bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factor Structure, Reliability and Validity of the Institutional Culture Assessment Scale (ICAS)
Authors: Monteiro Gabriela Massaro Carneiro , Moser Carolina Meira , de Oliveira Luciana Terra , Gabbard Glen Owens , Laskoski Pricilla Braga , Hauck Simone 
Published: September 2020

AbstractIntroductionWork environment can affect the employees, fostering well-being versus emotional burden. The aim of this study was to develop the Institutional Culture Assessment Scale (ICAS), and evaluate its Factor Structure, Reliability and Validity in a Brazilian sample of medical students and physicians in different settings and phases of the medical career.Method2,537 individuals were evaluated by an online questionnaire. The sample was split in half for independent testing of Exploratory Factor Analysis and Confirmatory Factor Analysis. We then used Confirmatory Factor Analysis (CFA) to test the best solutions in the second half of the sample. Then, considering a unidimensional model solution, an item response theory (IRT) analysis was conducted. Simple linear regression analysis was performed to investigate associations between ICAS factor scores and internal validators (burnout scores), using again the second half of the sample.ResultParallel analysis revealed two factors. The first factor encompassed items involving the institution and supervisors. The second factor encompassed items involving peers. We decided to performed the next analysis with a unidimensional construct based solely on institution/supervisor items. A unidimensional model including the remaining seven items from the ICAS instrument revealed an excellent fit with the data. All items loaded significantly on the unidimensional latent trait with factor loadings ranging from 0.583 to 0.869. McDonald’s Omega was 0.89, showing a high internal consistency.ConclusionThis study presents a valid and reliable scale to assess aspects of institutional culture connected to the relationships with superiors/supervisors and to the relation to the institutions themselves.
Stage-differentiated modelling of methylation patterns uncovers salient biomarkers and prognostic signatures in colorectal cancer progression
Authors: Raghavendran Abirami , Muthamilselvan Sangeetha , Palaniappan Ashok 
Published: September 2020

ABSTRACTBackgroundAberrant methylation of DNA acts epigenetically to skew the gene transcription rate up or down. In this study, we have developed a comprehensive computational framework for the stage-specific analysis of methylation patterns in colorectal cancer.MethodsCombining public-domain methylation and clinical data from TCGA, the methylation β - matrix was converted into M-value matrix, annotated with sample stages and analysed for stage-specific genes using multiple approaches involving stage-differentiated linear modelling of methylation patterns or their correlation with the phenotype and expression patterns. Differentially methylated genes (DMGs) were identified using a contrast against control samples (adjusted p-value <0.001 and |log fold-change of M-value| >2). These results were further filtered using a series of all possible pairwise stage contrasts (p-value <0.05) to obtain stage-specific DMGs. These were then subjected to a consensus analysis, followed by Kaplan–Meier survival analysis to explore the relationship between methylation and prognosis for the consensus stage-salient biomarkers.ResultsWe found significant genome-wide changes in methylation patterns in cancer samples relative to controls agnostic of stage. Our stage-differentiated analysis yielded the following stage-salient genes: one stage-I gene (“FBN1”), one stage II specific gene (“FOXG1”), one stage III specific gene (“HCN1”) and four stage IV specific genes (“NELL1”, “ZNF135”, “FAM123A”, “LAMA1”), which could be used for stage-specific diagnosis. All the biomarkers were hypermethylated, indicating down-regulation and signifying a CpG island Methylator Phenotype (CIMP) manifestation. A prognostic signature consisting of FBN1 and FOXG1was significantly associated with patient survival (p-value < 0.01) and could be used as a biomarker panel for early-stage CRC prognosis.ConclusionOur workflow for stage-differentiated consensus analysis has yielded stage-salient diagnostic biomarkers as well as an early-stage prognostic biomarker panel. In addition, our studies have affirmed a novel CIMP-like signature in colorectal cancer, urging clinical validation.Supplementary InformationSupplementary information could be found at https://doi.org/10.6084/m9.figshare.13013852
A Data-Driven Evaluation Approach for Assessing Student Nurse Training Effectiveness in Clinical Practice Using A Fuzzy Mathematics Model
Authors: Liu Yanmei , Chen Yuwen 
Published: September 2020

