Miracle-dz/UniFAR-FTUs huggingface dataset:
Constraints faced by urban poor in managing diabetes care: patients’ perspectives from South India

Background Four out of five adults with diabetes live in low- and middle-income countries (LMIC). India has the second highest number of diabetes patients in the world. Despite a huge burden, diabetes care remains suboptimal. While patients (and families) play an important role in managing chronic conditions, there is a dearth of studies in LMIC and virtually none in India capturing perspectives and experiences of patients in regard to diabetes care. Objective The objective of this study was to better understand constraints faced by patients from urban slums in managing care for type 2 diabetes in India. Design We conducted in-depth interviews, using a phenomenological approach, with 16 type 2- diabetes patients from a poor urban neighbourhood in South India. These patients were selected with the help of four community health workers (CHWs) and were interviewed by two trained researchers exploring patients’ experiences of living with and seeking care for diabetes. The sampling followed the principle of saturation. Data were initially coded using the NVivo software. Emerging themes were periodically discussed among the researchers and were refined over time through an iterative process using a mind-mapping tool. Results Despite an abundance of healthcare facilities in the vicinity, diabetes patients faced several constraints in accessing healthcare such as financial hardship, negative attitudes and inadequate communication by healthcare providers and a fragmented healthcare service system offering inadequate care. Strongly defined gender-based family roles disadvantaged women by restricting their mobility and autonomy to access healthcare. The prevailing nuclear family structure and inter-generational conflicts limited support and care for elderly adults. Conclusions There is a need to strengthen primary care services with a special focus on improving the availability and integration of health services for diabetes at the community level, enhancing patient centredness and continuity in delivery of care. Our findings also point to the need to provide social services in conjunction with health services aiming at improving status of women and elderly in families and society.
Phase II study of aflibercept in recurrent malignant glioma: a North American Brain Tumor Consortium study.

PURPOSE Antivascular endothelial growth factor (anti-VEGF) therapy is a promising treatment approach for patients with recurrent glioblastoma. This single-arm phase II study evaluated the efficacy of aflibercept (VEGF Trap), a recombinantly produced fusion protein that scavenges both VEGF and placental growth factor in patients with recurrent malignant glioma. PATIENTS AND METHODS Forty-two patients with glioblastoma and 16 patients with anaplastic glioma who had received concurrent radiation and temozolomide and adjuvant temozolomide were enrolled at first relapse. Aflibercept 4 mg/kg was administered intravenously on day 1 of every 2-week cycle. RESULTS The 6-month progression-free survival rate was 7.7% for the glioblastoma cohort and 25% for patients with anaplastic glioma. Overall radiographic response rate was 24% (18% for glioblastoma and 44% for anaplastic glioma). The median progression-free survival was 24 weeks for patients with anaplastic glioma (95% CI, 5 to 31 weeks) and 12 weeks for patients with glioblastoma (95% CI, 8 to 16 weeks). A total of 14 patients (25%) were removed from the study for toxicity, on average less than 2 months from treatment initiation. The main treatment-related National Cancer Institute Common Terminology Criteria grades 3 and 4 adverse events (38 total) included fatigue, hypertension, and lymphopenia. Two grade 4 CNS ischemias and one grade 4 systemic hemorrhage were reported. Aflibercept rapidly decreases permeability on dynamic contrast enhanced magnetic resonance imaging, and molecular analysis of baseline tumor tissue identified tumor-associated markers of response and resistance. CONCLUSION Aflibercept monotherapy has moderate toxicity and minimal evidence of single-agent activity in unselected patients with recurrent malignant glioma.
Zinc Supplementation Reduces the Incidence of Acute Lower Respiratory Infections in Infants and Preschool Children: A Double-blind, Controlled Trial

