Miracle-dz/UniFAR-FTUs huggingface dataset:
Adverse events associated with nevirapine use in pregnancy: a systematic review and meta-analysis

Introduction:The risk of adverse drug events associated with nevirapine (NVP) is suggested to be greater in pregnant women. We conducted a systematic review and meta-analysis of severe adverse events in HIV-positive women who initiated NVP while pregnant. Methods:We searched six databases for studies reporting adverse events among HIV-positive pregnant women who had received NVP-based antiretroviral therapy for at least 7 days. Data were pooled by the fixed-effects method. Results:Twenty studies (3582 pregnant women) from 14 countries were included in the final review. The pooled proportion of patients experiencing a severe hepatotoxic event was 3.2% [95% confidence interval (CI) 2.1–4.3%], severe rash was experienced by 3.3% of patients (95% CI 2.1–4.5%) and 6.1% (95% CI 3.9–8.3%) of patients discontinued NVP due to an adverse event. These results were comparable to frequencies observed in the general adult patient population, and to frequencies reported in non-pregnant women within the same cohort. For pregnant women with a CD4 cell count above 250 cells/&mgr;l there was a non-significant tendency towards an increased likelihood of severe cutaneous adverse events (OR 1.4, 95% CI 0.8–2.4) and severe hepatotoxic events (OR 1.5, 95%CI 0.9-2.3) and consequently an increased risk of toxicity-driven regimen substitution (OR 1.7, 95% CI 1.1–2.6). Discussion:These results suggest that the frequency of adverse events associated with NVP use in pregnant women, although high, is no higher than reported for NVP in the general adult population. Pregnant women with a high CD4 cell count may be at increased risk of adverse events, but evidence supporting this association is weak.
The accountability of Higher Education Institutional Leaders

This thesis addresses the research question ‘What are the accountability responsibilities and obligations for higher education institutional leaders? In this process, three tensions were identified for those leaders: first, the balancing of accountability responsibilities and obligations in the decision-making process; second, how stakeholders affect the balance between obligations and responsibilities; and third, how decisions based upon the balance between obligations and responsibilities have been affected by different stakeholders which then affect the stakeholders in turn. It was argued from evidence provided by twelve institutional leaders from eight institutions that policy changes affecting institutional funding and financial maintenance can lead institutional leaders, in response to both policy drivers and their accountability, to take institutional action through their agency that can lead to challenges to the academic identity of the staff working in their institutions. A theoretical framework drawing upon theories related to structure and agency was used as a lens to understand responses to questions relating to managerialism, new managerialism, new public management, accountability and academic identity. Halstead’s models of Accountability were used to analyse several reasons for accountability that were identified through this research. Those reasons for accountability were identified as being mostly legal, professional and moral, with both internal and external social dimensions. A typology of higher education institutional leaders was developed so as to better understand the relationship between leaders and their stakeholders. The two key findings were: the accountability of institutional leaders over time contributes to the construction and reconstruction of the academic identity of their academic staff; and how the accountability of institutional leaders is manifested and how that accountability affects the academic identity of their staff is dependent upon the political, institutional and personal contexts of those institutional leaders.
Absence of apolipoprotein B-3500 mutation in Turkish patients with coronary and cerebrovascular atherosclerosis.

OBJECTIVE The arginine- to-glutamine change at codon 3500 of the apolipoprotein B-100 (apo B) is a well- known genetic cause of hypercholesterolemia. Since increased cholesterol levels lead to atherosclerosis, identification of the carries of the apo B-3500 mutation is an important step in the risk stratification of individuals and families with hypercholesterolemia. The prevalence of this mutation in Turkish population is not well known. We aimed to investigate the frequency of apo B-100 mutations (codon 3500) C9774T (Arg 3500-->Trp) and G9775A (Arg 3500-->Gln) in patients with atherosclerosis in comparison with healthy subjects. METHODS This cross-sectional study included 442 unrelated subjects living on the West coast of Turkey. Subgroups consisted of 165 patients with coronary artery disease, 163 patients with ischemic stroke, and 114 healthy control subjects. RESULTS We did not find any apo B-100 mutation both in the patient and control groups. CONCLUSION As it is hypothesized that this mutation arose within the Central European region from a common ancestor approximately 7000 years ago and spread across Europe, our result of the absence of the R3500Q mutation in Turkish patients give an important information about the geographical distribution of the apo B-R3500Q, that the mutation has not reached to Anatolia.
Antifungal activity in vitro and in vivo of a salmon protamine peptide and its derived cyclic peptide against Candida albicans