ABSTRACTThe overall performance of student nurses during training and subsequent medical treatment practice has a direct effect on the quality of healthcare they provide in hospitals. The evaluation of student nurses’ overall performance is usually not straightforward, as the evaluation criteria includes many aspects and it’s difficult to develop a generic metric. Fuzzy mathematics provides a mathematical tool for processing data with fuzziness. Using fuzzy mathematics theory enables data-driven evaluation of the overall performance of student nurses after their training program.
Light-induced modulation of DNA recognition by the Rad4/XPC damage sensor protein
Authors: Tavakoli Amirrasoul , Paul Debamita , Mu Hong , Kuchlyan Jagannath , Baral Saroj , Ansari Anjum , Broyde Suse , Min Jung-Hyun 
Published: September 2020

ABSTRACTBiomolecular structural changes upon binding/unbinding are key to their functions. However, characterization of such dynamical processes with high spatial and temporal resolutions is difficult as it requires ways to rapidly trigger the assembly/disassembly as well as ways to monitor the structural changes over time. Recently, various chemical strategies have been developed to use light to trigger changes in oligonucleotide structures, thereby their activities. Here we report that photoswitchable DNA can be used to modulate the DNA binding of the Rad4/XPC DNA repair complex using light. Rad4/XPC specifically binds to diverse helix-destabilizing/distorting lesions including bulky organic adducts and functions as a key initiator for the eukaryotic nucleotide excision repair (NER) pathway. We show that the 6-nitropiperonyloxymethyl (NPOM)-modified DNA is recognized by the Rad4 protein as a specific substrate and that the specific binding can be abolished by light-induced cleavage of the NPOM group from DNA in a dose-dependent manner. Fluorescence lifetime-based analyses of the DNA conformations suggest that free NPOM-DNA retains B-DNA-like conformations despite its bulky NPOM adduct, but Rad4-binding renders it to be heterogeneously distorted. Subsequent extensive conformational searches and molecular dynamics simulations demonstrate that NPOM in DNA can be housed in the major groove of the DNA, with stacking interactions among the nucleotide pairs remaining largely unperturbed and thus retaining overall B-DNA conformation. Our work suggests that photoactivable DNA can be used as a DNA lesion surrogate to study DNA repair mechanisms such as nucleotide excision repair.Abstract FigureGraphical SummaryThis work shows that a photolabile 6-nitropiperonyloxymethyl (NPOM)-modified DNA is specifically recognized by the Rad4/XPC damage sensor protein complex that initiates the nucleotide excision repair pathway; light-induced cleavage of NPOM abolishes the specific binding to Rad4/XPC.
Genomic prediction of arsenic tolerance and grain yield in rice. Contribution of trait-specific markers and multi environment models
Authors: Ahmadi Nourollah , Cao Tuong-Vi , Frouin Julien , Norton Gareth J. , Price Adam H. 
Published: September 2020

AbstractMany rice-growing areas are affected by high concentrations of arsenic (As). Rice varieties that preventAsuptake and/or accumulation can mitigateAsthreats to human health. Genomic selection is known to facilitate rapid selection of superior genotypes for complex traits. We explored the predictive ability (PA) of genomic prediction with single-environment models, accounting or not for trait-specific markers, multi-environment models, and multi-trait and multi-environment models, using the genotypic (1600 K SNP) and phenotypic (grain arsenic content, grain yield and days to flowering, observed under two irrigation systems over two years) data of the Bengal and AssamAusPanel (BAAP). Under the base-line single environment model, PA of up to 0.707 and 0.654 was obtained for grain yield and grainAsrespectively, the three prediction methods (BL, GBLUP and RKHS) considered performed similarly, and marker selection based on linkage disequilibrium allowed to reduce the number of SNP to 17 K, without negative effect on PA of genomic predictions. Single environment models giving distinct weight to trait-specific markers in the genomic relationship matrix outperformed the base-line models up to 32%. Multi-environment models, accounting for G × E interactions, and multi-trait and multi-environment models outperformed the base-line models by up to 47% and 61%, respectively. Among the multi-trait and multi-environment models, the Bayesian multi-output regressor stacking function obtained the highest PA (0.831 for grainAs) with much higher efficiency for computing time. These findings pave the way for breeding forAs-tolerance in the progenies of biparental crosses involving members of the BAAP. It also applies to breeding for other complex traits evaluated under multiple environments.
Smart bionic graspers: background study and design process
Authors: Li Xinrui , Chizari Mahmoud 
Published: September 2020