Background. Increased acute lower respiratory infection incidence, severity, and mortality are associated with malnutrition, and reduced immunological competence may be a mechanism for this association. Because zinc deficiency results in impaired immunocompetence and zinc supplementation improves immune status, we hypothesized that zinc deficiency is associated with increased incidence and severity of acute lower respiratory infection. Methods. We evaluated the effect of daily supplementation with 10 mg of elemental zinc on the incidence and prevalence of acute lower respiratory infection in a double-blind, randomized, controlled trial in 609 children (zinc, n = 298; control, n = 311) 6 to 35 months of age. Supplementation and morbidity surveillance were done for 6 months. Results. After 120 days of supplementation, the percentage of children with plasma zinc concentrations <60 μg/dL decreased from 35.6% to 11.6% in the zinc group, whereas in the control group it increased from 36.8% to 43.6%. Zinc-supplemented children had 0.19 acute lower respiratory infection episodes/child/year compared with 0.35 episodes/child/year in the control children. After correction for correlation of data using generalized estimating equation regression methods, there was a reduction of 45% (95% confidence interval, 10% to 67%) in the incidence of acute lower respiratory infections in zinc-supplemented children. Conclusions. A dietary zinc supplement resulted in a significant reduction in respiratory morbidity in preschool children. These findings suggest that interventions to improve zinc intake will improve the health and survival of children in developing countries.
Varenicline for smoking cessation: A placebo‐controlled, randomized study

Background and objective: Varenicline tartrate, a novel, selective, nicotinic acetylcholine receptor partial agonist, has been developed specifically as a smoking cessation drug. This study evaluated the efficacy of a standard regimen of varenicline compared with placebo for smoking cessation in 333 subjects in China, Singapore and Thailand.
Elevated levels of D-dimers increase the risk of ischaemic and haemorrhagic stroke

Summary Elevated D-dimer levels are reportedly associated with coronary artery disease. It was the study objective to investigate the association of baseline D-dimer levels with strokes that occurred in the European Prospective Investigation into Cancer and Nutrition-Italy cohort. Using a nested case-cohort design, a centre-–stratified sample of 832 subjects (66 % women, age 35–71) was selected as subcohort and compared with 289 strokes in a mean follow-up of nine years. D-dimers were measured by an automated latex-enhanced immunoassay (HemosIL-IL). The multivariable hazard ratios were estimated by a Cox regression model using Prentice method. Individuals with elevated D-dimer levels had significantly higher risk of incident stroke. It was evident from the second quartile (D-dimers > 100 ng/ml) and persisted almost unchanged for higher D-dimers (hazard ratio [HR] 2.10, 95 % confidence interval [CI]: 1.28–3.47; 2.42, 95 %CI: 1.44–4.09 and 2.10, 95 %CI: 1.27–3.48 for the second, third or fourth quartile compared with the lowest quartile, respectively). The association was independent of several confounders, including triglycerides and C-reactive protein. No differences were observed in men and women (P for interaction= 0.46), in hypertensive or non-hypertensive subjects (P for interaction= 0.88) or in subjects with low (< 1 mg/l) or elevated (≥ 1 mg/l) C-reactive protein (P for interaction=0.35). After stratification for stroke type, the hazard ratio for every standard deviation increase was statistically significant both for ischaemic (1.21; 95 %CI: 1.01 to 1.45) and haemorrhagic (1.24; 95 %CI: 1.00 to 1.65) strokes. In conclusion, our data provide clear evidence that elevated levels of D-dimers are potential risk factors not only for ischaemic but also for haemorrhagic strokes.
Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

