Miracle-dz/UniFAR-FTUs huggingface dataset:
Resistance profile of etravirine: combined analysis of baseline genotypic and phenotypic data from the randomized, controlled Phase III clinical studies

Objective:To refine the genotypic and phenotypic correlates of response to the nonnucleoside reverse transcriptase inhibitor etravirine. Design:Initial analyses identified 13 etravirine resistance-associated mutations (RAMs) and clinical cutoffs (CCOs) for etravirine. A multivariate analysis was performed to refine the initial etravirine RAM list and improve the predictive value of genotypic resistance testing with regard to virologic response and relationship to phenotypic data. Methods:Week 24 data were pooled from the phase III studies with TMC125 to Demonstrate Undetectable viral load in patients Experienced with ARV Therapy (DUET). The effect of baseline resistance to etravirine on virologic response (<50 HIV-1 RNA copies/ml) was studied in patients not using de-novo enfuvirtide and excluding discontinuations for reasons other than virologic failure (n = 406). Clinical cutoffs for etravirine were established by analysis of covariance models and sliding fold change in 50% effective concentration (EC50) windows (Antivirogram; Virco BVBA, Mechelen, Belgium). Etravirine RAMs were identified as those associated with decreased virologic response/increased etravirine fold change in EC50. Relative weight factors were assigned to the etravirine RAMs using random forest and linear modeling techniques. Results:Baseline etravirine fold change in EC50 predicted virologic response at week 24, with lower and preliminary upper clinical cutoffs of 3.0 and 13.0, respectively. A fold change in EC50 value above which etravirine provided little or no additional efficacy benefit could not be established. Seventeen etravirine RAMs were identified and attributed a relative weight factor accounting for the differential impact on etravirine fold change in EC50. Virologic response was a function of etravirine-weighted genotypic score. Conclusion:The weighted genotypic scoring algorithm optimizes resistance interpretations for etravirine and guides treatment decisions regarding its use in treatment-experienced patients.
Strategic Political Emphasis (SPE), Environmental Uncertainty, and Firm Performance In Ghana

This paper reports on a survey of 125 managers concerning strategic politicalemphasis (SPE), environmental uncertainty, and firm performance in Ghana. Resultswith a 95% confidence interval identified technology uncertainty as a significantdriver of SPE, strategic emphasis on competitors, and strategic emphasis oncustomers. SPE was also a positive and significant driver of performance. Whena 90% confidence interval was applied, market uncertainty prompted strategicemphases on both competitors and customers, and strategic emphasis on competitorswas positively linked to performance. These findings underscore the influence ofSPE on firm performance in Ghana, and suggest that similar relationships could befound in other nations, particularly those with developing and emerging economies.
IFN-γ and IL-17: the two faces of T-cell pathology in giant cell arteritis

Purpose of reviewGranuloma formation in giant cell arteritis (GCA) emphasizes the role of adaptive immunity and highlights the role of antigen-specific T cells. Recent data demonstrate that at least two separate lineages of CD4 T cells participate in vascular inflammation, providing an important clue that multiple disease instigators may initiate pathogenic immunity. Recent findingIFN-γ-producing Th1 cells and IL-17-producing Th17 cells have been implicated in GCA. Patients with biopsy-positive GCA underwent two consecutive temporal artery biopsies, one prior to therapy and one while on corticosteroids. In untreated patients, Th1 and Th17 cells co-existed in the vascular lesions. Following therapy, Th17 cells were essentially lost, whereas Th1 cells persisted almost unaffected. In the peripheral blood of untreated patients Th17 frequencies were increased eight-fold, but normalized with therapy. Blood Th1 cells were doubled in frequency, independent of therapy. Corticosteroids functioned by selectively suppressing IL-1β, IL-6 and IL-23-releasing antigen-presenting cells (APCs), disrupting induction of Th17 cells. SummaryAt least two distinct CD4 T-cell subsets promote vascular inflammation in GCA. In early disease, APCs promote differentiation of Th17 as well as Th1 cells. Chronic disease is characterized by persistent Th1-inducing signals, independent of IL-17-mediated inflammation. More than one disease instigator may trigger APCs to induce multiple T-cell lineages. Cocktails of therapies will be needed for appropriate disease control.
Carbon dioxide exchange via the mucosa in healthy middle ear.

