bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Clinical Outcomes in Patients With Localized or Locally Advanced Urothelial Carcinoma Treated With Neoadjuvant Chemotherapy Involving Gemcitabine-Cisplatin and High Dose-Intensity MVAC
Authors: Lee Yongjune , Kim Young Seok , Hong Bumsik , Cho Yong Mee , Lee Jae-Lyun 
Published: February 2021

Abstract
PurposeTo compare the efficacy and safety of high dose-intensity combination of methotrexate, vinblastine, adriamycin and cisplatin (HD MVAC) with gemcitabine plus cisplatin (GC) as a neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) or locally advanced upper tract urothelial cancer (UTUC). Patients and MethodsA retrospective analysis was conducted for patients with UC (cT2-4aN0-1M0) who received NAC from January 2011 and December 2017 at Asan Medical Center. Pathologic complete response (pCR), down-staging (<ypT2 and no N upstaging), disease-free survival (DFS), OS and safety were compared for each regimen. ResultsOut of a total of 277 patients, 176 patients received GC and 41 patients received HD MVAC. With the exception of age (patients receiving GC were younger; p=0.002), other baseline characteristics were well balanced between groups. pCR rates were 27.0% for GC and 22.6% for HD MVAC (p=0.62), and down-staging rate was 50.8% for GC and 58.1% for HD MVAC (p=0.47). There were no differences in OS (72.1% vs 73.1% for GC vs HD MVAC; p=0.58) and DFS (54.9% vs 63.3% for GC vs HD MVAC; p=0.21) at 3 years. HD MVAC with prophylactic G-CSF was associated with a higher incidence of febrile neutropenia (p<0.001) than GC. The NAC regimen was not an independent prognostic factor for OS. ConclusionsOncologic outcomes were not significantly different between the GC and HD MVAC when used as NAC in MIBC/UTUC.
Multioutput Flyback DC-DC Converter for MIL Applications
Authors: Patil Sukumar , CV Bhanuprakash , Singh Bhoopendrakumar 
Published: February 2021

Abstract
This paperwork explains the design and development of isolated triple output dc-dc converter for military applications. Converter has designed with flyback topology with opto-coupler based feedback for regulated main output and regulators are used to provide another two outputs. It is realized with switching frequency of 190KHz (internal free run frequency) and can be able to operate up to 210KHz with external synchronization. LTM46xx micro-modules are used as buck regulators to provide required lower output voltages. Current mode pulse width modulation controller IC is used to drive the MOSFET switch. It has following features like inbuilt EMI filter, external inhibit function, external synchronization capability, input under voltage and over voltage protection, primary side over current, output over current and short circuit protection. Converter is designed to operate for wide input range from 18V to 36V with efficiency of more than 75% in full load conditions.
Changes in Water-Soluble Nitrogen and Organic Carbon in the Post-Fire Litter Layer of Dahurian Larch Forests
Authors: Weng Yuetai , Yang Guang , Wang Lixuan , Quan Xiankui , Di Xueying , Yu Hongzhou , Han Dongdong 
Published: February 2021

Abstract
Background and aimBoreal forests account for one third of terrestrial carbon stock. Wildfires are an important perturbation of this carbon pool, affecting in particular the litter layer. After forest fires, the litter layers may possess shifting chemical property and decomposition dynamics due to the changes in post-fire vegetations succession and abiotic factors.MethodsWe measured water-soluble organic carbon (WSOC) and water-soluble nitrogen (WSN) in the litter layers of Oi and Oe horizons in boreal forests along a gradient of fire history in northeastern China. ResultsWe found that WSOC and WSN concentrations in the Oi layer were higher than those in the Oe layer. The concentrations were markedly altered by fires and showed different responses to the ecological succession. The time since fire had significant positive correlations with WSOC in Oi and Oe layers. The distance-based redundancy analysis and the structural equation model analysis suggested that factors additional to the time since fire also influenced the litter water-soluble matter (WSM) properties. Biotic factors were more strongly correlated with the litter WSM properties in the Oe layer than in the Oi layer. Although biotic factors contributed less than abiotic factors to the WSM properties, they still play significant roles in litter WSM in burned area. ConclusionsOur results show that manipulating biotic factors can be an important management strategy for litter WSM restoration, which can assist the overall ecological restoration in burned forests faced with the increasing danger of wildfires in the changing global climate.
The Protective A673T mutation of Amyloid precursor protein (APP) in Alzheimer’s disease
Authors: Xia Qing , Yang XinYu , Shi JiaBin , Liu ZiJie , Peng YaHui , Wang WenJing , Li BoWen , Zhao Yu , Xiao JiaYing , Huang Lei , Wang DaYong , Gao Xu 
Published: February 2021

