markersin blood and urine were studied to identify the best predictive factors of early diagnosis of this bacterial infection.Results: Three-fourth of the patients had one of the four clinical symptoms of abdominal pain, constipation, dysuria, andvomiting, whileotherswere asymptomatic. A considerable frequency of pyuria(88.4%), Escherichia coli in urine (92%), leukocytosis (81.7%), and high ESR (> mm/h, 80%) and CRP (> 10mg/L, 82.8%) was observed. The kidney and urinary tract ultrasonography onlyin 32.7% of children showed in favor of pyelonephritis (cystitis, ureteral stones, and hydronephrosis).Conclusion: In the majority of patients, there was a high prevalence of clinical signs and laboratory markers associated with pyelonephritis. Since most patients have normal sonography, ultrasound alonecould notbe an efficient tool fortracingfebrile UTI.
A Comprehensive Analysis of 5-Year Outcomes in Patients With Cancer Admitted to Intensive Care Units
Authors: Hong Yoonki , Kim Woo Jin , Hong Ji Young , Jeong Yun-Jeong , Park Jinkyeong 
Published: November 2020

Abstract
BackgroundUntil recently, studies on long-term outcomes of critically ill patients with cancer have been mainly restricted to specific subgroups of patients. The aim of this study was to evaluate the long-term (5 years) clinical outcomes of patients who received intensive care unit (ICU) treatment using the Korean nationwide data.MethodsAll patients aged >18 years with ICU admission, according to the claims data from the Health Insurance Review and Assessment Service from January 2008 to December 2010, were enrolled. The enrolled patients were followed up until December 2015. We analyzed clinical outcomes, including mortality after admission to the ICU. Critically ill patients were categorized into four subgroups: patients without cancer; with solid cancer except lung; with lung cancer; and with hematologic malignancies.ResultsAmong all critically ill patients admitted to the ICU (n = 323,765), the proportion of patients with cancer continued to increase from 21.5% in 2008 to 27.8% in 2010. Critically ill patients with cancer showed higher ICU mortality (18.6%) than those without cancer (13.2%, p < 0.001). There was no difference in ICU mortality at day 28 among patients without cancer (14.5%) and those with cancer which was not lung cancer or hematologic malignancies (14.3%, p = 0.28). Hazard ratios for the ICU mortality at 5 years were: 1.90 (95% confidence interval [CI]: 1.87–1.94) for lung cancer; 1.44 (95% CI: 1.43–1.46) for other solid cancers; and 3.05 (95% CI: 2.95–3.16) for hematologic malignancies, versus patients without cancer.Conclusion﻿The results of this study suggest that, in the short term, the outcomes of critically ill patients with cancer were not significantly different from those of general patients, except for cases with lung cancer and hematologic malignancies. However, the long-term survival rate of patients with cancer was significantly worse than that of general critically ill patients.
Association Between Body Composition with Pulmonary Function Tests
Authors: Pouragha Hamidreza , Kazemi Hosein , Pouryaghoub Gholamreza , Mehrdad Ramin 
Published: November 2020

Abstract
Background: Why is bodyweight not a predictor of lung function, however, height, sex, race, and age are predictors of lung capacity and function. In this study, we want to investigate the association between body composition and pulmonary function. And as much as possible, answer the question of why bodyweight is not predictive of lung function.Method: This cross-sectional study was performed among 2967 employees of Tehran University of Medical Sciences (TUMS) who participated in the TUMS Employees Cohort (TEC) study. The body composition of the participants was measured using the Bioelectrical Impedance Analysis (BIA) method. Anthropometric variables were also measured as a confounder. The pulmonary function of participants was assessed by a forced spirometry test.Results: The correlation of BIA values including fat-free mass and total body water with a pulmonary function such as FEV1, FVC, and FEF25-75 is higher than most anthropometric values such as weight, wrist circumference, and the waist to hip ratio. Also, in regression analysis, age and sex had an association with pulmonary function, but the weight did not show a significant relationship. On the other hand, fat-free mass and visceral fat were significantly associated with pulmonary function. One is direct and the other is inverse.Conclusion: The hypothesis that the results of this study created in the minds of the authors were that; The direct association of fat-free mass with pulmonary function may be ineffective by the inverse association of visceral fat with pulmonary function, leading to a lack of association between weight and pulmonary function.
Network Pharmacology Integrated Molecular Docking Reveals The Mechanism of Huanglian Wendan Decotion Against Metabolic Syndrome
Authors: Bao Junli , Gao Xinyuan , Han Yubo , Zhang Ke , Liu Li 
Published: November 2020

