Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrase variability and susceptibility to HIV integrase inhibitors: impact of subtypes, antiretroviral experience and duration of HIV infection.

BACKGROUND Little is known about the extent and predictors of polymorphisms potentially influencing the susceptibility to HIV integrase inhibitors (INIs). METHODS Genetic sequences of HIV integrase were obtained from INI-naive patients at two European clinics. The 39 amino acid changes at 29 integrase positions so far associated with INI resistance were examined according to HIV clade, prior antiretroviral exposure and duration of HIV infection. RESULTS Integrase sequences were obtained from 418 patients, 294 (70.3%) infected with clade B and 124 (29.7%) infected with non-B variants (predominantly CRF02, A, C and D). Overall, 40% of patients were antiretroviral experienced and 32.8% were recent seroconverters. The most prevalent INI resistance-associated mutations were V72I (63.9%), V201I (54.8%), T206S (25.4%), I203M (9.8%) and K156N (7.4%). Major INI resistance mutations at positions 66, 92, 143, 148 and 155 were not detected. The mean number of polymorphic sites was greater in non-B than in B variants (2.17 versus 1.59; P < 0.001), and in antiretroviral-experienced than in drug-naive patients (1.89 versus 1.68; P = 0.034), whereas no significant differences were seen comparing recent seroconverters and chronically infected persons. CONCLUSIONS Major INI resistance-associated mutations are very rare, if indeed ever present, in INI-naive patients. However, polymorphisms at positions which may influence the genetic barrier and/or drive the selection of specific INI resistance pathways are common, especially in HIV non-B subtypes.
Regulatory Role of Intraislet Somatostatin on Insulin Secretion in the Isolated Perfused Human Pancreas

This study was undertaken to determine whether intraislet somatostatin inhibits insulin secretion in the human islet. A high-affinity monoclonal somatostatin antibody was used to immunoneutralize somatostatin in the isolated, perfused human pancreas. Single pass perfusion was performed in pancreata obtained from cadaveric organ donors using a modified Krebs medium with either 3.9 or 12.9 mM glucose. Sequential test periods separated by basal periods were performed with either somatostatin-14 (SS-14), somatostatin monoclonal antibody (CURE.S6), or a combined infusion. Infusion of SS-14 resulted in inhibition of insulin secretion under both low glucose (δ = −712 ± 212 pM) p < 0.05) and high glucose (δ = −21,913 * 10,003 pM) (p = 0.06) conditions. Immunoneutralization of intraislet somatostatin with CURE.S6 resulted in a significant increase in insulin secretion under both low glucose (454 ±162 pM) (p < 0.05) and high glucose (2,177 ± 829 pM) (p < 0.05) conditions. Combined infusion of SS-14 and CURE.S6 resulted in a reversal of the inhibitory effect of exogenous SS-14. The data suggest that intraislet somatostatin has an inhibitory role in the regulation of insulin secretion in the human islet.
Quality of life of patients with prostate cancer and their spouses. The value of a data base in clinical care

Background. Because of the dearth of information concerning the quality of life of patients with prostate cancer, a data base was established to examine the nature and extent of problems in patients' and spouses' adaptation and their interrelationships and to examine the effect of disease stage combined with treatment regimen on patients' quality of life.
How intestinal epithelial cell differentiation inhibits the cell-entry of Yersinia pseudotuberculosis in colon carcinoma Caco-2 cell line in culture.