Abstract
Alzheimer's Disease is a progressive neurodegenerative disorder characterized by extracellular amyloid beta peptides, and neurofibrillary tangles consisted of intracellular hyperphosphorylated Tau in the hippocampus and cerebral cortex. Most of the mutations in key genes that code for amyloid precursor protein can lead to significant accumulation of these peptides in the brain and cause Alzheimer's Disease. Moreover, Some point mutations in amyloid precursor protein can cause familial Alzheimer's Disease, such as Swedish mutation and A673V mutation. However, recent studies have found that the A673T mutation in amyloid precursor protein gene can protect against Alzheimer's Disease, even it is located next to the Swedish mutation and at the same site as A673V mutation, which are pathogenic. It makes us curious about the protective A673T mutation. Here, we summarize the most recent insights of A673T mutation, focus on their roles in protective mechanisms against Alzheimer's Disease, and discuss their involvement in future treatment.
Tertiary Gleason Pattern 5 is An Independent Risk Factor for Prostate Cancer with GS 7: A Retrospective Study from China.
Authors: Cai Desheng , Wang Zixin , Fan Yu , Cai Lin , Gong Kan 
Published: February 2021

Abstract
Background: Tertiary Gleason pattern 5 (TGP5) was found to be prognostic in prostate cancer (PCa) after radical prostatectomy (RP), but related data from China was rare. Our study was aimed at finding out the effect of TGP5 on PCa with Gleason score (GS) 7 and supplementing data from China in this field.Methods: A total of 229 cases met with inclusion criteria during Jan. 2014 to Dec. 2018 were reviewed. Cases were divided into GS 7 without TGP5 and GS 7 with TGP5. We compared age at diagnosis, preoperative PSA level, prostate volume, PSA density (PSAD), GS variation, clinical T staging, pathological T staging, T staging variation, extra-prostatic extension (EPE), positive surgical margin (PSM) and seminal vesicle invasion (SVI) between the groups. Effects of TGP5 on prognosis of PCa with GS 7 were evaluated using biochemical recurrence (BCR) as the primary end point.Results: TGP5 was related to higher PSM rate (P=0.001) and BCR rate (P=0.009) but not related to higher preoperative PSA level, larger prostate volume, higher PSAD, GS upgrade, poorer clinical/pathological T staging, T upstaging, EPE and SVI (all P>0.05). The median follow-up time was 24 months (interquartile range 17.5-45.5). TGP5 was an independent risk factor to PCa with GS 7 after RP using Kaplan-Meier log-rank test (P=0.018). Both univariable and multivariable cox-regression analysis pointed out that TGP5 increased the incidence of BCR in PCa with GS 7 (P<0.05). Stratified analyses were also done.Conclusion: TGP5 is an independent risk factor predicting of BCR after RP in PCa with GS 7 from China. TGP5 is related to higher PSM rate and BCR incidence. It is time to renew the contemporary Grading Group system with the consideration of TGP.
Identification and Clinical Characteristics Analysis of HNF-1A Mutations p.I27L, p.S487N and p.G574S in Chinese Patients with MODY3
Authors: Long Rong , Yu Chen-Xi , Yang Hui-Jun , Zhou Tai-Cheng , Yang Lei , Zhou Yuan-Yuan , Liang Hua-Su , Yang Ying , Yang Ke 
Published: February 2021

