Miracle-dz/UniFAR-FTUs huggingface dataset:
A clinical trial to maintain glycemic control in youth with type 2 diabetes.

BACKGROUND Despite the increasing prevalence of type 2 diabetes in youth, there are few data to guide treatment. We compared the efficacy of three treatment regimens to achieve durable glycemic control in children and adolescents with recent-onset type 2 diabetes. METHODS Eligible patients 10 to 17 years of age were treated with metformin (at a dose of 1000 mg twice daily) to attain a glycated hemoglobin level of less than 8% and were randomly assigned to continued treatment with metformin alone or to metformin combined with rosiglitazone (4 mg twice a day) or a lifestyle-intervention program focusing on weight loss through eating and activity behaviors. The primary outcome was loss of glycemic control, defined as a glycated hemoglobin level of at least 8% for 6 months or sustained metabolic decompensation requiring insulin. RESULTS Of the 699 randomly assigned participants (mean duration of diagnosed type 2 diabetes, 7.8 months), 319 (45.6%) reached the primary outcome over an average follow-up of 3.86 years. Rates of failure were 51.7% (120 of 232 participants), 38.6% (90 of 233), and 46.6% (109 of 234) for metformin alone, metformin plus rosiglitazone, and metformin plus lifestyle intervention, respectively. Metformin plus rosiglitazone was superior to metformin alone (P=0.006); metformin plus lifestyle intervention was intermediate but not significantly different from metformin alone or metformin plus rosiglitazone. Prespecified analyses according to sex and race or ethnic group showed differences in sustained effectiveness, with metformin alone least effective in non-Hispanic black participants and metformin plus rosiglitazone most effective in girls. Serious adverse events were reported in 19.2% of participants. CONCLUSIONS Monotherapy with metformin was associated with durable glycemic control in approximately half of children and adolescents with type 2 diabetes. The addition of rosiglitazone, but not an intensive lifestyle intervention, was superior to metformin alone. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; TODAY ClinicalTrials.gov number, NCT00081328.).
An  ${\oldstyle{H_{\infty}}}$  Fault Estimation Scheme of Wireless Networked Control Systems for Industrial Real-Time Applications

In this paper, the H∞ fault estimation (FE) problem is investigated for a class of wireless networked control systems (W-NCSs), where an information scheduler is embedded in. Based on time-division multiple access mechanism, the scheduler is modeled by periodic state-space equations, which can order the information medium access time without collision. The integration approach of the W-NCSs and scheduler is very suitable for the application of W-NCSs on industrial automatic control, since the communication is described as deterministic behavior by scheduler, and consequently the high real-time performance can be essentially guaranteed. Based on the integrated model, the FE algorithm is proposed in terms of solution to a set of Riccati difference equations. Compared with the general state-space model of this algorithm, it is worth mentioning that the solution is developed into solving the model with arbitrary inputs. Then, the performance of fault estimator is verified on a physical experimental platform WiNC integrated with three-tank system, which is formulated into discrete periodic system by multirate sampling. Finally, the effectiveness of the FE algorithm developed in this paper is demonstrated.
Relying on surveys to understand abortion behavior: some cautionary evidence.

OBJECTIVES The reliability of abortion self-reports has raised questions about the general usefulness of surveys in research about abortion behavior; however, the extent of underreporting remains a subject of some debate. This study sought to examine abortion reporting in a sample of welfare mothers and to determine factors in underreporting. METHODS In New Jersey, which covers abortions requested by welfare recipients under its Medicaid program, the responses of a randomly drawn sample of 1236 welfare mothers about abortion events were compared with the Medicaid claims records of these women. RESULTS Only 29% of actual abortions were self-reported by the women in the sample. This finding varied dramatically by race, with substantially higher rates of underreporting by Blacks than by Whites or Hispanics. CONCLUSIONS Although race is the most consistent predictor of underreporting behavior, attitudinal factors and survey technology also help in explaining abortion reporting behavior.
Molecular Evidence for Heterogeneity of the Multiple-Drug-Resistant Mycobacterium tuberculosisPopulation in Scotland (1990 to 1997)

