Miracle-dz/UniFAR-FTUs huggingface dataset:
High resistance to antiretroviral drugs: the Indian experience

Effective antiretroviral treatment (ART) has significantly reduced the morbidity and mortality among people living with HIV/AIDS. The emergence of drug resistance is the major obstacle to the successful implementation of long-term treatment strategy of HIV disease. Hence, monitoring the resistance to ART is an essential task. The MGM Medical College in Navi Mumbai is the only national facility with the capacity to monitor ART resistance using tissue culture technique. The main objective of the study was to determine the prevalence of primary and secondary resistance between May 1997 and April 2003. Four hundred and sixty viral isolates of 74 individuals were tested for ART resistance using tissue culture-based protocol (McGill University, Canada). These included 287 primary and 173 follow-up viral isolates. Following activation of tissue culture, a panel of 12 antiretroviral drugs in concentrations from 0.038 mg/mL to 0.090 mg/mL was tested. The resistance was determined on the basis of the production of p24 antigen at the end of 72 and 144 hours of incubation. The overall resistance against reverse transcriptase inhibitors (RTIs) was 33.7% and that to protease inhibitors (PIs) was 21.5%. However, prevalence of primary resistance among ART naïve to RTIs was 14/208 (6.7%) of isolates and that to (PIs) was 2/79(2.5%) of isolates. The incidence of resistance to RTI was 22/500 years (4.4/100 years) and that to PIs was 8/253.6 years (3.2/100 years). It is possible that non-B subtypes of HIV-1 that are prevalent in most developing countries are likely to develop resistance rapidly after ART. However, common factors that influence development of resistance such as poor adherence, inadequate 'wild' doses and regimens, and poor monitoring were not validated in the study. Unless active surveillance is instituted, these factors can pose major challenge for the management of people on ART in developing countries.
Erythropoietin after a century of research: younger than ever

In the light of the enthusiasm regarding the use of recombinant human erythropoietin (Epo) and its analogues for treatment of the anaemias of chronic renal failure and malignancies it is worth remembering that today's success has been based on a century of laborious research. The concept of the humoral regulation of haematopoiesis was first formulated in 1906. The term ‘erythropoietin’ for the erythropoiesis‐stimulating hormone was introduced in 1948. Native human Epo was isolated in 1977 and its gene cloned in 1985. During the last 15 yr, major progress has been made in identifying the molecules controlling Epo gene expression, primarily the hypoxia‐inducible transcription factors (HIF) that are regulated by specific O2 and oxoglutarate requiring Fe2+‐containing dioxygenases. With respect to the action of Epo, its dimeric receptor (Epo‐R) has been characterised and shown to signal through protein kinases, anti‐apoptotic proteins and transcription factors. The demonstration of Epo‐R in non‐haematopoietic tissues indicates that Epo is a pleiotropic viability and growth factor. The neuroprotective and cardioprotective potentials of Epo are reviewed with a focus on clinical research. In addition, studies utilising the Epo derivatives with prolonged half‐life, peptidic and non‐peptidic Epo mimetics, orally active drugs stimulating endogenous Epo production and Epo gene transfer are reviewed.
Optimal design of measurement-type current transformer using genetic algorithm

In this paper a new approach based on genetic algorithm (GA) for measurement-type current transformer (CT) design has been presented. This algorithm can present designed parameters of sample current transformer so that minimizes ratio and phase displacement errors to 1.2 times of rated current and transformer made cost also. Finally, several current transformers with different rated values are designed and results show that the proposed approach can be used for optimal design of current transformer perfectly.
Responses of Active Bacterial and Fungal Communities in Soils under Winter Wheat to Different Fertilizer and Pesticide Regimens

