bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling the β secretase cleavage site and humanizing Amyloid-Beta Precursor Protein in rat and mouse to study Alzheimer Disease.
Authors: Serneels Lutgarde , T'Syen Dries , Perez-Benito Laura , Theys Tom , De Strooper Bart 
Published: June 2020

Abstract
Background Three amino acid differences between rodent and human APP affect medically important features including β-secretase cleavage of APP and aggregation of the Aβ peptide(1–3). Most rodent models for Alzheimer’s disease (AD) are therefore based on the human APP sequence expressed from artificial mini-genes randomly inserted in the rodent genome. While these models mimic rather well biochemical aspects of the disease such as Aβ-aggregation, they are also prone to overexpression artifacts and to complex phenotypical alterations due to genes affected in or close to the insertion sites of the mini-genes(4,5). Knock-in strategies introducing clinical mutants in a humanized endogenous rodent APP sequence(6) represent useful improvements, but need to be compared with appropriate humanized wild type (WT) mice.Methods Computational modelling of the human β-CTF bound to BACE1 was used to study the differential processing of rodent and human APP. We humanized the three pivotal residues G676R, F681Y and R684H (labeled according to the human APP770 isoform) in the mouse as well as in the rat by a CRISPR-Cas9 approach. These new models, termed mouse and rat App hu/hu , express APP from the endogenous promotor. We also introduced the early-onset familial Alzheimer’s disease (FAD) mutation M139T into the endogenous Rat Psen 1 gene.Results We show that the three amino acid substitutions in the rodent sequence lower the affinity of APP substrate for BACE1 cleavage. The effect on β-secretase processing was confirmed as both humanized rodent models produce three times more (human) Aβ compared to their WT rodent original strain. These models represent suitable controls or starting points for studying the effect of transgenes or knock-in mutations on APP processing(6). We introduced the early-onset familial Alzheimer disease (FAD) mutation M139T into the endogenous Rat Psen 1 gene and provide an initial characterization of Aβ processing in this novel rat AD model.Conclusion The different humanized APP models (rat and mouse) expressing human Aβ and PSEN1 M139T are valuable controls to study APP processing in vivo and allow to implement the use of human Aβ Elisa which is more sensitive than their rodent counterpart. These animals will be made available to the research community.
Effect of COVID-19 pandemic on anxiety and burnout levels in emergency healthcare workers: a questionnaire study
Authors: Sahin Taner , Aslaner Humeyra , Eker Ozlem Olguner , Gokcek Mebrure Beyza , Dogan Murat 
Published: June 2020

Abstract
BackgroundDuring the COVID19 pandemic, an increase in anxiety and burnout levels may occur unwittingly due to the increased workload and intense stress experienced by emergency healthcare workers dealing with potential or suspected COVID-19 and other emergency patients. In our study, it is aimed to investigate whether there is an increase of anxiety and burnout levels of the healthcare workers working in ES and pandemic fields fighting against the outbreak of COVID-19 in Turkey, compared to other healthcare workers.MethodsThe study was carried out between April 1 to May 15, 2020, with the online questionnaire method with the participation of 920 healthcare workers that are working actively in pandemic hospitals, emergency call ambulances, primary healthcare institutions and dental hospitals across the country. In the questionnaire, the sociodemographic characteristics of the participants were questioned, and Beck anxiety scale (BAI) and Maslach Burnout Inventory (MBI) were applied. ResultsThe median age of the participants was 35.00 (minimum 20, maximum: 65), 59.2% were female and 40.8% were male. 22.3% of the personnel were working in the ES, 20.9% in the ambulance, 12.2% in the pandemic polyclinics. The pandemic area and the intensive care workers' BAI score are similar to those in the emergency service and ambulance (p = 0.05). The MBI-desensitization score of those working in the field of ED, ICUs and pandemics was higher than other places (p <0.05). The MBI-emotional score of the emergency and ambulance workers was higher (p = 0.001), and the MBI-personal accomplishment score was lower than radiology, laboratory and office personnel (p=0.049).ConclusionsThe COVID-19 outbreak may create stress in healthcare workers, leading to various psychiatric disorders such as anxiety, depression, and burnout syndrome. Early recognition, prevention and coping methods of burnout and anxiety in healthcare workers play a key role in during the pandemic period.
The Effectiveness of applying for Formative Assessment Objective Structured Clinical Examination (OSCE)for Undergraduate Students in Faculty of Medicine King Abdul Aziz University, Jeddah, Kingdom of Saudi Arabia
Authors: Allhiani Rajaa , Abdulwahab Sumaiah , Alamri Sultan Hassan 
Published: June 2020