ABSTRACT Multiple-drug-resistant Mycobacterium tuberculosis(MDR-MTB) has been well studied in hospitals or health care institutions and in human immunodeficiency virus-infected populations. However, the characteristics of MDR-MTB in the community have not been well investigated. An understanding of its prevalence and circulation within the community will help to estimate the problem and optimize the strategies for control and prevention of its development and transmission. In this study, MDR-MTB isolates from Scotland collected between 1990 and 1997 were characterized, along with non-drug-resistant isolates. The results showed that they were genetically diverse, suggesting they were unrelated to each other and had probably evolved independently. Several new alleles ofrpoB, katG, and ahpC were identified: rpoB codon 525 (ACC→AAC; Thr525Asn);katG codon 128 (CGG→CAG; Arg128Gln) and codon 291 (GCT→CCT; Ala291Pro); and the ahpC synonymous substitution at codon 6 (ATT→ATC). One of the MDR-MTB isolates from an Asian patient had an IS6110 restriction fragment length polymorphism pattern very similar to that of the MDR-MTB W strain and had the same drug resistance-related alleles but did not have any epidemiological connection with the W strains. Additionally, a cluster of M. tuberculosis isolates was identified in our collection of 715 clinical isolates; the isolates in this cluster had genetic backgrounds very similar to those of the W strains, one of which had already developed multiple drug resistances. The diverse population of MDR-MTB in Scotland, along with a low incidence of drug-resistant M. tuberculosis, has implications for the control of the organism and prevention of its spread.
Natural history of transthyretin Val30Met familial amyloid polyneuropathy: analysis of late-onset cases from non-endemic areas

Objective The objective of this study was to elucidate the natural history of late-onset transthyretin Val30Met-associated familial amyloid polyneuropathy (FAP ATTR Val30Met) in non-endemic areas. Methods The authors retrospectively assessed the development of major clinical landmarks and abnormalities of nerve conduction and cardiac examination indices in 50 patients with an age of onset older than 50 years and no relationship to endemic foci. Results Once the neuropathic process was initiated, sensory and motor symptoms of both the upper and lower extremities appeared within a period of one and a half years. Digestive and orthostatic symptoms also tended to occur in the early phase of the disease, whereas urinary symptoms appeared in the middle of the disease progress. Along with pain in the extremities, these symptoms progressed over time and significantly disturbed the quality of life during the late phase of the disease, resulting in the need for wheelchair use. Although cardiomyopathy became clinically apparent only in the late phase of the disease, it was found to be the major cause of death. The mean duration of the disease onset to death was 7.3 years. Although values at the time of diagnosis were extremely variable, serial measurements of electrophysiological indices, the cardiothoracic ratio and interventricular septum thickness indicated a steady exacerbation in these outcomes among patients within a span of a couple of years. Conclusions The ages of onset of each clinical landmark were extremely variable between patients. However, once an initial symptom appeared, the chronological sequence of other clinical landmarks tended to be uniform, occurring within a relatively short time span.
Molecular Cloning and Expression of a Gene EncodingCryptosporidium parvum Glycoproteins gp40 and gp15

ABSTRACT Cryptosporidium parvum is a significant cause of diarrheal disease worldwide. The specific molecules that mediateC. parvum-host cell interactions and the molecular mechanisms involved in the pathogenesis of cryptosporidiosis are unknown. In this study we have shown that gp40, a mucin-like glycoprotein, is localized to the surface and apical region of invasive stages of the parasite and is shed from its surface. gp40-specific antibodies neutralize infection in vitro, and native gp40 binds specifically to host cells, implicating this glycoprotein in C. parvum attachment to and invasion of host cells. We have cloned and sequenced a gene designated Cpgp40/15 that encodes gp40 as well as gp15, an antigenically distinct, surface glycoprotein also implicated in C. parvum-host cell interactions. Analysis of the deduced amino acid sequence of the 981-bp Cpgp40/15revealed the presence of an N-terminal signal peptide, a polyserine domain, multiple predicted O-glycosylation sites, a single potential N-glycosylation site, and a hydrophobic region at the C terminus, a finding consistent with what is required for the addition of a GPI anchor. There is a single copy ofCpgp40/15 in the C. parvum genome, and this gene does not contain introns. Our data indicate that the twoCpgp40/15-encoded proteins, gp40 and gp15, are products of proteolytic cleavage of a 49-kDa precursor protein which is expressed in intracellular stages of the parasite. The surface localization of gp40 and gp15 and their involvement in the host-parasite interaction suggest that either or both of these glycoproteins may serve as effective targets for specific preventive or therapeutic measures for cryptosporidiosis.
Striking Dichotomy of PD‐L1 and PD‐L2 Pathways in Regulating Alloreactive CD4+ and CD8+ T Cells In Vivo

