bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Whole-slide Imaging Based Workflow Reduces the Reading Time of Pathologists
Authors: Baidoshvili Alexi , Kacheishvili Mariam , Laak Jeroen van der , Diest Paul van 
Published: May 2021

Abstract
Aims: Even though entirely digitized microscopic tissue sections (whole slide images) are increasingly being used in histopathology diagnostics, little data is still available on the effect of this technique on pathologists’ reading time. This study aimed to compare the time required to perform microscopic assessment by pathologists between a conventional workflow (using an optical microscope and glass slides) and digitized whole slide images (WSI).Methods: The study was performed in the Laboratory for Pathology Eastern Netherlands (LabPON, Hengelo, The Netherlands), which has been using WSI in primary diagnostics for several years. Cases were either read in a conventional workflow, while the pathologist recorded the time required for diagnostics and reporting or were read using a fully digitized workflow. The digitized workflow was fully integrated with the laboratory information system, and reading times were extracted from the log files of the image management system. Results: Analysis of over 3800 cases showed a time gain in favour of the digital workflow for most case categories, with the highest gain (68% time gain) for prostate biopsies (prostate care program). On average, a gain of 12.3% was found for the digital workflow, taking the case distribution into account. Conclusions: It was concluded that transitioning from conventional microscopy to use of WSI significantly reduces the pathologists’ reading times. A fully integrated pathologist working environment is required to fully benefit from the benefits of a digital workflow.
Inhibition of Rho Kinase by Fasudil Ameliorates Cognition Impairment in APP/PS1 Transgenic Mice via Modulation of Gut Microbiota and Metabolites
Authors: Yan Yuqing , Gao Ye , Fang Qingli , Zhang Nianping , Kumar Gajendra , Yan Hailong , Song Lijuan , Li Jiehui , Zhang Yuna , Sun Jingxian , Wang Jiawei , Zhao Linhu , Skaggs Keith , Zhang Han-Ting , Ma Cun-Gen 
Published: May 2021

Abstract
Background: Fasudil, a Rho kinase inhibitor, exerts therapeutic effects in the mouse model of Alzheimer’s disease (AD), a chronic neurodegenerative disease with progressive loss of memory. However, the mechanisms remain unclear. In addition, the gut microbiota and its metabolites have been implicated in AD. Methods: Here, we examined the effect of fasudil on learning and memory using the Morris water-maze (MWM) test in APPswe/PSEN1dE9 transgenic (APP/PS1) mice (8 months old) treated (i.p.) with fasudil (25 mg/kg/day; ADF) or saline (ADNS) and in age- and gender-matched wild-type (WT) mice. Fecal metagenomics and metabolites were analyzed to identify novel biomarkers of AD and to elucidate the mechanisms whereby fasudil produced beneficial effects in AD mice. Results: Morris water maze test showed significant improvement of spatial memory in APP/PS1 mice treated with fasudil as compared to ADNS. The metagenomic analysis revealed the abundance of the dominant phyla in all the three groups, including Bacteroidetes (23.7% - 44%) and Firmicutes (6.4% - 26.6%), and the increased relative abundance ratio of Firmicutes/Bacteroidetes in ADNS (59.1%) compared to WT (31.7%). In contrast, the Firmicutes/Bacteroidetes ratio was decreased to the WT level in ADF (32.8%). Lefse analysis results of metagenomics showed s_Prevotella_sp_CAG873 as an ADF potential biomarker, while s_Helicobacter_typhlonius and s_Helicobacter_sp_MIT_03-1616 as ADNS potential biomarkers. Metabolite analysis revealed the increment of various metabolites, including glutamate, hypoxanthine, thymine, hexanoyl-CoA, and leukotriene, were relative to ADNS or ADF microbiota potential biomarkers and mainly involved in the metabolism of nucleotide, lipids, sugars, and the inflammatory pathway. Conclusions: Memory deficit in APP/PS1 mice was correlated with the gut microbiome and metabolite status. Fasudil reversed the abnormal gut microbiota and subsequently regulated the related metabolisms to normal in the AD mice. It is believed that fasudil can be a novel strategy for the treatment of AD via remodeling of the gut microbiota and metabolites. The novel results also provide valuable references for the use of gut microbiota and metabolites as diagnostic biomarkers and/or therapeutic targets in clinical studies of AD.
Do We Really Need to Repair the Pronator Quadratus in Volar Plating of Distal Radius Fracture？A Protocol for Systematic Review and Meta Analysis
Authors: Li Qiujiang , Long Xingxia , Wang Yinbin , Wang Zhaofu , Guo Donggeng , Lv Jinhan , Ma Feng , Cai Lijun 
Published: May 2021

