Miracle-dz/UniFAR-FTUs huggingface dataset:
Albumin Enhances the Rate at Which Coxsackievirus B3 Strain 28 Converts to A-Particles

A factor other than the virus receptor expressed by target cells has been found to accelerate the loss of an enterovirus (CVB3/28) infectious titer, with little effect on nearly identical mutant strains. The destabilizing factor in fetal bovine serum, identified as albumin, does not interfere with the catalytic activity of soluble receptor at saturating receptor concentrations and amplifies the catalytic activity of the soluble receptor at a concentration that otherwise produces about one-third the saturated receptor-catalyzed rate of virus decay. This finding evidences the possibility that other virus-“priming” ligands may also be nonessential activating cofactors that serve to accelerate receptor-catalyzed viral eclipse. ABSTRACT Three strains of coxsackievirus B3 (CVB3) differ by single mutations in capsid protein VP1 or VP3 and also differ in stability at 37°C in tissue culture medium. Among these strains, the CVB3/28 parent strain has been found to be uniquely sensitive to a component in fetal bovine serum (FBS) identified as serum albumin. In cell culture medium, serum increased the rate of CVB3/28 conversion to noninfectious particles at least 2-fold. The effect showed a saturable dose response. Rates of conversion to noninfectious virus with high concentrations of soluble coxsackievirus and adenovirus receptor (sCAR) were similar with and without FBS, but FBS amplified the catalytic effect of 100 nM sCAR nearly 3-fold. Such effects in other systems are due to nonessential activating cofactors. IMPORTANCE A factor other than the virus receptor expressed by target cells has been found to accelerate the loss of an enterovirus (CVB3/28) infectious titer, with little effect on nearly identical mutant strains. The destabilizing factor in fetal bovine serum, identified as albumin, does not interfere with the catalytic activity of soluble receptor at saturating receptor concentrations and amplifies the catalytic activity of the soluble receptor at a concentration that otherwise produces about one-third the saturated receptor-catalyzed rate of virus decay. This finding evidences the possibility that other virus-“priming” ligands may also be nonessential activating cofactors that serve to accelerate receptor-catalyzed viral eclipse.
The septate junction protein Mesh is required for epithelial morphogenesis, ion transport and paracellular permeability in the Drosophila Malpighian tubule.

Septate junctions (SJs) are occluding cell-cell junctions that have roles in paracellular permeability and barrier function in the epithelia of invertebrates. Arthropods have two types of SJs, pleated SJs (pSJs) and smooth SJs (sSJs). In Drosophila melanogaster, sSJs are found in the midgut and Malpighian tubules, but the functions of sSJs and their protein components in the tubule epithelium are unknown. Here we examined the role of the previously identified integral sSJ component, Mesh, in the Malpighian tubule. We genetically manipulated mesh specifically in the principal cells of the tubule at different life stages. Tubules of flies with developmental mesh knockdown revealed defects in epithelial architecture, sSJ molecular and structural organization, and lack of urine production in basal and kinin-stimulated conditions, resulting in edema and early adult lethality. Knockdown of mesh during adulthood did not disrupt tubule epithelial and sSJ integrity, but decreased the transepithelial potential, diminished transepithelial fluid and ion transport, and decreased paracellular permeability to 4 kDa dextran. Drosophila kinin decreased transepithelial potential and increased chloride permeability, and stimulated fluid secretion in both control and adult mesh knockdown tubules, but had no effect on 4 kDa dextran flux. Together, these data indicate roles for Mesh in the developmental maturation of the Drosophila Malpighian tubule and in ion and macromolecular transport in the adult tubule.
An evaluation of the impact of lifestyle interventions on body weight in postpartum women: A systematic review and meta‐analysis

The established efficacy in postpartum lifestyle interventions has not been translated into better outcomes. This systematic review and meta‐analysis assess the penetration (the proportion of women invited within the target population), implementation (fidelity), participation (the proportion of those invited who enrolled), and effect (weight loss compared to controls) (PIPE) of randomized controlled trials of lifestyle interventions in postpartum women (within two years after birth). MEDLINE, EMBASE, Pubmed, and other databases and clinical trial registries were searched up to the 3rd of May 2019. Data was extracted from published reports and missing data was obtained from study authors. The quality of the studies was appraised using the Cochrane Risk of Bias tool (2·0). Main outcomes were the PIPE impact metrics and changes in body weight. Thirty‐six trials (49 publications) were included (n=5,315 women). One study provided sufficient information to calculate the population penetration rate (2·5%). All studies provided implementation (fidelity) information, but over half had low program fidelity. The participation rate was calculated for nine studies (0·94% to 86%). There was significant change in body weight (mean difference (MD) (95% confidence interval, CI) of ‐2·33 (‐3·10 to ‐1·56). This highlights the inadequacy of conventional RCTs to inform implementation. Future research should broaden methods to pragmatic trials.
Human papillomavirus oncoproteins and post-translational modifications: generating multifunctional hubs for overriding cellular homeostasis