Programmed death‐1 (PD‐1) is a recently identified coinhibitory molecule that belongs to the CD28 superfamily. PD‐1 has two ligands PD‐L1 and PD‐L2. There is some evidence that PD‐L1 and PD‐L2 serve distinct functions, but their exact function in alloimmunity remains unclear. In the present study, we used a GVHD‐like model that allows detailed analyses of T‐cell activation at a single cell level in vivo to examine the role of PD‐1/PD‐L1 and PD‐1/PD‐L2 interactions in regulating proliferation of CD4+ and CD8+ T cells in response to alloantigen stimulation. We found that both CD4+ and CD8+ T cells proliferated vigorously in vivo and that PD‐L1 and PD‐L2 exhibit strikingly different effect on T‐cell proliferation. While blocking PD‐L1 did not affect the in vivo proliferation of CD4+ and CD8+ T cells regardless of CD28 costimulation, blocking PD‐L2 resulted in a marked increase in the responder frequency of CD8+ T‐cells in vivo. The effect of PD‐L2 on the CD8+ T‐cell proliferation is regulated by CD28 costimulation and by the CD4+ T cells. We conclude that PD‐L1 and PD‐L2 function differently in regulating alloreactive T‐cell activation in vivo, and PD‐L2 is predominant in this model in limiting alloreactive CD8+ T‐cell proliferation.
Hyperglycemia Alters the Protein Levels of Prominin-1 and VEGFA in the Retina of Albino Rats

In this study, we addressed the potential relationship between prominin-1 (prom1) and vascular endothelial growth factor (VEGFA) in diabetes-induced retinopathy. In total, we examined 28 retinas from 14 rats with streptozotocin-induced diabetes and 30 retinas from 15 untreated control rats. ELISA was used to measure the level of prom1 and VEGFA in retinal tissue homogenates. Immunohistochemical techniques were used with antibodies directed against prom1, VEGFA, and CASP-3. After 180 days of diabetes induction, we performed light and electron microscopy studies on rat eyes to evaluate histopathological changes and to estimate the de novo metric “Diabetic Retinopathy Histopathological Index” (DRHI). These changes were then correlated to the tissue and immunoexpression levels of prom1 and VEGFA. The data showed a significant upregulation of the tissue levels and optical densities (ODs) of VEGFA and prom1 immunoreactivity in diabetic retinas compared with controls. Both the tissue levels and OD values of prom1 and VEGFA correlated significantly with each other and to the diabetic structural changes as calculated by DRHI. Taken together, these data provide new insight into the potential role of prom1 and VEGFA in the development of diabetic retinopathy.
Depressive symptoms and cognitive decline in nondemented elderly women: a prospective study.