Abstract
IntroductionDistal radius fracture is a common type of fracture in clinical practice.Over recent years, Volar locking plate internal fixation remains the most commonly used surgical treatment method in the treatment of distal radius fractures. To better expose the distal radius and fracture segment, the surgeons have to cut the pronator quadratus(PQ) muscle.However, whether the PQ muscle need to be repaired remains controversial. This study aims to provide a plan to evaluate the clinical efficacy whether to repair the PQ muscle in volar plate fixation of distal radius fractures.Methods and analysisWe will search PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI),and Wanfang databases from the beginning to February 2021 to compare clinical outcomes whether to repair the PQ muscle. Quality assessment will be evaluated using the risk of bias tool recommended by the Cochrane Handbook 5.2.0. Subsequently, Revman software version 5.3 will be used for data analysis when a meta-analysis is allowed including subgroup and sensitivity analysis.PROSPERO registration number CRD42020206959
Proteomic Characterization of Primary and Metastatic Prostate Cancer Reveals Reduced Proteinase Activity in Aggressive Tumors
Authors: Li Qing Kay , Chen Jing , Hu Yingwei , Hoti Naseruddin , Thomas Stefani N , Chen Li , Roy Sujayita , Meeker Alan , Shah Punit , Chen Lijun , Bova G. Steven , Zhang Bai , Zhang Hui 
Published: May 2021

Abstract
BackgroundProstate cancer (PCa) is a heterogeneous group of tumors with variable clinical courses. Clinically, it is critical to separate and treat aggressive PCa (AG) from non-aggressive PCa (NAG). Although recent genomic studies have identified a spectrum of molecular abnormalities associated with PCa, it is still challenge to separate AG from NAG. To better understand the functional consequence of PCa progression and the unique features of AG from NAG, we studied proteomic signatures of primary AG, NAG and metastatic PCa.Methodes39 PCa and 10 benign prostate controls in discovery cohort and 57 PCa in independent-collected validation cohort were analyzed using data-independent acquisition (DIA) SWATH–MS platform. Proteins with the highest variances (top 500 proteins) were annotated for the pathway enrichment analysis. Functional analysis of differentially expressed proteins in NAG and AG was performed. Data was further validated using validation cohort, as well as by comparison with TCGA mRNA expression and immnunochemistry on PCa tissue microarray (TMA).Results4,415 proteins were identified in the tumor and benign control tissues, including 158 up-regulated and 116 down-regulated proteins in AG tumors. A functional analysis of tumor-associated proteins revealed the reduced expression of several proteinases, including dipeptidyl peptidase 4 (DPP4), carboxypeptidase E (CPE) and prostate specific antigen (KLK3) in AG and metastatic PCa. A targeted analysis using SWATH data further identified that the reduced expression of DPP4 was associated with the accumulation of DPP4 substrates in AG tumors, including the reduced ratio of DPP4 cleaved peptide to intact substrate peptide. Findings were further validated using independent-collected cohort, by comparison with TCGA mRNA data, and the immunochemical stains of our tumor microarray (TMA).ConclusionsOur study is the first large-scale proteomics analysis of PCa tissue using DIA SWATH-MS platform. It not only provides an interrogative proteomic signature of PCa subtypes, but also indicates critical roles of certain proteinases, especially DPP4, in PCa progression. The spectrum map and protein profile generated in the study can be used to investigate potential biological mechanisms involved in the PCa progression as well as for the development of a clinical assay to distinguish aggressive from indolent PCa.
Knowledge, Attitude, and Awareness of Health Insurance in Travel during the Covid-19 Pandemics
Authors: Yang Chia-Jung , Lu Chia-Wen , Chiang Chien-Hsieh , Chang Hao-Hsiang , Yao Chien-An , Huang Kuo-Chin 
Published: May 2021