Abstract
Background: Metabolic syndrome (MetS) is a group of abnormalities which includes abdominal obesity, hypertension, insulin resistance, and dyslipidemia. Many clinical studies showed that Huanglian Wendan Decoction(HWD) is effective in the treatment of MetS.Methods: In this study, the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, STITCH database and Swisstargetpredicition database were used to excavate the active components of HWD and to predict the potential targets. The key targets of MetS are screened through GeneCards database and DisGeNET database. Moreover, we obtained the overlapping target of HWD and MetS based on venndiagram of "R program". Next, we performed enrichment analysis for common-target network and protein-protein interaction (PPI) network. Afterwards, Cytoscape was used to construct the components-targets core network for HWD in treating MetS, and R program was used to perform GO-BP and KEGG pathway enrichment analysis on these core targets. Last, we further investigated our predictions of crucial targets by performing molecular docking studies with components of HWD.Results: The component-target core network of HWD against MetS was screened to contain 22 active components, which corresponded to 77 core targets. Additionally, enrichment analysis suggested that targets of HWD against MetS were mainly clustered into multiple biological processes (response to nutrient levels, gland development, response to steroid hormone, cellular response to oxidative stress, reproductive structure development etc and related pathways (AGE-RAGE, AMPK, JAK-STAT, MAPK), indicating the underlying mechanisms of HWD on MetS. The results of molecular docking showed that beta-sitost, naringenin, berberine and baicalein bound well to IL6 and AKT1.Conclusion: The network pharmacological strategy integrated molecular docking to explore the mechanism of HWD against MetS. Our present outcomes might shed light on the further clinical application of HWD on MetS treatment.
Effective Treatment of a BRAF V600E-Mutant Epithelioid Glioblastoma Patient By Vemurafenib: A Case Report
Authors: Lin Zhiying , Yi Guozhong , Yang Runwei , Li Zhiyong , Zheng Haojie , Zhang Zhu , Peng Junxiang , Zhang Xian , Qi Songtao , Liu Yawei , Huang Guanglong 
Published: November 2020

Abstract
Background: Novel therapeutic targets in epithelioid glioblastoma (E-GBM) patients are urgently needed. About half of these tumors show the point mutations of the B-Raf proto-oncogene (BRAF). Therefore, this is a target of special interest for this group of patients. Meanwhile, unlike conventional glioblastoma, E-GBM lacks specific prognostic markers.Case presentation: We present a case report of a long-term surviving 37-years-old male patient diagnosed with a BRAF V600E-mutated E–GBM with IDH wild-type. The tumor displayed atypical exophytic growth and an obvious proliferation of vascular endothelial cells. Notably, tumor tissue was found under subarachnoid space. After conventional postoperative treatment options (including radiotherapy and temozolomide chemotherapy) were exhausted, vemurafenib treatment was initiated. The patient maintained clinically stable, and follow-up MRI was consistent with stable disease for the following fifteen months up to now. To identify potential therapeutic targets of E-GBM, we carried out whole exome sequencing analysis and RNA-sequence to study the molecular characteristics of this E-GBM sample. The mutant genes were profiled using glioma RNA-sequencing data from Chinese Glioma Genome Atlas (CGGA) database. We found that CNTNAP3, mTOR, NFATC3, and NOM1 shared by DNA-sequence data and RNA-sequence data were independent prognostic factors. Biological function was associated with phenotypes of focal adhesion and cell cycle. A prognostic risk model was constructed based on the mutant genes for predicting the survival of glioma patients. Survival plot and a nomogram was used to verify that our prognostic risk model is reliable and accurate.Conclusions: Our findings provided a new sight on the BRAF inhibitor, in combination with which CNTNAP3, mTOR, NFATC3, and NOM1 inhibitors seem to be a valuable salvage treatment option for E-GBM.
Baseline Evaluation of Bioinformatics Capacity in Tanzania
Authors: Sangeda Raphael Zozimus , Mwakilili Aneth David , Masamu Upendo , Nkya Siana , Mwita Liberata Alexander , Massawe Deogracious Protas , Lyantagaye Sylvester L. , Makani Julie 
Published: November 2020

