Miracle-dz/UniFAR-FTUs huggingface dataset:
High recovery of Haemophilus influenzae and group A streptococci in recurrent tonsillar infection or hypertrophy as compared with normal tonsils

Abstract One hundred and twenty-six patients who underwent tonsillectomy because of recurrent acute tonsillitis, tonsillar hypertrophy or sleep apnoea were evaluated by tonsillar core culturing. The sleep apnoea patients served as controls, since none of them had tonsillar hypertrophy at ENT examination or any history of recurrent acute tonsillitis, and thus their tonsillar core flora could be regarded as normal. The isolation rate of H. influenzae was much lower among sleep apnoea controls (2.7 per cent) than among either the patients with recurrent acute tonsillitis (20.3 per cent) or those with tonsillar hypertrophy (36.7 per cent) (p<0.05), as was that of group A streptococci, 5.4 per cent versus16.9 and 20 per cent, respectively (though the latter differences were not statistically significant). The isolation frequencies of B. catarrhalis, pneumococci, group C and G streptococci did not differ between the three groups. The high tonsillar core recovery rates of H. influenzae and group A streptococci both in patients with recurrent acute tonsillitis and in those with tonsillar hypertrophy, as compared with normal controls, suggests the possible involvement of these bacteria in both conditions.
An Analysis of Genetic Diversity and Inbreeding in Wuchereria bancrofti: Implications for the Spread and Detection of Drug Resistance

Estimates of genetic diversity in helminth infections of humans often have to rely on genotyping (immature) parasite transmission stages instead of adult worms. Here we analyse the results of one such study investigating a single polymorphic locus (a change at position 200 of the β-tubulin gene) in microfilariae of the lymphatic filarial parasite Wuchereria bancrofti. The presence of this genetic change has been implicated in benzimidazole resistance in parasitic nematodes of farmed ruminants. Microfilariae were obtained from patients of three West African villages, two of which were sampled prior to the introduction of mass drug administration. An individual-based stochastic model was developed showing that a wide range of allele frequencies in the adult worm populations could have generated the observed microfilarial genetic diversity. This suggests that appropriate theoretical null models are required in order to interpret studies that genotype transmission stages. Wright's hierarchical F-statistic was used to investigate the population structure in W. bancrofti microfilariae and showed significant deficiency of heterozygotes compared to the Hardy-Weinberg equilibrium; this may be partially caused by a high degree of parasite genetic differentiation between hosts. Studies seeking to quantify accurately the genetic diversity of helminth populations by analysing transmission stages should increase their sample size to account for the variability in allele frequency between different parasite life-stages. Helminth genetic differentiation between hosts and non-random mating will also increase the number of hosts (and the number of samples per host) that need to be genotyped, and could enhance the rate of spread of anthelmintic resistance.
Menopause and Metabolic Syndrome in Tunisian Women

Objectives. This study aimed to evaluate the effect of menopausal status on the risk of metabolic syndrome (MetS) in Tunisian women. Methods. We analyzed a total of 2680 women aged between 35 and 70 years. Blood pressure, anthropometric indices, fasting glucose, and lipid profile were measured. The MetS was assessed by the modified NCEP-ATPIII definition. Results. The mean values of waist circumference, blood pressure, plasma lipids, and fasting glucose were significantly higher in postmenopausal than in premenopausal women, a difference that was no longer present when adjusting for age. Except for hypertriglyceridaemia, the frequency of central obesity, hyperglycemia, high blood pressure, and high total cholesterol was significantly higher in postmenopausal than in premenopausal women. After adjusting for age, the significance persisted only for hyperglycemia. The overall prevalence of MetS was 35.9%, higher in postmenopausal (45.7% versus 25.6%) than in premenopausal women. A binary logistic regression analysis showed that menopause was independently associated with MetS (OR = 1.41, 95% CI 1.10–1.82) after adjusting for age, residence area, marital status, family history of cardiovascular disease, education level, and occupation. Conclusions. The present study provides evidence that the MetS is highly prevalent in this group of women. Menopause can be a predictor of MetS independent of age in Tunisian women.
Trypanosoma cruzi Triggers an Early Type I IFN Response In Vivo at the Site of Intradermal Infection1