BACKGROUND Recent studies have shown that gas exchange via the middle ear mucosa, which is performed between the middle ear cleft and capillaries in the submucosal connective tissue, has an essential role in ventilation and pressure regulation in the middle ear cleft. We speculated that gas exchange via the mucosa is induced by the gas diffusion caused by the partial pressure gradient of gas between the middle ear cleft and submucosal capillaries. OBJECTIVE To evaluate the capacity of the gas exchange via the mucosa in the healthy middle ear of humans by examining the effect of the respiratory mode on middle ear pressure. SUBJECTS AND METHODS We selected 13 volunteers ranging in age from 25 to 44 years with healthy ear drums and type A tympanograms. Middle ear pressure was measured in 1 ear of each subject every 2 minutes using tympanometry while the respiratory mode was altered, with the subject in the supine position. RESULTS The partial pressure of carbon dioxide in the venous blood (PvCO2) and middle ear pressure were decreased by hyperventilation and increased by hypoventilation. The partial pressure of oxygen in the venous blood showed little change. CONCLUSIONS Carbon dioxide diffused into the blood from the middle ear cleft in accord with the partial pressure gradient when the PvCO2 was reduced by hyperventilation, resulting in a decrease of middle ear pressure, whereas CO2 diffused into the middle ear cleft when the PvCO2 was elevated by hypoventilation, resulting in an increase of middle ear pressure. These findings suggest that a bidirectional CO2 exchange via the middle ear mucosa functions in the normal human middle ear.
Optic Disc Surface Compliance Testing Using Confocal Scanning Laser Tomography in the Normal Monkey Eye

PurposeTo determine the effect of acute, experimentally increased intraocular pressure on deformation of the surface of the optic nerve head (optic nerve head surface compliance testing) in normal monkey eyes using confocal scanning laser tomography. MethodsA total of 156 compliance tests were performed on 48 normal eyes of 30 monkeys in three separate studies. Compliance testing involved obtaining confocal scanning laser tomographic images using a 10° and/or 15° and/or 20° scan angle at various times after intraocular pressure was raised from 10 to 30 or 45 mm Hg. At each point, six images were analyzed to provide a value for a parameter, called mean position of the disc, which was used to express the amount of deformation the surface of the optic nerve head had undergone at that point. Statistical analysis (ANOVA) was performed to evaluate differences in the amounts of deformation in individual eyes at different intraocular pressures and at different compliance testing sessions (studies 1 and 2) and in the two eyes of individual monkeys under the same conditions (study 3). ResultsThe majority of eyes showed posterior deformation of the surface of the optic nerve head ranging from 15 to 86 &mgr;m as early as 10 minutes after intraocular pressure was increased from 10 to 30 mm Hg. When pressure was increased from 30 to 45 mm Hg in a subset of these eyes, most showed additional deformation. Of the 12 eyes for which both 15° and 20° images were obtained at the same compliance test, 7 showed larger amounts of deformation in the 20° images. Of the 18 monkeys tested in both eyes, 12 showed some differences and 4 showed substantial differences between the two eyes. ConclusionsIn the normal monkey eye, the surface of the optic nerve head deforms rapidly (in as few as 10 minutes) in response to increased intraocular pressure. The amount of deformation varies between subjects and even within the two eyes of individual monkeys. Increasing the scan angle from 15° to 20° frequently increases the amount of deformation detected, suggesting that the peripapillary sclera and the optic nerve head may be involved in the deformation in some eyes.
[Association between levels of plasma lipid profile with apolipoprotein B gene polymorphism in 93 children].

