Miracle-dz/UniFAR-FTUs huggingface dataset:
Insulin Stimulates Syntaxin4 SNARE Complex Assembly via a Novel Regulatory Mechanism

ABSTRACT Insulin stimulates glucose transport into fat and muscle cells by increasing the exocytic trafficking rate of the GLUT4 facilitative glucose transporter from intracellular stores to the plasma membrane. Delivery of GLUT4 to the plasma membrane is mediated by formation of functional SNARE complexes containing syntaxin4, SNAP23, and VAMP2. Here we have used an in situ proximity ligation assay to integrate these two observations by demonstrating for the first time that insulin stimulation causes an increase in syntaxin4-containing SNARE complex formation in adipocytes. Furthermore, we demonstrate that insulin brings about this increase in SNARE complex formation by mobilizing a pool of syntaxin4 held in an inactive state under basal conditions. Finally, we have identified phosphorylation of the regulatory protein Munc18c, a direct target of the insulin receptor, as a molecular switch to coordinate this process. Hence, this report provides molecular detail of how the cell alters membrane traffic in response to an external stimulus, in this case, insulin.
Efficacy of repifermin (keratinocyte growth factor‐2) against abnormalities in gastrointestinal mucosal transport in a murine model of colitis

Human keratinocyte growth factor‐2 (KGF‐2) is a member of the fibroblast growth factor family that promotes healing of experimental small intestinal ulceration and colitis. The aim of this study was to determine whether repifermin, a truncated form of recombinant human KGF‐2, reverses abnormalities in colonic mucosal transport in a murine model of dextran sulfate sodium (DSS)‐induced colitis. Male Swiss‐Webster mice were given 4% DSS in drinking water for 7 days and then normal drinking water for 3 days. Repifermin (5 mg kg−1, i.p.) or vehicle was administered daily for 7 days starting on Day 4 of DSS exposure. On Day 10, net ion transport was measured electrophysiologically in colonic mucosal sheets. Repifermin significantly reduced DSS‐induced colonic inflammation measured by tissue myeloperoxidase activity. Concurrently, in colonic tissue taken from mice treated with repifermin, there was a normalization of basal potential difference and short circuit current, and an improvement in the secretory responses to stimulation of muscarinic and ganglionic cholinoceptors. In control mice, repifermin did not interact directly with colonic epithelial cells or intramural neurones to induce immediate changes in net electrogenic transport. The results suggest that repifermin therapy may improve the mucosal electrogenic transport that is impaired during colitis.
HIV infections acquired through heterosexual intercourse in the United Kingdom: findings from national surveillance

The trends underlying the rapid and substantial increases in HIV diagnoses among heterosexual people in the United Kingdom are complex and sometimes misunderstood. Although the number of people becoming infected with HIV through heterosexual intercourse in the United Kingdom is rising steadily, most of the overall rise in HIV diagnoses among heterosexuals is among people who originate from and were infected abroad, mainly in Africa.1 We describe HIV diagnoses where infection was probably acquired through heterosexual intercourse in the United Kingdom. The Health Protection Agency Centre for Infections receives voluntary and confidential reports of HIV diagnoses in England, Wales, and Northern Ireland.2 For all reports, the centre collects the probable route of infection and the probable country of infection for patients who were infected through heterosexual intercourse. A research nurse/counsellor follows up where data are incomplete. Where more than one possible country of infection is given, the country with the highest prevalence of HIV is allocated by an epidemiologist or a research nurse/counsellor. If an individual was probably infected in the United Kingdom, further information concerning the partner's probable route and country of infection are recorded. If it is uncertain but possible that the partner was infected in the United Kingdom, …
Detection of Human Topoisomerase IIα in Cell Lines and Tissues: Characterization of Five Novel Monoclonal Antibodies