ABSTRACTThis paper has focused on reviewing passive bionic grasper and designing a virtual prototype using a computer modelling technique. The main aim of this study is to review existing research and compare their functionalities. This has been followed by introducing a concept design with suitable components. To start the project, generating a clear overview form the most updated and relative knowledge and information on existing designs was the intention of the study. The concept design part of this study uses an iterative process (similar to the Double Diamond Model introduced by Frances et al (2019)) including Discover, Define, Develop and Deliver to complete the design components. Following the concept design process, the detailed theoretical considerations and the features of components selection were then defined. In Develop Phase, the goal was to decide the final design and generate the computer model using SolidWorks. The fourth phase of process was Delivery leading the design evaluation and validation of the generated model or virtual prototype. By completing the process, it is possible to determine the feasibility of the design and the need for improvement. In final stage of the design, a finite element approach using SolidWorks Simulation was performed on the concept. Final design was decided after comparing the concepts in terms of several considerations. A series of simulations were performed on the design to evaluate the durability of the design and extend its functionality. The results showed that the supporting pad was robust enough when dropped down from 1.5 meters height, while the hinge which connecting the finger straps would need further improvement to avoid failure during its practical loading.
Simulation of bacterial populations with SLiM
Authors: Cury Jean , Haller Benjamin C. , Achaz Guillaume , Jay Flora 
Published: September 2020

AbstractSimulation of genomic data is a key tool in population genetics, yet, to date, there is no forward-in-time simulator of bacterial populations that is both computationally efficient and adaptable to a wide range of scenarios. Here we demonstrate how to simulate bacterial populations with SLiM, a forward-in-time simulator built for eukaryotes. SLiM has gained many users in recent years, due to its speed and power, and has extensive documentation showcasing various scenarios that it can simulate. This paper focuses on a simple demographic scenario, to explore unique aspects of modeling bacteria in SLiM’s scripting language. In addition, we illustrate the flexibility of SLiM by simulating the growth of bacteria on a Petri dish with antibiotic. To foster the development of bacterial simulations based upon this recipe, we explain the inner workings of its code. We also validate the simulator, by extensively testing the results of simulations against existing simulators, and against theoretical expectations for some summary statistics. This protocol, with the flexibility and power of SLiM, will enable the community to simulate bacterial populations efficiently under a wide range of evolutionary scenarios.
Amyloid beta acts synergistically as a pro-inflammatory cytokine
Authors: LaRocca Thomas J. , Cavalier Alyssa N. , Roberts Christine M. , Lemieux Maddie R. , Link Christopher D. 
Published: September 2020

SUMMARYThe amyloid beta (Aβ) peptide is believed to play a central role in Alzheimer’s disease (AD), the most common age-related neurodegenerative disorder. However, the natural, evolutionarily-selected functions of Aβ are incompletely understood. Here, we report that nanomolar concentrations of Aβ act synergistically with known cytokines to promote pro-inflammatory activation in primary human astrocytes (a cell type increasingly implicated in brain aging and AD). Using transcriptomics (RNA-seq), we show that Aβ can directly substitute for the complement component C1q in a cytokine cocktail previously shown to induce astrocyte immune activation. Furthermore, we show that astrocytes synergistically activated by Aβ have a transcriptional signature similar to neurotoxic “A1” astrocytes known to accumulate with age and in AD. Interestingly, we find that this biological action of Aβ at low concentrations is distinct from the transcriptome changes induced by the high/supraphysiological doses of Aβ often used inin vitrostudies. Collectively, our results suggest an important, cytokine-like function for Aβ and a novel mechanism by which it may directly contribute to the neuroinflammation associated with brain aging and AD.
Effect of Cellular and ECM Aging on Human iPSC-derived Cardiomyocyte Performance, Maturity and Senescence
Authors: Ozcebe S. Gulberk , Bahcecioglu Gokhan , Yue Xiaoshan S. , Zorlutuna Pinar 
Published: September 2020