Abstract
BackgroundEven though the genomics technologies have grown to a large extent, Sub Saharan Africa countries have not entirely reaped the benefits due to the lack of enough capacity to use these technologies. The lack of documentation on existing bioinformatics capacity in these countries hinders the guidance on leveraging the resources and in the identification of areas for improvement. The main objective of this study was to map out the interest and capacity for conducting bioinformatics and related research in Tanzania. Our findings identify critical areas for skills and infrastructure development for bioinformatics research. The study is a cross-sectional, explorative, descriptive study, among Tanzanian researchers in public and private academic and research institutionsResultsOut of 84 respondents, 50 (59.5%) were males. More than half of these 44 (52.4%) were in the age between 26-32 years. The majority 41 (48.8%) were master's degree holders with at least one publication related to bioinformatics. Eighty (95.2%) were willing to join the bioinformatics network and initiative in Tanzania. The major challenge faced by 22 (26.2%) of respondents was the lack of training and skills. The most used resources for bioinformatics analyses were the BLAST, PubMed and GenBank. Most performed analyses include sequence alignment and phylogenetic, which was reported by 57 (67.9%) and 42 (50%) of respondents, respectively. The most frequently used statistical software packages were SPSS and R. A quarter of the respondents were conversant with computer programming.ConclusionEarly career and young scientists were the largest group of responders engaged in bioinformatics research and activities across surveyed institutions in Tanzania. The use of bioinformatics tools for analysis is still low, including basic analysis tools such as BLAST, GenBank, sequence alignment software, Swiss-prot and TrEMBL. There is also poor access to resources and tools for bioinformatics analyses. As a way to address the skills and resources gaps, we recommend various modes of training and capacity building of relevant bioinformatics skills and provision of infrastructure so as to improve bioinformatics capacity in Tanzania.
Migrating Curlews on Schedule: Departure and Arrival Patterns of a Long-distance Migrant Depend on time and Breeding Location Rather than on Wind Conditions
Authors: Schwemmer Philipp , Mercker Moritz , Vanselow Klaus Heinrich , Bocher Pierrick , Garthe Stefan 
Published: November 2020

Abstract
Background: Departure decisions in long-distance migratory bird species may depend on favourable weather conditions and beneficial resources at the destination location, overarched by genetic triggers. However, few studies have tried to validate the significance of these three concepts simultaneously, and long-term, high-resolution tagging datasets recording individual movements across consecutive years are scarce. We used such a dataset to explore intraspecific and intra-individual variabilities in departure and arrival decisions from/to wintering grounds in relation to these three different concepts in bird migration.Methods: We equipped 23 curlews (Numenius arquata) wintering in the Wadden Sea with Global Positioning System data loggers to record their spatio-temporal patterns of departure from and arrival at their wintering site, and the first part of their migration. We obtained data for 42 migrations over 6 years, with 12 individuals performing repeat migrations in consecutive years. Departure and arrival dates were related to 73 meteorological and bird-related predictors using the least absolute shrinkage and selection operator (LASSO) to identify drivers of departure and arrival decisions.Results: Curlews migrated almost exclusively to Arctic and sub-Arctic Russia for breeding. They left their wintering site mainly during the evening from mid- to late April and returned between the end of June and mid-July. There was no difference in departure times between the sexes. Weather parameters did not impact departure decisions; if departure days coincided with headwind conditions, the birds accounted for this by flying at higher altitudes of up to several kilometres. Curlews breeding further away in areas with late snowmelt departed later. Departures dates varied by only <4 days in individual curlews tagged over consecutive years.Conclusions: These results suggest that the trigger for migration in a long-distance migrant is largely independent of weather conditions but is subject to resource availability in breeding areas. The high intra-individual repeatability of departure days among subsequent years and the lack of relationship to weather parameters suggest the importance of genetic triggers in prompting the start of migration. Further insights into the timing of migration in immatures and closely related birds might help to further unravel the genetic mechanisms triggering migration patterns.
Normalization of γ-glutamyl Transferase Levels is Associated with Better Metabolic Control in Individuals with Nonalcoholic Fatty Liver Disease
Authors: Ma Qianqian , Liao Xianhua , Shao Congxiang , Lin Yansong , Wu Tingfeng , Sun Yanhong , Feng Shi-Ting , Ye Junzhao , Zhong Bihui 
Published: November 2020