In the human intestine, target cells of enteropathogens differentiate during cell migration along the crypt-villus axis. We have recently provided evidence that intestinal cell differentiation up-regulates intestinal cell infection by the noninvasive enterotoxigenic Escherichia coli [5, 23]. Several enterovirulent bacteria can penetrate intestinal epithelial cells, which are normally nonphagocytic. To document the role of intestinal epithelial cell differentiation in the pathogenesis of enteroinvasive bacteria, we examined here the intestinal cell-association and cell-entry of Yersinia pseudotuberculosis as a function of cell differentiation. For this purpose we used the colon carcinoma Caco-2 cell line in culture, which provides the most useful tool for the study of intestinal epithelial cell differentiation, because of its unique ability to spontaneously differentiate upon reaching confluence in normal culture condition. We report here that the thermoregulated inv and ail loci of Y. pseudotuberculosis have distinct roles in infection of Caco-2 cells. The ail locus initiates the cell-association and the inv locus initiates both the cell-association and the cell-entry processes. Moreover, we observed that: (i) both the bacterial cell-association (ail) and the bacterial cell-invasion (inv) occur at subconfluence when the Caco-2 cells are undifferentiated, and (ii) these processes are arrested when the differentiation commences. Since the integrin-beta 1 heterodimers are involved in cell-entry of Y. pseudotuberculosis in several mammalian cells, we further examined which beta 1 integrin promotes bacterial cell-entry in Caco-2 cells. (ABSTRACT TRUNCATED AT 250 WORDS)
Cardiovascular disease. Physician attitudes toward prevention and treatment.

OBJECTIVE Survey of physician attitudes toward practising cardiovascular disease prevention. DESIGN Questionnaire administered via telecommunication from 1992 through 1994. SETTING The FAMUS (Family Medicine, University of Sherbrooke) project, between 1992 and 1996, used weekly telecommunication to collect data from 200 general practitioners throughout the province of Quebec on cardiovascular disease risk factors and their treatment. PARTICIPANTS Of 200 physicians contributing to the FAMUS project, 156 completed questionnaires (response rate 78%). MAIN OUTCOME MEASURES Variations in attitudes to prevention policy and risk factor interventions. RESULTS Survey results revealed physicians knew important risk factors for cardiovascular disease but differed in attitudes toward efficacy of treatment. Intervention to control cholesterol was thought to be very effective by 21.2% (95% confidence interval [CI] 21.2 +/- 6.4) and without effect by 10.3% (95% CI 10.3 +/- 4.8). Intervention to improve dietary habits was considered ineffective by 48.1% (95% CI 48.1 +/- 7.8). Confidence in managing risk factors varied; most respondents described themselves as only moderately skilled. A few practitioners (30.1%; 95% CI 30.1 +/- 7.2) acknowledged practice guidelines as an important source of information on which to base preventive interventions. Only 14.7% (95% CI 14.7 +/- 5.6) of those surveyed included remuneration as contributing to their implementation of prevention activities in practice. CONCLUSIONS Variations in physician attitudes could influence risk factor intervention. Interventions to change lifestyle are associated with uncertainty about patient compliance, efficacy of treatment, and ability to effect lifestyle changes.
Langerhans cells in human lung tumours: an immunohistological study

In an immunocytochemical study of 41 human lung tumours we have shown that Langerhans cells can be reliably identified using the anti‐CD1 monoclonal antibody NA1/34. Langerhans cells are present in all the main varieties of human lung tumour although they are infrequent in both small cell carcinoma and carcinoid tumour. There is considerable variation in numbers of Langerhans cells in both adenocarcinomas and squamous cell carcinomas. In this study tumours were divided into those with high numbers of Langerhans cells (> 2 per high power field) and those with low numbers (< 2 per high power field). Analysing these results against patient survival showed a markedly worse survival in those tumours with a high number of Langerhans cells for all the tumours as a single group and for squamous cell carcinoma as a single entity.
Pressure induces loss of gap junction communication and redistribution of connexin 43 in astrocytes

