Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetic Profiles of Nevirapine and Indinavir in Various Fractions of Seminal Plasma

ABSTRACT Limited data are available on antiretroviral drug concentrations in seminal plasma during a dosing interval. Further, since human ejaculate is composed of fluids originating from the testes, the seminal vesicles, and the prostate, all having different physiological characteristics, drug concentrations in total seminal plasma do not necessarily reflect concentrations in the separate compartments. Five human immunodeficiency virus type 1-infected patients on nevirapine (NVP; 200 mg twice a day [b.i.d.]) and/or indinavir (IDV; 800 mg b.i.d. with ritonavir, 100 mg b.i.d.) regimens used a split ejaculate technique to separate seminal plasma in two fractions, representing fluids from the testes and prostate (first fraction) and fluids from the seminal vesicles (second fraction). Split-ejaculate samples were provided at 0, 2, 5, and 8 h after drug ingestion, on separate days after 3 days of sexual abstinence. NVP and IDV showed time-dependent concentrations in seminal plasma, with peak concentrations in both fractions at 2 and 2 to 5 h, respectively, after drug ingestion. The NVP concentrations were not significantly different between the first and second fractions of the ejaculate at all time points measured and were in the therapeutic range, except for the predose concentration in two patients. The median (range) predose IDV concentrations in the first and second fractions of the ejaculate were 448 (353 to 1,015) ng/ml and 527 (240 to 849) ng/ml, respectively (P = 0.7). In conclusion, NVP and IDV concentrations in seminal plasma are dependent on the time after drug ingestion. Furthermore, our data suggest that NVP and IDV achieve therapeutic concentrations in both the testes and prostate and the seminal vesicles throughout the dosing interval.
Spatial and temporal hydro-climatic trends in the transboundary Jhelum River basin

The present study examined the hydro-meteorological trends and their magnitudes using the Mann–Kendall, Sen9s slope, and linear regression methods in the Jhelum River basin. Maximum and minimum temperatures showed increasing trends in the basin. However, the increasing trends of maximum temperature in all seasons as well as in annual datasets were stronger and statistically more significant than minimum temperature. Precipitation showed non-significant increasing and decreasing trends spread evenly throughout the basin. However, decreasing trends dominated in the basin, except in winter, with an average annual decrease of 3.3 mm. In case of streamflow, seasonal and annual decreasing trends dominated in the basin. Summer showed stronger and significant decreasing trends at most of the hydrometric stations in the basin. An annual decrease of 8 mm was observed at Azad Pattan. These decreasing trends are most probably due to decreasing trends in precipitation and increasing trends in temperature, though other factors such as land use changes, industrialization, and urbanization can also affect the changes in streamflow. These decreasing trends in precipitation and stream flow can have some serious implications in the reduction of water availability to the Mangla reservoir, thus producing many challenges for efficient reservoir operation and management.
CD40 Ligand (CD154) Enhances the Th1 and Antibody Responses to Respiratory Syncytial Virus in the BALB/c Mouse

CD40 ligand (CD40L) is a cell surface costimulatory molecule expressed mainly by activated T cells. CD40L is critically important for T-B cell and T cell-dendritic cell interactions. CD40L expression promotes Th1 cytokine responses to protein Ags and is responsible for Ig isotype switching in B cells. Respiratory syncytial virus (RSV) is an important pathogen of young children and the elderly, which causes bronchiolitis and pneumonia. Studies of mice infected with RSV suggest that a Th2 cytokine response may be responsible for enhanced pulmonary disease. To investigate the effect CD40L has on RSV immunity, mice were infected simultaneously with RSV and either an empty control adenovirus vector or one expressing CD40L or were coimmunized with plasmid DNA vectors expressing CD40L and RSV F and/or G proteins and subsequently challenged with RSV. The kinetics of the intracellular and secreted cytokine responses, the cytotoxic T lymphocyte precursor frequency, NO levels in lung lavage, rates of virus clearance, and anti-RSV Ab titers were determined. These studies show that coincident expression of CD40L enhances the Th1 (IL-2 and IFN-γ) cytokine responses, increases the expression of TNF-α and NO, accelerates virus clearance, and increases the anti-F and anti-G Ab responses. These data suggest that CD40L may have the adjuvant properties needed to optimize the safety and efficacy of RSV vaccines.
Effects of cardioversion of atrial fibrillation on endothelial function in hypertension or diabetes