Abstract Human papillomaviruses (HPVs) are major human carcinogens, causing around 5% of all human cancers, with cervical cancer being the most important. These tumors are all driven by the two HPV oncoproteins E6 and E7. Whilst their mechanisms of action are becoming increasingly clear through their abilities to target essential cellular tumor suppressor and growth control pathways, the roles that post-translational modifications (PTMs) of E6 and E7 play in the regulation of these activities remain unclear. Here, we discuss the direct consequences of some of the most common PTMs of E6 and E7, and how this impacts upon the multi-functionality of these viral proteins, and thereby contribute to the viral life cycle and to the induction of malignancy. Furthermore, it is becoming increasingly clear that these modifications, may, in some cases, offer novel routes for therapeutic intervention in HPV-induced disease.
Leadership for success in transforming medical abortion policy in Canada

Objectives Mifepristone was approved for use in medical abortion by Health Canada in 2015. Approval was accompanied by regulations that prohibited pharmacist dispensing of the medication. Reproductive health advocates in Canada recognized this regulation would limit access to medical abortion and successfully worked to have this regulation removed in 2017. The purpose of this study was to assess the leadership involved in changing these regulations so that the success may be replicated by other groups advocating for health policy change. Methods This study involved a mixed methods instrumental design in the context of British Columbia, Canada. Our data collection included: a) interviews with seven key individuals, representing the organizations that worked in concert for change to Canadian mifepristone regulations, and b) document analysis of press articles, correspondence, briefing notes, and meeting minutes. We conducted a thematic analysis of transcripts of audio-recorded interviews. We identified strengths and weaknesses of the team dynamic using the Develop Coalitions, Achieve Results and Systems Transformation domains of the LEADS Framework. Results Our analysis of participant interviews indicates that autonomy, shared values, and clarity in communication were integral to the success of the group’s work. Analysis using the LEADS Framework showed that individuals possessed many of the capabilities identified as being necessary for successful health policy leadership. A lack of post-project assessment was identified as a possible limitation and could be incorporated in future work to strengthen dynamics especially when a desired outcome is not achieved. Document analysis provided a clear time-line of the work completed and suggested that strong communication between team members was another key to success. Conclusions The results of our analysis of the interviews and documents provide valuable insight into the workings of a successful group committed to a common goal. The existing collegial and trusting relationships between key stakeholders allowed for interdisciplinary collaboration, rapid mobilization, and identification of issues that facilitated successful Canadian global-first deregulation of mifepristone dispensing.
Partners’ Daily Love and Desire as Predictors of Engagement in and Enjoyment of Sexual Activity

Abstract Romantic love and sexual desire have often been seen as two distinct constructs and studied separately. However, in most romantic relationships love, desire, and sex are intertwined. The purpose of the present study was to examine whether daily feelings of love and desire influence engagement in and enjoyment of sexual activity. Ninety mixed-sex couples (N = 180) completed a 30-day daily diary. The results were analyzed using hierarchical linear modeling and showed that both love and desire significantly predicted engagement in and enjoyment of sexual activity with desire being a stronger predictor. Clinical implications and future directions are discussed.
Optimal dose of buprenorphine in opioid use disorder treatment: a review of pharmacodynamic and efficacy data

Abstract Context: There is currently no consensus regarding optimal dose or dose-range of buprenorphine (BUP) for treatment of opioid use disorder (OUD). Objective: To elucidate the relationship between BUP dose and opioid receptor blockade, retention in treatment and illicit opioid drug use. Methods: Systematic review of the scientific literature through searches in the databases MEDLINE and PubMed. Results: The review of the opioid receptor blockade studies did not find evidence that a daily sublingual (SL) BUP tablet dose higher than 16 mg confers added blockade benefit, while doses under 8 mg are insufficient to produce opioid receptor blockade. The data are inconclusive regarding the relative effectiveness of an 8 mg SL BUP tablet dose versus a 16 mg SL BUP tablet dose in terms of opioid receptor blockade. The review did not establish any clear relationship between BUP dose and treatment retention or illicit opioid use. Conclusions: The BUP dose in treatment of OUD should be individualized based on a continuous clinical benefit-risk assessment. Further research is needed to better understand the relationship between dose and efficacy over time in patients with this complex disorder.
Evaluation of psychiatric diagnosis, substance use situations, sociodemographic and clinical features of cases in forensic psychiatry unit