Early interactions between the protozoan parasite Trypanosoma cruzi and mammalian hosts at primary sites of infection (skin and mucosal membranes) are predicted to be critical determinants of parasite survival and dissemination in the host. To investigate the early host response triggered by three different strains of T. cruzi at a local infection site, changes in host gene expression were monitored in a murine intradermal infection model using Affymetrix oligonucleotide arrays. Robust induction of IFN-stimulated genes was observed in excised skin 24 h postinfection where the level of IFN-stimulated gene induction was parasite strain-dependent, with the least virulent strain triggering a muted IFN response. Infection of mice immunodepleted of IFN-γ-producing cells or infection of IFN-γ-deficient mice had minimal impact on the IFN response generated in T. cruzi-infected mice. In contrast, infection of mice lacking the type I IFN receptor demonstrated that type I IFNs are largely responsible for the IFN response generated at the site of infection. These data highlight type I IFNs as important components of the innate immune response to T. cruzi at the site of inoculation and their role in shaping the early transcriptional response to this pathogen.
Effects of Simulator Practice and Real-World Experience on Cell-Phone—Related Driver Distraction

Objective: Our research examined the effects of practice on cell-phone—related driver distraction. Background: The driving literature is ambiguous as to whether practice can reduce driver distraction from concurrent cell phone conversation. Methods: Drivers reporting either high or low real-world cell phone usage were selected to participate in four 90-min simulated driving sessions on successive days. The research consisted of two phases: a practice phase and a novel transfer phase. Results: Dual-task performance deficits persisted through practice and transfer driving conditions. Moreover, groups reporting high and low real-world experience exhibited similar driving impairments when conversing on a hands-free cell phone. Conclusions: These data indicate that practice is unlikely to eliminate the disruptive effects of concurrent cell phone use on driving. Application: Multiple regulatory agencies have considered, or are currently considering, legislation to restrict in-vehicle cell phone use. Findings reported herein may be useful to inform these public policy decisions.
RSS-based localization of a moving node in homogeneous environments

In this paper, we deal with the problem of RSS-based self-localization of a wireless blind node using a statistical path loss model for the measurements. The considered environment is homogeneous, i.e., the attenuation factors of the various links are one and the same while the transmitted powers are different. The blind node is moving along a trajectory that is unknown. We propose a two-stage procedure: the first stage exploits measurements between anchors, i.e., nodes of known position, to compute the ML estimate of the transmitted powers and the attenuation factor. Then, a ML solution, using measurements at the blind node only, is proposed to estimate the unknown trajectory, based upon the Viterbi algorithm. The performance assessment, carried out also in comparison to other algorithms, shows that the proposed approach could be a viable means to handle localization of moving nodes in uncertain scenarios.
Dopamine D2 Receptor‐Deficient Mice Exhibit Decreased Dopamine Transporter Function but No Changes in Dopamine Release in Dorsal Striatum

Abstract : Presynaptic D2 dopamine (DA) autoreceptors, which are well known to modulate DA release, have recently been shown to regulate DA transporter (DAT) activity. To examine the effects of D2 DA receptor deficiency on DA release and DAT activity in dorsal striatum, we used mice genetically engineered to have two (D2+/+), one (D2+/‐), or no (D2‐/‐) functional copies of the gene coding for the D2 DA receptor. In vivo microdialysis studies demonstrated that basal and K+‐evoked extracellular DA concentrations were similar in all three genotypes. However, using in vivo electrochemistry, the D2‐/‐ mice were found to have decreased DAT function, i.e., clearance of locally applied DA was decreased by 50% relative to that in D2+/+ mice. In D2+/+ mice, but not D2‐/‐ mice, local application of the D2‐like receptor antagonist raclopride increased DA signal amplitude, indicating decreased DA clearance. Binding assays with the cocaine analogue [3H]WIN 35,428 showed no genotypic differences in either density or affinity of DAT binding sites in striatum or substantia nigra, indicating that the differences seen in DAT activity were not a result of decreased DAT expression. These results further strengthen the idea that the D2 DA receptor subtype modulates activity of the striatal DAT.
Structural Basis for the Inhibition of Voltage-gated Sodium Channels by Conotoxin μO§-GVIIJ*