Abstract
Background: Due to the rarity, the type 3 of maturity-onset diabetes of the young (MODY3) has not been explored comprehensively. The study aimed to describe and analyze the molecular and clinical characteristics of MODY3, which could help physicians understand the subtype of diabetes and increase the diagnosis rates in the future.Methods: Ten unrelated patients with suspected maturity-onset diabetes of the young (MODY) were included in the study based on information on family history and onset age. Sanger sequencing was used to identify cases with mutations in the hepatic nuclear factor 1A gene (HNF-1A). Results: Five patients were identified with MODY3, three cases (60%) with p.I27L mutation, one case (20%) with p.S487N mutation, and one case (20%) with p.G574S mutation. The average onset age was (23.00±3.00) years and the average age of diagnosis was (28.67±9.29) years. Most patients had typical clinical symptoms (polydipsia, polyuria, polyphagia, and weight loss). The main complications included diabetic ketoacidosis (DKA, 3/5,60%), diabetic macroangiopathy (2/5,40%), diabetic peripheral neuropathy (DPN,3/5,60%), diabetic nephropathy (DN,1/5,20%) and diabetic retinopathy (DR,1/5,20%). Four patients (80%) had fatty liver. The average body mass index (BMI) (26.39±4.67) kg/㎡, triglyceride (TG 2.95±1.43 mmol/L) and low-density lipoprotein (LDL-C 3.37±0.65 mmol/L) were beyond normal value. The glycosylated hemoglobin A1c (HbA1c 12.45±4.60 %), fasting plasma glucose (FPG 10.10±3.57 mmol/L) and postprandial plasma glucose (PPG 21.88±2.53 mmol/L) also increased dramatically. In addition, islet function examination revealed impaired secretion and slightly poor reserve function, which was similar to the changes inT2DM. All five patients used insulin, three (60%) also using antidiabetic drugs which did not include sulfonylureas.Conclusions: In brief, five patients were identified with MODY3. The mutation site could influence the onset age, the islet function and the incidence of complications. The age at diagnosis was 4.2 years later than the onset age. The control of diabetes was poor due to the inappropriate treatment. It is vital to make an early diagnosis and provide appropriate treatment for MODY3 patients.
A Protocol for a Systematic Review of the Effectiveness of Interprofessional Education Interventions in Pre-Licensure Health Professions Education
Authors: Azzam Mohammad , Puvirajah Anton 
Published: February 2021

Abstract
Background: A growing body of research demonstrates that interprofessional education (IPE) has the potential to lead to successful interprofessional collaborative practice (IPCP). In turn, IPCP has potential to mitigate the negative effects associated with an underfunded and shrinking healthcare workforce and population growth. Nonetheless, over the past decade, there has been a lack of systematic reviews that have examined the effectiveness of IPE in preparing pre-licensure health professions students for IPCP. The purpose of this paper is to provide a protocol for a systematic review that will explore and identify (1) whether IPE interventions in the past decade have addressed the shortcomings of past interventions, (2) the effectiveness of recent IPE in preparing students for IPCP, and (3) current knowledge gaps within the field. Methods: We used the Cochrane Collaboration and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines to articulate this protocol. Furthermore, we used the Population, Intervention, Comparison, Outcomes, and Study Design (PICOS) framework to formulate our research questions, “What are the major trends and findings of IPE implementation studies conducted over the last decade (2010–2020)?” and “How do the trends and findings of IPE studies conducted over the last decade compare with IPE studies in the decade prior?” Discussion: The systematic review is ongoing. We expect to complete it by September 2021. This systematic review will provide a useful synthesis of best practices in the implementation of IPE between 2010 and 2020 as well as their effectiveness in preparing health professions students for IPCP. Systematic review registration: We submitted this protocol with PROSPERO on January 19th, 2021.
LA reservoir Strain: A Sensitive Parameter for Estimating LV Filling Pressure in Patients with Preserved EF
Authors: Tan Turkan Seda , Akbulut Irem Muge , Demirtola Ayse Irem , Serifler Nazli Turan , Ozyuncu Nil , Esenboga Kerim , Kurklu Haci Ali , Kozluca Volkan , Ongun Aydan , Uludag Demet Menekse Gerede , Tutar Eralp , Dincer Irem 
Published: February 2021