We report five novel monoclonal antibodies (Ki-S1, Ki-S4, Ki-S6, Ki-S7, and Ki-S8) reactive with a proliferation-related nuclear antigen. In immunoprecipitation and Western blot experiments using crude nuclear extracts, they recognized a protein of 170 kD that, after proteolytic digestion of the immunoprecipitate and sequencing of the resulting peptides, was identified as the α-isoform of human topoisomerase II. This was confirmed by testing the antibodies on a highly purified enzyme preparation. Crossreactivity with topoisomerase IIβ was ruled out by testing the antibodies on crude extracts from yeast cells expressing the β-isoform exclusively. The antibodies bind the antigen with different affinities and at different epitopes, apparently located within the carboxyl third of the enzyme. All five antibodies are suitable for archival material after adequate antigen retrieval, thereby enabling retrospective studies. This report illustrates the tissue and subcellular distribution of the antigen through the cell cycle by immunohistochemistry and confocal fluorescence microscopy. The antibodies will be useful tools in further analysis of morphological and functional aspects of topoisomerase II and may serve diagnostic purposes, as well as providing prognostic information in tumor pathology.
Immunoglobulin A subclass distribution of naturally occurring salivary antibodies to microbial antigens

The distribution of immunoglobulin A1 (IgA1) and IgA2 antibodies to various microbial antigens was determined in human parotid saliva by using monoclonal antibodies to the IgA subclasses in a solid-phase radioimmunoassay. In 12 subjects examined, antibodies to Streptococcus mutans glucosyl transferase, protein antigen I/II, and cell wall carbohydrate, as well as dextrans B1355 fraction S and B512 and phosphorylcholine, occurred predominantly in the IgA1 subclass. In contrast, antibodies to lipoteichoic acid from Streptococcus pyogenes and whole lipopolysaccharides from Bacteroides gingivalis, Bacteroides fragilis, and Escherichia coli were predominantly of the IgA2 subclass. The data indicate that in most individuals naturally occurring antibodies to a given antigen are predominantly associated with one of the two subclasses of IgA.
Functional Outcomes of Cleft Lip Surgery. Part IV: Between- and Within-Participant Variables Affecting Lip Vermilion Sensory Thresholds

Objective: Compare neurosensory assessments for participants with and without a cleft lip; identify between- and within-participant variables affecting sensory thresholds on the vermilion of participants with cleft lip. Design: A parallel group, nonrandomized clinical trial. Subjects: There were 56 participants with cleft lip and 37 noncleft participants. Analysis: Two-point perception and warmth and cool detection thresholds were measured on the right and left sides of the upper and lower vermilion. A cotton-tip stick, stroked across the skin, was used to identify altered sensation. Linear mixed effects modeling was used to examine the effects of between- and within-participant variables on the thresholds. Results: Threshold values on the upper and lower vermilion were similar for cleft and noncleft participants and were unaffected by the presence of a cleft on the side tested. Participants with cleft lip who reported hyposensitive altered sensations had higher two-point thresholds on the upper lip than those who reported hypersensitivity. Participants with cleft lip who reported altered midface sensation had lower warmth detection, but higher cool detection thresholds, on the lower vermilion than participants with cleft lip who did not report altered sensation. Participants with bilateral cleft lip had lower warmth detection thresholds on the upper vermilion than participants with unilateral cleft lip. Conclusions: Although participants with cleft lip and noncleft participants exhibit similar thermal and two-point discrimination, on average, differences exist among subgroups of participants with cleft lip that may reflect central disturbances in the processing of somatosensory stimuli.
The Evolving Role of Geriatric Emergency Department Social Work in the Era of Health Care Reform

In the era of Medicaid Redesign and the Affordable Care Act, the emergency department (ED) presents major opportunities for social workers to assume a leading role in the delivery of care. Through GEDI WISE—Geriatric Emergency Department Innovations in care through Workforce, Informatics and Structural Enhancements,—a unique multidisciplinary partnership made possible by an award from the Center for Medicare and Medicaid Innovation, social workers in The Mount Sinai ED have successfully contributed to improvements in health outcomes and transitions for older adults receiving emergency care. This article will describe the pivotal and highly valued role of the ED social worker in contributing to the multidisciplinary accomplishments of GEDI WISE objectives in this new model of care.
A Finite Element Dynamic Analysis of Flexible Manipulators