BACKGROUND Antithrombotic therapy in valvular disease is important to mitigate thromboembolism, but the hemorrhagic risk imposed must be considered. METHODS The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. RESULTS In rheumatic mitral disease, we recommend vitamin K antagonist (VKA) therapy when the left atrial diameter is > 55 mm (Grade 2C) or when complicated by left atrial thrombus (Grade 1A). In candidates for percutaneous mitral valvotomy with left atrial thrombus, we recommend VKA therapy until thrombus resolution, and we recommend abandoning valvotomy if the thrombus fails to resolve (Grade 1A). In patients with patent foramen ovale (PFO) and stroke or transient ischemic attack, we recommend initial aspirin therapy (Grade 1B) and suggest substitution of VKA if recurrence (Grade 2C). In patients with cryptogenic stroke and DVT and a PFO, we recommend VKA therapy for 3 months (Grade 1B) and consideration of PFO closure (Grade 2C). We recommend against the use of anticoagulant (Grade 1C) and antiplatelet therapy (Grade 1B) for native valve endocarditis. We suggest holding VKA therapy until the patient is stabilized without neurologic complications for infective endocarditis of a prosthetic valve (Grade 2C). In the first 3 months after bioprosthetic valve implantation, we recommend aspirin for aortic valves (Grade 2C), the addition of clopidogrel to aspirin if the aortic valve is transcatheter (Grade 2C), and VKA therapy with a target international normalized ratio (INR) of 2.5 for mitral valves (Grade 2C). After 3 months, we suggest aspirin therapy (Grade 2C). We recommend early bridging of mechanical valve patients to VKA therapy with unfractionated heparin (DVT dosing) or low-molecular-weight heparin (Grade 2C). We recommend long-term VKA therapy for all mechanical valves (Grade 1B): target INR 2.5 for aortic (Grade 1B) and 3.0 for mitral or double valve (Grade 2C). In patients with mechanical valves at low bleeding risk, we suggest the addition of low-dose aspirin (50-100 mg/d) (Grade 1B). In valve repair patients, we suggest aspirin therapy (Grade 2C). In patients with thrombosed prosthetic valve, we recommend fibrinolysis for right-sided valves and left-sided valves with thrombus area < 0.8 cm(2) (Grade 2C). For patients with left-sided prosthetic valve thrombosis and thrombus area ≥ 0.8 cm(2), we recommend early surgery (Grade 2C). CONCLUSIONS These antithrombotic guidelines provide recommendations based on the optimal balance of thrombotic and hemorrhagic risk.
Relationships between physiological variables and race performance in French standardbred trotters

The relationships between V4 (the velocity for a blood lactate concentration of 4 mmol/litre) and V200 (the velocity for a heart rate of 200 bpm) and the performance indices of 223 healthy French trotters were analysed. They were divided into four age groups of three, four, five and six years and over, and into three performance groups (good, intermediate and poor performers) defined by the index of trot (ITR), an annual index of performance calculated by the national stud. V4 and V200 were assessed during the performance of a three-step standardised field exercise test, and four performance indexes (ITR, earnings, best time and the number of starts) were calculated for each group. An analysis of variance showed that V4 and V200 were highly correlated with the horses’ age and level of performance (P<0·05). The correlation between the physiological variables and ITR was better for the three- and four-year-old horses than for the older horses.
La relación entre crisis cambiarias y bancarias en países emergentes: los problemas de información y expectativas

El papel del sistema bancario ha sido clave en la crisis de balanza de pagos de varias economias emergentes. Se pueden destacar tres tipos de modelos en los que se analizan diferentes factores relacionados con las crisis cambiarias recientes. Por norma general, las crisis financieras se deben al menos en parte a problemas de balanza de pagos. La vulnerabilidad financiera hace que se desplome la moneda y deteriore el sistema bancario, generandose asi un circulo vicioso. Este trabajo muestra que la estabilidad financiera no esta garantizada, especialmente en un sistema financiero globalizado. Los paises emergentes tienen que encontrar un equilibrio entre la estabilizacion economica y la financiera, sin dejar de participar en las nuevas corrientes de capital. La tarea es dificil pero indispensable para evitar episodios como los del pasado y cuya amenaza no parece descartada para el futuro
Human ABCA1 contains a large amino-terminal extracellular domain homologous to an epitope of Sjögren's Syndrome.

ABCA1 has been suggested to play a key role in cellular lipid release from peripheral cells. In order to study structure-function relationship of this protein, the protein product of a full-length human ABCA1 cDNA was examined for its functions and topological orientation. The electrophoretic mobilities of human ABCA1 expressed in transfected cells increased when treated with N-glycosidase F, suggesting that ABCA1 is highly glycosylated. The ABCA1 was photoaffinity-labeled with ATP and mediated the apoA-I-dependent-release of cholesterol and phospholipid. The influenza hemagglutinin (HA) epitope was introduced into the amino-terminus (N-HA) or between the residues 207 and 208 (207-HA) of the protein. While an antibody against the C-terminus peptide of ABCA1 detected both fusion proteins, an anti-HA antibody did not react with the N-HA fusion protein. Confocal microscopy demonstrated strong cell surface signal with the anti-HA antibody of nonpermeabilized HEK293 cells expressing the 207-HA fusion protein. The results suggested that the signal peptide in the amino-terminal region is cleaved off in its mature form and that the following large hydrophilic region is exposed to outside of cells unlike previously proposed models. We found that this amino-terminal extracellular domain contains a segment homologous to the autoantigen SS-N, an epitope of Sjögren's syndrome, and further identified that ABCA7 codes for the autoantigen SS-N.
Impact of Pitx3 gene knockdown on glial cell line-derived neurotrophic factor transcriptional activity in dopaminergic neurons