ABSTRACT The composition of the active microbial (bacterial and fungal) soil community in an arable wheat field subjected to different management practices was examined at five times during a 1-year period. Field sections were fertilized either at good agricultural practice (GAP) levels or at reduced levels (0.5× GAP) and were inoculated with vesicular arbuscular mycorrhizae (VAM) at the same time. Field subsections were treated either with or without pesticides. Changes in the active microbial communities were investigated by denaturing gradient gel electrophoresis analysis of reverse transcription-PCR-amplified 16S and 18S rRNA. Microbial community structure was primarily determined by season, and the seasonal trends were similar for the fungal and bacterial components. Between-sample microbial heterogeneity decreased under a mature crop in the summer but increased following harvesting and plowing. Although similar overall trends were seen for the two microbial components, sample variability was greater for the fungal community than for the bacterial community. The greatest management effects were due to GAP fertilization, which caused increases in the bacterial numbers in the total and culturable communities. Microbial biomass similarly increased. GAP fertilization also caused large shifts in both the active bacterial community structure and the active fungal community structure and additionally resulted in a decrease in the heterogeneity of the active bacterial community. Pesticide addition did not significantly affect bacterial numbers or heterogeneity, but it led to major shifts in the active soil bacterial community structure. PCR primers specific for Glomales 25S rRNA genes were used to monitor the VAM population following inoculation. Glomales were detected initially only in VAM-inoculated field sections but were subsequently detected in noninoculated field sections as the season progressed. After plowing, the level of Glomales was reduced in noninoculated field sections but remained high in VAM-inoculated field sections. Inoculation of VAM correlated with elevated soil phosphate and carbon levels.
Approximation dans les bases de données contraintes

Le modele des bases de donnees contraintes, introduit par Kanellakis, Kuper et Revesz [KKR95] permet la prise en compte d'informations geometriques, comme les donnees cartographiques. Les objets geometriques sont representes comme la solution d'un systeme d'equations ou d'inequations, sans limitation sur leur dimension. La complexite en temps de l'evaluation des requetes du premier ordre ou du volume est raisonnable lorsque la dimension des objets est fixe. Lorsque la dimension des objets est une variable du probleme, cette complexite est prohibitive (globalement exponentielle dans la dimension). Dans cette these, nous nous interessons a l'obtention d'algorithmes d'evaluation en temps polynomial dans la dimension, par des techniques d'approximation probabiliste. En etendant les travaux de Dyer, Frieze et Kannan [DFK91], nous obtenons : - un algorithme d'echantillonnage de points avec distribution presque uniforme dans l'ensemble defini par une requete du premier ordre ; - un algorithme estimant le volume et la forme de cet ensemble [GdR00]. Sous certaines conditions, le volume peut etre estime sans evaluation prealable de la requete. Nous considerons ensuite la robustesse des relations topologiques entre objets apres utilisation d'algorithmes d'approximation. Enfin, nous presentons un prototype de base de donnees spatiales mettant en oeuvre certains de ces algorithmes probabilistes sur des donnees reelles.
The Role of Growth Hormone in Neural Development

Growth hormone (GH) is integrally involved in the development of the central nervous system (CNS), as well as during its recovery from injury, two processes that share many similarities and may influence CNS functionality. This review discusses some of the most recent findings in the field and, in particular, the ontogeny, distribution, regulation and putative functions of GH and its receptor within the CNS, particularly during development. The relative roles of peripheral GH, acting in part through insulin-like growth factor-I, and of the autocrine/paracrine GH system within the brain are considered. The potential role of GH as a therapeutic agent to influence brain development and function is discussed.
Ampulla of Vater Carcinoma in Real-World Clinical Practice: A Case Series

Aims and Background The aim of this report was to describe the way in which a rare and niche disease like ampulla of Vater carcinoma (AVC) was treated in real-world clinical practice. Methods and Study Design A retrospective analysis of consecutive patients with a diagnosis of AVC treated at our medical oncology unit between August 2004 and August 2013 was performed. Results We evaluated 8 consecutive patients with a median age of 60 years (range 56–84). At the last follow-up, 4 patients were alive without evidence of disease and 4 patients had died. The median follow-up time was 21.51 months (range 1–100.43), the median overall survival 23.19 months (range 7.07–102.2), and the median disease-free survival 18.26 months (range 0–102.2). Six patients underwent surgery, which consisted of pylorus-preserving pancreaticoduodenectomy, R0 in all cases. Tumor histology was adenocarcinoma in all patients. Two patients presented with locally advanced disease. Only 1 patient presented with metastases while 3 patients subsequently developed metastases. Two patients received chemotherapy for metastatic disease; in both cases disease progression was observed at the first disease evaluation. Conclusions We can consider AVC as a pathology niche and pancreaticoduodenectomy as the effective treatment for these patients.
Endothelial Junction Regulation: A Prerequisite for Leukocytes Crossing the Vessel Wall