Background Cardioversion (CV) to sinus rhythm corrects endothelial dysfunction secondary to atrial fibrillation (AF). As AF often complicates hypertension and diabetes (disorders associated with impaired endothelial function) the study probed whether these comorbidities to AF produced an additive effect and to what extent CV might be advantageous.
Adherence to WCRF/AICR cancer prevention recommendations and metabolic syndrome in breast cancer patients

Metabolic syndrome (MetS), conventionally defined by the presence of at least three out of five dismetabolic traits (abdominal obesity, hypertension, low plasma HDL‐cholesterol and high plasma glucose and triglycerides), has been associated with both breast cancer (BC) incidence and prognosis. We investigated the association between the prevalence of MetS and a score of adherence to the World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) recommendations for the prevention of cancer in a cross‐sectional study of BC patients. The DIet and ANdrogen‐5study (DIANA‐5) for the prevention of BC recurrences recruited 2092 early stage BC survivors aged 35–70. At recruitment, all women completed a 24‐hour food frequency and physical activity diary on their consumption and activity of the previous day. Using these diaries we created a score of adherence to five relevant WCRF/AICR recommendations. The prevalence ratios (PRs) and 95% confidence intervals (CIs) of MetS associated with the number of recommendations met were estimated using a binomial regression model. The adjusted PRs of MetS decreased with increasing number of recommendations met (p < 0.001). Meeting all the five recommendations versus meeting none or only one was significantly associated with a 57% lower MetS prevalence (95% CI 0.35–0.73). Our results suggest that adherence to WCRF/AICR recommendations is a major determinant of MetS and may have a clinical impact.
Adjunctive Thalidomide Therapy for Childhood Tuberculous Meningitis: Results of a Randomized Study

Childhood tuberculous meningitis is associated with serious long-term sequelae, including mental retardation, behavior disturbances, and motor handicap. Brain damage in tuberculous meningitis results from a cytokine-mediated inflammatory response, which causes vasculitis and obstructive hydrocephalus. Thalidomide, a potent tumor necrosis factor α inhibitor, was well tolerated and possibly showed some clinical benefit in children with tuberculous meningitis during a pilot study. The purpose of the present study was to assess the effect of adjunctive thalidomide in addition to standard antituberculosis and corticosteroid therapy on the outcome of tuberculous meningitis. Thalidomide (24 mg/kg/day orally) or placebo was administered in a double-blind randomized fashion for 1 month to patients with stage 2 or 3 tuberculous meningitis. The study was terminated early because all adverse events and deaths occurred in one arm of the study (thalidomide group). Thirty of the 47 children enrolled received adjunctive thalidomide, of whom 6 (20%) developed a skin rash, 8 (26%) hepatitis, and 2 (6%) neutropenia or thrombocytopenia. Four deaths (13%) occurred in patients with very severe neurologic compromise at baseline; two deaths were associated with a rash. Motor outcome after 6 months of antituberculosis therapy was similar in the two groups, even though the thalidomide group showed greater neurologic compromise on admission. In addition, the mean IQ of the two treatment groups did not differ significantly (mean IQ thalidomide group 57.8 versus mean IQ control group 67.5; P = 16). These results do not support the use of adjunctive high-dose thalidomide therapy in the treatment of tuberculous meningitis. (J Child Neurol 2004;19:250-257).
Crystal Structure of Poliovirus 3CD Protein: Virally Encoded Protease and Precursor to the RNA-Dependent RNA Polymerase