OBJECTIVE To study the relationship between levels of plasma lipid profile and variation of apolipoprotein (Apo) B gene. METHODS The relationship between frequency of polymorphism genotype of Apo B gene Xba I locus and levels of plasma lipid profile was studied in 93 children aged eight to eleven years. RESULTS The frequency of dominant X- allele (common allele) in Xba I locus was 0.967 in the children and that of uncommon X+ allele 0.033. Average levels of plasma total cholesterol (TC) and low density lipoprotein cholesterol (LDL-ch) in children with X- X+ genotype (4.59 and 2.98 mmol/L, respectively) were significantly higher than those with X-X- genotype (3.84 and 2.32 mmol/L, respectively). Levels of TC and/or LDL-ch in 4 of 6, cases of X-X+ genotype exceeded their the 90th percentile, indicating association between X+ allele and high plasma cholesterol level. CONCLUSION To certain extent, there is association between polymorphism of Xba I locus of Apo B gene and levels of plasma lipid profile in children, which may be a genetic marker for abnormal level of plasma lipid profile during childhood.
Increased interleukin (IL)-1beta messenger ribonucleic acid expression in beta -cells of individuals with type 2 diabetes and regulation of IL-1beta in human islets by glucose and autostimulation.

CONTEXT Elevated glucose levels impair islet function and survival, and it has been proposed that intraislet expression of IL-1beta contributes to glucotoxicity. OBJECTIVE The objective was to investigate IL-1beta mRNA expression in near-pure beta-cells of patients with type 2 diabetes (T2DM) and study the regulation of IL-1beta by glucose in isolated human islets. METHODS Laser capture microdissection was performed to isolate beta-cells from pancreas sections of 10 type 2 diabetic donors and nine controls, and IL-1beta mRNA expression was analyzed using gene arrays and PCR. Cultured human islets and fluorescence-activated cell sorter-purified human beta-cells were used to study the regulation of IL-1beta expression by glucose and IL-1beta. RESULTS Gene array analysis of RNA from beta-cells of individuals with T2DM revealed increased expression of IL-1beta mRNA. Real-time PCR confirmed increased IL-1beta expression in six of 10 T2DM samples, with minimal or no expression in nine control samples. In cultured human islets, IL-1beta mRNA and protein expression was induced by high glucose and IL-1beta autostimulation and decreased by the IL-1 receptor antagonist IL-1Ra. The glucose response was negatively correlated with basal IL-1beta expression levels. Autostimulation was transient and nuclear factor-kappaB dependent. Glucose-induced IL-1beta was biologically active and stimulated IL-8 release. Low picogram per milliliter concentrations of IL-1beta up-regulated inflammatory factors IL-8 and IL-6. CONCLUSION Evidence that IL-1beta mRNA expression is up-regulated in beta-cells of patients with T2DM is presented, and glucose-promoted IL-1beta autostimulation may be a possible contributor.
Time to Coronary Angiography and Outcomes Among Patients With High-Risk Non–ST-Segment–Elevation Acute Coronary Syndromes: Results From the SYNERGY Trial

Background— Optimal timing for an early invasive strategy in patients with non–ST-segment–elevation acute coronary syndrome remains unclear. We evaluated the relationship between time from hospital admission to coronary angiography and outcomes in high-risk patients with non–ST-segment–elevation acute coronary syndrome who underwent angiography within 48 hours of admission. Methods and Results— Data from 10 027 patients enrolled in the Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial were analyzed. Patients were grouped by 6-hour intervals of time from hospital admission to coronary angiography. Primary outcomes were 30-day death or myocardial infarction, in-hospital Thrombolysis In Myocardial Infarction (TIMI) and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) major bleeding, and blood transfusion. Adjusted estimates of event rates were obtained by use of a multivariable methodology that included possible confounders through baseline and accounted for propensity of time to angiography. The landmark method was used to calculate odds ratios and 95% confidence intervals of outcomes for each time period adjusted for baseline and postbaseline clinical events. Overall, 9216 patients (92%) underwent angiography, 6352 (63%) within 48 hours. Unadjusted and adjusted rates of death/myocardial infarction increased with increasing time to angiography. The adjusted odds ratio for death/myocardial infarction in patients receiving angiography in <6 hours was 0.56 (95% confidence interval 0.41 to 0.74), whereas after 30 hours, there was no significant benefit compared with further delayed angiography. Major bleeding and transfusion did not vary significantly across time-to-angiography intervals. Conclusions— A decrease in the time to coronary angiography was associated with fewer ischemic outcomes and no increase in bleeding. Randomized clinical trials are needed to provide definitive evidence on optimal timing of coronary angiography but are difficult to design and conduct. Ongoing trials should instead clarify whether delaying angiography to administer aggressive upstream antithrombotic therapies is effective in the current setting of non–ST-segment–elevation acute coronary syndrome management.
Use of the Evidence Theory to Combine Change Detection Indices and a priori Information

