Miracle-dz/UniFAR-FTUs huggingface dataset:
Determinants of physicians' career choices in Ukraine

Political and economic changes have created challenges for physician attrition rates in Ukraine. This study examined how a cross-section of Ukrainian physicians prioritised the factors hypothesised to influence decisions about continuing to work in medicine. A survey was conducted with 443 physicians in Ukraine. Latent class choice analysis (LCA) was used to model the heterogeneity in pair-wise comparisons of factors related to physician continued employment in medicine. The response rate was 70% (N = 310). Respondents, on average, were 45.4 years old, practiced 21.6 years. Four groups were identified on the basis of how they prioritised factors about work. Group 1 (47.7%) was ‘culture-focused’, group 2 (27.7%) was ‘advancement-focused’, group 3 (16.2%) was ‘routinisation-focused’, and group 4 (8.5%) was ‘externally-focused’. The use of a person-centred analytical approach represents an alternative for examining career decision issues that should be considered for subgroups within the workforce.
Phosphorylation and turnover of paxillin in focal contacts is controlled by force and defines the dynamic state of the adhesion site

Micro‐environmental clues are critical to cell behavior. One of the key elements of migration is the generation and response to forces. Up to now there is no definitive concept on how the generation and responses to cellular forces influence cell behavior. Here, we show that phosphorylation of paxillin is a crucial event in the response to exogenous forces. Application of force induced growth of adhesion sites and this phenomenon was accompanied by a downregulation of Src family kinase activity, which in turn led to a decrease in the phosphorylation of paxillin at the tyrosine residues Y31 and Y118. The force‐dependent growth of adhesion sites is mediated by a decrease in the turnover‐rate of paxillin in focal contacts. This turnover critically depended on the phosphorylation state of paxillin at Y31/118. Paxillin is an important regulator in the control of the aggregate state of the whole adhesion site since the turnover of other adhesion site proteins such as vinculin is influenced by the phosphorylation state of paxillin as well. Taken together these data suggest that SFK dependent phosphorylation of paxillin is a crucial event in the regulation of adhesion site function in response to force. © 2015 Wiley Periodicals, Inc.
A risk score to identify HIV-infected women most likely to become lost to follow-up in the postpartum period*

ABSTRACT Access to lifelong combination antiretroviral therapy (cART) is expanding among HIV-infected pregnant and breastfeeding women throughout sub-Saharan Africa (SSA). For this strategy to meaningfully improve maternal HIV outcomes, retention in HIV care is essential. We developed a risk score to identify women with high likelihood of loss to follow-up (LTFU) at 6 months postpartum from HIV care, using data from public health facilities in Lusaka, Zambia. LTFU was defined as not presenting for HIV care within 60 days of the last scheduled appointment. We used logistic regression to assess demographic, obstetric and HIV predictors of LTFU and to develop a simple risk score. Sensitivity and specificity were assessed at each risk score cut-point. Among 2029 pregnant women initiating cART between 2009 and 2011, 507 (25%) were LTFU by 6 months postpartum. Parity, education, employment status, WHO clinical stage, duration of cART during pregnancy and number of antenatal care visits were associated with LTFU (p-value < .10). A risk score cut-point of 11 (42nd percentile) had 85% sensitivity (95% CI 82%, 88%) and 22% specificity (95% CI 20%, 24%) to detect women LTFU and would exclude 20% of women from a retention intervention. A risk score cut-point of 18 (69th percentile) identified the 23% of women with the highest probability of LTFU and had sensitivity 32% (95% CI 28%, 36%) and specificity 80% (95% CI 78%, 82%). A risk score approach may be useful to triage a subset of women most likely to be LTFU for targeted retention interventions.
Cannabinoid receptor signalling in neurodegenerative diseases: a potential role for membrane fluidity disturbance