ABSTRACT Poliovirus 3CD is a multifunctional protein that serves as a precursor to the protease 3Cpro and the viral polymerase 3Dpol and also plays a role in the control of viral replication. Although 3CD is a fully functional protease, it lacks polymerase activity. We have solved the crystal structures of 3CD at a 3.4-Å resolution and the G64S fidelity mutant of 3Dpol at a 3.0-Å resolution. In the 3CD structure, the 3C and 3D domains are joined by a poorly ordered polypeptide linker, possibly to facilitate its cleavage, in an arrangement that precludes intramolecular proteolysis. The polymerase active site is intact in both the 3CD and the 3Dpol G64S structures, despite the disruption of a network proposed to position key residues in the active site. Therefore, changes in molecular flexibility may be responsible for the differences in fidelity and polymerase activities. Extensive packing contacts between symmetry-related 3CD molecules and the approach of the 3C domain's N terminus to the VPg binding site suggest how 3Dpol makes biologically relevant interactions with the 3C, 3CD, and 3BCD proteins that control the uridylylation of VPg during the initiation of viral replication. Indeed, mutations designed to disrupt these interfaces have pronounced effects on the uridylylation reaction in vitro.
Cortisol levels and prospective and retrospective memory in humans.

OBJECTIVES The aim of this study was to examine (i) the influence of cortisol on both prospective and retrospective memory performance and (ii) the role of emotional valence in both types of memory. METHODS Thirty-four male students participated in a memory task, which measured both prospective and retrospective memory performance. Baseline salivary cortisol levels were assessed. RESULTS Spearman's rank order correlation analysis showed a significant positive correlation between salivary cortisol levels and retrospective memory performance for neutral words. Cortisol levels were not significantly correlated with prospective memory performance for either negative nor neutral words. CONCLUSIONS The present results indicate chronic cortisol levels are positively associated with retrospective memory at relatively low concentration ranges, but not prospective memory, in healthy young men. Implications for evaluating the beneficial effects of low-dose cortisol treatment on posttraumatic stress disorder is discussed.
Family member involvement in audiology appointments with older people with hearing impairment

Abstract Objective: This study aimed to investigate family members’ involvement in audiology rehabilitation appointments. Design: Audiology appointments were video-recorded and analysed using quantitative coding and conversation analysis (CA). Study sample: The study sample included 13 audiologists, 17 older adults with hearing impairment, and 17 family members. Results: Initial coding showed that family members participated in 12% of the total talk time during audiology appointments. The CA results demonstrated that family members were not typically invited to join the conversation. However, family members would self-select to speak by: (1) responding to questions from the audiologist which were directed at the client; (2) self-initiating expansions on clients’ turns; and (3) self-initiating questions. When family members did participate in the interaction, audiologists typically responded by shifting the conversation back to the client. Conclusion: While family members currently have minimal participation in audiology appointments, they display a strong interest in being involved and sharing their experiences of the client's hearing impairment. The findings suggest support for implementing family-centred care principles in audiology practice.
Pedicled Vascularized Bone Grafts for Scaphoid and Lunate Reconstruction

&NA; Conventional bone grafts have some osteogenic potential, whereas vascularized bone grafts retain live, functional osteocytes and osteoblasts. High rates of scaphoid union have been achieved with conventional bone grafting in the absence of osteonecrosis or prior surgery. Vascularized bone grafting is valuable in the management of wrist disorders with compromised bone vascularity (eg, scaphoid nonunion with proximal pole necrosis, Preiser disease, Kienböck disease) or when previous grafting has failed. Improved understanding of the vascular anatomy of the wrist has allowed the use of an array of vascularized bone grafts that do not require microsurgical anastomosis. Successful outcome depends on careful patient selection and appropriate surgical technique.
Unilateral versus bilateral endoscopic hepatic duct drainage in patients with malignant hilar biliary obstruction: results of a prospective, randomized, and controlled study.