Digital change detection deals with the quantification, from multi-date imagery, of temporal phenomena, such as Aforestation-Reforestation-Deforestation, agricultural field rotation, abnormal evolution of the land surface. Despites the numerous change detection indices already proposed, none is sufficiently precise and reliable. We propose then to detect changes by considering not only one but several change indices, as well as information available from other source than remote sensing, i.e. derived from surface evolution model or a priori. For fusion, we chose the framework of the Dempster-Shafer evidence theory. It allows for some global ignorance, which is either present at the borders between the 'No-Change' and 'Change' classes, or is due to the poor quality of some change indices. The performance of the Non Remote Sensing (NRS) data change prediction, when known (e.g. statistical error of a model), can be taken into account the discounting of the mass functions. We present the results obtained in two different cases of application: forest logging and winter vegetation cover of fields in intensive farming areas. Remote sensing data are SPOT/HRV images. Considering the performance in terms of Non-Detection and False Detection rates, the interest of combining at least two change indices was clearly stated. The interest of NRS information has been then evaluated in the case of the field winter coverage application.
The original Lujan syndrome family has a novel missense mutation (p.N1007S) in the MED12 gene

A novel missense mutation in the mediator of RNA polymerase II transcription subunit 12 (MED12) gene has been found in the original family with Lujan syndrome and in a second family (K9359) that was initially considered to have Opitz–Kaveggia (FG) syndrome. A different missense mutation in the MED12 gene has been reported previously in the original family with FG syndrome and in five other families with compatible clinical findings. Neither sequence alteration has been found in over 1400 control X chromosomes. Lujan (Lujan–Fryns) syndrome is characterised by tall stature with asthenic habitus, macrocephaly, a tall narrow face, maxillary hypoplasia, a high narrow palate with dental crowding, a small or receding chin, long hands with hyperextensible digits, hypernasal speech, hypotonia, mild-to-moderate mental retardation, behavioural aberrations and dysgenesis of the corpus callosum. Although Lujan syndrome has not been previously considered to be in the differential diagnosis of FG syndrome, there are some overlapping clinical manifestations. Specifically, these are dysgenesis of the corpus callosum, macrocephaly/relative macrocephaly, a tall forehead, hypotonia, mental retardation and behavioural disturbances. Thus, it seems that these two X-linked mental retardation syndromes are allelic, with mutations in the MED12 gene.
Klebsiella Pneumoniae Liver Abscess: A Case Series of Six Asian Patients

Case series Patient: Female, 60 • Male, 45 • Male, 56 • Male, 65 • Female, 57 • Male, 35 Final Diagnosis: Klebsiella pneumoniae liver abscess Symptoms: Fever Medication: — Clinical Procedure: — Specialty: Infectious Diseases Objective: Rare co-existance of disease or pathology Background: Liver abscesses represent a serious infection of hepatic parenchyma and are associated with significant morbidity and mortality. The emergence of a new hypervirulent variant of Klebsiella pneumoniae, which can cause serious infections in the Asian population, is under investigation. We report a case series of six Asian patients hospitalized at our institution from January 2013 to November 2015 for liver abscess due to Klebsiella pneumoniae. Case Report: Charts of six Asian patients were retrospectively reviewed. Four patients were male and two were female. The mean age was 53 years (range: 35–64 years). All patients had no known past medical history of immunodeficiency. Three patients had multiple liver abscesses at the time of initial presentation. In five patients, the source of entry of the pathogenic microorganism was unknown and in one patient the suspected source of entry was the gastrointestinal tract. In three patients there was also concomitant Klebsiella pneumoniae bacteremia. The mean duration of antibiotic treatment was seven weeks and the mean duration of hospital stay was 13.5 days. Conclusions: Liver abscess should always be included in the differential diagnosis in cases of sepsis without obvious source and/or in the clinical scenarios of fever, abdominal pain, and liver lesions.
Protein synthesis in plasma cells is regulated by crosstalk between endoplasmic reticulum stress and mTOR signaling

