bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathogenesis, MicroRNA‐122 Gene‐Regulation, and Protective Immune Responses After Acute Equine Hepacivirus Infection
Authors: Tomlinson Joy E. , Wolfisberg Raphael , Fahnøe Ulrik , Patel Roosheel S. , Trivedi Sheetal , Kumar Arvind , Sharma Himanshu , Nielsen Louise , McDonough Sean P. , Bukh Jens , Tennant Bud C. , Kapoor Amit , Rosenberg Brad R. , Rice Charles M. , Divers Thomas J. , Van de Walle Gerlinde R. , Scheel Troels K.H. 
Published: March 2021

Background and Aims
Equine hepacivirus (EqHV) is phylogenetically the closest relative of HCV and shares genome organization, hepatotropism, transient or persistent infection outcome, and the ability to cause hepatitis. Thus, EqHV studies are important to understand equine liver disease and further as an outbred surrogate animal model for HCV pathogenesis and protective immune responses. Here, we aimed to characterize the course of EqHV infection and associated protective immune responses.

Approach and Results
Seven horses were experimentally inoculated with EqHV, monitored for 6 months, and rechallenged with the same and, subsequently, a heterologous EqHV. Clearance was the primary outcome (6 of 7) and was associated with subclinical hepatitis characterized by lymphocytic infiltrate and individual hepatocyte necrosis. Seroconversion was delayed and antibody titers waned slowly. Clearance of primary infection conferred nonsterilizing immunity, resulting in shortened duration of viremia after rechallenge. Peripheral blood mononuclear cell responses in horses were minimal, although EqHV‐specific T cells were identified. Additionally, an interferon‐stimulated gene signature was detected in the liver during EqHV infection, similar to acute HCV in humans. EqHV, as HCV, is stimulated by direct binding of the liver‐specific microRNA (miR), miR‐122. Interestingly, we found that EqHV infection sequesters enough miR‐122 to functionally affect gene regulation in the liver. This RNA‐based mechanism thus could have consequences for pathology.

Conclusions
EqHV infection in horses typically has an acute resolving course, and the protective immune response lasts for at least a year and broadly attenuates subsequent infections. This could have important implications to achieve the primary goal of an HCV vaccine; to prevent chronicity while accepting acute resolving infection after virus exposure.
Perceived impact of the characteristics of the Indigenous Queensland B.strong brief intervention training program on uptake and implementation
Authors: Sebastian Saji , Thomas David P. , Brimblecombe Julie , Arley Brian , Cunningham Frances C. 
Published: March 2021

AbstractIssue addressedBrief interventions (BIs) in primary health care (PHC) settings can be effective in addressing behavioural risk factors of chronic conditions. However, the impact of the characteristics of BI training programs on the uptake of the program and implementation of BIs in Indigenous PHC settings is not fully understood. The B.strong Program was an Indigenous health worker BI training program delivered in Queensland from 2017 to 2020. This study examines the impact of the characteristics of the B.strong Program on its uptake and implementation in PHC settings.MethodsSemi‐structured interviews were conducted in 2019 and 2020 with 20 B.strong Program trainees and four health service managers from eight purposively sampled Queensland PHC services, and one Queensland Department of Health manager, to collect their perceptions of the implementation of the B.strong Program. The Consolidated Framework for Implementation Research guided data collection.ResultsKey program characteristics that facilitated both the program uptake and the implementation of BIs were: ensuring the cultural appropriateness of the program from development, to engagement with health services and through to delivery, the applicability of the program to trainees’ daily clinical work, program credibility, and its ease of access and availability. Participants preferred face‐to‐face workshop training for online module training.ConclusionsRelevance to practice, easy access, program credibility and measures taken to ensure cultural appropriateness of the B.strong Program in development, in engagement stages with health services, and in program delivery facilitated program uptake and implementation of BIs. Online BI training may be of limited value compared to face‐to‐face training in this setting.So what?To enhance participation by Indigenous PHC services in health worker BI training programs and implementation of BIs posttraining by health staff, it is important to ensure the cultural appropriateness of the program's characteristics, and its development, engagement and delivery processes.
Barriers and facilitators to participation in breast, bowel and cervical cancer screening in rural Victoria: A qualitative study
Authors: Azar Denise , Murphy Michael , Fishman Alana , Sewell Lauren , Barnes Megan , Proposch Amanda 
Published: March 2021

