Miracle-dz/UniFAR-FTUs huggingface dataset:
An Update on HIV-1 Protease Inhibitor Resistance

Protease inhibitors (PIs) are a potent class of antiretroviral agents which have been used to successfully treat many patients with HIV disease. As with other classes of antiretroviral agents, drug resistance has been described with each of the PIs. PI resistance can occur in newly infected individuals due to transmission of drug resistant strains or, more commonly, evolves from the selective pressure of antiretroviral therapy. When present, PI resistance results in an increased likelihood of drug failure. Individual protease gene mutations have been identified which are associated with phenotypic resistance to these agents. However, protease mutations can exert different effects on individual PIs, as some will produce resistance to one agent and may enhance susceptibility to another. In patients failing PIs, particularly in the setting of prior treatment with multiple agents, protease resistance patterns may be complex and result in broad cross-resistance to the class. Strategies to limit the development of resistance to these agents and manage its occurrence are important for the on-going care of individuals with HIV infection.
The presentation of elderly people at an emergency department in Singapore.

OBJECTIVE This study aims to provide demographic and clinical data of elderly people attending one of the hospital emergency departments in Singapore. DESIGN Patients aged 60 years and above who attended the Emergency Department (ED) at Alexandra Hospital, Singapore, during 4 randomly selected one-week periods in 1996 were retrospectively studied. MAIN OUTCOME MEASURES Patient profile; presenting symptoms; diagnoses; types of investigations done, and outcome following attendance. RESULTS A total of 455 ED attendance cards were analysed. The age of patients ranged from 60 to 102 years with a mean age of 72.8 years. Two hundred and sixty-one (57.4%) were males and 194 (42.6%) were females. Four hundred and twenty-seven (93.9%) were emergencies, 25 (5.5%) were non-emergencies and in 3 (0.6%) the priority rating was unknown. Two hundred and ninety (63.7%) were admitted, of whom 166 (57.2%) were males. One (0.2%) was admitted for social reason. The 3 most common symptoms were abnormalities of breathing (10.6%), falls (9.4%) and musculoskeletal pain (8.2%). Majority had 1 (40.4%) or 2 (41.6%) symptoms. The symptoms were mainly acute (1 day, 45.2%) or less than a week (25.7%). The 3 most common diagnoses were chest infection or pneumonia (8.2%), non-fracture head injury (7.2%) and heart failure (6.6%). Most patients (90.5%) had only 1 diagnosis. The 3 most common tests done were chest X-ray (172 patients, 37.8%), electrocardiography (119 patients, 26.2%) and blood glucose (86 patients, 19.0%). One hundred and twenty (26.4%) patients did not require any investigation. CONCLUSION The elderly constituted 12.4% of attendance at the ED but formed 34.5% of admissions. They were more likely to have emergency problems. Understanding the common presenting symptoms and diagnoses of the elderly will help doctors at the ED provide better care. Elderly patients with complex problems who are not hospitalised would probably benefit from further geriatric assessment.
NF-κB1 p105 Regulates T Cell Homeostasis and Prevents Chronic Inflammation1

Transcription factor NF-κB is regulated by a family of inhibitors, IκBs, as well as the NF-κB1 and NF-κB2 precursor proteins, p105 and p100. Although the different NF-κB inhibitors can all inhibit NF-κB in vitro, their physiological functions are incompletely understood. In this study, we demonstrate that p105 plays an important role in the regulation of T cell homeostasis and prevention of chronic inflammation. Mice lacking p105, but expressing the mature NF-κB1 p50, spontaneously develop intestinal inflammation with features of human inflammatory bowel disease. This inflammatory disorder occurs under specific pathogen-free conditions and critically involves T cells. Consistently, the p105-deficient mice have reduced frequency of naive T cells and increased frequency of memory/effector T cells in the peripheral lymphoid organs. Although p105 is dispensable for the production of immunosuppressive regulatory T cells, p105 deficiency renders CD4 T cells more resistant to Treg-mediated inhibition. We further show that the loss of p105 results in hyperproduction of Th17 subset of inflammatory T cells. Together, these findings suggest a critical role for NF-κB1 p105 in the regulation of T cell homeostasis and differentiation and the control of chronic inflammation.
Chorioamnionitis and pregnancy outcome in HIV-infected African women. Pregnancy and HIV Study Group.