AbstractCardiovascular diseases are the leading cause of death worldwide and their occurrence is highly associated with age. However, lack of knowledge in cardiac tissue aging is a major roadblock in devising novel therapies. Here, we studied the effects of cell and cardiac extracellular matrix (ECM) aging on the induced pluripotent stem cell (iPSC)-derived cardiomyocyte cell state, function, as well as response to myocardial infarction (MI)-mimicking stress conditionsin vitro. Within 3-weeks, young ECM promoted proliferation and drug responsiveness in young cells, and induced cell cycle re-entry, and protection against stress in the aged cells. Adult ECM improved cardiac function, while aged ECM accelerated the aging phenotype, and impaired cardiac function and stress defense machinery of the cells. In summary, we have gained a comprehensive understanding of cardiac aging and highlighted the importance of cell-ECM interactions. This study is the first to investigate the individual effects of cellular and environmental aging and identify the biochemical changes that occur upon cardiac aging.
Epigenomic features related to microglia are associated with attenuated effect of APOE ε4 on alzheimer’s disease risk in humans
Authors: Ma Yiyi , Yu Lei , Olah Marta , Smith Rebecca , Oatman Stephanie R. , Allen Mariet , Pishva Ehsan , Zhang Bin , Menon Vilas , Ertekin-Taner Nilüfer , Lunnon Katie , Bennett David A. , Klein Hans-Ulrich , De Jager Philip L. 
Published: September 2020

AbstractINTRODUCTIONNot allAPOEε4 carriers who survive to advanced age develop Alzheimer’s disease (AD); factors attenuating the risk of ε4 on AD may exist.METHODSGuided by the top ε4-attenuating signals from methylome-wide association analyses (N=572, ε4+ and ε4-) of neurofibrillary tangles and neuritic plaques, we conducted a meta-analysis for pathological AD within the ε4+ subgroups (N=235) across four independent collections of brains. Cortical RNA-seq and microglial morphology measurements were used in functional analyses.RESULTSThree out of the four significant CpG dinucleotides were captured by one principle component (PC1), which interacts with ε4 on AD, and is associated with expression of innate immune genes and activated microglia. In ε4 carriers, reduction in each unit of PC1 attenuated the odds of AD by 58% (OR=2.39, 95%CI=[1.64,3.46],P=7.08×10−6).DISCUSSIONAn epigenomic factor associated with a reduced proportion of activated microglia appears to attenuate the risk of ε4 on AD.
Sonographic Analysis of Abscess Maturation in a Porcine Model
Authors: Leotta Daniel F. , Bruce Matthew , Wang Yak-Nam , Kucewicz John , Khokhlova Tatiana , Chan Keith , Monsky Wayne , Matula Thomas J. 
Published: September 2020

AbstractAbscesses are walled-off collections of infected fluids that often develop as complications in the setting of surgery and trauma. Abscess care depends on size, location, composition and complexity, among other patient factors. The goal of this work is to describe, using the latest ultrasound imaging technologies, the progression of abscess development in a porcine animal model. Intramuscular or subcutaneous injections of bacteria plus dextran particles as an irritant led to identifiable abscesses over a 2- to 3-week period. The abscesses were imaged at least weekly with B-mode, 3D B-mode, shear-wave elastography (SWE) and color flow imaging. Mature abscesses were characterized by a well-defined core of varying echogenicity surrounded by a hypoechoic capsule that was highly vascularized on Doppler imaging. Size and shape changes during development were quantified with 3D imaging. With SWE, the lesion stiffness varied interiorly and generally decreased over time. These ultrasound features potentially provide biomarkers to facilitate improved selection of treatment strategies for abscesses.
The novel anti-CRISPR AcrIIA22 relieves DNA torsion in target plasmids and impairs SpyCas9 activity
Authors: Forsberg Kevin J. , Schmidtke Danica T. , Werther Rachel , Uribe Ruben V. , Hausman Deanna , Sommer Morten O.A. , Stoddard Barry L. , Kaiser Brett K. , Malik Harmit S. 
Published: September 2020