Abstract
Background

Travel has become one of the most popular leisure activities in the world, especially international traveling. The risk of accident and travel related illness including infectious and non-communicable diseases should not be neglected. To provide more comprehensive pre-travel consultation to the international travelers, we aimed to investigate the knowledge, attitude, and awareness of travel health insurance for travelers.
Methods

Anonymous structured questionnaires were distributed to 1,000 visitors of the Taiwan International Travel Fair in May 2019.
Results

The top three kinds of travel health insurance were accidental death and disablement insurance (92%), accidental medical reimbursement (90.4%) and 24 hours of emergency assistance (89%). In addition to education level, travel-associated illness, and special activities during travel, a significant association was observed between the willingness to buy various travel insurance and willingness of pre-travel consultation.
Conclusions

Although most travelers would buy travel health insurance, disproportional respondents understood the content of travel insurance. Most travelers considered travel clinics to be the most reliable information resources of travel insurance. Therefore, travel specialists are encouraged to offer more information about travel insurance during pre-travel consultation, especially during the COVID-19 pandemic.
Insights Into the Diversity of Terrestrial Soil Bacterial Communities Associated With Four Contrasting Köppen Climatic Zones.
Authors: Nair Girish R , Raja Suresh S.S. 
Published: May 2021

Abstract
Background: The multidirectional relationship between soil, its microbiota, and climate is crucial in modulating the bacterial community diversity and its survival in the terrestrial ecosystem. Therefore, it is imperative to understand the dynamics of soil bacterial communities thriving in geographical areas of varied climatic exposure. Results: The diversity of terrestrial soil bacterial communities thriving in four contrasting Köppen climatic zones of India was investigated for the first time using high-throughput sequencing. The results revealed that the bacterial species diversity, evenness and richness were highest in HSCZ (humid subtropical climatic zone). Firmicutes was the most abundant phylum in TWCZ (tropical wet climatic zone), ACZ (arid climatic zone), and HSCZ (humid subtropical climatic zone) while Proteobacteria in MCZ (Mountain climatic zone). The predominance of class Alphaproteobacteria, Actinobacteria with genera Bradyrhizobium, Chthoniobacter, and Mycobacterium, was observed in MCZ in contrast to class Bacilli with genera Bacillus and Paenibacillus in the rest of the zones. Correlation analysis showed that H’ (Shannon diversity) index, S (species richness), OTU abundance were positively correlated with moisture, TOC, K, MAP (mean annual precipitation) and negatively correlated with pH, Ca, N, B. Fe, P, Mg and MAT (mean annual temperature). Conclusion: This work mapped the occurrence and distribution of terrestrial soil bacterial communities in contrasting climatic zones that enabled us to assess the effect of climate in mentioned Köppen climatic zones on a taxonomic scale.
Emergence of SARS-CoV-2 Spike Escape Mutation Q493R After Bamlanivimab/Etesevimab Treatment for COVID-19
Authors: Focosi Daniele , Novazzi Federica , Genoni Angelo , Dentali Francesco , gasperina Daniela Dalla , Baj Andreina , Maggi Fabrizio 
Published: May 2021

Abstract
We report here the first in vivo selection of a Spike mutation (Q493R) conferring simultaneoius full resistance to both bamlanivimab and etesivimab.
Delay to initiate treatment is associated with unsuccessful treatment outcome among new pulmonary tuberculosis patients in Tigray, Northern Ethiopia: a follow up study
Authors: Tedla kiros , Medhin Girmay , Berhe Gebretsadik , Mulugeta Afework , Berhe Nega 
Published: May 2021