Astrocytes, the major glia in the nonmyelinated optic nerve head (ONH), connect via gap junctions built of connexin‐43 (Cx43) to form a functional syncytium allowing communication and control of ionic and metabolic homeostasis of retinal ganglion cells (RGCs) axon. We examined gap junction intercellular communication (GJIC) by scrape loading assays in human ONH astrocytes exposed to hydrostatic (HP) or ambient pressure (CP) in vitro. Immunostaining, immunoprecipitation, and immunoblots were used to detect Cx43 distribution and phosphorylation in astrocytes exposed to HP with/without EGF receptor (EGFR) tyrosine kinase inhibitors AG1478 and AG82 and MAPK inhibitors U0126, PD98059, and SB203580. The data indicates that upon exposure to HP, astrocytes decrease GJIC and exhibit altered cellular localization and phosphorylation of Cx43. Inhibition of EGFR blocked the effects of HP on GJIC and HP‐induced Cx43 tyrosine phosphorylation. Inhibitors of MAPK‐ ERK1/2 and ‐p38 caused partial closure of GJIC under CP and HP, which was maintained for 6 h. Inhibition of Big Mitogen‐Activated Kinase 1/ERK5 (BMK1/ERK5) caused partial closure under CP and HP followed by full recovery after 6 h. Inhibition of MAPK did not affect the HP‐induced increase in Cx43 serine 279/282 phosphorylation. We conclude that activation of the EGFR pathway in response to HP leads to decrease of GJIC via tyrosine phosphorylation of Cx43 in ONH astrocytes. In glaucoma under conditions of elevated intraocular pressure (IOP), astrocytes may lose GJIC altering the homeostasis of RGC axons, adopting the reactive phenotype, contributing to glaucomatous neuropathy. © 2007 Wiley‐Liss, Inc.
Age Differences and Divided Attention: Is there a General Deficit?

It was the goal of this study to determine whether there were age differences specifically associated with the ability to simultaneously execute two tasks, and whether cognitive costs correlated across different situations. Eighty-one young and 86 older adults underwent nine tasks, administered both in single and in dual conditions. Results showed large age differences in raw performances in all conditions. However, a larger cognitive cost in the older adults sample, as assessed by an Age 2 Condition interaction, was observed only for four out of the nine tasks. Furthermore, age effects were greatly diminished once performance in the single tasks was controlled for. Correlations between the dual tasks, or between the cognitive cost scores, were very low once age was partialled out. Results do not support the notion of general coordination costs and speak against a generalized increase in divided attention costs with advancing age.
Evidence for a Spatial–Numerical Association in Kindergartners Using a Number Line Task

In Western cultures, small numbers are often associated with the left and large with the right space. We investigated whether this association is already present in kindergartners and second graders. Children (N = 59) estimated the position of numbers on a number line that was labeled either with a small number on the left side and a large number on the right side (i.e., left-to-right orientation) or vice versa (i.e., right-to-left orientation). The estimations were less accurate if the number line was oriented from right to left and if the children started with this condition. The results suggest that already kindergartners possess a culture-typical spatial–numerical association that develops before the acquisition of reading and writing skills and significantly affects the accuracy of numerical estimations. The performance of second graders, too, was affected by the orientation of the number line, but to a smaller degree than that of kindergartners.
DEVELOPMENT AND EVALUATION OF BANKFULL HYDRAULIC GEOMETRY RELATIONSHIPS FOR THE PHYSIOGRAPHIC REGIONS OF THE UNITED STATES 1

Bankfull hydraulic geometry relationships are used to estimate channel dimensions for streamflow simulation models, which require channel geometry data as input parameters. Often, one nationwide curve is used across the entire United States (U.S.) (e.g., in Soil and Water Assessment Tool), even though studies have shown that the use of regional curves can improve the reliability of predictions considerably. In this study, regional regression equations predicting bankfull width, depth, and cross-sectional area as a function of drainage area are developed for the Physiographic Divisions and Provinces of the U.S. and compared to a nationwide equation. Results show that the regional curves at division level are more reliable than the nationwide curve. Reliability of the curves depends largely on the number of observations per region and how well the sample represents the population. Regional regression equations at province level yield even better results than the division-level models, but because of small sample sizes, the development of meaningful regression models is not possible in some provinces. Results also show that drainage area is a less reliable predictor of bankfull channel dimensions than bankfull discharge. It is likely that the regional curves can be improved using multiple regression models to incorporate additional explanatory variables. (KEY TERMS: streams; fluvial geomorphology; bankfull discharge; nationwide and regional regression equations; hydrologic modeling.) Bieger, Katrin, Hendrik Rathjens, Peter M. Allen, and Jeffrey G. Arnold, 2015. Development and Evaluation of Bankfull Hydraulic Geometry Relationships for the Physiographic Regions of the United States. Journal of the American Water Resources Association (JAWRA) 1-17. DOI: 10.1111/jawr.12282
Relationship between expression of matrix metalloproteinase-9 and adenylyl cyclase-associated protein 1 in chronic obstructive pulmonary disease