OBJECTIVE To assess the role of chorioamnionitis (CAM) on pregnancy outcome in HIV-1-infected (HIV-positive) pregnant women, treated for sexually transmitted diseases (STDs), during the last trimester of pregnancy in Kigali, Rwanda. METHODS At inclusion in a prospective cohort, from July 1992 to August 1993, 561 pregnant women between 24 and 28 weeks were systematically screened for HIV infection, STDs, anemia, malaria, and hepatitis B infection; a CD4 lymphocyte count was performed. Until delivery, each woman enrolled had a monthly clinical follow-up with STD treatment when needed. The pregnancy outcome was recorded. Diagnosis of CAM was based on histologic examination of the placenta. RESULTS Among the 275 placentas of HIV-negative women and 286 placentas of HIV-positive women examined, CAM was diagnosed (CAM-positive) in 27 HIV-positive women (9.8%) and in 28 HIV-negative women (9.8%). No statistical association was found between CAM and the following variables, independent of the HIV serostatus: age, parity, hepatitis B, anemia, STDs, and immune deficiency. Among HIV-negative women, CAM was significantly associated with prematurity (relative risk [RR] = 3.0; 95% confidence interval [CI] = 1.5-6.3), stillbirth (RR = 4.2; 95% CI = 1.6-11.0) and premature rupture of membranes (RR = 2.9; 95% CI = 1.4-6.1). Among HIV-positive women, early neonatal mortality was the only adverse outcome associated with CAM (RR = 2.0; 95% CI = 1.6-11.0). CONCLUSIONS In our study, the prevalence of CAM was low and no risk factor of CAM was identified, a probable consequence of the control factor of STDs. CAM was strongly associated with adverse pregnancy outcomes in HIV-infected women, reflecting a possible deleterious effect of HIV.
Donor phosphorus levels and recipient outcomes in living-donor kidney transplantation.

BACKGROUND AND OBJECTIVES In living-donor kidney transplantation, various donor factors, including gender, age, and baseline kidney function, predict allograft function and recipient outcomes after transplantation. Because higher phosphorus is predictive of vascular injury in healthy adults, the effect of donor phosphorus levels on recipient renal function after transplantation was investigated. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS Phosphorus levels in 241 living donors were analyzed from a 7-year period, and recipient renal function and acute rejection at 1 year posttransplantation were examined controlling for other influencing factors, including multiple donor variables, HLA matching, and acute rejection. RESULTS Female and African-American donors had significantly higher phosphorus levels predonation. By multivariable analysis, higher donor phosphorus correlated with higher recipient serum creatinine (slope=0.087, 95% confidence interval [CI]: 0.004 to 0.169, P=0.041) and lower recipient estimated GFR (slope=-4.321, 95% CI: -8.165 to -0.476, P=0.028) at 12 months. Higher donor phosphorus also displayed an independent correlation with biopsy-proven acute rejection and delayed or slow graft function after transplantation. CONCLUSIONS In a cohort of living kidney donors, higher donor phosphorus correlated with female gender and African-American ethnicity and was an independent risk factor for early allograft dysfunction after living-donor kidney transplantation.
Convergence and Divergence in the European Monetary Union