Abstract
Background : Previous studies in Ethiopia indicated that tuberculosis (TB) patient’s elapse long time before treatment initiation. However, there is very limited evidence on the association of delay to initiate treatment with treatment outcome.
Objective : To investigate the association of time to treatment initiation delay with treatment outcomes of new adult TB patients in Tigray region of Ethiopia.
Methods : We conducted a follow up study from October 2018 to April 2020 by recruiting 875 newly diagnosed Pulmonary Tuberculosis (PTB) patients from 21 randomly selected health facilities. Study participants were selected using simple random sampling technique during treatment initiation from October 1/2018 to October 30/2019. Delay to initiate treatment and treatment outcome were collected using standardized questionnaire and laboratory investigation. Adherence of TB patients to their treatment was collected using a 10 points linear visual analogue scale (VAS) at the end of treatment. The association of delay to initiate treatment with treatment outcome was modeled using log binomial regression model. Statistical significance was reported whenever p-value was less than 0.05. Data was analyzed using SPSS software version 21.
Result : The median total delay to treatment initiation was 62 days with inter-quartile range of 16-221 days. A unite increase in a day to initiate treatment results in increment of risk of unsuccessful treatment outcome by 2.3. Other factors associated with unsuccessful treatment outcomes were being less adherent to the treatment, HIV co infection, being smear positive at initiation of treatment and after 2 months of treatment initiation.
Conclusion : delay in a day to initiate treatment is associated with increased risk of unsuccessful treatment outcome. Any effort targeted towards reducing the negative effects of PTB should target on strategies that reduces the length of delay to initiate treatment and strengthen community engagement to improve treatment adherence of patients that have started treatment.
Investigation of the Role of Crown Crack in Cohesive Soil Slope and Its Effect on Slope Stability Based on Extended Finite Element Method
Authors: Bao Yiding , Li Yuchao , Zhang Yansong , Yan Jianhua , Zhou Xin 
Published: May 2021

Abstract
Tensile cracks in soil slopes, especially developing at the crown, have been increasingly recognized as the signal of slope metastability. In this paper, the role of crown cracks in natural soil slopes was investigated and their effect on stability was studied. A numerical slope model based on the extended finite element method (XFEM) simulating the tensile behavior of soil was used. Before the simulation, a numerical soil tensile test was applied to validate the use of XFEM on tensile behavior of soil. Slope failure was simulated by using strength reduction technique, which can determine the potential slip surface of slope. The simulation results show that the crown crack forms in natural soil slopes when the plastic zone starts penetrating, and therefore it is reasonable to consider the crown crack as the signal of slope metastability. A sensitivity analysis shows that cracks are at the position of the tension zone or very long can obviously affect the slope stability. The stress variation analysis from the initial deformation to slip surface penetration shows that the slope is at a state of compressive stress initially. When plastic zone starts to penetrate, the upper part of slope generates tension zone, but the extent of tension zone is limited until slope failure. This shows why tensile cracks are difficult to form and be stretched in the deep part of the slope. The application of XFEM on slope stability analysis can be used to assess the tensile strength of soil and predict slope failure disaster.
IGF- I induced growth and metatasis suppressed by calycosin via STAT3/ BATF2/ NF-κB /FOXM1 in colorectal cancer cells
Authors: Wang Qun , Lu Weijun , Lu Li , Pi Guoliang , De Wu Dong , Wei Shaozhong 
Published: May 2021

Abstract
To determine whether up-regulation of BATF2 by calycosin suppresses IGF- I induced growth and metastasis in human CRC,Cells were cultured and treated with calycosin and IGF-I. Protein and mRNA levels were determined by western-blot and real-time PCR respectively. Cell migration and invasion were assessed by transwell experiments. Apoptosis was measured by Flow cytometry. Cell proliferation was evaluated by the MTT assay.Co-immunoprecipitation and luciferase assays were used to analyze the interaction between BATF2 and MAT2Aand FOXM1.Cytoimmunofluorescence staining was applied for β-catenin and FOXM1 cellular localization.As results,Calycosin induced the up-regulation of BATF2 antagonized by IGF- I via STAT3, STAT1and NF-κB pathways resulting in cell apoptosis promotion via increasing BAX/Bcl-2 ratio subsequent contribute to caspase-3 and caspase-9 release. IGF- I induced cell migration,invasion and EMT suppressed by calycosin via BATF2 to block FOXM1 mediated β-catenin nuclear accumulation in three CRC cells. IGF- I induced cell proliferation was inhibited by calycosin down-regulating MAT2A and FOXM1. IGF-I and calycosin impacted MAT2A on transcriptional level. BATF2 interated with MAT2A and FOXM1 directly.We believed up-regulation of BATF2 may be a practicable treatment strategy for suppression IGF-1 induced growth and metatasis in CRC.
Full-length Genome of the Ogataea polymorpha strain HU-11 reveals large duplicated segments in subtelomeric regions
Authors: Chang jia , Bei Jinlong , Wang Hemu , Yang Jun , Li Xin , Yau Tung On , Bu Wenjun , Ruan Jishou , Duan Guangyou , Gao Shan 
Published: May 2021