Objectives: The aim of the study is to investigate the diagnosis, substance use situations, sociodemographic and clinical features of cases referred from forensic medicine to our forensic psychiatry clinic. Method: In this study archive files and reports of 412 cases referred from forensic medicine to Gaziantep University Faculty of Medicine Forensic Psychiatry Clinic between 2007-2011 years were investigated retrospectively. Results: Cases in which substance use and dependence were evaluated, cannabis was found to be 57.1%, heroin 14.6%, multiple substances 13.1% and drug 0.5%. Cases that were evaluated with regards to TCK 32, multiple substances were found to be 7.7%, cannabis 6.9%, and heroin 3.8%. Male sex was found to be significantly higher and educational levels were found to be significantly lower in cases in terms of crime, substance use and dependence and evaluated for criminal liability. In our study, cases involved in crime, had the psychiatric diagnoses in order of frequency as substance dependence, psychotic disorders and mood disorders. Discussion: People with substance use and dependence are too much involved in crime directlyor indirectly depending upon the substance use. These people are frequently enrolled in the judicial system and in this process they are subjects of forensic psychiatry.
How the Reputation of Orthopaedic Residency Programs Is Associated with Orthopaedic Fellowship Match Results.

BACKGROUND The primary goal of the present study was to determine if applicants from higher-ranking U.S. orthopaedic surgery residency programs match at a more desired position on their fellowship match-rank list compared with those applicants from lower-ranked residency programs. METHODS San Francisco Match provided results regarding applicant data and match results from 2014 to 2018 for all orthopaedic subspecialties except the hand and the shoulder and elbow. Unmatched applicants and international medical graduates were excluded. Residency programs were divided into 5 tiers (with tier 1 being the highest-ranked residency programs and tier 5 being the lowest-ranked programs) on the basis of 2018 Doximity rankings of orthopaedic residency programs. Statistical analysis consisted of descriptive statistics, chi-square tests, and analysis of variance. RESULTS Two thousand eight hundred and eleven applicants met inclusion criteria. Applicants from residency programs in tiers 1 and 2 applied to significantly fewer programs than those from tiers 3, 4, or 5 (p < 0.0001). Applicants from each tier were significantly more likely to attain interviews than applicants from all tiers below them (p < 0.01). Applicants from tier-1 residency programs matched at a significantly higher position on their rank list (p < 0.001) and were more desirably ranked by fellowship programs (p = 0.003) compared with all other tiers. CONCLUSIONS Applicants from the highest-ranking residency programs apply to fewer programs, interview at a greater percentage of these programs, and are more likely to match to 1 of their top-ranking programs than applicants from lower-ranking programs. However, the association of the applicant match position with the program ranking appears to be most pronounced when it comes to fellowships selecting which applicants to interview. These findings may help future applicants when determining which programs to apply to during the match.
Examining policy implementation for type 2 diabetes : exploring barriers and enablers associated with uptake of structured patient education

Background: Diabetes remains an incurable disease and as the search for a cure continues, the need to minimise complications and enhance the quality of life of patients is essential. A key UK policy initiative in the management of diabetes is empowerment through education. However, implementation of policy in the context of healthcare delivery in general may be challenging at times and the provision and uptake of diabetes education is not an exception. Aims: This thesis aims to examine the barriers and enhancing factors that are associated with the uptake of structured patient education for patients newly diagnosed with type 2 diabetes. Methods: The study used a sequential mixed methods approach. The data were collected using a focus group and face-to-face individual interviews of multiprofessionals delivering the education, a questionnaire/survey of patients and individual face-to-face interviews of referring practitioners working in GP surgeries within a PCT. Findings: Factors influencing non-attendance at diabetes education centres relate to barriers associated with the patients, practitioners and government regulations. The patients were affected by their healthcare beliefs and personal circumstances such as work patterns, childcare problems, forgetfulness, bad weather and ill health. The practitioners’ barriers were mainly around patient versus practitioner communication, inter-professional collaboration and administrative protocols. The barriers associated with the government directives relate to government regulations and funding issues. In contrast to barriers, the predictors of attendance are personal motivation, individual perceptions and beliefs coupled with the guidance given by the practitioners. Whilst it may be difficult to avoid non-attendance completely, positive steps to reduce nonattendance include enhanced communication, a positive pay-for-performance system and adequate support to develop a positive attitude towards diabetes education. Conclusion: The results indicate that barriers to attendance are multifactorial and complex; therefore, response to improve uptake requires diverse interventions.
A prospective multisite examination of dynamic sexual violence risk: Extension and update to Olver, Nicholaichuk, Kingston, and Wong (2014).