AbstractIssue addressedPopulation cancer screening rates are around 50% for the general population and even lower in rural areas. This study aimed to explore knowledge, attitudes, behaviours, motivators and barriers to breast, bowel and cervical screening participation in under‐screened men and women.MethodsWe used a qualitative research design. Focus groups were segmented by age, sex and screening participation. Participants were under‐screened in at least one of the cancer screening programs, with separate groups for each of the programs. The discussion guides were designed around the Health Belief Model and group discussions were coded using a thematic content analysis approach.ResultsFourteen focus groups were held with 80 participants. Key themes were that the concept of cancer screening was not well understood, a low priority for preventive health behaviours, issues relating to local general practitioners (GP) and screening was unpleasant, embarrassing and/or inconvenient. A key determinant of participation in cancer screening was exposure to prompts to action, and it was evident that participants often required multiple prompts before they took action.ConclusionsOpportunities that develop attitudes to health that place disease prevention as a high priority; improve understanding of the benefit of screening in terms of early detection and treatment; improve GP availability and the patient‐practitioner relationship; and the development of messages for each of the screening programs should be further explored as factors that may influence rural population screening rates.So what?Addressing health attitudes, beliefs, knowledge, health practitioner and test‐related barriers and improving messaging may increase cancer screening participation in under‐screened rural populations.
Iran hospital accreditation standards: challenges and solutions
Authors: Ghazanfari Fatemeh , Mosadeghrad Ali Mohammad , Jaafari Pooyan Ebrahim , Mobaraki Hossein 
Published: March 2021

AbstractObjectiveThe purpose of this study was to identify the challenges of Iranian hospital accreditation standards and provide solutions.DesignA qualitative research design was used in this study. Open and semi‐structured interviews were conducted in 2018. Thematic analysis was used to analyse qualitative data.SettingPublic, private, semi‐public, charity and military hospitals in Tehran, Iran.ParticipantsA pluralistic evaluation approach was employed and 151 participants including policy makers, hospital management and staff, accreditation surveyors and university professors participated in this study.ResultsChallenges of hospital accreditation standards were grouped into two groups: standards development process and standards content. Lack of an independent standards development committee, insufficient expertise of committee members, inconsistencies among the standards’ constructs, inappropriate standard classification, ambiguity of standards, unmeasurable standards, vague and inflexible scoring system, and inability to use some standards were the main challenges of Iran hospital accreditation standards. Establishing a scientific committee consisting of representative from hospitals, health insurance companies, professional and scientific associations and universities for standard development, training the committee members, and utilizing hospital's feedback will help address these problems.ConclusionIran's hospital accreditation standards face challenges that prevent them from achieving their goals, that is, improving the quality, safety, effectiveness and efficiency of hospital services. Necessary measures should be taken to solve these problems.
Numerical simulation of natural convection heat transfer from a heated square cylinder in a square cavity filled with micropolar fluid
Authors: Sivarami Reddy C. , Ramachandra Prasad V. , Jayalakshmi K. 
Published: March 2021

AbstractA numerical investigation has been performed to visualize the magnetohydrodynamic natural convective heat transfer from a heated square cylinder situated within a square enclosure subjected to nonuniform temperature distributions on the left wall. The flow inside the enclosure is unsteady, incompressible, and laminar and the working fluid is micropolar fluid with constant Prandtl number (Pr = 7). The governing equations of the flow problem are the conservation of mass, energy, and linear momentum, as well as the angular momentum equations. Governing equations formulated in dimensionless velocity and pressure form has been solved by Marker and Cell method with second‐order accuracy finite difference scheme. Comprehensive verification of the utilized numerical method and mathematical model has shown a good agreement with numerical data of other authors. The results are discussed in terms of the distribution of streamlines and isotherms and surface‐averaged Nusselt number, for combinations of Rayleigh number, Ra (103–106), Vortex viscosity parameter, K (0–5), and Ha parameter (0–50). It has been shown that an increase in the vortex viscosity parameter leads to attenuation of the convective flow and heat transfer inside the cavity.
Drug repositioning to target NSP15 protein on SARS‐CoV‐2 as possible COVID‐19 treatment
Authors: Sixto‐López Yudibeth , Martínez‐Archundia Marlet 
Published: March 2021