Abstract Protamine peptide (PP) derived from salmon is a 14‐mer with 10 arginine residues. We investigated the in vitro and in vivo antifungal activity of PP against Candida albicans. PP showed a concentration‐dependent dual mode of action, with fungicidal activity and inhibitory activity for hyphal development in vitro. At lethal concentrations of PP, intracellular accumulation of PP was energy‐dependent but independent of endocytosis, and resulted in ATP efflux and the generation of reactive oxygen species in the cells. PP at sublethal concentrations inhibited hyphal development in C. albicans by binding to the cell surface. Though antifungal activity of PP was inactivated by high concentrations of NaCl, the antifungal activity of the synthetic cyclic (via a disulfide bond) form of PP (cyclic PP) was not. Cyclic PP also showed the concentration‐dependent dual mode of action, and had five‐fold greater antifungal activity than PP. The advantage of antifungal activity of cyclic PP compared with PP in vitro resulted in a high in vivo efficacy in a murine oral candidiasis model. Oral treatment with cyclic PP inhibited hyphal development of C. albicans on mouse tongues and protected against the development of severe candidiasis. This study shows the therapeutic potential of cyclic PP as an antifungal peptide against C. albicans.
Trade Shocks, Taxes, and Inequality

We study the impact of trade shocks on inequality using newly constructed micro and macro data. First, we use the Current Population Survey’s (CPS) Merged Outgoing Rotation Group (MORG) from 1979 to 2010 combined with new annual measures of imported inputs, a proxy for offshoring. We find that in periods when US relative prices are high, and imports surge relative to exports, workers in sectors with greater initial exposure to international trade were more likely to be unemployed a year later, but did not experience significant declines in wages conditional on being employed. Contrary to the usual narrative, we find negative wage effects for higher-wage, but not lower-wage workers, particularly for those who are less-educated. Second, sectors most exposed to trade shocks do not experience relative increases in inequality. Third, using aggregate international data for 31 countries, we find that various trade shocks, such as increases in trade with China, are not generally correlated with changes in the income distribution. Instead, using new historical data, we confirm a close connection between top marginal tax rates and top income shares, and find that the level of top marginal tax rates impacts changes in the top 1% share of income, implying that top income shares are a function of historical marginal tax rates.
Costimulation of cytokine gene expression in T cells by the human T leukemia/lymphotropic virus type 1 trans activator Tax

Many cell signals such as CD28 and CD4 binding can costimulate cytokine gene expression in activated T cells. We have found that the human T leukemia/lymphotropic virus type 1 viral protein Tax can also strongly costimulate expression of interleukin-2 (IL-2), IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA in T cells activated with the phorbol ester phorbol myristate acetate (PMA) and calcium ionophore, which can mimic activation through the antigen specific T-cell receptor. Reporter constructs also showed strong synergy between both stimuli and showed that Tax and the PMA-Ca2+ ionophore act through different regions of the IL-2 and GM-CSF genes. Furthermore, the Tax-responsive regions (TxRR) from both GM-CSF and IL-2 respond to costimulation through the CD28 surface receptor. The GM-CSF and IL-2 TxRRs showed significantly higher levels of NF-kappaB/rel binding, following induction by Tax, compared with that of the PMA-Ca2+ ionophore with only Tax capable of inducing c-Rel binding to a Consensus kappaB element within the GM-CSF TxRR. Tax protein mutants, however, showed that a pathway(s) other than NF-kappaB/rel induction could also cooperate with the PMA-Ca2+ ionophore to activate the GM-CSF and IL-2 genes. This high-level costimulation by Tax, through multiple pathways, may be important in the early stages of leukemia and in the nervous system disorder tropical spastic paraparesis.
Use of the Thiol-specific Derivatizing Agent N-Iodoacetyl-3-Iiodotyrosine to Demonstrate Conformational Differences between the Unbound and hsp90-bound Glucocorticoid Receptor Hormone Binding Domain (*)