A finite element - based method is presented for analyzing the dynamic behavior of flexible manipulators, including the effects of the manipulator's control system. The method involves a nonlinear finite-element formulation in which both links and joints are considered as specific finite elements. The governing equations of motion are formulated in terms of two sets of coordinates, namely generalized coordinates of the manipulator with rigid links and deformation mode coordinates that characterize deformation of the links. The method also permits generation of locally linearized models about a nominal trajectory. The numerical performance of the presented finite element method is demonstrated by analyzing the closed-loop behav ior of a flexible three-degree-of-freedom manipulator in which the position of the end effector is to be sensed. On the basis of the linearized system description, controllability is discussed in terms of the modal representations of the system. Uncontrollable manipulator configurations have been indi cated for bending vibrations of the out-of-plane motion of the manipulator. Fast and precise closed-loop tip position control has been obtained for the in-plane motion with a bandwidth that is three times the bandwidth achieved with actuator joint feedback. However, no significant increase in the bandwidth has been obtained for the out-of-plane motion. The improve ment for the latter motion is strongly limited by the nonmini mum phase behavior.
Ochratoxin A in wines from 2002 to 2008 harvest marketed in Rio de Janeiro, Brazil

The occurrence of ochratoxin A (OTA) in wine from 2002 to 2008 harvest, traded in Rio de Janeiro State, was evaluated by analysing 43 national and 37 imported wines from Argentina (32) and Chile (5), adding up to 80 samples in total. OTA determination was performed using immunoaffinity columns and high-performance liquid chromatography. In 80 wine samples analysed, 25 (31.3%) were positive, presenting levels greater than 0.020 ng OTA mL−1. It was not detected in imported wines. Within national wines, 58.1% of the samples were contaminated, with levels ranging from 0.020 to 0.050 ng mL−1. The toxin was detected in 18 (69.2%) of 26 samples analysed of red table wine. Wines from 2008 harvest presented 84.6% of samples contaminated in 13 samples analysed. Despite the levels found in this study, they are below Brazilian tolerance limits. Nevertheless, the presence of OTA as found contributes to the human exposure to this toxin.
Cancer cells that survive checkpoint adaptation contain micronuclei that harbor damaged DNA

ABSTRACT We have examined the relationship between checkpoint adaptation (mitosis with damaged DNA) and micronuclei. Micronuclei in cancer cells are linked to genomic change, and may induce chromothripsis (chromosome shattering). We measured the cytotoxicity of the cancer drug cisplatin in M059K (glioma fibroblasts, IC50 15 μM). Nearly 100% of M059K cells were positive for histone γH2AX staining after 48 h treatment with a cytotoxic concentration of cisplatin. The proportion of micronucleated cells, as confirmed by microscopy using DAPI and lamin A/C staining, increased from 24% to 48%, and the total micronuclei in surviving cells accumulated over time. Promoting entry into mitosis with a checkpoint inhibitor increased the number of micronuclei in cells whereas blocking checkpoint adaptation with a Cdk inhibitor reduced the number of micronuclei. Interestingly, some micronuclei underwent asynchronous DNA replication, relative to the main nuclei, as measured by deoxy-bromo-uracil (BrdU) staining. These micronuclei stained positive for histone γH2AX, which was linked to DNA replication, suggesting that micronuclei arise from checkpoint adaptation and that micronuclei may continue to damage DNA. By contrast the normal cell line WI-38 did not undergo checkpoint adaptation when treated with cisplatin and did not show changes in micronuclei number. These data reveal that the production of micronuclei by checkpoint adaptation is part of a process that contributes to genomic change.
Perception of heaviness in Parkinson's disease

The present study investigated whether a specific aspect of proprioception, the sense of heaviness or weight is affected in PD. We determined detection thresholds for the perception of a gravito‐inertial load in 10 PD patients and 11 age‐matched control subjects. A gradually increasing weight was applied to the index finger by means of two slings of different width (low vs. high skin pressure). For the controls, mean detection thresholds were 31.3 g at skin high pressure and 33.0 g under low pressure. PD patients revealed significantly higher thresholds than the control group in both pressure conditions (mean high pressure,47.7 g; mean low pressure, 52.3 g; group effect, P = 0.001). Thresholds of PD patients tended to increase with disease severity as measured by the Unified Parkinson's Disease Rating Scale Motor score (r = 0.55) but did not correlate significantly with levodopa equivalent dosage. The results demonstrate that the perception of heaviness or weight is already affected in the early stages of PD. These findings underline the growing evidence that proprioceptive and possibly haptic dysfunction is a common feature of PD. © 2006 Movement Disorder Society
A Note on the Masking of Pictures