The leukocytes of the innate immune system, especially neutrophils and monocytes, exit the circulation early in the response to local inflammation and infection. This is necessary to control and prevent the spread of infections before an adaptive immune response can be raised. The endothelial cells and the intercellular junctions that connect them form a barrier that leukocytes need to pass in order to get to the site of inflammation. The junctions are tightly regulated which ensures that leukocytes only exit when and where they are needed. This regulation is disturbed in many chronic inflammatory diseases which are characterized by ongoing recruitment and interstitial accumulation of leukocytes. In this review, we summarize the molecular mechanisms that regulate endothelial cell-cell junctions and prevent or permit leukocyte transendothelial migration.
Results of a phase III, randomized, placebo-controlled study of sorafenib in combination with carboplatin and paclitaxel as second-line treatment in patients with unresectable stage III or stage IV melanoma.

PURPOSE This phase III, randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy and safety of sorafenib with carboplatin and paclitaxel (CP) in patients with advanced melanoma who had progressed on a dacarbazine- or temozolomide-containing regimen. PATIENTS AND METHODS A total of 270 patients were randomly assigned to receive intravenous paclitaxel 225 mg/m2 plus intravenous carboplatin at area under curve 6 (AUC 6) on day 1 of a 21-day cycle followed by either placebo (n = 135) or oral sorafenib 400 mg (n = 135) twice daily on days 2 to 19. The primary efficacy end point was progression-free survival (PFS); secondary and tertiary end points included overall survival and incidence of best response, respectively. RESULTS The median PFS was 17.9 weeks for the placebo plus CP arm and 17.4 weeks for the sorafenib plus CP arm (hazard ratio, 0.91; 99% CI, 0.63 to 1.31; two-sided log-rank test P = .49). Response rate was 11% with placebo versus 12% with sorafenib. Dermatologic events, grade 3 thrombocytopenia, diarrhea, and fatigue were more common in patients treated with sorafenib plus CP versus placebo plus CP. CONCLUSION In this study, the addition of sorafenib to CP did not improve any of the end points over placebo plus CP and cannot be recommended in the second-line setting for patients with advanced melanoma. Both regimens had clinically acceptable toxicity profiles with no unexpected adverse events. A trial of similar design for the first-line treatment of patients with advanced melanoma (intergroup trial E2603) is currently ongoing.
A utilização da tecnologia da informação em benefício do rendimento de atletas

Este artigo tem como objetivo mostrar em como a Tecnologia da Informacao auxilia na pratica de esportes, especialmente no ciclismo, que vem ganhando cada vez mais espaco. Atualmente, ha diversas solucoes para auxiliar os ciclistas durante todo o percurso monitorando seus parâmetros. Tais recursos podem ser dispositivos especificos dentre os quais se destaca o Garmin com os modelos Edge 820 e Edge 1000, bem como aplicativos para smartphones como o Strava, o Endomondo e o Runtastic. Tais recursos utilizam os servicos de satelite GPS e/ou GLONASS para monitorar e mostrar sua localizacao, velocidade e trajetoria dentre outros parâmetros que registram suas acoes atraves de calculos matematicos, obtendo por base os sistemas de geoprocessamento, que permitem, por intermedio de consultas a base de dados ou por determinacao direta de resposta de satelites. Este trabalho apresenta a utilizacao destes dispositivos como recursos de tecnologia da informacao em beneficio do rendimento do atleta.
GENETIC TRANSFORMATION AND HYBRIDIZATION