OBJECTIVE The present study is an extension and update of Olver, Nicholaichuk, Kingston, and Wong's (2014) prospective multisite examination of sexual violence risk and treatment change on a large federal Canadian sample of 570 treated sexual offenders rated pretreatment and posttreatment on the Violence Risk Scale-Sexual Offense version (VRS-SO). METHOD The present study featured the clinical application of a risk assessment and treatment planning tool, the VRS-SO, with recidivism outcome data updated by 4 years to a total of 10.2 years. VRS-SO change scores, representing reductions in sexual violence risk from treatment or other change agents (e.g., aging), were reanalyzed in terms of their associations with community sexual, violent, and general recidivism postrelease. RESULTS Recidivism base rates increased with the concordant increase in follow-up time. VRS-SO risk scores significantly predicted all recidivism outcomes, whereas change scores were consistently associated with decreases in sexual and violent recidivism after controlling for baseline risk through bivariate (d = -.24 to -.61) and Cox regression survival analyses (eB = .878 to .938). CONCLUSIONS The results affirm the dynamic nature of sexual violence risk and demonstrate that structured assessments of change, linked to participation in sexual offense specific treatment, to be associated with decreases in future sexual offending as well as other recidivism outcomes. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
The protective potential of Fc‐mediated antibody functions against influenza virus and other viral pathogens

In recent years, there has been a renewed interest in utilizing antibody fragment crystallizable (Fc) functions to prevent and control viral infections. The protective and therapeutic potential of Fc‐mediated antibody functions have been assessed for some clinically important human viruses, including HIV, hemorrhagic fever viruses and influenza virus. There is mounting evidence that influenza‐specific antibodies with Fc‐mediated functions, such as antibody‐dependent cellular cytotoxicity and antibody‐dependent phagocytosis, can aid in the clearance of influenza virus infection. Recent influenza challenge studies and intravenous immunoglobulin G therapy studies in humans suggest a protective role for Fc effector functions in vivo. Broadly reactive influenza antibodies with Fc‐mediated functions are prevalent in the human population and could inform the development of a universally protective influenza vaccine or therapy. In this review, we explore the utility of antibodies with Fc‐mediated effector functions against viral infections with a focus on influenza virus.
Rutaecarpine derivative R3 attenuates atherosclerosis via inhibiting NLRP3 inflammasome‐related inflammation and modulating cholesterol transport

Atherosclerosis is a chronic disease characterized by lipid deposition and inflammatory response. NOD‐, LRR‐ and pyrin domain‐containing protein 3 (NLRP3) inflammasome‐facilitated inflammatory responses are crucial in the pathogenesis of atherosclerosis, and thus new therapeutic approaches are emerging that target NLRP3 and inflammation. Here, we explored the anti‐atherosclerotic effect and mechanisms of a new rutaecarpine derivative, 5‐deoxy‐rutaecarpine (R3) in vitro and in vivo. R3 treatment attenuated atherosclerosis development and increased plaque stability in Apoe−/− mice fed a high‐fat diet, and decreased levels of inflammatory mediators, such as interleukin‐1β, in the serum of Apoe−/− mice and in oxidized low‐density lipoprotein (ox‐LDL)‐stimulated murine macrophages. R3 treatment inhibited NLRP3 inflammasome activation in the livers of Apoe−/− mice and ox‐LDL‐stimulated murine macrophages by inhibiting NF‐κB and MAPK pathways. Additionally, R3 significantly decreased total cholesterol in the serum and livers of Apoe−/− mice and promoted cholesterol efflux in murine macrophages through upregulating protein expression of ATP‐binding cassette subfamily A member 1 and scavenger receptor class B type I/human CD36 and lysosomal integral membrane protein‐II analogous‐1. Our results demonstrated that R3 prevented atherosclerotic progression via attenuating NLRP3 inflammasome‐related inflammation and modulating cholesterol transport.
Relationships Between Abdominal Pain and Fatigue With Psychological Distress as a Mediator in Women With Irritable Bowel Syndrome

Supplemental Digital Content is Available in the Text. Women with irritable bowel syndrome often report fatigue, along with abdominal pain and psychological distress (i.e., depression and anxiety). There is little information about the relationships among these symptoms. Using a secondary data analysis (N = 356), we examined the relationship between abdominal pain and fatigue and whether psychological distress mediates the effect of abdominal pain on fatigue in both across women and within woman with irritable bowel syndrome. Data gathered through a 28-day diary were analyzed with linear regressions. The across-women and within-woman relationships among same-day abdominal pain, fatigue, and psychological distress were examined. Within-woman relationships were also examined for directionality among symptoms (i.e., prior-day abdominal pain predicts next-day fatigue and prior-day fatigue predicts next-day abdominal pain). In across-women and within-woman analyses on the same day, abdominal pain and fatigue were positively correlated. In within-woman analyses, abdominal pain predicted next-day fatigue, but fatigue did not predict next-day pain. In across-women and within-woman analyses, psychological distress partially mediated the effects of abdominal pain on fatigue. Symptom management incorporating strategies to decrease both abdominal pain and psychological distress are likely to reduce fatigue. Nursing interventions, such as self-management skills to reduce abdominal pain and psychological distress, may have the added benefit of reducing fatigue in irritable bowel syndrome.