BACKGROUND The association between depressive disorders and subsequent cognitive decline is controversial. We tested the hypothesis that elderly women (aged 65 years and older) without dementia but with depressive symptoms have worse cognitive function and greater cognitive decline than women with few or no symptoms. METHODS As part of an ongoing prospective study, we evaluated 5781 elderly, mostly white, community-dwelling women. Women completed the Geriatric Depression Scale short form. Three cognitive tests--Trails B, Digit Symbol, and a modified Mini-Mental State Examination--were administered at baseline and approximately 4 years later. Baseline, follow-up, and change scores for the cognitive tests were analyzed by analysis of covariance and Kruskal-Wallis analysis; the odds of cognitive deterioration (> or =3-point decline on the modified Mini-Mental State Examination) were determined by logistic regression. RESULTS At baseline, 211 (3.6%) of the women had 6 or more depressive symptoms. Only 16 (7.6%) of these women were receiving antidepressant medication. Increasing symptoms of depression were associated with worse performance at baseline and follow-up on all 3 tests of cognitive function (P<.001 for all comparisons). For example, the baseline Digit Symbol score (mean +/- SD) was 45.5 +/- 10.7 among women with 0 to 2 symptoms of depression, 40.3 +/- 10.7 for women with 3 to 5 symptoms, and 39.0 +/- 11.3 for women with 6 or more symptoms. After adjusting for the baseline score, cognitive change scores were also inversely associated with the number of depressive symptoms (P<.001 for all comparisons). Odds ratios for cognitive deterioration using 0 to 2 symptoms as the reference were 1.6 (95% confidence interval, 1.3-2.1) for 3 to 5 symptoms and 2.3 (95% confidence interval, 1.6-3.3) for 6 or more symptoms. Results were similar after being adjusted for education, age, health status, exercise, alcohol use, functional status, and clinic site. CONCLUSIONS Depressive symptoms in older women are associated with both poor cognitive function and subsequent cognitive decline. Mechanisms underlying the association between these 2 common conditions need further exploration.
Clinicopathological diagnosis and treatment of malignant histiocytosis

Summary. The diagnostic findings of malignant histiocytosis (MH) were analysed in 12 consecutive patients in a single institution. Most patients presented with systemic symptoms and lymphadenopathy (92%), splenomegaly (100%) and hepatomegaly (67%). Neurologic symptoms were present in three patients, while involvement of other organs was present in five patients. The incidence of severe thrombocytopenia was 92%, of anaemia 92% and of leucocytopenia 67%. Serum angiotensin converting enzyme, α1‐antitrypsin and lysozyme were independently increased in 6/9, 3/10 and 1/9 patients respectively. High serum levels of tumour necrosis factor (TNF) were present in 3/10 patients, while serum levels of interleukin‐1 were normal in 10/10 patients. Histologic evidence of MH was obtained in all patients by repeated biopsies of involved tissues. Four patients died prior to treatment. Seven patients were treated with combination chemotherapy, consisting of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or MOPP (chloromethine, vincristine, procarbazine, prednisone), in some cases followed by non‐cross‐resistant second line chemotherapy, if no complete response was attained. The response rate of treated patients was 5 7%, and progression was observed in two patients. The median duration of response was 38 months. Three patients are alive without evidence of disease and off therapy (30+, 83+, 85+ months).
Physiologic action of glucagon on liver glucose metabolism

Glucagon is a primary regulator of hepatic glucose production (HGP) in vivo during fasting, exercise and hypoglycaemia. Glucagon also plays a role in limiting hepatic glucose uptake and producing the hyperglycaemic phenotype associated with insulin deficiency and insulin resistance. In response to a physiological rise in glucagon, HGP is rapidly stimulated. This increase in HGP is entirely attributable to an enhancement of glycogenolysis, with little to no acute effect on gluconeogenesis. This dramatic rise in glycogenolysis in response to hyperglucagonemia wanes with time. A component of this waning effect is known to be independent of hyperglycemia, though the molecular basis for this tachyphylaxis is not fully understood. In the overnight fasted state, the presence of basal glucagon secretion is essential in countering the suppressive effects of basal insulin, resulting in the maintenance of appropriate levels of glycogenolysis, fasting HGP and blood glucose. The enhancement of glycogenolysis in response to elevated glucagon is critical in the life‐preserving counterregulatory response to hypoglycaemia, as well as a key factor in providing adequate circulating glucose for working muscle during exercise. Finally, glucagon has a key role in promoting the catabolic consequences associated with states of deficient insulin action, which supports the therapeutic potential in developing glucagon receptor antagonists or inhibitors of glucagon secretion.
Critical Thinking in Health Professions Education: Summary and Consensus Statements of the Millennium Conference 2011