Objective To investigate the relationship between expression of matrix metalloproteinase (MMP)-9 and expression of adenylyl cyclase-associated protein (CAP)-1 in chronic obstructive pulmonary disease (COPD). Methods Patients with possible respiratory disease were recruited into the study and divided into a COPD group and a non-COPD group on diagnosis. Pulmonary function tests were performed and serum concentrations of MMP-9 were measured using an enzyme-linked immunosorbent assay. MMP-9 and CAP1 expression were analysed in lung tissue and bronchoalveolar lavage fluid in all available samples using immunohistochemistry and Western blot, respectively. In addition, expression of MMP-9 and CAP1 in vitro was investigated using immunofluorescence. Expression of CAP1 in response to MMP-9 was measured in the human alveolar epithelial cell line HP-AEpiC, using Western blot. Results A total of 90 patients were included in the study: 52 were in the COPD group and 38 in the non-COPD group. Serum MMP-9 concentrations were significantly higher in the COPD than in the non-COPD group. MMP-9 serum concentrations were negatively correlated with forced expiratory volume in 1 s (FEV1), FEV1 as a percentage of the normal predicted value and the ratio of FEV1 to forced vital capacity, and were positively correlated with residual volume (RV), total lung capacity (TLC) and RV/TLC values. In lung tissue and bronchoalveolar lavage fluid samples, MMP-9 and CAP1 expression were inversely related. This relationship was confirmed in HP-AEpiC cells. High expression of MMP-9 and low expression of CAP1 was demonstrated in the COPD group compared with the non-COPD group. Conclusions This study demonstrated an inverse relationship between CAP1 and MMP-9 expression, and high expression of MMP-9 and low expression of CAP1 in those with COPD compared with the non-COPD group. Overexpression of MMP-9 in lung tissue and its interaction with CAP1 is likely to play a major role in airway obstruction in COPD.
Impact of perceived stress, major life events and pregnancy attitudes on low birth weight.

CONTEXT While low birth weight is the leading cause of infant mortality and morbidity, the factors influencing low birth weight are not well understood. In particular, the relationship between stressful life events and birth outcomes is unclear. It is important for health care providers to better understand the impact of stress on health outcomes. METHODS Data from a statewide case-control study of 2,378 Missouri mothers are used to examine the relationship of perceived stress, pregnancy attitudes and major life events as psychosocial risk factors on very low birth weight (i.e., birth weight lower than 1,500 g). Such births are contrasted with moderately low birth weight births (those weighing between 1,500 and 2,499 g) and normal-birth-weight infants (those weighing 2,500 g or more). A stepwise logistic regression model is used to control for all study and control variables. RESULTS The risk of very low birth weight is one and one-half times greater if the mother perceived that she "almost always" felt stress during her pregnancy. The regression model confirms that besides perceived stress, several other factors are independently associated with an increased risk of very low or moderately low birth weight. For example, getting back with a husband or partner or experiencing a major injury accident or illness were associated with an elevated risk of low birth weight (odds ratio, 1. 7), as was pregnancy denial (1.4-1.6) and unhappiness about the pregnancy (1.3). On the other hand, a few factors (taking out a mortgage or loan, having a close relative die and having a mistimed pregnancy) appear to have reduced the odds of low birth weight (odds ratio, 0.5-0.8). CONCLUSIONS Interventions with pregnant women, especially those assessing perceived stress and attitudes toward the pregnancy, have the potential to improve pregnancy outcomes. Additional prospective research with pregnant women on the origins and effects of stress, including the biological effects of stress, is needed.
Prevention of Autoimmune Diabetes With Nonactivating Anti-CD3 Monoclonal Antibody