Type‐1 cannabinoid receptor (CB1) is the most abundant G‐protein‐coupled receptor (GPCR) in the brain. CB1 and its endogenous agonists, the so‐called ‘endocannabinoids (eCBs)’, belong to an ancient neurosignalling system that plays important functions in neurodegenerative and neuroinflammatory disorders like Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and multiple sclerosis. For this reason, research on the therapeutic potential of drugs modulating the endogenous tone of eCBs is very intense. Several GPCRs reside within subdomains of the plasma membranes that contain high concentrations of cholesterol: the lipid rafts. Here, the hypothesis that changes in membrane fluidity alter function of the endocannabinoid system, as well as progression of particular neurodegenerative diseases, is described. To this end, the impact of membrane cholesterol on membrane properties and hence on neurodegenerative diseases, as well as on CB1 signalling in vitro and on CB1‐dependent neurotransmission within the striatum, is discussed. Overall, present evidence points to the membrane environment as a critical regulator of signal transduction triggered by CB1, and calls for further studies aimed at better clarifying the contribution of membrane lipids to eCBs signalling. The results of these investigations might be exploited also for the development of novel therapeutics able to combat disorders associated with abnormal activity of CB1.
Welcome back survey: exploring concerns impacting HIV care engagement and retention

ABSTRACT The current study describes the development of a short pre-clinic survey that helped multidiscipline providers to elicit patient perspective on barriers to HIV primary care. The survey was piloted with 318 patients returning to care after being lost to care for at least 12 months. Reasons for breaks in care were dependent on age, gender, and race. Concerns about confidentiality in care were more commonly reported by African-American, Latino, and younger patients, while concerns relating to acceptance of diagnosis and side effects were greater for women, African-American, and Latino participants. Further, Intimate Partner Violence (IPV) and transportation were greater concerns for women and younger patients in the sample.
Structure and quality of outpatient care for people living with an HIV infection

ABSTRACT Policy-makers and clinicians are faced with a gap of evidence to guide policy on standards for HIV outpatient care. Ongoing debates include which settings of care improve health outcomes, and how many HIV-infected patients a health-care provider should treat to gain and maintain expertise. In this article, we evaluate the studies that link health-care facility and care provider characteristics (i.e., structural factors) to health outcomes in HIV-infected patients. We searched the electronic databases MEDLINE, PUBMED, and EMBASE from inception until 1 January 2015. We included a total of 28 observational studies that were conducted after the introduction of combination antiretroviral therapy in 1996. Three aspects of the available research linking the structure to quality of HIV outpatient care were evaluated: (1) assessed structural characteristics (i.e., health-care facility and care provider characteristics); (2) measures of quality of HIV outpatient care; and (3) reported associations between structural characteristics and quality of care. Rather than scarcity of data, it is the diversity in methodology in the identified studies and the inconsistency of their results that led us to the conclusion that the scientific evidence is too weak to guide policy in HIV outpatient care. We provide recommendations on how to address this heterogeneity in future studies and offer specific suggestions for further reading that could be of interest for clinicians and researchers.
Keeping the focus on biophysics and actin filaments in Nagoya: A report of the 2016 “now in actin” symposium

Regulatory systems in living cells are highly organized, enabling cells to response to various changes in their environments. Actin polymerization and depolymerization are crucial to establish cytoskeletal networks to maintain muscle contraction, cell motility, cell division, adhesion, organism development and more. To share and promote the biophysical understanding of such mechanisms in living creatures, the “Now in Actin Study: ‐Motor protein research reaching a new stage‐” symposium was organized at Nagoya University, Japan on 12 and 13, December 2016. The organizers invited emeritus professor of Nagoya and Osaka Universities Fumio Oosawa and leading scientists worldwide as keynote speakers, in addition to poster presentations on cell motility studies by many researchers. Studies employing various biophysical, biochemical, cell and molecular biological and mathematical approaches provided the latest understanding of mechanisms of cell motility functions driven by actin, microtubules, actin‐binding proteins, and other motor proteins.
Liposome‐encapsulated dexamethasone attenuates ventilator‐induced lung inflammation