Abstract
The use of formative and summative assessment for students have been always a concern for medical professionals such as teachers and students especially when students are at graduating level. This can be supported with increasing the effectiveness and comprehensiveness of the students with appropriate clinical training using a defined structure with questionnaire-based system defined in the methodology to support student’s skills using clinical competencies to form perspective. It has been found that with Objective Structured Clinical Examination can be used as the method to assess the adequacy to support clinical skills of medical students following their competence level. This can be used to support a variety of tests to work on underpinning emergency procedures to interpret investigational data to ensure in-depth and breadth coverage of clinical skills following 5th-year medical students.
SARS-CoV-2 and mosquitoes: an extreme challenge
Authors: Huang Yan-Jang S. , Vanlandingham Dana L. , Bilyeu Ashley N. , Sharp Haelea M. , Hettenbach Susan M. , Higgs Stephen 
Published: June 2020

Abstract
The research addresses public speculation that SARS-CoV-2 might be transmitted by mosquitoes. The World Health Organization has stated “To date there has been no information nor evidence to suggest that the new coronavirus could be transmitted by mosquitoes”. Here we provide the first experimental data to the capacity of SARS-CoV-2 to infect and be transmitted by mosquitoes. Using three species of mosquitoes from both genera involved in transmission of most arboviruses that infect humans we demonstrate that SARS-CoV-2 virus is unable to replicate in mosquitoes and therefore cannot be transmitted to people.
Testing pipelines for genome-wide SNP calling from Genotyping-By-Sequencing (GBS) data for Pinus ponderosa
Authors: Shu Mengjun , Moran Emily V. 
Published: June 2020

Abstract
Background

Single Nucleotide Polymorphism (SNP) markers have rapidly gained popularity due to their abundance in most genomes and their amenability to high-throughput genotyping techniques. Reduced-representation restriction-enzyme-based sequencing methods (GBS or RADseq) have been demonstrated to be robust and cost-effective genotyping methods. While previous studies have shown that alignment of the short-read fragments to a genome sequence results in better SNP calling than de novo approaches, only a few tree species - and few conifers in particular - have an annotated sequence. While these could be used to align sequence fragments from related species, sequence divergence might result in SNPs being missed if they are in fragments that don't align properly. Producing a new annotated genome sequence for every conifer species before SNP analyses are conducted is still prohibitive, as many conifer genomes are huge (> 19 GB) and include a large proportion of repeat sequences, making assembly difficult. Here we compare four bioinformatics pipelines, two of which require a reference genome (TASSEL-GBS V2 and Stacks), two of which are de novo pipelines (UNEAK and Stacks). We used Illumina sequence data from 94 ponderosa pines, with loblolly pine as the reference genome.
Results

The number of SNPs called was much lower without a reference genome (62–196 thousand vs. 2.1–2.7 million SNPs). UNEAK was the fastest overall and identified more SNPs than Stacks de novo. Stacks with a reference genome produced the highest number of SNPs with lowest proportion of paralogs, while SNPs identified by TASSEL-GBS V2 exhibited the highest heterozygosity, minor allele frequency, and proportion of paralogs. More SNPs were uniquely identified by Stacks than TASSEL, though there was high overlap between methods.
Conclusion

The present case study provides a comprehensive comparison between four commonly-used SNP calling pipelines, and identifies the Stacks reference-based approach as the best overall for conifers (or other species with large repetitive genomes) that do not have a published reference genome for the same species. However, all four pipelines had distinct benefits and limitations, with Stacks for instance being less user-friendly than some of the other pipelines. In addition, researchers studying other conifer species using similar approaches should be prepared to analyze very large numbers of SNPs.
The Relationship Between Padi4 -94G/A Polymorphism and Rheumatoid Arthritis: A Meta-analysis in Multi Ethnic Groups
Authors: Jian Changchun , Pu Jingsong 
Published: June 2020