AbstractSARS‐CoV and SARS‐CoV‐2 belong to the subfamily Coronaviridae and infect humans, they are constituted by four structural proteins: Spike glycoprotein (S), membrane (M), envelope (E) and nucleocapsid (N), and nonstructural proteins, such as Nsp15 protein which is exclusively present on nidoviruses and is absent in other RNA viruses, making it an ideal target in the field of drug design. A virtual screening strategy to search for potential drugs was proposed, using molecular docking to explore a library of approved drugs available in the DrugBank database in order to identify possible NSP15 inhibitors to treat Covid19 disease. We found from the docking analysis that the antiviral drugs: Paritaprevir and Elbasvir, currently both approved for hepatitis C treatment which showed some of the lowest free binding energy values were considered as repositioning drugs to combat SARS‐CoV‐2. Furthermore, molecular dynamics simulations of the Apo and Holo‐Nsp15 systems were performed in order to get insights about the stability of these protein‐ligand complexes.
A quantitative detection of Cardiotrophin‐1 in chronic heart failure by chemiluminescence immunoassay
Authors: Ping Ying , Wang Xuchu , Dai Yibei , Wang Danhua , Liu Weiwei , Yu Pan , Tao Zhihua 
Published: March 2021

AbstractBackgroundCardiotrophin‐1 (CT‐1) is a cytokine that could induce cardiomyocytes hypertrophy and dysfunction. Plasma CT‐1 might serve as a cardiac biomarker both in diagnosis, staging, and prognostic assessment of heart failure.MethodsIn this study, a one‐step paramagnetic particles‐based chemiluminescence immunoassay (MPs‐CILA) for rapid and sensitive detection of plasma CT‐1 was established. Plasma samples were directly incubated with biotin‐labeled anti‐CT‐1 antibody (bio‐Ab) and acridine ester labeled anti‐CT‐1 antibody (AE‐Ab) to form sandwiched complex. The sandwiched CT‐1 was then captured by streptavidin modified paramagnetic particles (MPs‐SA) for rapid separation and signal generation.ResultsThe proposed MPs‐CLIA presents a laudable linear relationship ranging from 7.8 pg/mL to 200 ng/mL with a detection limit of 1.0 pg/mL. The recoveries of spiked human plasma samples at low (10pg/mL), medium (100 pg/mL), and high (800 pg/mL) levels of CT‐1 were 96%, 104%, and 110% respectively. The intra‐analysis coefficient variation (CVs) of the 3 samples was 8.92%, 6.69%, and 3.54%, respectively. And the inter‐analysis coefficient variation (CVs) was 9.25%, 10.9%, and 4.3%, respectively. These results strongly indicate high sensitivity, wide linear range, acceptable precision, and applicable reproducibility of the proposed method to detect plasma level of CT‐1. Finally, Plasma CT‐1 from 140 subjects with or without chronic heart failure was analyzed to assess the clinical application of MPs‐CILA.ConclusionsNoteworthily, the MPs‐CLIA method is highly automated such that it is suitable for high‐throughput detection of CT‐1 in clinical inspection.
Ribociclib Population Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Analysis of Neutrophils in Cancer Patients
Authors: Lu Yasong , Yang Shu , Ho Yu‐Yun , Ji Yan 
Published: March 2021