BACKGROUND AND PURPOSE Systemic glucocorticoid therapy may effectively attenuate lung inflammation but also induce severe side‐effects. Delivery of glucocorticoids by liposomes could therefore be beneficial. We investigated if liposome‐encapsulated dexamethasone inhibited ventilator‐induced lung inflammation. Furthermore, we evaluated whether targeting of cellular Fcγ‐receptors (FcγRs) by conjugating immunoglobulin G (IgG) to liposomes, would improve the efficacy of dexamethasone‐liposomes in attenuating granulocyte infiltration, one of the hallmarks of lung inflammation.
Translational neuropharmacology and the appropriate and effective use of animal models

This issue of the British Journal of Pharmacology is dedicated to reviews of the major animal models used in neuropharmacology to examine drugs for both neurological and psychiatric conditions. Almost all major conditions are reviewed. In general, regulatory authorities require evidence for the efficacy of novel compounds in appropriate animal models. However, the failure of many compounds in clinical trials following clear demonstration of efficacy in animal models has called into question both the value of the models and the discovery process in general. These matters are expertly reviewed in this issue and proposals for better models outlined. In this editorial, we further suggest that more attention be made to incorporate pharmacokinetic knowledge into the studies (quantitative pharmacology). We also suggest that more attention be made to ensure that full methodological details are published and recommend that journals should be more amenable to publishing negative data. Finally, we propose that new approaches must be used in drug discovery so that preclinical studies become more reflective of the clinical situation, and studies using animal models mimic the anticipated design of studies to be performed in humans, as closely as possible.
“They said “be careful’”: sexual health communication sources and messages for adolescent girls living with perintally-acquired HIV infection

ABSTRACT Due to advances in highly active antiretroviral treatment (HAART), children “who perinatally acquired HIV infection” (PHIV+) in the United States have been reaching adolescence and adulthood in large numbers. As youth PHIV + become sexually active it is important to understand their sources of sexual health information and the messages communicated by those sources to safeguard their sexual health and that of their partners. This paper explores sexual health communication for adolescent girls PHIV + in comparison to adolescent girls who were exposed but did not acquire HIV perinatally (PHIV−) to understand how HIV infection influences the sexual health communication needs of the former. A convenience sample size of 30 (20 PHIV + and 10 PHIV−, mean age 14.5) girls completed survey and participated in a 45–90 min developmentally appropriate semi-structured interview. The interviews aimed to elicit the girls’ sources of sexual health communication, the sexual health messages they receive, their comfort or discomfort with these communications, and to determine how their sexual health communication experiences differ from those of their PHIV− peers. Transcripts of the interviews were coded and analyzed for themes related to sexual health communication sources, sexual health communication messages and comfort/discomfort with sexual health communication sources. Our findings suggest that girls PHIV + do not differ significantly from Girls PHIV− in their sources of sexual health information, yet girls PHIV + are most comfortable receiving sexual health information from their health providers, whereas for girls PHIV, the comfort is higher with caregivers. However, the messages Girls PHIV + reported receiving from their providers and caregivers were vague. Both providers and caregivers of Girls PHIV + are uniquely positioned to provide information to adolescents about sexuality and responsible sex decision-making. Some caregivers and providers may need training to prepare them to provide appropriate and accurate sexual health information to girls PHIV + .
VOLUME AND COMPOSITION OF REFLUX AFTER INTRAVITREAL INJECTION

Purpose: To quantify the amount of drug loss from cadaveric human eyes, which are injected via the pars plana with a known volume of dye at variable intraocular pressures. Methods: Eight cadaver eyes were divided into 2 intraocular pressure groups: normal (15 mmHg; 4 eyes) or high (30 mmHg; 4 eyes). Each eye was injected with 50 &mgr;L of hematoxylin dye, and the subsequent reflux was immediately collected on a Schirmer’s test strip. The test strip was scanned and digitally analyzed to determine the area of saturation and total color intensity present. Using a previously established equation, total volume of reflux and the amount of dye within that reflux were calculated. Results: The average total volume of refluxed fluid was 1.68 &mgr;L (median, 0.62 &mgr;L), with a range of 0 &mgr;L to 8.05 &mgr;L. The average volume of refluxed dye was 0.37 &mgr;L (median, 0.08 &mgr;L), with a range of 0 &mgr;L to 2.15 &mgr;L. On average, only 0.74% of the original 50 &mgr;L of injected dye was lost (median, 0.15%), with a range from 0% to 4.30%. Conclusion: Although the presence of subconjunctival bleb formation after intravitreal injection may be a concern to the clinician, data from the present study shows that only a very small amount of the injected therapeutic agent is lost in the reflux.
Celastrol inhibits proliferation and induces chemosensitization through down‐regulation of NF‐κB and STAT3 regulated gene products in multiple myeloma cells