AbstractTo overcome CRISPR-Cas defense systems, many phages and mobile genetic elements encode CRISPR-Cas inhibitors called anti-CRISPRs (Acrs). Nearly all characterized Acrs directly bind Cas proteins to inactivate CRISPR immunity. Here, using functional metagenomic selection, we describe AcrIIA22, an unconventional Acr found in hypervariable genomic regions of clostridial bacteria and their prophages from human gut microbiomes. AcrIIA22 does not bind strongly to SpyCas9 but nonetheless potently inhibits its activity against plasmids. To gain insight into its mechanism, we obtained an X-ray crystal structure of AcrIIA22, which revealed homology to PC4-like nucleic-acid binding proteins. Based on mutational analyses and functional assays, we deduced thatacrIIA22encodes a DNA nickase that relieves torsional stress in supercoiled plasmids. This may render them less susceptible to SpyCas9, which uses free energy from negative supercoils to form stable R-loops. Modifying DNA topology may provide an additional route to CRISPR-Cas resistance in phages and mobile genetic elements.
Genome-wide analysis of experimentally evolvedCandida aurisreveals multiple novel mechanisms of multidrug-resistance
Authors: Carolus Hans , Pierson Siebe , Muñoz José F. , Subotić Ana , Cruz Rita B. , Cuomo Christina A. , Van Dijck Patrick 
Published: September 2020

AbstractCandida aurisis globally recognized as an opportunistic fungal pathogen of high concern, due to its extensive multidrug-resistance (MDR). Still, molecular mechanisms of MDR are largely unexplored. This is the first account of genome wide evolution of MDR inC. aurisobtained through serialin vitroexposure to azoles, polyenes and echinocandins. We show the stepwise accumulation of multiple novel mutations in genes known and unknown in antifungal drug resistance, albeit almost all new forC. auris. Echinocandin resistance evolved through a codon deletion inFKS1accompanied by a substitution inFKS1hot spot 3. Mutations inERG3andCIS2further increased the echinocandin MIC. Decreased azole susceptibility was acquired through a gain of function mutation in transcription factorTAC1byielding overexpression of the drug efflux pump Cdr1; a segmental duplication of chromosome 1 containingERG11; and a whole chromosome 5 duplication, which containsTAC1b. The latter was associated with increased expression ofERG11, TAC1bandCDR2, but notCDR1. The simultaneous emergence of nonsense mutations inERG3andERG11, presumably leading to the abrogation of ergosterol synthesis, was shown to decrease amphotericin B susceptibility, accompanied with fluconazole cross resistance. A mutation inMEC3, a gene mainly known for its role in DNA damage homeostasis, further increased the polyene MIC. Overall, this study shows the alarming potential and diversity for MDR development inC. auris, even in a clade until now not associated with MDR (clade II), hereby stressing its clinical importance and the urge for future research.ImportanceC. aurisis a recently discovered human fungal pathogens and has shown an alarming potential for multi- and pan-resistance towards all classes of antifungals most commonly used in the clinic. Currently,C. aurishas been globally recognized as a nosocomial pathogen of high concern due to this evolutionary potential. So far, this is the first study in which the stepwise progression of MDR inC. aurisis monitoredin vitro. Multiple novel mutations in known ‘resistance genes’ and genes previously not or vaguely associated with drug resistance reveal rapid MDR evolution in aC. aurisclade II isolate. Additionally, this study shows thatin vitroexperimental evolution can be a powerful tool to discover new drug resistance mechanisms, although it has its limitations.
Coding Complete Genome Sequences of Twenty-three SARS-CoV-2 Strains Isolated in the Philippines
Authors: Velasco John Mark , Chinnawirotpisan Piyawan , Joonlasak Khajohn , Manasatienkij Wudtichai , Huang Angkana , Valderama Ma.. Theresa , Diones Paula Corazon , Leonardia Susie , Timbol Ma.Leanor , Navarro Fatima Claire , Villa Vicente , Tabinas Henry , Chua Domingo , Fernandez Stefan , Jones Anthony , Klungthong Chonticha 
Published: September 2020

AbstractHere, we report the coding complete genome sequences of 23 severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) strains from the Philippines. Sequences were obtained from nasopharyngeal and oropharyngeal swabs from COVID-19 positive patients. Mutation analysis showed the presence of the D614G mutation in the spike protein in 22 of 23 genomes.