BACKGROUND The necessity for drainage of both liver lobes in tumors arising at the biliary bifurcation is controversial. The aim of this study was to compare the outcome of unilateral versus bilateral drainage in patients with biliary obstruction at the hilum. METHODS One hundred fifty-seven consecutive patients with primary cholangiocarcinoma, gallbladder cancer, or periportal lymph node metastases were randomly allocated to unilateral (group A) or bilateral (group B) hepatic duct drainage. RESULTS In intention-to treat analysis, group A had a significantly higher rate of successful endoscopic stent insertion than group B (88.6% vs. 76.9%, p = 0.041). Group B had a significantly higher rate of complications than group A (26.9% vs. 18.9%, p = 0.026) because of the higher rate of early cholangitis (16.6% vs. 8.8%, p = 0.013). In per-protocol analysis the rate of successful drainage, complications, and mortality did not differ between the two groups. Median survival did not differ between the two groups but was significantly different for patients with cholangiocarcinoma and those with gallbladder cancer versus patients with metastatic tumors (p = 0.0247). CONCLUSION The insertion of more than one stent would not appear justified as a routine procedure in patients with biliary bifurcation tumors.
Microbiome in Parturition and Preterm Birth

Abstract Preterm parturition is a one of the most significant global maternal-child health problem. In recent years, there has been an explosion in reports on a role for microbiomes (i.e., a microbial biomass) on a plethora of physiologic and pathologic human conditions. This review aims to describe our current understanding of the microbiome and its impact on parturition, with particular emphasis on preterm birth. We will focus on the roles of vaginal and oral mucosal microbiomes in premature parturition and describe the state-of-the-art methodologies used in microbiome studies. Next, we will present new studies on a potential microbiome in the placenta and how it may affect pregnancy outcomes. Finally, we will propose that host genetic factors can perturb the normal “pregnancy microbiome” and trigger adverse pregnancy outcomes.
The Association of Social Inhibition and Posttraumatic Stress Disorder: A Vicious Circle? Results From the Population-Based KORA F4 Study With 1232 Participants With Trauma Exposure

Abstract This cross-sectional analysis investigated the association between posttraumatic stress disorder (PTSD) and social inhibition (SI). A total of 1232 individuals aged 32–71 years with a history of traumatic experience were identified from the population-based Cooperative Health Research in the Region of Augsburg F4 study conducted in 2006–2008. PTSD was assessed by the Impact of Event Scale, Posttraumatic Diagnostic Scale, and interview data. SI was measured by the SI subscale of the German version of the Type-D scale and dichotomized in a high (score of ≥10) and nonhigh group. Even in the fully adjusted multinomial logistic regression model (adjusted for age, sex, sociodemographic and metabolic risk factors, anxiety, depression), high levels of SI were significantly associated with PTSD (partial: odds ratio, 1.58; 95% confidence interval, 1.19–2.09; p = 0.002; full: odds ratio, 2.45; 95% confidence interval, 1.25–4.82; p = 0.009). Our findings suggest a dose-response relationship between PTSD and SI and should be integrated in individual therapy plans, especially of patients with interpersonal violence experience.
Understanding Open Data Policy: Evidence from Bulgaria

ABSTRACT This paper provides an overview of Bulgaria’s policy on open data by using the framework of a novel Open Data stage model, showing that the country is still at the first stage of opening data. We also present a detailed overview of the data landscape of the public sector in the country and outline the first milestones and successes in its efforts to publish some of that data for reuse. A complete data audit reveals persistent technological and cultural barriers to publishing public sector information but also outlines the potential of doing so. The paper summarizes the limited knowledge about the actual benefits of open data and proposes moving beyond anecdotal evidence and usage metrics toward a more complete impact evaluation.
Intravenous self-administration of heroin/cocaine combinations (speedball) using nose-poke or lever-press operant responding in mice