Abstract
Background: The normalization of liver biochemical parameters usually reflects the histological response to treatment for nonalcoholic fatty liver disease (NAFLD). Researchers have not clearly determined whether different liver enzymes exhibited various metabolic changes during the follow-up of patients with NAFLD.Methods: We conducted a retrospective analysis of patients with NAFLD who were receiving therapy from January 2011 to December 2019. Metabolism indexes, including glucose levels, lipid profiles, uric acid levels and liver biochemical parameters, were measured. Magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) and liver ultrasound were used to evaluate steatosis.Results: Overall, 1048 patients with NAFLD were included and received lifestyle and pharmaceutical interventions, including 637 (60.7%) patients with abnormal GGT levels and 467 (44.6%) patients with abnormal ALT levels. Patients with concurrent ALT and GGT abnormalities presented higher levels of metabolism indexes and higher liver fat contents than patients with single or no abnormalities. After 12 months of follow-up, the cumulative normalization rate of GGT was much lower than that of ALT (33% vs. 52%, P < 0.001). Greater weight loss resulted in higher cumulative normalization rates of GGT and ALT. Weight loss (OR = 1.27, 95%CI: 1.15~1.41, P < 0.001), ALT normalization (OR = 4.32, 95%CI: 1.87~9.96, P = 0.01) and HOMA-IR decreased to normal levels (OR = 3.48, 95%CI: 1.60~7.57, P = 0.01) were independent protective factors for GGT normalization. Elevated baseline GGT (OR = 0.99, 95%CI: 0.98~0.99, P = 0.01), CHOL (OR = 0.47, 95%CI: 0.23~0.96, P = 0.04) and fasting insulin levels (OR = 0.91,95%CI: 0.86~0.96, P = 0.01) were risk factors.Conclusions: For NAFLD patients with concurrently increased ALT and GGT levels, a lower normalization rate of GGT was observed rather than ALT. Good control of weight and insulin resistance was reliable predictors of GGT normalization.
Systematic Review and Meta-analysis:Real-world Data Rates of Deep Remission With Anti-TNFα in Inflammatory Bowel Disease
Authors: Alipour Omeed , Gulati Alakh , Shao Ling , Zhang Bing 
Published: November 2020

Abstract
Background & Aims Deep remission (DR) is a treatment target in IBD associated with reduced hospitalization and improved outcome. Randomized control trial (RCT) data demonstrates efficacy of anti-TNFα agents in achieving DR; however, RCTs may not be generalizable to clinical practice. In this systematic review with meta-analysis, we use real-world data (RWD) to determine rates of DR in IBD treated with anti-TNFα. Methods We completed a systematic search of MEDLINE and EMBASE on July 8, 2019 with review of major gastrointestinal conference abstracts from 2012-2019. Studies utilizing RWD (data not from phase I-III RCTs) of adult IBD patients treated with anti-TNFα agents were included. DR was defined by clinical and endoscopic remission at minimum. DR was assessed at 8 weeks, 6 months, 1 year, and 2 years.Results 29,033 publications were found on initial search. Fifteen publications, nine manuscripts and six conference abstracts, were included encompassing 1,212 patients (769 Crohn’s disease-CD, 443 ulcerative colitis-UC). Rate of DR was 36.4% (95%-CI: 12.6-69.4%) at eight weeks, 39.1% (95%-CI: 10.4-78%) at six months, 44.4% (95%-CI: 34.6-54.6%) at one year, and 36% (95%-CI: 18.7-58%) at two years. DR in CD at one year was 48.6% (95%-CI: 32.8-64.7%) and in UC was 43.6% (95%-CI: 32.8-55.1%).Conclusions The rate of DR was highest after one year of therapy, in nearly 45% of IBD patients treated with anti-TNFα. Similar rates were achieved between patients with UC and CD. The findings highlight the efficacy of anti-TNFα in real-world setting. Future studies using RWD can determine efficacy of newer IBD therapeutics in routine clinical practice.