The hormone binding domain (HBD) of the glucocorticoid receptor (GR) contains five cysteine residues, with three of them being spaced close to one another in the steroid binding pocket. The HBD also contains the contact region for the chaperone protein hsp90, which must be bound to the GR for it to have a steroid binding conformation. Binding of hsp90 to the receptor through its HBD inactivates the DNA binding domain (DBD). The DBD contains a number of cysteines essential to its DNA binding activity. Here, we assess the effects of hsp90 binding on the accessibility of cysteine residues in both the HBD and DBD to derivatization by a thiol-specific reagent. We report that N-iodoacetyltyrosine (IAT) inactivates steroid binding activity of the immunopurified, untransformed GRhsp90 complex in a manner that is prevented by the sulfhydryl reagents cysteine and dithiothreitol but is not reversed by them. The I-labeled IAT derivative N-iodoacetyl-3-[I]iodotyrosine ([I]IAIT) covalently labels the immunopurified, hsp90-bound receptor in a thiol-specific manner. Dissociation of hsp90 leads to an 2-fold increase in [I]IAIT labeling of the full-length, 100-kDa GR. The increase in thiol labeling is related to the presence of hsp90 because it is blocked by molybdate, which prevents hsp90 dissociation. Cleavage of the [I]IAIT-labeled receptor with trypsin yields a 15-kDa labeled fragment containing the DBD and a 30-kDa labeled fragment containing all of the cysteines in the HBD and the contact region for hsp90. Dissociation of hsp90 from the GR results in a 2.3-fold increase in [I]IAIT labeling of the 15-kDa fragment and a 50% decrease in labeling of the 30-kDa fragment. These data are consistent with the proposal that dissociation of hsp90 from the GR produces a conformational change in the HBD such that some of the thiols that are exposed in the GRhsp90 complex become buried and are no longer accessible to the [I]IAIT probe. In contrast, binding of the GR to hsp90 restricts access of cysteines in the DBD to this small thiol-derivatizing agent, a restriction that is relieved as a result of unmasking or conformational change accompanying hsp90 dissociation.
Time-resolved cellular effects induced by TcdA from Clostridium difficile.

RATIONALE The anaerobe Clostridium difficile is a common pathogen that causes infection of the colon leading to diarrhea or pseudomembranous colitis. Its major virulence factors are toxin A (TcdA) and toxin B (TcdB), which specifically inactivate small GTPases by glucosylation leading to reorganization of the cytoskeleton and finally to cell death. In the present work a quantitative proteome analysis using the isotope-coded protein label (ICPL) approach was conducted to investigate proteome changes in the colon cell line Caco-2 after treatment with recombinant wild-type TcdA (rTcdA-wt) or a glucosyltransferase-deficient mutant TcdA (rTcdA-mut). METHODS Proteins from crude cell lysates or cellular subfractions were identified by liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS). Two time points (5 h, 24 h) of toxin treatment were analyzed and about 4000 proteins were identified in each case. RESULTS After 5 h treatment with rTcdA-wt, 150 proteins had a significantly altered abundance; rTcdA-mut caused regulation of 50 proteins at this time point. After 24 h treatment with rTcdA-wt changes in abundance of 61 proteins were observed, but no changes in protein abundance were detected after 24 h if cells were treated with rTcdA-mut. TcdA affected several proteins involved in signaling events, cytoskeleton and cell-cell contact organization, translation, and metabolic processes. The ICPL-dependent quantification was verified by label-free targeted MS techniques based on multiple reaction monitoring (MRM) and triple quadrupole mass spectrometry. CONCLUSIONS LC/MS-based proteome analyses and the ICPL approach revealed comprehensive and reproducible proteome date and provided new insights into the cellular effects of clostridial glucosylating toxins (CGT).
Protective effect of bismuth nitrate against injury to the bone marrow by gamma-irradiation in mice: possible involvement of induction of metallothionein synthesis.