An experiment is described in which photographs of everyday objects were masked by frequency-filtered random visual noise. The masking functions obtained were of the same type as those obtained by masking letters and words with random noise or a pattern mask. That is, the high-frequency mask produced a type A function while the low-frequency mask produced a type B function. This result is discussed in terms of the general applicability of models of visual information processing constructed on the basis of experiments with letter or word stimuli. It is suggested that spatial-frequency concepts may usefully be employed to describe the relevant features of different types of mask.
Quantifying the impact of survivor treatment bias in observational studies.

RATIONALE Observational cohort studies are frequently used to measure the impact of therapies on the time to a particular outcome. Treatment often has a time-variant nature since it is frequently initiated at varying times during a patient's follow-up. Studies in the medical literature frequently ignore the time-dependent nature of treatment exposure. Survivor treatment bias can arise when the time dependent nature of treatment exposure is ignored since patients who survived to receive treatment may be healthier than patients who died prior to receipt of treatment. AIMS AND OBJECTIVES The objective of the current study was to explicitly quantify the magnitude of survivor-treatment bias. METHODS Monte Carlo simulations using parameters obtained from an analysis of patients admitted to hospital with a diagnosis of acute myocardial infarction in Ontario, Canada. RESULTS AND CONCLUSIONS When the true treatment was null (hazard ratio of 1), estimated treatment effects varied from a 4% reduction in mortality to a reduction in mortality of 27% when the time varying nature of the treatment was ignored. Furthermore, survivor-treatment bias increased as the time required foe exposed patients to receive treatment increased. Similarly, survivor treatment bias was amplified as exposure was defined to be exposure at any time prior to mortality compared to exposure within a fixed time interval starting at the time origin. Ignoring the time-dependent nature of treatment results in overly optimistic estimates of treatment effects. Depending on the period required for patients to initiate therapy, treatments with no effect on survival can appear to be strongly associated with improved survival. The current study is the first to explicitly quantify the magnitude of bias that results from ignoring the time-varying nature of treatment exposure in survival studies.
MAPKAP kinase 3 suppresses Ifng gene expression and attenuates NK cell cytotoxicity and Th1 CD4 T‐cell development upon influenza A virus infection

MK2 and MK3 are downstream targets of p38 and ERK1/2. They control the mRNA stability of several inflammatory cytokines, including TNF‐α and IL‐10. Whereas MK2 is expressed ubiquitously, the expression of MK3 is restricted to muscle, liver, and heart tissues and T and NK cells. Using Mk‐deficient and wild‐type (WT) mice, we demonstrated an inhibitory effect of MK3, but not of MK2, on interferon (IFN)‐γ expression in T and NK lymphocytes. The results provided evidence that the inhibitory effect of MK3 is based on negative feedback phosphorylation of p38 and ERK1/2, which causes decreased binding of Stat4 to the IFN‐γ promoter and reduced expression of IFN‐γ mRNA and protein. Consequently, all Mk3–/–mice challenged with the Th1‐inducing influenza A virus (IAV) survived the WT LD50 virus dose. The reduced disease severity in the Mk3–/– mice was accompanied by a >10‐fold reduction in viral lung titer and an increase in the number of activated NK cells and enhanced Th1 activation of CD4 T cells. Thus, our data describe the protein kinase MK3 as a novel regulator of the innate and adaptive immune responses. —Köther, K. , Nordhoff, C. , Masemann, D. , Varga, G. , Bream, J. H. , Gaestel, M. , Wixler, V. , Ludwig, S. , MAPKAP kinase 3 suppresses Ifng gene expression and attenuates NK cell cytotoxicity and Th1 CD4 T‐cell development upon influenza A virus infection. FASEB J. 28, 4235‐4246 (2014). www.fasebj. org
Aspirin use among adults with diabetes: recent trends and emerging sex disparities.