Pitx3 is strongly associated with the phenotype, differentiation, and survival of dopaminergic neurons. The relationship between Pitx3 and glial cell line-derived neurotrophic factor (GDNF) in dopaminergic neurons remains poorly understood. The present investigation sought to construct and screen a lentivirus expression plasmid carrying a rat Pitx3 short hairpin (sh)RNA and to assess the impact of Pitx3 gene knockdown on GDNF transcriptional activity in MES23.5 dopaminergic neurons. Three pairs of interference sequences were designed and separately ligated into GV102 expression vectors. These recombinant plasmids were transfected into MES23.5 cells and western blot assays were performed to detect Pitx3 protein expression. Finally, the most effective Pitx3 shRNA and a dual-luciferase reporter gene plasmid carrying the GDNF promoter region (GDNF-luciferase) were cotransfected into MES23.5 cells. Sequencing showed that the synthesized sequences were identical to the three Pitx3 interference sequences. Inverted fluorescence microscopy revealed that the lentivirus expression plasmids carrying Pitx3-shRNA had 40–50% transfection efficiency. Western blot assay confirmed that the corresponding Pitx3 of the third knockdown sequence had the lowest expression level. Dual-luciferase reporter gene results showed that the GDNF transcriptional activity in dopaminergic cells cotransfected with both plasmids was decreased compared with those transfected with GDNF-luciferase alone. Together, the results showed that the designed Pitx3-shRNA interference sequence decreased Pitx3 protein expression, which decreased GDNF transcriptional activity.
Tooth Morphogenesis and Pattern of Odontoblast Differentiation

The terminal differentiation of odontoblasts is controlled by the inner dental epithelium (IDE) and occurs according to a tooth-specific pattern. It requires temporospatially regulated epigenetic signaling and the expression of specific competence. The patterning of cusp formation was compared with that of odontoblast differentiation in the first lower molar in mice. Histology, immunostaining, and three dimensional reconstructions were completed by experimental approaches in vitro. The mesenchyme controls the pattern of cusp formation. During the cap-bell transition in the molar, a subpopulation of nondividing IDE cells from the enamel knot (EK) undergo a tooth-specific segregation in as many subpopulations as cusps will form. Epithelial cell-basement membrane interactions seem to be involved in the segregation of EK cells. The timing and spatial pattern of the segregation of EK cells correlate with cusps formation. However, the temporal pattern of odontoblast terminal differentiation is different. This discrepancy might result from cusp-specific differences either in the timing of the initiation of odontoblast terminal differentiation and/or in cell proliferation kinetics.
Considerations for Lossy-Mode Resonance-Based Optical Fiber Sensor

This paper presents the fabrication of optical fiber relative humidity (RH) sensors by means of polymeric thin-films as lossy-mode resonance (LMR) supporting coatings. In particular, LMRs are observed because of the fabrication of polyallylamine hydrochloride (PAH) and polyacrylic acid (PAA) polymeric coatings onto cladding-removed multimode optical fibers on applying the layer-by-layer self-assembly method. More than one LMR can be generated as a function of the coating thickness. The generation of multiple LMRs produces notch band filter with a rejection band in the visible region. To compare the parameters of different LMRs, two devices with PAH/PAA coating thicknesses of 140 and 470 nm, respectively, are fabricated. The thickness and the refractive index of the PAH/PAA film can be modified as a function of the surrounding medium refractive index. Thus, surrounding medium relative humidity can be easily determined through the wavelength shift of the resonance (~ 34 nm between 20% and 80% RH).
Phosphatidylinositol 3‐kinase is required for the transcriptional activation of cyclin D2 in BCR activated primary mouse B lymphocytes