Acquisition and dose-related self-administration of heroin (H)/cocaine (C) combinations in C57BL/6 × SJL mice were studied in nose-poke or lever-press operant responding procedures. C57BL/6 × SJL mice readily acquired self-administration in both operant procedures with a combination of doses known to be ineffective when each drug was used alone (H:15 μg/kg and C:150 μg/kg per injection). Similar numbers of infusions were obtained under conditions of fixed-ratio (FR) 3 versus 1 for the nose-poke and lever-press responses, respectively. Dose–effect curves for heroin:cocaine combinations revealed a pattern corresponding to a leftward shift of the dose-response for intravenous cocaine self-administration. Curves were similar whether generated with 1 or 3 days of availability per dose, or including subjects that did not respond preferentially (>70% responses) to the hole or lever associated with drug delivery, along with those that did. Motor activity induced by a combination of low doses for each drug was examined (H: 0.375 mg/kg and C: 3.75 mg/kg, i.p.). Under these conditions, the combination of both drugs induced an initial cocaine-like stimulation of horizontal activity, in contrast to the tendency of heroin to decrease activity. It is concluded that heroin:cocaine combinations used in the present study had reinforcing effects in C57BL/6 × SJL mice, and produced a cocaine-like effect in the early part of drug-induced activity sessions, followed by a locomotor profile corresponding to the average of both drugs.
Quercetin and ovarian cancer: An evaluation based on a systematic review

Some studies have suggested chemopreventive and therapeutic effects of quercetin (Q) on carcinogenesis. The aim of this review was to evaluate the association between Q and ovarian cancer risk among human researches and induced sensitivity to some types of chemotherapeutic drugs and antiproliferative effects of this flavonoid in the animals and cell lines studies. Data for this systematic review were achieved through searches of the MEDLINE (PubMed), Google Scholar, Science Direct, Scopus, Cochrane, SID, and Magiran databases for studies published up to May 2015. Relevant studies were reviewed based on Preferred Reporting Item for Systematic Review and Meta analysis guidelines. From the total number of 220 papers obtained at the initial search, 13 publications including 1 prospective, 2 case -control, 1 animal, and 9 in vitro human and animal cancer cell lines studies were eligible. Despite findings in laboratory settings, results from the epidemiological studies commented that the potentially protective effects of Q not be able to significantly decrease ovarian cancer risk at levels commonly consumed (1.01–31.7 mg/day) in a typical diet. However, animal and in vitro studies suggest that Q exerts anticancer effects via inhibiting tumor growth, and angiogenesis, interrupt the cell cycle, and induce apoptosis. It is highlighted the need for more studies to be conducted.
Employee ambidexterity, high performance work systems and innovative work behaviour: How much balance do we need?

Abstract This study examines whether and how innovative work behaviour is related to explorative and exploitative activities. Polynomial regression analyses are used to test the relationship between ambidexterity (being engaged in explorative and exploitative activities in equal amounts) and innovative work behaviour, as well as between specialisation (being engaged in either explorative or exploitative activities) and innovative work behaviour. Furthermore, we use moderated polynomial regression analyses to examine a possible moderating effect of high-performance work systems (HPWS) on these relationships. Results indicate that balance at a high level, as well as specialisation, are conducive to innovative work behaviour. A moderating effect of HPWS was not supported by our data.
Social exclusion and psychopathology in an online cohort of Moroccan-Dutch migrants: Results of the MEDINA-study

Introduction Migration is seen as a risk factor for developing psychiatric symptoms and experiencing social exclusion. In the Netherlands, the Moroccan-Dutch population is the second largest migrant group. 70% of all young Moroccan-Dutch people meet each other in the online community www.marokko. nl. Within this community, we investigated the association between experiences of social exclusion and self-reported depressive symptoms and psychotic experiences. Materials and methods Participants were recruited via the website www.marokko. nl. They completed an online survey, with screening instruments for depressive symptoms (K10) and psychotic experiences (PQ-16), measures of social exclusion (perceived discrimination, social defeat and social support), and questions about demographical information. With regression analysis the association between social exclusion and psychiatric symptoms was investigated. Results We included 267 participants; 87% were female. 27% of the sample has received mental healthcare in the past. Over 50% of these people screened positive for depressive symptoms and psychotic experiences. Perceived discrimination and social defeat were significantly associated with psychotic experiences and social defeat was associated with depressive symptoms. Social support and higher education were associated with less depressive symptoms and psychotic experiences. Discussion Our findings suggest that the online environment allows for epidemiological research and early symptom detection. Levels of psychopathology were high in our sample. This suggests that a part of this young ethnic minority population might not get adequate mental healthcare. Since this population can be reached through Internet, the online environment may therefore also offer an appropriate setting for intervention, to increase resilience towards social exclusion.