We describe herein a simple and efficient transformation procedure for the production of transgenic Lotus japonicus plants. In this new procedure, dedifferentiated root explants, used as starting material, are the source of a large number of cells that are competent for the regeneration procedure, with a high susceptibility to Agrobacterium infection. The application of this protocol resulted in a tenfold increase in the number of transformants produced by a single plant in comparison to the widely used hypocotyl transformation procedure. Furthermore, our procedure allowed the use of intact plants stored for a long time at 4 C, thus providing a potential continuous supply of explants for transformation experiments. The overall time of incubation under tissue culture conditions required to obtain a plant transferable into soil is 4 months. The transgenic nature of the transformants was demonstrated by the detection of b-glucuronidase (GUS) activity in the primary transformants and by molecular analysis. Stable transformation was indicated by Mendelian segregation of the hygromycin selectable marker and of the gusA activity after selfing of the transgenic plants.
Pulmonary Embolism Following Thrombolysis of Dialysis Access: Is Anticoagulation Really Necessary?

Vascular access thrombosis frequently complicates maintenance hemodialysis (HD) therapy. It is costly and time consuming to patients and practitioners. Alternatives to surgical thrombectomy have been developed using percutaneous thrombolysis (PT) with pharmacologic lysis, mechanical destruction of thrombus, or a combination of the two. These techniques have been used to successfully restore blood flow through thrombosed HD arteriovenous grafts (AVG), but there is a risk of dislodging thrombi into the venous circulation resulting in pulmonary embolism (PE); it is usually clinically insignificant. We examined our practice and reviewed three cases of dialysis access thrombosis treated with PT complicated by symptomatic PE. Two important questions arose: what is the risk of symptomatic PE after PT, and do patients benefit from systemic anticoagulation?
Two studies of the clinical effectiveness of the nicotine patch with different counseling treatments.

OBJECTIVE To assess the effectiveness of transdermal nicotine therapy for smoking cessation and suppression of withdrawal severity in conjunction with two different adjuvant counseling treatments. DESIGN Two independent randomized placebo-controlled double-blind trials. SETTING Smoking cessation clinic. SUBJECTS Eighty-eight (study 1) and 112 (study 2) adult volunteers motivated to quit smoking. INTERVENTIONS Eight weeks of 22-mg transdermal nicotine therapy with group counseling (study 1); 4 weeks of 22 mg followed by 2 weeks of 11-mg transdermal nicotine therapy with brief individual counseling (study 2). MAIN OUTCOME MEASURES Modified point prevalence (7 consecutive days of nonsmoking) at the end of patch treatment and 6 months after treatment initiation was assessed by self-report and biochemically confirmed; survival analyses were also conducted for both studies to compare treatment efficacy. Also, we examined the impact of the nicotine patch on specific withdrawal symptoms (anger, anxiety, awakening, difficulty concentrating, depression, hunger, impatience, and craving). RESULTS Transdermal nicotine treatment produced higher cessation rates at the end of treatment than did placebo with both adjuvant counseling interventions: 59 percent vs 40 percent (p < 0.05 in study 1) and 37 percent vs 20 percent (p < 0.05 in study 2), respectively. Smoking cessation efficacy was maintained 6 months after initiation of treatment: 34 percent vs 21 percent (p = 0.08 in study 1) and 18 percent vs 7 percent (p = 0.05 in study 2). Survival analyses also revealed significant group differences in efficacy in both studies. Nicotine patches also suppressed a variety of withdrawal symptoms, including craving in the first weeks after patients quit smoking. CONCLUSION Transdermal nicotine effectively augments smoking cessation rates with two different types of counseling treatment. Overall, the nicotine patch approximately doubles the sustained rate of smoking cessation. Additionally, the nicotine patch provides relief from some tobacco withdrawal symptoms.
Tuberculosis and the role of war in the modern era.