The effects of bismuth nitrate (BN) on the lethal effect of and injury to bone marrow by gamma-irradiation were examined. Mice were given daily s.c. injections of BN for 2 days and were exposed to whole-body irradiation (137Cs; 8 grays) 24 hr after the second injection of BN. All mice exposed to gamma-irradiation without treatment with BN died within 30 days, but the lethal effect of gamma-irradiation was markedly reduced in mice given BN before irradiation. Irradiation (3 grays) significantly reduced the total number of leukocytes 1 day after irradiation but the number of leukocytes subsequently increased in both nontreated and BN-treated irradiated mice. However, the rate of recovery of the total number of leukocytes, as monitored from 5 days after irradiation, was significantly higher in BN-treated mice than in the nontreated mice. Reductions in the viability of hematopoietic stem cells (determined by monitoring the number of colony-forming units in the spleen) that were induced by gamma-irradiation (3 grays) were considerably diminished by the treatment of mice with BN before irradiation. BN significantly increased the concentration of metallothionein in the bone marrow cells of mice, but levels of other cellular antioxidants, such as catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase and glutathione, were unchanged. These results suggest that BN protects bone marrow cells against the toxic effects of gamma-irradiation by inducing the synthesis of metallothionein in the bone marrow. Metallothionein might play an important role in determining the sensitivity of animals to gamma-irradiation.
Deductive Sort and Climbing Sort: New Methods for Non-Dominated Sorting

In recent years an increasing number of real-world many-dimensional optimisation problems have been identified across the spectrum of research fields. Many popular evolutionary algorithms use non-dominance as a measure for selecting solutions for future generations. The process of sorting populations into non-dominated fronts is usually the controlling order of computational complexity and can be expensive for large populations or for a high number of objectives. This paper presents two novel methods for non-dominated sorting: deductive sort and climbing sort. The two new methods are compared to the fast non-dominated sort of NSGA-II and the non-dominated rank sort of the omni-optimizer. The results demonstrate the improved efficiencies of the deductive sort and the reductions in comparisons that can be made when applying inferred dominance relationships defined in this paper.
Sound Localization in Bilateral Users of MED-EL COMBI 40/40+ Cochlear Implants

Objective: The purpose of the study was to investigate sound localization with bilateral and unilateral cochlear implants. Design: Sound localization tests were performed on 20 bilaterally implanted MED-EL COMBI 40/40+ users. All subjects were bilaterally implanted during adolescence or later. Sound localization was tested in the frontal horizontal plane by using 9 equally spaced loudspeakers and speech-shaped noise bursts at randomized levels. Results: The group of subjects who were bilaterally deafened after 5 to 6 yr of age (18 subjects) showed a statistically significant improvement in sound localization when using both implants, compared with when using only one. The mean deviation between the presentation azimuth and the response azimuth was 16.6° when using both implants, which was on average 37.1° smaller than when using one implant only. When adjusted for the localization error that was constant across loudspeakers, the mean deviation was 15.9° for bilateral implant use, representing an improvement of 30.1° over unilateral implant use. Statistical analysis showed that in this group, performance measures were not correlated with subject details such as age at onset of deafness or duration of unilateral implant use. In contrast, subjects who were bilaterally deafened before 6 yr of age (2 subjects) did not show a benefit in sound localization from bilateral implants. Conclusions: Bilateral cochlear implants offer a substantial benefit in sound localization to late-deafened, late-implanted subjects. The very limited data from early-deafened subjects implanted at a later age could suggest that these subjects may not benefit in sound localization from bilateral cochlear implants. It is possible that early implantation for early deafened subjects might allow better acquisition of spatial hearing, thus leading to improved localization performance.
Design of a slot-coupled Ultra-Wideband 180° hybrid coupler