Cone snail toxins are well known blockers of voltage-gated sodium channels, a property that is of broad interest in biology and therapeutically in treating neuropathic pain and neurological disorders. Although most conotoxin channel blockers function by direct binding to a channel and disrupting its normal ion movement, conotoxin μO§-GVIIJ channel blocking is unique, using both favorable binding interactions with the channel and a direct tether via an intermolecular disulfide bond. Disulfide exchange is possible because conotoxin μO§-GVIIJ contains an S-cysteinylated Cys-24 residue that is capable of exchanging with a free cysteine thiol on the channel surface. Here, we present the solution structure of an analog of μO§-GVIIJ (GVIIJ[C24S]) and the results of structure-activity studies with synthetic μO§-GVIIJ variants. GVIIJ[C24S] adopts an inhibitor cystine knot structure, with two antiparallel β-strands stabilized by three disulfide bridges. The loop region linking the β-strands (loop 4) presents residue 24 in a configuration where it could bind to the proposed free cysteine of the channel (Cys-910, rat NaV1.2 numbering; at site 8). The structure-activity study shows that three residues (Lys-12, Arg-14, and Tyr-16) located in loop 2 and spatially close to residue 24 were also important for functional activity. We propose that the interaction of μO§-GVIIJ with the channel depends on not only disulfide tethering via Cys-24 to a free cysteine at site 8 on the channel but also the participation of key residues of μO§-GVIIJ on a distinct surface of the peptide.
Public Opinions about Overdiagnosis: A National Community Survey

Background Despite evidence about the "modern epidemic" of overdiagnosis, and expanding disease definitions that medicalize more people, data are lacking on public views about these issues. Our objective was to measure public perceptions about overdiagnosis and views about financial ties of panels setting disease definitions. Methods We conducted a 15 minute Computer Assisted Telephone Interview with a randomly selected community sample of 500 Australians in January 2014. We iteratively developed and piloted a questionnaire, with a convenience sample (n=20), then with participants recruited by a research company (n=20). Questions included whether respondents had been informed about overdiagnosis; opinions on informing people; and views about financial ties among panels writing disease definitions. Findings Our sample was generally representative, but included a higher proportion of females and seniors, typical of similar surveys. American Association for Public Opinion Research response rate was 20% and cooperation rate was 44%. Only 10% (95% CI 8%–13%) of people reported ever being told about overdiagnosis by a doctor. 18% (95% CI 11%–28%) of men who reported having prostate cancer screening, and 10% (95% CI 6%–15%) of women who reported having mammography said they were told about overdiagnosis. 93% (95% CI 90%–95%) agreed along with screening benefits, people should be informed about overdiagnosis. On panels setting disease definitions, 78% (95% CI 74%–82%) felt ties to pharmaceutical companies inappropriate, and 91% (95% CI 82%–100%) believed panels should have a minority or no members with ties. Limitations included questionnaire novelty and complexity. Conclusions A small minority of Australians surveyed, including those reporting being screened for prostate or breast cancer, reported being informed of overdiagnosis; most believed people should be informed; and a majority felt it inappropriate that doctors with ties to pharmaceutical companies write disease definitions. Results suggest strategies to better inform people about overdiagnosis, and review disease definition processes, have significant public sympathy.
Neural GPUs Learn Algorithms

Learning an algorithm from examples is a fundamental problem that has been widely studied. Recently it has been addressed using neural networks, in particular by Neural Turing Machines (NTMs). These are fully differentiable computers that use backpropagation to learn their own programming. Despite their appeal NTMs have a weakness that is caused by their sequential nature: they are not parallel and are are hard to train due to their large depth when unfolded. We present a neural network architecture to address this problem: the Neural GPU. It is based on a type of convolutional gated recurrent unit and, like the NTM, is computationally universal. Unlike the NTM, the Neural GPU is highly parallel which makes it easier to train and efficient to run. An essential property of algorithms is their ability to handle inputs of arbitrary size. We show that the Neural GPU can be trained on short instances of an algorithmic task and successfully generalize to long instances. We verified it on a number of tasks including long addition and long multiplication of numbers represented in binary. We train the Neural GPU on numbers with upto 20 bits and observe no errors whatsoever while testing it, even on much longer numbers. To achieve these results we introduce a technique for training deep recurrent networks: parameter sharing relaxation. We also found a small amount of dropout and gradient noise to have a large positive effect on learning and generalization.
Development of Angiotensin IV Analogs as Hepatocyte Growth Factor/Met Modifiers