Induction of cyclin D2 is essential for mediating cell cycle entry in B cells activated by BCR cross‐linking. In the present study we show that, like B lymphocytes lacking cyclin D2, the p85α subunit of phosphatidylinositol 3‐kinase (PI3K) or other components of the B cell signalosome, p110δ‐null B cells fail to induce cyclin D2 and enter early G1 but not S phase of the cell cycle. The inhibitors of PI3K activity, LY294002 and Wortmannin, also abrogate cyclin D2 induction by BCR cross‐linking, confirming that the class IA PI3K is necessary for cyclin D2 induction in response to BCR stimulation. Furthermore, using both p85α‐null and p110δ‐null B cells and inhibitors of PI3K, this study demonstrates for the first time, that BCR cross‐linking induces cyclin D2 mRNA expression via transcriptional activation of the cyclin D2 promoter and that this transcriptional activation of cyclin D2 requires PI3K activity. Moreover, we identify a region between nucleotides ‐1624 and ‐1303 of the cyclin D2 promoter containing elements responsive to anti‐IgM, which are PI3K dependent. Further characterisation of signalling intermediates downstream of the BCR revealed a perturbation of MAPK signalling pathways in p85α‐null and p110δ‐null B cells, and our data suggests that cross‐talk exists between the PI3K and JNK pathways.
The 11,600-MW protein encoded by region E3 of adenovirus is expressed early but is greatly amplified at late stages of infection

We have reported that an 11,600-MW (11.6K) protein is coded by region E3 of adenovirus. We have now prepared two new antipeptide antisera that have allowed us to characterize this protein further. The 11.6K protein migrates as multiple diffuse bands having apparent Mws of about 14,000, 21,000, and 31,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunoblotting as well as virus mutants with deletions in the 11.6K gene were used to show that the various gel bands represent forms of 11.6K. The 11.6K protein was synthesized in very low amounts during early stages of infection, from the scarce E3 mRNAs d and e which initiate from the E3 promoter. However, 11.6K was synthesized very abundantly at late stages of infection, approximately 400 times the rate at early stages, from new mRNAs termed d' and e'. Reverse transcriptase-polymerase chain reaction and RNA blot experiments indicated that mRNAs d' and e' had the same body (the coding portion) and the same middle exon (the y leader) as early E3 mRNAs d and e, but mRNAs d' and e' were spliced at their 5' termini to the major late tripartite leader which is found in all mRNAs in the major late transcription unit. mRNAs d' and e' and the 11.6K protein were the only E3 mRNAs and protein that were scarce early and were greatly amplified at late stages of infection. This suggests that specific cis- or trans-acting sequences may function to enhance the splicing of mRNAs d' and e' at late stages of infection and perhaps to suppress the splicing of mRNAs d and e at early stages of infection. We propose that the 11.6K gene be considered not only a member of region E3 but also a member of the major late transcription unit.
Phase II, Open-Label Study of Brivanib as First-Line Therapy in Patients with Advanced Hepatocellular Carcinoma

Purpose: Brivanib, a selective dual inhibitor of fibroblast growth factor and VEGF signaling, has demonstrated encouraging antitumor activity in preclinical and phase I studies. We performed a phase II open-label study of brivanib as first-line therapy in patients with unresectable, locally advanced, or metastatic hepatocellular carcinoma. Experimental Design: Brivanib was administered orally at a dose of 800 mg once daily. The primary objective was 6-month progression-free survival, progression-free survival rate; secondary objectives were tumor response rate, time to response, duration of response, median progression-free survival, median overall survival, disease control rate (complete response, partial response, or stable disease ≥ 42 days), and safety and tolerability. Results: Between March 2007 and May 2009, 55 patients were treated and were evaluable for response. Patients were assessed using modified World Health Organization (mWHO) criteria. According to mWHO criteria and as assessed by Independent Response Review Committee, the six-month progression-free survival rate (95% CI) was 18.2% (9.1%–30.9%). Median progression-free survival (95% CI) was 2.7 months (1.4–3.0). One patient achieved a complete response and three achieved a partial response. Twenty-two had stable disease. Median overall survival (95% CI) was 10 (6.8–15.2) months. Brivanib was generally well tolerated; the most common adverse events included fatigue, hypertension, and diarrhea. Conclusion: Brivanib as first-line therapy demonstrates promising antitumor activity and a manageable safety profile in patients with advanced, unresectable HCC. Clin Cancer Res; 17(7); 1973–83. ©2011 AACR.