After the outbreak of the global financial crisis in 2008, macroeconomic disequilibria began to emerge and to grow within the eurozone. The original goal of real convergence which characterized and strengthened the European integration process has since been violated with increasing frequency, thus producing disappointment and the first signs of a legitimation crisis within the European Union. The convergence process which for a long time united the members of the European Union and later of the eurozone has recently been superseded increasingly by a divergence process which endangers the on-going European integration process. This paper describes and analyses this process, highlights new empirical evidence and draws some politico-economic implications. 1. Convergence as an original goal of European integration Convergence was an original goal of the European integration process; initially a hope, in time it became an expectation of the less wealthy member states and a demand from the acceding countries, respectively. Thus, it was a major goal of the European integration process from the beginning to reach an adjustment in institutions and in GNP per capita level among its member states. This was formulated in the preamble to the EC Treaty of 1957 as the aim to "strengthen the unity of (the) economies (of the member states) and to ensure their harmonious development by reducing the differences existing between the various regions and the backwardness of the less favoured". Later, in the preamble to the EU Treaty of 1992, the goal articulated was to "achieve the strengthening and the convergence of their economies". This expected development seemed to have the potential for manifestation in reality for a time, at least until the introduction of the monetary union and the advent of the "euro crisis" in the course of the global financial crisis. In the event it seems that through the construction of the monetary union a potential for destabilization has arisen that only becomes manifest when bigger shocks occur. In the beginning, optimistic expectations regarding a rapid convergence of the periphery countries still dominated (see Blanchard and Giavazzi 2002); these, fuelled by the interest rate adjustments in the first decade of this century, led to an imprudent minimum reform policy (to avoid the costs and pain of more fundamental reforms) in these countries. However, a sudden increase in divergent tendencies has occurred during the past five years leading to great disillusionment in the eurozone.
Style Comparison of U.S. Islamic Equity Market Indexes

Differences between the stock selection criteria of stock indexes can cause them to behave differently. This study compared the styles of four Islamic indexes from major index providers, whose Shariah screening criteria are at variance. To ensure fairness in comparison, the authors chose Islamic indexes that represent only the U.S. stock market because conditions vary across markets and financial markets have been found to be segmented by countries. Likewise, a fixed set of style benchmarks and T-bills were used as asset classes in determining the style of each Islamic index. A thorough comparison revealed important differences in the styles of the analyzed Islamic indexes, much of which can be attributed to differences in their screening criteria in light of the relevant literature.
Communist Party Members : Incentives and Gains

The communist movement, its top leadership, its ideology, and socialist party-states have been extensively investigated by social scientists. But analyses of the general membership of the Communist Party (CP), especially within socialist states, have been rare, largely because good data are scarce. In this article we analyze longitudinal data on a sample of Estonians born in the late 1940s who graduated from secondary school in 1966. We compare CP members and nonmembers, addressing the following issues: Which people were especially likely to join the CP? How did the life careers of CP members and nonmembers differ? How did the values of CP members and nonmembers compare? What were the objective benefits of CP membership?
Development of novel pharmacotherapeutics for tobacco dependence: progress and future directions.

INTRODUCTION The vast majority of tobacco smokers seeking to quit will relapse within the first month of abstinence. Currently available smoking cessation agents have limited utility in increasing rates of smoking cessation and in some cases there are notable safety concerns related to their use. Hence, there is a pressing need to develop safer and more efficacious smoking cessation medications. METHODS Here, we provide an overview of current efforts to develop new pharmacotherapeutic agents to facilitate smoking cessation, identified from ongoing clinical trials and published reports. RESULTS Nicotine is considered the major addictive agent in tobacco smoke, and the vast majority of currently available smoking cessation agents act by modulating nicotinic acetylcholine receptor (nAChR) signaling. Accordingly, there is much effort directed toward developing novel small molecule therapeutics and biological agents such as nicotine vaccines for smoking cessation that act by modulating nAChR activity. Our increasing knowledge of the neurobiology of nicotine addiction has revealed new targets for novel smoking cessation therapeutics. Indeed, we highlight many examples of novel small molecule drug development around non-nAChR targets. Finally, there is a growing appreciation that medications already approved for other disease indications could show promise as smoking cessation agents, and we consider examples of such repurposing efforts. CONCLUSION Ongoing clinical assessment of potential smoking cessation agents offers the promise of new effective medications. Nevertheless, much of our current knowledge of molecular mechanisms of nicotine addiction derived from preclinical studies has not yet been leveraged for medications development.
Simple pyrazinamidase and urease tests for routine identification of mycobacteria.