BACKGROUND AND PURPOSE Activation of pro‐inflammatory transcription factors NF‐κB and signal transducer and activator of transcription 3 (STAT3) is one of the major contributors to both pathogenesis and chemoresistance in multiple myeloma (MM), which results in high mortality rate. Thus, in the present study, we investigated whether celastrol could suppress the proliferation and induce chemosensitization of MM cells by interfering with NF‐κB and STAT3 activation pathways.
Prevalence of and risk factors for depressive symptoms among people living with HIV/AIDS receiving antiretroviral treatment in Wuhan, China: a short report

ABSTRACT We aimed to explore the prevalence of and risk factors for depressive symptoms (DS) among people living with HIV/AIDS (PLWHA) receiving antiretroviral treatment (ART) in Wuhan, Hubei, China. A cross-sectional study evaluating adult PLWHA receiving ART in nine designated clinical hospitals was conducted from October to December 2015. The validated Beck Depression Inventory (BDI) was used to assess DS in eligible participants. Socio-demographical, epidemiological and clinical data were directly extracted from the case reporting database of the China HIV/AIDS Information Network. Multinomial regression analysis was used to explore the risk factors for DS. 394 participants were finally included in all analyses. 40.3% were found to have DS with 13.7% having mild DS and 26.6% having moderate to severe DS. The results of multinomial regression analysis suggested that being married or living with a partner, recent experience of ART-related side effects, and/or history of HCV infection were positively associated with mild DS, while increasing age was positively associated with moderate to severe DS.
Abstract PD05-02: Genome-Wide Associations of Breast Events and Functional Genomic Studies in High-Risk Women Receiving Tamoxifen or Raloxifene on NSABP P1 and P2 Prevention Trials. A Pharmacogenomics Research Network-RIKEN-NSABP Collaboration

Background: NSABP P1 and P2 are the largest prevention trials of tamoxifen and raloxifene in women at high risk of developing breast cancer. Both agents have been shown to decrease, but not eliminate breast cancer risk in these women. The goal of our study was to identify single nucleotide polymorphisms (SNPs) associated with development of breast cancer in high-risk women treated with tamoxifen or raloxifene. Methods: We performed a nested matched case-control genome-wide association study (GWAS) in subjects entered on the P2, which included only postmenopausal women, and subjects at least 50 years old entered on the P1 phase III prevention trials who were treated with tamoxifen or raloxifene. Cases were defined as subjects who developed invasive breast cancer or ductal carcinoma in situ and each was matched to two controls based on trial (P1, P2), age at trial entry, Gail risk score, history of lobular carcinoma in situ, and time on study. The study was restricted to the 94% of subjects self-identified as Caucasian. Genotyping was performed with the Illumina Human610-Quad chip. Eigenstrat analyses were performed to control for population stratification. SNPs were imputed within 200 Kb on either side of regions containing SNPs with p ≤ 3E-05. CYP2D6 genotyping was performed on all subjects. Results: The GWAS included 592 cases and 1171 controls. 547,356 SNPs were used in the analyses after removing 14,019 for call rates less than 98%, 30,560 for minor allele frequencies ZNF423, a gene known to encode a protein that associates with SMAD family members. In lymphoblastoid cell lines genotyped for the 2 top SNPs in ZNF423 (rs8060157 and rs11076499) and stably transfected with estrogen receptor-α, the variant and wild type SNPs displayed striking differences in estradiol-induced expression of ZNF423, SMAD3, BRCA1, and BRCA2. Conclusions: This GWAS revealed SNPs associated with the development of breast cancer in high-risk women treated with tamoxifen or raloxifene. Genome-wide significance was not achieved, but SNPs in ZNF423 identified on Chr 16 were associated with differential expression of ZNF423, SMAD3, BRCA1, and BRCA2 in response to estradiol in vitro, providing direction for future research. (Supported in part by NIH grants U01GM61388, U01GM63173, P50CA116201, U10CA77202, U10CA37377, U10CA69974, U24CA114732, and the Biobank Japan Project funded by the Ministry of Education, Culture, Sports, Science and Technology, Japan) Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD05-02.
From in vivo gene targeting of oestrogen receptors to optimization of their modulation in menopause