OBJECTIVE Tuberculosis (TB) remains a major global health problem; historically, major wars have increased TB notifications. This study evaluated whether modern conflicts worldwide affected TB notifications between 1975 and 1995. DESIGN Dates of conflicts were obtained and matched with national TB notification data reported to the World Health Organization. Overall notification rates were calculated pre and post conflict. Poisson regression analysis was applied to all conflicts with sufficient data for detailed trend analysis. RESULTS Thirty-six conflicts were identified, for which 3-year population and notification data were obtained. Overall crude TB notification rates were 81.9 and 105.1/100,000 pre and post start of conflict in these countries. Sufficient data existed in 16 countries to apply Poisson regression analysis to model 5-year pre and post start of conflict trends. This analysis indicated that the risk of presenting with TB in any country 2.5 years after the outbreak of conflict relative to 2.5 years before the outbreak was 1.016 (95%CI 0.9435-1.095). CONCLUSION The modelling suggested that in the modern era war may not significantly damage efforts to control TB in the long term. This might be due to the limited scale of most of these conflicts compared to the large-scale civilian disruption associated with 'world wars'. The management of TB should be considered in planning post-conflict refugee and reconstruction programmes.
Mechanism of 2‐methoxyestradiol‐induced apoptosis and growth arrest in human breast cancer cells

2‐Methoxyestradiol, a well‐known nonpolar endogenous metabolite of 17β‐estradiol, has been shown to selectively induce apoptosis in a number of cancer cell lines, but not in normal cells. The mechanism of 2‐methoxyestradiol‐induced apoptosis appears to vary considerably in different cell lines examined. In the present study, we systematically analyzed the mechanisms of 2‐methoxyestradiol‐induced apoptosis in the estrogen receptor‐negative MDA‐MB‐435s human breast cancer cells. We found that 2‐methoxyestradiol induced the activation of JNK, ERK, and p38 MAPKs. 2‐methoxyestradiol‐induced JNK activation was associated with the induction of apoptosis through the mitochondrial pathways as a result of increased phosphorylation (inactivation) of the anti‐apoptotic Bcl‐2 and Bcl‐xL proteins. In comparison, 2‐methoxyestradiol‐induced activation of ERK and p38 in these cells was found to have a protective effect against 2‐MeO‐E2‐induced apoptosis. Consistent with this observation, the presence of pharmacological inhibitor of ERK or p38 enhanced 2‐methoxyestradiol‐induced apoptosis. Mechanistically, inhibition of ERK and p38 activity was associated with activation of various caspases and PARP cleavage, and it also stabilized the pro‐apoptotic proteins Bax and Bim, thereby preventing them from degradation during 2‐methoxyestradiol treatment. These results suggest that ERK and p38 MAPKs may serve as viable targets for the sensitization of human breast cancer cells to 2‐methoxyestradiol‐induced apoptosis. © 2008 Wiley‐Liss, Inc.
Local inhibition of converting enzyme and vascular responses to angiotensin and bradykinin in the human forearm.

1. The function of angiotensin converting enzyme was investigated in twenty‐four healthy men. Forearm blood flow was measured under basal conditions and during administration of enalaprilat (a converting enzyme inhibitor) and/or peptide substrates of converting enzyme into the left brachial artery. Blood flow was compared in the two arms. 2. Enalaprilat had no effect on basal blood flow. The concentration of enalaprilat in venous blood from the control arm was low, and plasma renin activity was not increased, indicating that systemic inhibition of converting enzyme did not occur. 3. Effects of angiotensin and of bradykinin, administered intra‐arterially, were limited to the infused arm. Enalaprilat (13 nmol min‐1) inhibited converting enzyme in the infused arm, in which it caused approximately a 100‐fold reduction in sensitivity to angiotensin I, while having no effect on the vasoconstriction caused by angiotensin II. Enalaprilat increased vasodilatation caused by bradykinin. 4. Aspirin, an inhibitor of cyclo‐oxygenase, did not inhibit vasodilatation caused by bradykinin whether infused alone or with enalaprilat, indicating that these responses are not mediated by prostaglandins. 5. We conclude that under basal conditions neither conversion of angiotensin I to angiotensin II nor degradation of bradykinin determines resistance vessel tone in the human forearm. Converting enzyme may affect vascular tone in situations in which intravascular concentrations of peptides are increased over those present under basal conditions.