A specific assay for free pyrazinoic acid has been applied to a study of pyrazinamidase activity of mycobacteria. Evidence is presented for differences in rates of appearance of enzymatic activity, which helps to explain variability in test results often seen in mycobacterial identification. A simple technique is described for pyrazinamidase testing that can be applied to identification of mycobacteria in a routine diagnostic laboratory. An evaluation of a simple urease test is also presented.
Parliamentary scrutiny as a function of interparliamentary cooperation among subnational parliaments

ABSTRACT The paper analyses the scrutiny activities of three different types of institutionalised form of interparliamentary cooperation with participation of subnational parliaments: the Conference of European Legislative Assemblies; the Baltic Sea Parliamentary Conference; and the Interregional Parliamentary Council of the Grande Région. For the purpose of analysis, the analytical parameters of parliamentary functions are modified and applied to the forms of institutionalised interparliamentary cooperation. It is shown that the exertion of scrutiny activities increases in relation to the age and institutionalisation of an interparliamentary cooperation. Ex ante control, which may consist of as little as demands, develops more easily than ex post control. Moreover, the exercise of the scrutiny function becomes more difficult when the level(s) that populate(s) the interparliamentary cooperation is/are not congruent with the level(s) that populate(s) the executive body of the respective international organisation. Interparliamentary cooperation of subnational parliaments struggles to scrutinise an organisation in which national executives play a major role.
Understanding the Impacts of Dark Pools on Price Discovery

This paper investigates the impact of dark pools on price discovery (the efficiency of prices on stock exchanges to aggregate information). Assets are traded in either an exchange or a dark pool, with the dark pool offering better prices but lower execution rates. Informed traders receive noisy and heterogeneous signals about an asset's fundamental. We find that informed traders use dark pools to mitigate their information risk and there is a sorting effect: in equilibrium, traders with strong signals trade in exchanges, traders with moderate signals trade in dark pools, and traders with weak signals do not trade. As a result, dark pools have an amplification effect on price discovery. That is, when information precision is high (information risk is low), the majority of informed traders trade in the exchange hence adding a dark pool enhances price discovery, whereas when information precision is low (information risk is high), the majority of the informed traders trade in the dark pool hence adding a dark pool impairs price discovery. The paper reconciles the conflicting empirical evidence and produces novel empirical predictions. The paper also provides regulatory suggestions with dark pools on current equity markets and in emerging markets.
Economic Impacts of Renewable Energy Promotion in Germany

ABSTRACT Over the last decade Germany has boosted renewable energy in power production by means of massive subsidies. The flip side are very high electricity prices which raise concerns that the transition cost towards a renewable energy system will be mainly borne by poor households. In this paper, we combine computable general equilibrium and microsimulation analyses to investigate the economic impacts of Germany’s renewable energy promotion. We find that the regressive effects of renewable energy promotion could be attenuated by alternative subsidy financing mechanisms.
High intra‐abdominal pressure during experimental laparoscopic liver resection reduces bleeding but increases the risk of gas embolism

Various recommendations exist regarding intra‐abdominal pressure (IAP) during laparoscopic liver resection. A high IAP may reduce bleeding but at the same time increase the risk of gas embolism. This study investigated the effects of two different IAPs during laparoscopic left liver lobe resection in piglets.
Organisation of care for Swedish patients with an implantable cardioverter defibrillator, a national survey.