Abstract
Background: A number of studies have reported the association between peptidylarginine deiminase 4 (PADI4) -94G/A polymorphisms and rheumatoid arthritis (RA) risk in different populations, however, the results remained inconclusive. Objecitve: We therefore aim to address this association by performed an updated meta-analysis in multi ethnic groups. Methods: The PubMed and Chinese related databases were searched up to January 2019. The strength of association between PADI -94G/A polymorphism and RA susceptibility was assessed with odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 22 studies with 14514 RA cases and 21138 controls were finally included in the analysis. Six ethnic groups such as China, Japan, USA, UK, Sweden and Spain were contained. In the overall population, it revealed that PADI -94G/A polymorphism was significantly associated with an increased risk of RA. In the subgroup analyses by ethnicity, significant association was found in China as well as in Japan and USA. Conclusions: This meta-analysis demonstrates that the PADI4 -94G/A polymorphisms may represent a significant risk factor for RA in China, in Japan and USA. Further studies are needed to clarify this finding, since most available studies were conducted among Chinese and Japanese in this study.
Autophagy-related signature as Indicators for the Prognosis of Hepatocellular carcinoma
Authors: Ye Wen , Shi Zhehao , Zhang Zhongjing , Zhou Yi , Chen Bicheng , Zhang Qiyu 
Published: June 2020

Abstract
Background

Hepatocellular carcinoma (HCC) is the most common and deadly type of liver cancer. Autophagy is the process of transporting damaged or aging cellular components into lysosomes for digestion and degradation. There is an accumulative evidence implies that autophagy is a key factor of the progression of cancer. The aim of this study was to determine a panel of a novel autophagy-related prognostic marker for liver cancer.
Methods

We conducted a comprehensive analysis of ARGs expression profiles and corresponding clinical information based on The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) database. The univariate Cox proportional regression model was used to screen candidate autophagy-related prognostic genes. In addition, the multivariate Cox proportional regression model were helped to prove five key prognostic autophagy-related genes (ATIC, BAX, BIRC5, CAPNS1 and FKBP1A), which were used to construct prognostic signature.
Results

Based on the prognostic signature, liver cancer patients were significantly divided into high-risk and low-risk groups in terms of overall survival (OS). Further multivariate Cox regression analysis indicated that the prognostic signature remained as an independent prognostic factor for OS. The prognostic signature in possession of a better Area Under Curves (AUC) has a better performance in predicting the survival of patients with HCC, compared with other clinical parameters.
Conclusion

This study provides a prospective biomarker for monitoring the outcomes in the patients with HCC.
Reconstruction of time-consistent species trees
Authors: Lafond Manuel , Hellmuth Marc 
Published: June 2020

Abstract
Background: The history of gene families -- which are equivalent to event-labeled gene trees -- can to some extent be reconstructed from empirically estimated evolutionary event-relations containing pairs of orthologous, paralogous or xenologous genes. The question then arises as whether inferred event-labeled gene trees are "biologically feasible" which is the case if one can find a species tree with which the gene tree can be reconciled in a time-consistent way.Results: In this contribution, we consider event-labeled gene trees that contain speciations, duplications as well as horizontal gene transfer (HGT) and we assume that the species tree is unknown. Although many problems become NP-hard as soon as HGT and time-consistency are involved, we show, in contrast, that the problem of finding a time-consistent species tree for a given event-labeled gene can be solved in polynomial-time. We provide a cubic-time algorithm to decide whether a "time-consistent" species for a given event-labeled gene tree exists and, in the affirmative case, to construct the species tree within the same time-complexity.
Discovery of a potent angiotensin converting enzyme 2 inhibitor from Chinese Medicinal and Edible Plant via Docking-based Virtual Screening
Authors: Zi Cheng-Ting , Zhang Ning , Yang Liu , Wang Li-Xia , Wu Yi-Long , Su Yin-Shan , Wang Xuan-Jun 
Published: June 2020

Abstract
COVID-19 has outbreaked in Wuhan city, Hubei province of China since December 30th 2019, and spread nationwide and widely spilled over to other countries around the world that has been declared a public health emergency. However, there is no specific drug for the treatment of the disease. Therefore, identifying effective antiviral drugs to combat the disease is urgently needed. Angiotensin converting enzyme 2 (ACE2) has become the promising target to discovery new antiviral drugs to treat COVID-19, we have attempted to discover novel ACE2 inhibitors through ligand-based virtual screening. Finally, eight compounds were selected and tested ACE2 kinase inhibitory assay using fluorescence assays method. The results showed that four compounds (monoammonium glycyrrhizinate, glycyrrhizic acid methyl ester, ginsenoside Rg6 and ginsenoside F1) from 101 kinds of Chinese medicinal and edible plants which could inhibit ACE2 activity in vitro. Further efforts on chemical modification of these lead compounds are undergoing can lead to discover better agents against COVID-19.
Functional Conservation of Mitochondrial RNA Levels Despite Divergent mtDNA Organization
Authors: Held James P , Patel Maulik R 
Published: June 2020