Abstract
Background: Currently, methylotrophic yeasts (e.g., Pichia pastoris, Hansenula polymorpha, and Candida boindii) are subjects of intense genomics studies in basic research and industrial applications. In the genus Ogataea, most research is focused on three basic O. polymorpha strains—CBS4732, NCYC495, and DL-1. However, these three strains are of independent origin and unclear relationship. As a high-yield engineered O. polymorpha strain, HU-11 can be regarded as identical to CBS4732, because the only difference between them is a 5-bp insertion. Results: In the present study, we have assembled the full-length genome of O. polymorpha HU-11 using high-depth PacBio and Illumina data. Long terminal repeat (LTR) retrotransposons, rDNA, 5' and 3' telomeric, subtelomeric, low complexity and other repeat regions were curated to improve the genome quality. We took advantage of the full-length HU-11 genome sequence for the genome annotation and comparison. Particularly, we determined the exact location of the rDNA genes and LTR retrotransposons in seven chromosomes and detected large duplicated segments in the subtelomeric regions. Three novel findings are: (1) O. polymorpha NCYC495 is so phylogenetically close to CBS4732/HU-11 that the syntenic regions covers nearly 100% of their genomes with a nucleotide identity of 99.5%, while NCYC495 is significantly distinct from DL-1; (2) large segment duplication in subtelomeric regions is the main reason for genome expansion in yeasts; and (3) the duplicated segments in subtelomeric regions may be integrated at telomeric tandem repeats (TRs) through a molecular mechanism, which can be used to develop a simple and highly efficient genome editing system to integrate or cleave large segments into yeast genomes. Conclusions: Our findings provide new opportunities for in-depth understanding of genome evolution in methylotrophic yeasts and lay the foundations for the industrial applications of O. polymorpha HU-11 and CBS4732. The full-length genome of the O. polymorpha strain HU-11 should be included into the NCBI RefSeq database for future studies of O. polymorpha CBS4732, NCYC495, and their derivative strains.
The effects of estimated remnant-like particle cholesterol on incident cardiovascular disease: Insights from a general Chinese population
Authors: Chen Yanli , Li Guangxiao , Guo Xiaofan , Ouyang Nanxiang , Li Zhao , Ye Ning , Yu Shasha , Yang Hongmei , Sun Yingxian 
Published: May 2021

Abstract
Background

Growing evidence suggests that remnant cholesterol (RC) may contribute to residual atherosclerotic cardiovascular disease (ASCVD) risk. But the cut-off point to treat RC for reducing ASCVD is still not known. This study was aimed to investigate the relationships between RC and combined cardiovascular diseases (CVDs) in a general China cohort, with 11,956 subjects aged ≥ 35 years.
Methods

Baseline RC was estimated with the Friedewald formula for 8782 subjects. The outcome was the incidence of combined CVD, including fatal and nonfatal stroke and coronary heart disease (CHD). Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals. Restricted cubic spline model was used to evaluate dose-response relationship between continuous RC and the natural log of HRs.
Results

After a mean follow-up of 4.66 years, 431 CVD events occurred. In the cox proportional models, participants with high level of categorial RC had significantly higher risk for combined CVD (HR: 1.37; 95% CI: 1.07–1.74) and CHD (HR: 1.63; 95% CI: 1.06–2.53), compared to those with medium level of RC. In the stratification analyses, high level of RC significantly increased combined CVD risk for subgroups females, age < 65years, non-current smokers, non-current drinkers, normal weight, renal dysfunction, and no hyperuricemia. Same trends were found for CHD among subgroups males, age < 65 years, overweight, renal dysfunction, and normal uric acid; stroke for subgroup females. In the restricted cubic spline models, significantly linear association between RC and combined CVD and non-linear association between RC and CHD were shown. The risk of outcomes was relatively flat until 0.84mmol/l of RC and increased rapidly afterwards, with HR of 1.308 (1.102 to 1.553) for combined CVD and 1.411 (1.061 to 1.876) for CHD. Stratified analyses showed significant nonlinearity association between RC and CVD outcomes in subgroup aged < 65 years or subgroup diabetes.
Conclusions

In this large-scale and long-term follow-up cohort study, participants with higher RC levels had significantly worse prognosis, especially for subgroup aged 35–65 years or subgroup diabetes mellitus.