BACKGROUND Despite high cardiovascular risk among adults with diabetes mellitus, aspirin use has been low. METHODS To assess recent self-reported regular aspirin use among adults 35 years or older with diabetes, we used statewide telephone surveys conducted in 7 states in 1997 and 20 states in 1999 and 2001 including 875, 3205, and 4272 subjects in 1997, 1999, and 2001, respectively. RESULTS Aspirin use increased from 37.5% in 1997 to 48.7% in 2001. In 2001, 74.2% (95% confidence interval [CI], 70.9%-77.5%) of diabetic adults with cardiovascular disease, but only 37.9% (95% CI, 35.1%-40.7%) of those without cardiovascular disease, used aspirin regularly, including less than 40% with diagnosed hypertension or hypercholesterolemia or who smoked. After adjusting for cardiac risk factors and socioeconomic characteristics, among those without cardiovascular disease, aspirin use was less common in women aged 35 to 49 years (adjusted rate ratio [RR], 0.35; 95% CI, 0.24-0.51) and 50 to 64 years (RR, 0.69; 95% CI, 0.53-0.88) and in men aged 35 to 49 years (RR, 0.62; 95% CI, 0.43-0.85) compared with men 65 years and older. For those with diagnosed cardiovascular disease, aspirin use was lower among women (RR, 0.81 compared with men; 95% CI, 0.70-0.90) and adults younger than 50 years (RR compared with those >/=65 years, 0.81; 95% CI, 0.61-0.98). The disparity in aspirin use between men and women appeared between 1997 and 2001. CONCLUSIONS Aspirin use among adults with diabetes has increased. However, many high-risk individuals, especially women and those younger than 50 years, do not use this effective and inexpensive therapy.
IMIPENEM/CILASTATIN TREATMENT IN CAPD PERITONITIS SAPD PERİTONİTİNİN TEDAVİSİNDE IMIPENEM/CILASTATIN

Objectives: In this open trial, the efficacy of imipenem/cilastatin was investigated in 88 peritonitis episodes in 50 chronic renal failure patients on continues ambulatory peritoneal dialysis (CAPD) in one year. Methods: Biphasic Castenada medium (Blood culture system), blood base agar and Me Conkey media (plate method) were used for microbiological determination. Imipenem/cilastatin was used as the empirical therapy in all patients. One g loading dose of Imipenem/cilastatin IV was given to all patients at the first day. 100 mg Imipenem/cilastatin in 2 liter dialysis solution was administered to all patients as the standard therapy for the following 9 days. Primary response was accepted to occur when PMNL number in the dialysis solution decreased to 100/mm3. Results: Primary response, relapse and overall cure rate were 93%, 4%, 89% respectively in imipenem/cilastatin treatment. Blood culture system (77%) was found to be more sensitive than plate method (43%) in isolating the micro-organisms which were as follows in order of decreasing frequency: Staphylococcus epidermidis (50%), E. Coli (17%), Staphylococcus aureus (13%) and Klebsiella spp. (7%). Conclusion: It can be concluded that Imipenem/cilastatin first-line treatment is highly efficient in CAPD peritonitis.
Comparison of non-parametric methods for assessing classifier performance in terms of ROC parameters

The most common metric to assess a classifier's performance is the classification error rate, or the probability of misclassification (PMC). Receiver operating characteristic (ROC) analysis is a more general way to measure the performance. Some metrics that summarize the ROC curve are the two normal-deviate-axes parameters, i.e., a and b, and the area under the curve (AUC). The parameters "a" and "b" represent the intercept and slope, respectively, for the ROC curve if plotted on normal-deviate-axes scale. AUC represents the average of the classifier TPF over FPF resulting from considering different threshold values. In the present work, we used Monte-Carlo simulations to compare different bootstrap-based estimators, e.g., leave-one-out, . 632, and . 632+ bootstraps, to estimate the AUC. The results show the comparable performance of the different estimators in terms of RMS, while the . 632+ is the least biased.
Communicating With Pediatricians: Developing Social Work Practice in Primary Care

While social work models of interdisciplinary collaboration suggest that communication is important, the research literature on social worker–physician collaboration infrequently considers work with pediatricians or practice outside the hospital setting. A cross-sectional survey was sent to a stratified random sample of social workers to assess their communication satisfaction with pediatricians. The study found that social workers in health settings were more satisfied than those in mental health settings. The implications of this finding for the development of colocated, collaborative care models are discussed.