Abstract
Objective: Mitochondria-encoded ribosomal RNA (rRNA) genes in humans are expressed at a higher rate than protein coding genes of the mitochondria. The organization of the human mitochondrial genome (mtDNA) is amenable to differential expression of rRNAs as it contains a promoter specific to the transcription of the two rRNAs. However, mtDNA is not organized in the same way as humans in all metazoans. In the nematode, Caenorhabditis elegans, the rRNA genes are on opposite sides of the mtDNA molecule and there are no obvious promoter sequences specific to the rRNA genes. Thus, we asked whether rRNA levels are higher relative to mRNAs in mitochondria of C. elegans as they are in humans.Results: Using droplet digital PCR, we discovered that steady-state mitochondrial rRNA transcript levels are approximately 120 times higher than the levels of mitochondrial mRNAs. These data demonstrate that despite the lack of conservation in mitochondrial genome organization, a high mitochondrial rRNA-to-mRNA ratio is a conserved feature of metazoans.
Performance Assessment of Two Motion Management Systems for Frameless Stereotactic Radiosurgery
Authors: Wang Hao , Xu Zhiyong , Grantham Kevin , Zhou Yongkang , Cui Taoran , Zhang Yin , Liu Bo , Wang Xiao , Vergalasova Irina , Reyhan Meral , Weiner Joseph Paul , Shabbar Danish , Yue Ning , Nie Ke 
Published: June 2020

Abstract
Background/PurposeFrameless stereotactic radiosurgery (SRS) requires dedicated systems to monitor patient motion in order to avoid inaccurate radiation delivery due to involuntary shifts. The purpose of this study is to assess the accuracy and sensitivity of two distinct motion monitoring systems used for frameless SRS.MethodsA surface image-guided system known as Optical Surface Monitoring System (OSMS), and a fiducial marker-based system known as High Definition Motion Management (HDMM) as part of the latest Gamma Knife Icon® were compared with each other. A 3D printer-based cranial motion phantom was developed to evaluate the accuracy and sensitivity of these two systems in terms of: (1) the capability to recognize predefined shifts up to 3 cm, and (2) the capability to recognize predefined speeds up to 3 cm/s. The performance of OSMS, in terms of different reference surfaces, was also evaluated.ResultsTranslational motion could be accurately detected by both systems, with an accuracy of 0.3 mm for displacement up to 1 cm, and 0.5 mm for larger displacements. The reference surface selection had an impact OSMS performance, with flat surface resulting in less accuracy. HDMM was in general more sensitive when compared with OSMS in capturing the motion, due to its faster frame rate, but a delay in response was observed with faster speeds. Both systems were less sensitive in detection of superior-inferior motion when compared to lateral or vertical displacement directions.ConclusionTranslational motion can be accurately and sensitively detected by OSMS and HDMM real-time monitoring systems. However, performance variations were observed along different motion directions, as well as amongst the selection of reference images. Caution is needed when using real-time monitoring systems for frameless SRS treatment.
Magnetic properties, anticancer and antibacterial effectiveness of sonochemically produced Ce3+/Dy3+ co-activated Mn-Zn nanospinel ferrites
Authors: almessiere munirah , Slimani Yassine , Rehman Suriya , Khan Firdos A. , Guner S. , Shirsath Sagar E. , Baykal Abdulhadi 
Published: June 2020