Autoreactive T cells mediate diabetes in animal models of insulin-dependent diabetes mellitus (IDDM) and are believed to cause the disease in humans. Therefore, immunotherapies directed against T cells are of particular interest for the treatment of IDDM. One candidate for such immunotherapy is anti-CD3 monoclonal antibodies (MoAbs), but clinical side effects are common with anti-CD3 treatment due to the ability of these MoAbs to activate T cells in vivo. However, F(a′)2 fragments of anti-CD3 are nonactivating and immunosuppressive. We evaluated the effects of whole anti-CD3 MoAb and F(ab′)2 fragments in the setting of experimental autoimmune diabetes. Treatment with whole MoAb or F(ab′)2 fragments significantly reduced the hyperglycemia induced with multiple low dosages of streptozocin (MDSDM; 232 ± 23 mg/dl, P < 0.01 and 235 ± 16 mg/dl, P < 0.01 vs. 325 ± 25 mg/dl, respectively) in male CD1 mice. Both whole MoAb and F(ab′)2 fragments suppressed the development of insulitis (P < 0.001). Treatment with whole MoAb resulted in marked weight loss (10.4 ± 1.5% of total body wt), and the mice appeared ill and listless, whereas, mice treated with F(ab′)2 fragments gained weight (4.9 ± 5.5% of total body wt) and appeared healthy. Treatment with whole MoAb caused activation of T cells in vivo as reflected by proliferation of freshly isolated spleen cells to recombinant interleukin-2. Depletion of T cells with whole MoAb was more pronounced than with F(ab′)2 fragments, and T-cell receptor (TCR) reexpression on remaining cells occurred with F(ab′)2 fragments within 48 h after F(ab′)2 treatment. Despite the expression of this surface molecule, signaling by the TCR complex was blocked because T cells stimulated with anti-CD3 MoAb failed to produce lymphokines. We conclude that treatment with either whole anti-CD3 MoAb or F(ab′)2 fragments suppresses the hyperglycemia and insulitis of MDSDM. The morbidity seen with whole MoAb does not occur with F(ab′)2 fragments and is correlated with the failure of the latter to activate T cells in vivo. Nonactivating forms of anti-CD3 MoAbs may be a useful form of immunosuppressive treatment for incipient IDDM because they do not cause morbidity associated with activation of T cells, which occurs with whole MoAb.
From the Society for Clinical Vascular Surgery Duplex ultrasound imaging alone is sufficient for midterm endovascular aneurysm repair surveillance : A cost analysis study and prospective comparison with computed tomography scan

Objective: Early in our experience with endovascular aortic aneurysm repair (EVAR) we performed both serial computed tomography scans and duplex ultrasound (DU) imaging in our post-EVAR surveillance regimen. Later we conducted a prospective study with DU imaging as the sole surveillance study and determined cost savings and outcome using this strategy. Methods: From September 21, 1998, to May 30, 2008, 250 patients underwent EVAR at our hospital. Before July 1, 2004, EVAR patients underwent CT and DU imaging performed every 6 months during the first year and then annually if no problems were identified (group 1). We compared aneurysm sac size, presence of endoleak, and graft patency between the two scanning modalities. After July 1, 2004, patients underwent surveillance using DU imaging as the sole surveillance study unless a problem was detected (group 2). CT and DU imaging charges for each regimen were compared using our 2008 health system pricing and Medicare reimbursements. All DU examinations were performed in our accredited noninvasive vascular laboratory by experienced technologists. Statistical analysis was performed using Pearson correlation coefficient. Results: DU and CT scans were equivalent in determining aneurysm sac diameter after EVAR (P < .001). DU and CT were each as likely to falsely suggest an endoleak when none existed and were as likely to miss an endoleak. Using DU imaging alone would have reduced cost of EVAR surveillance by 29% ($534,356) in group 1. Cost savings of $1595 per patient per year were realized in group 2 by eliminating CT scan surveillance. None of the group 2 patients sustained an adverse event such as rupture, graft migration, or limb occlusion as a result of having DU imaging performed as the sole follow-up modality. Conclusion: Surveillance of EVAR patients can be performed accurately, safely, and cost-effectively with DU as the sole imaging study. (J Vasc Surg 2009;50:1019-24.)