Abstract
Aims: An elevated left ventricular (LV) filling pressure is the main finding in patients with heart failure with preserved ejection fraction, which is estimated with an algorithm by the recent ASE/EACVI guideline. In this study, we sought to determine the efficacy of the LA global longitudinal strain to estimate the elevated LV filling pressure. Methods and Results: Consecutive patients who underwent left ventricular catheterization between January 2016 and December 2018 were included. Transthoracic echocardiography was performed within 24hrs before the catheterization. The LV filling pressure was estimated using echo parameters based on the 2016 ASE/EACVI algorithm. Moreover, to evaluate left atrial function, the LA GLS was measured using 2D speckle tracking echocardiography on four chamber-view (GE, Vivid E9 USA). Invasive LV pre-A pressure corresponding to mean left atrial pressure (LAP) was used as a reference, and >12 mm Hg was defined as elevated.71 patients (mean age of 63.2±9.75, 70.4% male) underwent left heart catheterization. Invasive LV filling pressure was defined as elevated in 41 (57.8%) and normal in 30 patients (42.2%). 9(12.7%) patients of 71 were defined as indeterminate based on the 2016 algorithm. Using the ROC method, the accuracy of the algorithm was found as AUC:0.75 with 77% specificity and 70% sensitivity. The accuracy of 25.5 % cut point of LASr was found as AUC:0.79 with 77% specificity and 80% sensitivity for estimating LAP.Conclusions: LASr with higher sensitivity may add an incremental value to estimate LV filling pressure, and hence may be used for HFpEF diagnosis.
HIV-1 Vpr activates host CRL4-DCAF1 E3 ligase to degrade histone deacetylase SIRT7
Authors: Zhou Xiaohong , Monnie Christina , Delucia Maria , Ahn Jinwoo 
Published: February 2021

Abstract
Background: Vpr is a virion-associated protein that is encoded by lentiviruses and serves to counteract intrinsic immunity factors that restrict infection. HIV-1 Vpr mediates proteasome-dependent degradation of several DNA repair/modification proteins. Mechanistically, Vpr directly recruits cellular targets onto DCAF1, a substrate receptor of Cullin 4 RING E3 ubiquitin ligase (CRL4) for poly-ubiquitination. Further, Vpr can mediate poly-ubiquitination of DCAF1-interacting proteins by the CRL4. Because Vpr-mediated degradation of its known targets can not explain the primary cell-cycle arrest phenotype that Vpr expression induces, we surveyed the literature for DNA-repair-associated proteins that interact with the CRL4-DCAF1. One such protein is SIRT7, a deacetylase of histone 3 that belongs to the Sirtuin family and regulates a wide range of cellular processes. We wondered whether Vpr can mediate degradation of SIRT7 via the CRL4-DCAF1.Methods: HEK293T cells were transfected with cocktails of plasmids expressing DCAF1, DDB1, SIRT7 and Vpr. Ectopic and endogeneous levels of SIRT7 were monitered by immunoblotting and protein-protein interactions were assessed by immunoprecipitation. For in vitro reconstitution assays, recombinant CRL4-DCAF1-Vpr complexes and SIRT7 were prepared and poly-ubiqutination of SIRT7 was monitored with immunoblotting. Results: We demonstrate SIRT7 polyubiquitination and degradation upon Vpr expression. Specifically, SIRT7 is shown to interact with the CRL4-DCAF1 complex, and expression of Vpr in HEK293T cells results in SIRT7 degradation, which is partially rescued by CRL inhibitor MNL4924 and proteasome inhibitor MG132. Further, in vitro reconstitution assays show that Vpr induces poly-ubiquitination of SIRT7 by the CRL4-DCAF1. Importantly, we find that Vpr from several different HIV-1 strains, but not HIV-2 strains, mediates SIRT7 poly-ubiquitination in the reconstitution assay and degradation in cells. Finally, we show that SIRT7 degradation by Vpr is independent of the known, distinctive phenotype of Vpr-induced cell cycle arrest at the G2 phase,Conclusions: Targeting histone deacetylase SIRT7 for degradation is a conserved feature of HIV-1 Vpr. Altogether, our findings reveal that HIV-1 Vpr mediates down-regulation of SIRT7 by a mechanism that does not involve novel target recruitment to the CRL4-DCAF1 but instead involves regulation of the E3 ligase activity.
Community Intervention for Child Tuberculosis Active Contact Investigation and Management: study protocol for a parallel cluster randomized controlled trial
Authors: Vasiliu Anca , Eymard-Duvernay Sabrina , Tchounga Boris , Atwine Daniel , de Carvalho Elisabete , Ouedraogo Sayouba , Kakinda Michael , Tchendjou Patrice , Turyahabwe Stavia , Kuate Albert Kuate , Tiendrebeogo Georges , Dodd Peter J , Graham Stephen M , Cohn Jennifer , Casenghi Martina , Bonnet Maryline 
Published: February 2021