AbstractThe population pharmacokinetics (popPK) of ribociclib and population pharmacokinetic/pharmacodynamic (PK/PD) relationship between ribociclib and absolute neutrophil count (ANC) were characterized in patients with cancer. PopPK and ANC PK/PD modeling were both conducted in 2 rounds per data availability. Initial models were developed based on data sets from early‐phase trials and qualified using external data from the phase III MONALEESA‐2 trial. The second round of analyses was performed using updated data sets that included 2 more phase III trials (MONALEESA‐3 and ‐7). The popPK and ANC PK/PD models adequately described the data and demonstrated reasonable predictive ability. Covariate analysis showed that ribociclib PK were not affected by age, sex, race, baseline Eastern Cooperative Oncology Group (ECOG) status (grade 1), mild/moderate renal impairment, mild hepatic impairment, or concomitant use of combination partners, including aromatase inhibitors (letrozole, anastrozole) or fulvestrant, proton‐pump inhibitors, or weak cytochrome P450 3A4/5 inhibitors. Body weight had no impact on ribociclib clearance to warrant dose adjustment. The ANC PK/PD relationship was not affected by age, weight, sex, race, baseline ECOG status (grade 1), or concomitant use of letrozole, anastrozole, or fulvestrant. The PK/PD analysis confirmed reversibility of ribociclib's effect on ANC; it also suggested that lowering the dose of ribociclib would mitigate ANC decrease and neutropenia risk. The popPK and ANC PK/PD analyses support the use of ribociclib in combination with an aromatase inhibitor or fulvestrant in patients with hormone receptor–positive, human epidermal growth factor receptor‐2–negative advanced or metastatic breast cancer without dose adjustment in subpopulations, and the use of dose interruption/reduction to mitigate potential treatment‐emergent neutropenia.
Identification of lncRNA expression profiles and analysis of ceRNA in the hippocampus of perinatal glyphosate‐exposed mice
Authors: Fan Xingli , Wang Dawei , Shen Xiangdi , Qiu Jianing , Wu Lihui , Yan Jie , Ji Hua 
Published: March 2021

AbstractObjectiveIn order to understand the role of long noncoding RNAs (lncRNAs) played in the mechanisms of glyphosate neurotoxicity in neuronal development.MethodsPerinatal glyphosate exposure (PGE) mouse model was constructed, and a lncRNA microarray was used to study the lncRNA expression changes in the hippocampus tissue of perinatal glyphosate exposure mice. Then we used GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) databases to analyze the function of the differentially expressed mRNAs and lncRNAs.ResultsLncRNA microarray analysis revealed that 1759 lncRNAs and 759 mRNAs were differentially expressed in the perinatal glyphosate exposure (PGE) mice group (G group) compared with the normal control mice group (C group). The functions of the DEmRNAs are involved in the cellular response to hormone stimulus. The ceRNA analysis showed that some interaction networks existed, including (ENSMUST00000137546, ENSMUST00000160950)/(miR‐34a‐3p, miR‐130a‐3p)/(Il12b, Irf1). Further analysis of the target mRNAs of miRNAs indicated that the possible functions involved the neuroactive ligand‐receptor interaction and calcium signaling pathway, which are involved in perinatal glyphosate exposure‐induced neurotoxicity.ConclusionThe aberrant expression of lncRNAs is related to the perinatal glyphosate‐exposed neurotoxicity. These lncRNAs affect the target gene expression level, might by regulating neuroactive ligand‐receptor interactions. The (ENSMUST00000137546, ENSMUST00000160950)/ (miRNA‐34a‐5p, miR‐130a‐3p) / mRNAs (e.g., Il12b, Irf1) interaction network may functions in perinatal glyphosate exposure‐induced neurotoxicity.
Stimulated emission depletion microscopy for biological imaging in four dimensions: A review
Authors: Wu Zhaoyang , Xu Xinzhu , Xi Peng 
Published: March 2021

AbstractStimulated emission depletion (STED) microscopy allows high lateral and axial resolution, long term imaging in living cells. Here we review recent technical advances in STED microscopy, with emphasis on resolution and measurement range of XYZt four dimensions. Different STED technical advances and novel STED probes are discussed with their respective application in biological subcellular imaging. This review may serve as a practical guide for choosing a suitable approach to the advanced STED super‐resolution imaging.
Characterization of genetic counselor practices in inpatient care settings
Authors: Magness Emily , Magoulas Pilar , Moscarello Tia , Ma Daria , Helm Benjamin M. , Mizerik Elizabeth 
Published: March 2021