Purpose: Critical thinking is central to the function of health care professionals. However, this topic is not explicitly taught or assessed within current programs, yet the need is greater than ever, in an era of information explosion, spiraling health care costs, and increased understanding about metacognition. To address the importance of teaching critical thinking in health professions education, the Shapiro Institute for Education and Research and the Josiah Macy Jr. Foundation jointly sponsored the Millennium Conference 2011 on Critical Thinking. Summary: Teams of physician and nurse educators were selected through an application process. Attendees proposed strategies for integrating principles of critical thinking more explicitly into health professions curricula. Working in interprofessional, multi-institutional groups, participants tackled questions about teaching, assessment, and faculty development. Deliberations were summarized into consensus statements. Conclusions: Educational leaders participated in a structured dialogue about the enhancement of critical thinking in health professions education and recommend strategies to teach critical thinking.
Rutin and quercetin show greater efficacy than nifedipin in ameliorating hemodynamic, redox, and metabolite imbalances in sodium chloride-induced hypertensive rats

Rutin and quercetin were investigated for their effects on blood pressure and antioxidant defense system of rats fed with 8% sodium chloride-supplemented diet (high salt diet) for 6 weeks. Animals fed with high salt diet demonstrated an increase in systolic, diastolic, pulse, and mean arterial blood pressures (p < 0.05) as well as lipid peroxidation but decreases in the activities of antioxidant enzymes compared with control group. Groups post-treated with rutin and quercetin for 2 weeks showed significant reversals in the values of these indices compared with the group fed with only the high salt diet but not post-treated. The high salt diet also led to significant increase in serum glucose, urea, creatinine, triglycerides, low-density-lipoprotein, and total cholesterol concentrations. Treatment with rutin and quercetin ameliorated the effects of high salt diet on these biochemical indices. The reference standard, nifedipin was less effective than rutin and quercetin. The results of this study highlight the risk of high salt consumption on cardiovascular health and the potent antioxidant and antihypertensive property of rutin and quercetin.
Conformational Space Sampling Method Using Multi-Subpopulation Differential Evolution for De novo Protein Structure Prediction

Protein structure prediction can be considered as a multimodal optimization problem for sampling the protein conformational space associated with an extremely complex energy landscape. To address this problem, a conformational space sampling method using multi-subpopulation differential evolution, MDE, is proposed. MDE first devotes to generate given numbers of concerned modal under the ultrafast shape recognition-based modal identification protocol, which regards each individual as one modal at beginning. Then, differential evolution is used for keeping the preserved modal survival in the evolution process. Meanwhile, a local descent direction used to sample along with is constructed based on the abstract convex underestimate technique for modal enhancement, which could enhance the ability of sampling in the region with lower energy. Through the sampling process of evolution, several certain clusters contain a series of conformations in proportion to the energy score will be obtained. Representative conformations in the generated clusters can be directly picked out as decoy conformations for further refinement with no extra clustering operation needs. A total of 20 target proteins are tested, in which ten target proteins are tested for comparison with Rosetta and three evolutionary algorithms, and ten easy/hard target proteins in CASP 11 are tested for further verifying the effectiveness of MDE. Test results show strong sampling ability that MDE holds, and near-native conformations can be effectively obtained.
The effect of exercise therapy on fatigue in multiple sclerosis

Background: Fatigue occurs in the majority of patients with multiple sclerosis (MS) and therapeutic possibilities are few. Exercise therapy is a therapeutic option but no studies have systematically reviewed the existing literature evaluating the effect of exercise therapy on MS fatigue. Objective: To determine the effect of exercise therapy on MS fatigue by systematically reviewing the literature. Methods: A comprehensive literature search (PubMed, SweMed +, Embase, Cochrane, CINAHL, PEDro, Sport Discuss and Bibliotek.dk) was conducted. Results: Studies evaluating the effect of exercise therapy on MS fatigue show heterogeneous results and only few studies have evaluated MS fatigue as the primary outcome. The heterogeneous findings seem to be related to the selected study population, which in many studies are non-fatigued. Most studies that have included fatigued patients with MS show positive effects, although it is not clear whether any exercise modalities are superior to others because there are no comparative studies regarding different exercise interventions. Conclusion: Exercise therapy has the potential to induce a positive effect on MS fatigue, but findings are heterogeneous probably because many studies have applied non-fatigued study populations. Furthermore, only few studies have evaluated MS fatigue as the primary outcome measure, emphasizing the need for future studies within this field.