In this paper a wideband microstrip 180° hybrid coupler is proposed. The coupler is designed using a double sided single layer substrate for Ultra-Wideband (UWB) applications. The device is constructed from Wilkinson Power Divider (WPD) employing microstrip line to slot transition for the construction of a delta (Δ) port. The input port (Σ port) of the WPD acts as the in phase power divider. The Σ and Δ ports are located opposite to each other, making the overall size compact and easy for measurements. The proposed method of design results in a 180° hybrid coupler with good UWB performance. The return loss of the sum port and delta port is less than 10 dB. The power imbalance and the phase imbalance between the output ports is less than 0.5 dB and 0.8°, respectively, for complete UWB frequency range. The isolation between sum and delta ports is more than 40 dB.
Fundamental limits of disk flexure resonators

High performance PZT-on-silicon disk flexure resonators were recently demonstrated with peak |S21| of −1 dB with direct 50 Ω termination, high bandwidth tunability, and high coupling at 22 MHz. This paper explores the performance limits and design optimization of this new resonator in the space of radius and silicon thickness of the (1,1) disk flexure mode. This effort is enabled by the Rapid Analytical/FEA Technique, a novel method for expedited acoustic resonator simulation. Simulations indicate that monolithic integration of disk resonators with −0.5 dB max|S21| may be achieved across a wide range of HF and low-VHF frequencies without the need for external impedance matching.
Improving Classification Performance by Combining Feature Vectors with a Boosting Approach for Brain Computer Interface (BCI)

Brain-computer interfaces (BCI) are an interesting emerging technology providing an efficient communication system between human brain and external devices like computers or neuroprosthesis. Among assorts of neuroimaging techniques, electroencephalogram (EEG) is among one of the non-invasive methods exploited mostly in BCI studies. Recent studies have shown that Motor Imagery (MI) based BCI can be used as a rehabilitation tool for patients with severe neuromuscular disabilities. The spatial and spectral information related to brain activities associated with BCI paradigms are usually pre-determined as default in EEG analysis without speculation, which can lead to loses effects in practical applications due to individual variability across different subjects. Recent studies have shown that feature combination of each specifically tailored for different physiological phenomena such as Readiness Potential (RP) and Event Related Desynchronization (ERD) might benefit BCI making it robust against artifacts. Hence, the objective is to design a CSSBP with combined feature vectors, where the signal is divided into several sub bands using a band pass filter, and this channel and frequency configurations are then modeled as preconditions before learning base learners and introducing a new heuristic of stochastic gradient boost for training the base learners under these preconditions. The effectiveness and robustness of this algorithm along with feature combination is evaluated on two different data sets recorded from distinct populations. Results showed that Boosting approach with feature combination clearly outperformed the state-of-the-art algorithms, and improved the classification performance and resulted in increased robustness. This method can also be used to explore the neurophysiological mechanism of underlying brain activities.
Identifying current and remitted major depressive disorder with the Hurst exponent: a comparative study on two automated anatomical labeling atlases

Major depressive disorder (MDD) is a leading world-wide psychiatric disorder with high recurrence rate, therefore, it is desirable to identify current MDD (cMDD) and remitted MDD (rMDD) for their appropriate therapeutic interventions. In the study, 19 cMDD, 19 rMDD and 19 well-matched healthy controls (HC) were enrolled and scanned with the resting-state functional magnetic resonance imaging (rs-fMRI). The Hurst exponent (HE) of rs-fMRI in AAL-90 and AAL-1024 atlases were calculated and compared between groups. Then, a radial basis function (RBF) based support vector machine was proposed to identify every pair of the cMDD, rMDD and HC groups using the abnormal HE features, and a leave-one-out cross-validation was used to evaluate the classification performance. Applying the proposed method with AAL-1024 and AAL-90 atlas respectively, 87% and 84% subjects were correctly identified between cMDD and HC, 84% and 71% between rMDD and HC, and 89% and 74% between cMDD and rMDD. Our results indicated that the HE was an effective feature to distinguish cMDD and rMDD from HC, and the recognition performances with AAL-1024 parcellation were better than that with the conventional AAL-90 parcellation.