AbstractRapid genomic testing is increasingly used in inpatient settings for diagnostic and treatment purposes. With the expansion of genetic testing in this setting, requests for inpatient genetics consultations have increased. There have been reports of genetic counselors working in inpatient care, though their specific roles are not well described. In this study, we characterized the roles of genetic counselors practicing in inpatient care settings in the United States and Canada. Genetic counselors were recruited via professional organization listservs to complete an online survey. The survey gathered information on participants' roles and workflow of inpatient genetics consultation services at their institution. Responses from 132 participants demonstrate that 50.4% of genetic counselors cover genetics consultations as needed or on a rotating schedule (34.6%). They practice in general pediatric (59.1%), neonatal (42.5%), cancer (28.3%), and/or prenatal (18.9%) specialties, among others. Participants reported working independently (16.1%) or with other providers (54.8%), including geneticists and other attending physicians. The workflow of genetics consultation services varies between institutions in the delivery of consults, members of the inpatient genetics consultation care team, and administrative support. Fifty percent of participants reported having no exposure to inpatients during graduate training, and 87.3% of participants reported receiving no institutional training for their inpatient role. This is the first study to describe roles of genetic counselors in inpatient care. It establishes a foundation for future research on inpatient genetic counseling and genetic counseling outcomes in inpatient services. As demand for genetics expertise in inpatient care grows, genetic counselors can be hired to serve inpatient populations alongside genetics and non‐genetics providers.
Real‐world treatment patterns, adverse events and clinical outcomes in patients with chronic lymphocytic leukaemia treated with ibrutinib in the UK
Authors: Hillmen Peter , Xie Jing , Yong Alan S. M. , Waweru Catherine , Sorof Thuy Anh , Goyal Ravi K. , Davis Keith L. 
Published: March 2021

AbstractChronic lymphocytic leukaemia (CLL) is the most common leukaemia in adults in the UK. Ibrutinib, an oral Bruton tyrosine kinase inhibitor (BTKi) for CLL approved by the UK's National Institute for Health and Care Excellence in January 2017, represented a major shift in CLL management. Real‐world data on ibrutinib use in routine clinical practice will inform patients’ and physicians’ decision‐making. We conducted a retrospective medical chart review of UK patients with CLL who initiated ibrutinib between January 2017 and July 2018. Data for 259 patients were contributed by 34 haematology‐oncology specialists, with a median follow‐up duration of 16.7 months. Median age at ibrutinib initiation was 71 years. Ibrutinib first‐line monotherapy was prescribed in 20.1% of patients. Ibrutinib was permanently discontinued in 15.4% of patients, mostly owing to progressive disease. Adverse events (AEs) were reported in 151 patients (58.3%). The most common were bruising (19.3% of patients), cytopenias (17.0%) and diarrhoea (11.6%). Ibrutinib dose reduction was observed in 14.3% of patients and was temporarily discontinued in 10.4% of patients, with the main reason for both being toxicity. These results expand the real‐world evidence on ibrutinib therapy and demonstrate a high burden of AEs, highlighting the need for more tolerable BTKis.
Fe3O4@SiO2@D‐NHCS‐Tr as an efficient and reusable catalyst for the synthesis of indol‐3‐yl‐4H‐chromene via a multi‐component reaction under solvent‐free conditions
Authors: Baharfar Robabeh , Peiman Sahar , Maleki Behrooz 
Published: March 2021

AbstractFe3O4@SiO2@D‐NHCS‐Tr was used as an efficient catalyst in the three‐component reaction between indole derivatives, salicylaldehyde, and active methylene compounds under solvent‐free conditions to the synthesis of indol‐3‐yl‐4H‐chromene derivatives. The features of this method include the green conditions of the reaction, easy separation, eco‐friendly and cost‐effectiveness of the catalyst, and high yield in short reaction times.
Design, synthesis, anticancer activity, and in silico studies of novel imidazo[1,2‐a]pyridine based 1H‐1,2,3‐triazole derivatives
Authors: Endoori Srinivas , Gulipalli Kali Charan , Bodige Srinu , Ravula Parameshwar , Seelam Nareshvarma 
Published: March 2021

AbstractA novel series of imidazo[1,2‐a]pyridine based 1H‐1,2,3‐triazole derivatives were designed, synthesized, and evaluated for their anticancer activity against two different human cancer cell lines. Most of the synthesized compounds displayed anticancer activity with IC50 values from 2.35 to 120.46 μM. Furthermore, compounds 9b, 9c, 9d, 9f, and 9j showed potent inhibitory activity against cancer cell lines, with IC50 values close to that of standard drug. It is important to note that compound 9d was more potent than the standard drug cisplatin with IC50 values of 10.89 and 2.35 μM against Hela cell line and MCF‐7 cell line, respectively.