The ancestral status of oestrogen receptor (ER) in the family of the steroid receptors has probably contributed to the pleiotropic actions of oestrogens, and in particular, that of 17β‐oestradiol (E2). Indeed, in addition to their well‐described role in sexual development and reproduction, they influence most of the physiological processes. The pathophysiological counterpart of these actions includes prevention of osteoporosis, atheroma and type 2 diabetes, and also the promotion of uterus and breast cancer growth. Thus, the major challenge consists in uncoupling some beneficial actions from other deleterious ones, that is, selective ER modulation. Tamoxifen and raloxifene are already used, as they prevent the recurrence of breast cancer and mimic oestrogen action mainly on bone. Both E2 and tamoxifen exhibit a proliferative and, thus, a protumoural action on the endometrium. Activation of ERα and ERβ regulates target gene transcription (genomic action) through two independent activation functions, AF‐1 and AF‐2, but can also elicit rapid membrane‐initiated steroid signals. In the present review, we attempted to summarize recent advances provided by the in vivo molecular ‘dissection’ of ERα, allowing the uncoupling of some of its actions and potentially paving the way to optimized selective ER modulators.
Circadian variation in methotrexate toxicity in streptozotocin-induced diabetes mellitus rats

Abstract The effects of diabetes mellitus and circadian rhythm on pharmacokinetics or pharmacodynamics of drugs have been previously separately reviewed. In our previous study, a circadian rhythm has been described in the pharmacokinetics of MTX in streptozotocin-induced diabetes mellitus (SIDM) rats. The aim of the present study was to investigate the effects of circadian rhythm on the toxicity of MTX in SIDM rats. The hematologic parameters and serum folic acid levels were measured in control and SIDM groups before and after MTX administration to evaluate its toxicity. We observed that circadian rhythm in basal peripheral WBC counts disappeared after MTX administration in the first hour and were phase shifted on the fifth day. Circadian variations were not observed in the other blood cells. One hour after MTX administration, folic acid levels were high in both groups. However, a circadian rhythm was present only in the diabetic group. The alteration in the rhythm of WBC counts in diabetic rats may originate not only from the effect of MTX but also physiological alterations due to diabetes and/or the varying cell cycle entry rates in the hematopoetic stem cells.
Early stages of HIV treatment cascade in people living with HIV in Saint-Petersburg, Russia

ABSTRACT The proportion of people living with HIV (PLWH) in need of antiretroviral therapy (ART) is growing rapidly in Russia. Successful treatment outcomes reduces disease progression and contributes to HIV epidemic control. We conducted a pilot study following 100 PLWH newly found eligible for ART in St. Petersburg, Russia. We determined the proportion of PLWH who initiated ART, remained in treatment, and achieved an undetectable VL during 6-month follow up. Semi-structured interviews were conducted prior the initiation of ART and progress along the cascade was assessed through medical chart review. Individual characteristics associated with successful ART outcomes were assessed as part of efforts to generate hypotheses. Almost all (96%) participants initiated ART, full retention was demonstrated by 80%, among whom 71% achieved undetectable VL. Optimal retention was associated with older age and higher education (p < 0.05). There was no significant difference in ART outcomes between those who used illicit drugs and those had not. Interventions to improve treatment effectiveness should emphasize that initiation, optimal retention and achieving an undetectable VL are independent of drug abuse status. However, our pilot study highlights the need for the further research in the examining links between individual and structural factors and ART effectiveness.