AIM To describe the clinical aspects of implantable cardioverter defibrillators care in Sweden with focus on organisation, the role and education of nurses, patient information and education and areas in need of improvement. BACKGROUND Implantable cardioverter defibrillators implantations have developed rapidly in recent years and are now an established arrhythmia treatment. The expanding indication for implantable cardioverter defibrillators implantation demands new competencies and resources in the implantable cardioverter defibrillators team members. METHODS Participants were recruited among physicians and nurses in all of the hospitals implanting implantable cardioverter defibrillators (n = 16). Data were collected by a questionnaire. Additionally, all written educational materials provided to patients pre- and postimplant were collected from all 16 hospitals. Deductive content analysis using Sarvimäki and Stenbock-Hult's five holistic dimensions was employed to ascertain how information was provided in brochures and information materials. RESULTS Half of the hospitals (n=8) had nurse-based outpatient clinics and several others planned to introduce them. Three hospitals carried out distance follow-ups by means of tele-monitoring. The nurses had received specific implantable cardioverter defibrillators education from implantable cardioverter defibrillators companies and/or various university courses. The biophysical dimension dominated in the information material, while the emotional, intellectual and socio-cultural dimensions were scarcely described, and the spiritual-existential was not referred to at all. CONCLUSION Holistic care of implantable cardioverter defibrillators patients can be achieved by means of a multidisciplinary implantable cardioverter defibrillators team and more patient-centred educational strategies. In Sweden, the organisation of implantable cardioverter defibrillators care and follow-up is developing towards more nurse-based clinics. RELEVANCE TO CLINICAL PRACTICE Development and implementation of structured care programmes with a more holistic approach can improve future implantable cardioverter defibrillators care. The content of the written educational materials need to be more holistic, rather than mainly focusing on the biophysical and technical aspects of living with an implantable cardioverter defibrillators.
Transcriptional Profiling of Candida glabrata during Phagocytosis by Neutrophils and in the Infected Mouse Spleen

ABSTRACT Expression microarray analysis of Candida glabrata following phagocytosis by human neutrophils was performed, and results were compared with those from C. glabrata incubated under conditions of carbohydrate or nitrogen deprivation. Twenty genes were selected to represent the major cell processes altered by phagocytosis or nutrient deprivation. Quantitative real-time PCR (qRT-PCR) with TaqMan chemistry was used to assess expression of the same genes in spleens of mice infected intravenously with Candida glabrata. The results in spleen closely paralleled gene expression in neutrophils or following carbohydrate deprivation. Fungal cells responded by upregulating alternative energy sources through gluconeogenesis, glyoxylate cycle, and long-chain fatty acid metabolism. Autophagy was likely employed to conserve intracellular resources. Aspartyl protease upregulation occurred and may represent defense against attacks on cell wall integrity. Downregulated genes were in the pathways of protein and ergosterol synthesis. Upregulation of the sterol transport gene AUS1 suggested that murine cholesterol may have been used to replace ergosterol, as has been reported in vitro. C. glabrata isolates in spleens of gp91phox−/− knockout mice with reduced oxidative phagocyte defenses were grossly similar although with a reduced level of response. These results are consistent with reported results of other fungi responding to phagocytosis, indicating that a rapid shift in metabolism is required for growth in a carbohydrate-limited intracellular environment.
MicroRNA-148a Promotes Myogenic Differentiation by Targeting the ROCK1 Gene*

Background: miRNAs participate in the regulation of skeletal muscle development. Results: miR-148a promotes myogenic differentiation and down-regulates ROCK1 gene at the translational level. Conclusion: miR-148a plays a positive role in skeletal muscle development via ROCK1 down-regulation. Significance: Our findings reveal a novel mechanism in which miR-148a controls myogenesis through the RhoA/ROCK pathyway. MicroRNAs are evolutionarily conserved small RNAs that post-transcriptionally regulate gene expression and have emerged as critical regulators of skeletal muscle development. Here, we identified miR-148a as a novel myogenic microRNA that mediated myogenic differentiation. The expression levels of miR-148a increased during C2C12 myoblast differentiation. Overexpression of miR-148a significantly promoted myogenic differentiation of both C2C12 myoblast and primary muscle cells. Blocking the function of miR-148a with a 2′-O-methylated antisense oligonucleotide inhibitor repressed C2C12 myoblast differentiation. Using a bioinformatics approach, we identified Rho-associated coiled-coil containing protein kinase 1 (ROCK1), a known inhibitor of myogenesis, as a target of miR-148a. A dual-luciferase reporter assay was used to demonstrate that miR-148a directly targeted the 3′-UTR of ROCK1. In addition, the overexpression of miR-148a decreased the protein expression of ROCK1 in C2C12 myoblast and primary muscle cells. Furthermore, ROCK1 inhibition with specific siRNA leaded to accelerated myogenic differentiation progression, underscoring a negative regulatory function of ROCK1 in myogenesis. Therefore, our results revealed a novel mechanism in which miR-148a positively regulates myogenic differentiation via ROCK1 down-regulation.