Abstract
Background: There are major gaps in the management of pediatric tuberculosis (TB) contact investigation for rapid identification of active tuberculosis and initiation of preventive therapy. This study aims to evaluate the impact of a community-based intervention as compared to facility-based model for the management of children in contact with bacteriologically confirmed pulmonary TB adults in low-resource high-burden settings.Methods/design: This multicenter parallel open label cluster-randomized controlled trial is composed of three phases: I, baseline phase in which retrospective data are collected, quality of data recording in facility registers is checked and expected acceptability and feasibility of the intervention is assessed; II, intervention phase with enrolment of index cases and contact cases in either facility- or community based models; and III, explanatory phase including endpoint data analysis, cost effectiveness analysis and post-intervention acceptability assessment by heath care providers and beneficiaries. The study uses both quantitative and qualitative analysis methods. The community-based intervention includes identification and screening of all household contacts, referral of contact with TB-suggestive symptoms to the facility for investigation, and household initiation of preventive therapy with follow-up of eligible child contacts by community healthcare workers, i.e. all young (<5 years) child contacts or older (5-14 years) child contacts living with HIV, and with no evidence of TB disease. Twenty clusters representing TB diagnostic and treatment facilities with their catchment areas are randomized in a 1:1 ratio to either the community-based intervention arm or the facility-based standard of care arm in Cameroon and Uganda. Randomization was stratified by country and constrained on the number of index cases per cluster. The primary endpoint is the proportion of eligible child contacts who initiate and complete the preventive therapy. The sample size is of 1500 child contacts to identify a 10% difference between the arms with the assumption that 60% of children will complete the preventive therapy in the standard of care arm.Discussion: This study will provide evidence of the impact of a community-based intervention on household child contact screening, and management of TB preventive therapy in order to improve care and prevention of childhood TB in high low resource high-burden settings.
Metatranscriptomic analysis of functional response of colonic microbiota to different dietary fibers in growing pigs
Authors: Xu Jie , Xu Rongying , Jia Menglan , Su Yong , Zhu Weiyun 
Published: February 2021

Abstract
BackgroundDietary fibers are widely considered to be beneficial to health as they produce nutrients through gut microbial fermentation while facilitating weight management and boosting gut health. To date, the gene expression profiles of the carbohydrate active enzymes (CAZymes) that respond to different types of fibers (raw potato starch, RPS; inulin, INU; pectin, PEC) in the gut microbes of pigs are not well understood. Therefore, we investigated the functional response of colonic microbiota to different dietary fibers in pigs through metatranscriptomic analysis.ResultsThe results showed that the microbial composition and CAZyme structure of the three experimental groups changed significantly compared with the control group (CON). Based on a comparative analysis with the control diet, RPS increased the abundance of Parabacteroides, Ruminococcus, Faecalibacterium and Alloprevotella but decreased Sutterella; INU increased the relative abundance of Fusobacterium and Rhodococcus but decreased Bacillus; and PEC increased the relative abundance of the Streptococcus and Bacteroidetes groups but decreased Clostridium, Clostridioides, Intestinibacter, Gemmiger, Muribaculum and Vibrio. The gene expression of CAZymes GH8, GH14, GH24, GH38, GT14, GT31, GT77 and GT91 downregulated but that of GH77, GH97, GT3, GT10 and GT27 upregulated in the RPS diet group; the gene expression of AA4, AA7, GH14, GH15, GH24, GH26, GH27, GH38, GH101, GT26, GT27 and GT38 downregulated in the INU group; and the gene expression of PL4, AA1, GT32, GH18, GH37, GH101 and GH112 downregulated but that of CE14, AA3, AA12, GH5, GH102 and GH103 upregulated in the PEC group. Compared with the RPS and INU groups, the composition of colonic microbiota in the PEC group exhibited more diverse changes with the variation of CAZymes and Streptococcus as the main contributor to CBM61, which greatly promoted the digestion of pectin.ConclusionThe results of this exploratory study provided a comprehensive overview of the effects of different fibers on nutrient digestibility, gut microbiota and CAZymes in pig colon, which will furnish new insights into the impacts of the use of dietary fibers on animal and human health.