Plasma cells (PCs) secrete copious levels of immunoglobulins. To achieve this, their endoplasmic reticulum (ER) undergoes expansion in a process that requires continuous ER stress and activation of the unfolded protein response. It is important that protein synthesis, the driver of ER stress, is regulated in a manner that does not induce apoptosis. We followed protein synthesis in murine splenic B cells activated in vitro with LPS. Total protein synthesis levels increased and then steeply decreased when the cells acquired a secretory phenotype. We explored the involvement of two mechanisms in controlling protein synthesis levels, namely ER stress‐mediated phosphorylation of eukaryote initiation factor 2α (eIF2α) and the mammalian target of rapamycin (mTOR) pathway, which attenuate or activate mRNA translation, respectively. We show that induction of ER stress in activated B cells counter‐intuitively led to dephosphorylation of eIF2α. Despite the reduction in phosphorylated eIF2α, expression of activating transcription factor 4, an effector of hyper eIF2α phosphorylation, was induced. In addition, ER stress attenuated the mTOR pathway, which ultimately reduced protein synthesis. Finally, B cells engineered to overactivate the mTOR pathway exhibited higher apoptosis in the course of LPS stimulation. We conclude that protein synthesis in PCs is controlled by an ER stress‐mediated mTOR regulation, which is needed for optimal cell viability.
Informações da mídia eletrônica e de redes sociais como subsídio ao monitoramento de desastres naturais

Atualmente, novas ferramentas de midia, como weblogs, plataformas de mensagens instant âneas, videoconferencias e redes sociais tem ganhado espaco como suporte as mais diversas atividades e servicos. As redes sociais, como Facebook e Twitter sao ferramentas de comunicacao para varios tipos de negocios e as informacoes ali divulgadas podem ser usadas por empresas de recrutamento e selecao (CREWS; STETT-GOHDES, 2012), pesquisadores de tendencias de mercado, ativistas diversos, entre outros
Psychotherapy in the treatment of alcohol and substance abusing adolescents with suicidal behavior

Adolescence is a unique time period in an individual's life, one in which suicide and substance abuse become substantial health risks. Currently, suicide accounts for approximately 14% of all deaths among 15-24 year olds in the U.S.A. Drug, alcohol abuse and dependence are the most prevalent causes of adolescent morbidity and mortality in the USA. Numerous studies have demonstrated the link between adolescent alcohol, substance abuse and suicide. When compared to community controls, the rate of a substance abuse disorder was 8.5 times higher in a sample of adolescent suicide completers and the rate of alcohol abuse was 7.5 times higher. Genetic and biological variables may also be responsible for either alcohol and substance abuse or suicide or both alcohol and substance abuse and suicide. There is little empirical research evaluating the effectiveness of alcohol and substance abuse treatments for adolescents. Therapies such as multisystemic therapy, functional family therapy, motivational interviewing, community reinforcement, the 12-step approach and contingency management reinforcement seem to be effective treatments. Despite the strong association between adolescent alcohol and substance use and suicidal behaviors, few studies have investigated the combined treatment of these two issues. Cognitive behavioral therapy, particularly dialectical behavior therapy, seems to be a promising psychotherapy treatment for suicidality in alcohol and substance abusing adolescents. Further research is needed to determine the efficacy of various treatments of alcohol and substance abusing adolescents with suicidal behavior.
The impact of exchange rates on stock market returns: new evidence from seven free-floating currencies

ABSTRACT This paper provides evidence of a significant exchange rate effect on stock index returns using data from seven selected countries practicing free-floating exchange rate regimes. This research uses parity and asset pricing theories, thus placing it within the monetary-cum-economics framework for international asset pricing. In this study, we apply a system of seemingly unrelated regression to control for unobserved heterogeneity and cross-sectional dependence. The findings constitute evidence of a statistically significant exchange rate impact on stock index returns across selected countries. These findings can be considered as falling under the arbitrage pricing approach of the international capital asset pricing model of Solnik who also used the parity-theoretical framework on exchange rate determination.