Abstract
Some new types of Ce3+ and Dy3+ co-doped manganese-zinc nanospinel ferrites (CDMZNSFs) of the form (Mn0.5Zn0.5)[Fe2 − 2xCexDyx]O4 (with 0.0 ≤ x ≤ 0.1) were sonochemically produced and characterized. The structure, morphology, optical and magnetic behaviors of these NSFs were determined as a function of co-dopant (Ce3+ and Dy3+) contents. In addition, the bactericidal (on the gram-positive and gram-negative bacterial strains) and anti-cancerous effectiveness of these NSFs were assessed. The cancer cells' growth inhibitory action of these NSFs was tested against both normal (HEK-293) and cancerous (HCT-116) human cells. The direct optical band gap energies of the studied NSFs were ranged from 1.54 to 1.85 eV. The measured hysteresis loop and temperature-dependent magnetization of the NSFs disclosed a phase transformation from the superparamagnetic (SPM) at room temperature (RT) to ferromagnetic (FM) below the blocking temperature (TB). The saturation magnetization and TB were decreased with the increase in co-dopant contents. After 48 h of treatment of the cancerous cells with the NSFs, their population was significantly dropped as shown by the MTT assay, indicating the selective inhibition of the cancer cells growth by the proposed NSFs. Conversely, the non-cancerous cells (HEK-293) population remained unaffected. The IC50 values of the NSFs-treated cancerous cells (HCT-116) were in the range of 0.74–2.35 µg/mL. The results of the MIC and MBC assays revealed the reasonable antibacterial efficacy (growth inhibitory activity) of these NSFs when tested against the E. coli and S. aureus bacterial strains. It is established that the proposed Ce3+/Dy3+ co-activated CDMZNSFs may be beneficial for the anti-cancerous and bactericidal applications.
Micropapillary pattern of pathologic IIIA-N2 lung adenocarcinoma is a prognostic factor after adjuvant chemoradiotherapy.
Authors: Zeng Jian , Cui Xiaoying , Cheng Lei , Chen Ying , Du Xianghui , sheng liming 
Published: June 2020

Abstract
Objectives: Lung adenocarcinoma with a micropapillary pattern is a highly aggressive disease and related to locoregional recurrence after surgery. This study aims to investigate the role of micropapillary pattern in pathologic IIIA-N2 lung adenocarcinoma after adjuvant chemoradiotherapy. Methods: A total of consecutive 257 patients with pathologic IIIA-N2 lung adenocarcinoma who received adjuvant chemoradiotherapy were enrolled in this retrospective study. Patients were classified into three groups based on the proportion of micropapillary components: micropapillary negative (MPN), micropapillary minor component (MPM, positive but not predominant), and micropapillary predominant component (MPP, positive and predominant). The disease-free survival (DFS) and overall survival (OS) were analyzed using SPSS software. Results: The five-year DFS and OS rates in the whole population were 41.0% and 62.7%, respectively. MPP group had the shortest median DFS time and OS time, compared with the MPM group and the MPN group (Median DFS time: 27 months Vs. 39 months Vs. 62 months, p=0.032; Median OS time: 54 months Vs. 64 months Vs. not reached, p=0.004). Furthermore, the micropapillary pattern was an independent prognostic factor for DFS and OS by multivariate analysis (p＜0.05). Conclusion: Micropapillary pattern of pathologic IIIA-N2 lung adenocarcinoma was related to the earlier treatment failure and worse prognosis after adjuvant chemoradiotherapy.
Efficacy and Toxicity of Re-irradiation for Esophageal Cancer Patients with Locoregional Recurrence: a retrospective analysis
Authors: Zhao Kaikai , Si Youjiao , Sun Liangchao , Meng Xiangjiao , Yu Jinming 
Published: June 2020

Abstract
Introduction: There is no standard treatment for locoregional recurrent (LR) esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy (RT) previously. This retrospective study aimed to examine the efficacy and toxicity of re-irradiation (re-RT) for ESCC patients with LR. Patients and Methods: A total of 252 patients were enrolled. Gross tumor volumes for re-RT were defined using contrast enhanced computed tomography and/or positron emission tomography/computed tomography. Overall survival (OS), after recurrence survival (ARS) and toxicities were assessed. Results: Through a median follow-up of 38 months, the median OS and ARS were 39.0 and 13.0 months, respectively. The 6-, 12-, and 24-month ARS rates were 81.9%, 50.5%, and 21.8%, respectively. Multivariate analyses showed that chemotherapy, esophageal stenosis and RFI may be independent prognostic factors for ARS. The incidence of esophageal fistula/ perforation, radiation-induced pneumonitis and esophagorrhagia was 21.4%, 12.8% and 9.1%, respectively. RFI≤12 months, esophageal stenosis and fat space between tumor and adjacent tissue disappeared were independent risk factors for the development of EP after re-RT. Conclusions: Re-RT was feasible for LR ESCC patients after RT initially, the complications occurred in re-RT is acceptable. Patients with RFI≤12 months, esophageal stenosis and fat space between tumor and adjacent tissue disappeared should be closely observed during and after re-RT.