The 6-AH family [d-Nle-X-Ile-NH-(CH2)5-CONH2; where X = various amino acids] of angiotensin IV (Ang IV) analogs binds directly to hepatocyte growth factor (HGF) and inhibit HGF's ability to form functional dimers. The metabolically stabilized 6-AH family member, d-Nle-Tyr-Ile-NH-(CH2)5-CONH2, had a t1/2 in blood of 80 min compared with the parent compound norleual [Nle-Tyr-Leu-Ψ-(CH2-NH2)3-4-His-Pro-Phe], which had a t1/2 in blood of <5 min. 6-AH family members were found to act as mimics of the dimerization domain of HGF (hinge region) and inhibited the interaction of an HGF molecule with a 3H-hinge region peptide resulting in an attenuated capacity of HGF to activate its receptor Met. This interference translated into inhibition of HGF-dependent signaling, proliferation, and scattering in multiple cell types at concentrations down into the low picomolar range. We also noted a significant correlation between the ability of the 6-AH family members to block HGF dimerization and inhibition of the cellular activity. Furthermore, a member of the 6-AH family with cysteine at position 2, was a particularly effective antagonist of HGF-dependent cellular activities. This compound suppressed pulmonary colonization by B16-F10 murine melanoma cells, which are characterized by an overactive HGF/Met system. Together, these data indicate that the 6-AH family of Ang IV analogs exerts its biological activity by modifying the activity of the HGF/Met system and offers the potential as therapeutic agents in disorders that are dependent on or possess an overactivation of the HGF/Met system.
Reduction of cardiovascular events and microvascular complications in diabetes with ACE inhibitor treatment: HOPE and MICRO‐HOPE

The Heart Outcomes Prevention Evaluation (HOPE) study, an international randomized trial, was designed to evaluate the effects of the angiotensin‐converting enzyme (ACE) inhibitor ramipril and vitamin E in patients at high risk for cardiovascular events. The study did not detect any cardiovascular benefit or harm using vitamin E. Results for the vitamin E arm are not discussed here. Of 9541 patients, 3577 with diabetes received either ramipril (10 mg) or placebo. Among these patients, ramipril use was associated with a significant 25% reduction in risk for the composite endpoint of myocardial infarction (MI), stroke, or cardiovascular death after a median follow‐up period of 4.5 years. This benefit was independent of any blood pressure‐lowering effect. The Microalbuminuria, Cardiovascular, and Renal Outcomes in HOPE (MICRO‐HOPE) substudy in this patient population showed that ramipril treatment was associated with a decreased risk of development of overt nephropathy. Use of a composite measure of microvascular complications also suggested a protective effect of ramipril treatment. An interesting finding in the HOPE study is that ramipril treatment was associated with a significant 34% reduction in new diagnoses of diabetes. The possibility that ACE inhibitor treatment with ramipril may prevent new diabetes in non‐diabetic patients at high risk of the disease is to be examined prospectively in the Diabetes Reduction Assessment with ramipril and rosiglitazone (DREAM) trial. Copyright © 2002 John Wiley & Sons, Ltd.
Modulation of acto-myosin contractility in skeletal muscle myoblasts uncouples growth arrest from differentiation

Cell-substratum interactions trigger key signaling pathways that modulate growth control and tissue-specific gene expression. We have previously shown that abolishing adhesive interactions by suspension culture results in G0 arrest of myoblasts. We report that blocking intracellular transmission of adhesion-dependent signals in adherent cells mimics the absence of adhesive contacts. We investigated the effects of pharmacological inhibitors of acto-myosin contractility on growth and differentiation of C2C12 myogenic cells. ML7 (5-iodonaphthalene-1-sulfonyl homopiperazine) and BDM (2,3, butanedione monoxime) are specific inhibitors of myosin light chain kinase, and myosin heavy chain ATPase, respectively. ML7 and BDM affected cell shape by reducing focal adhesions and stress fibers. Both inhibitors rapidly blocked DNA synthesis in a dose-dependent, reversible fashion. Furthermore, both ML7 and BDM suppressed expression of MyoD and myogenin, induced p27kip1 but not p21cip1, and inhibited differentiation. Thus, as with suspension-arrest, inhibition of acto-myosin contractility in adherent cells led to arrest uncoupled from differentiation. Over-expression of inhibitors of the small GTPase RhoA (dominant negative RhoA and C3 transferase) mimicked the effects of myosin inhibitors. By contrast, wild-type RhoA induced arrest, maintained MyoD and activated myogenin and p21 expression. The Rho effector kinase ROCK did not appear to mediate Rho's effects on MyoD. Thus, ROCK and MLCK play different roles in the myogenic program. Signals regulated by MLCK are critical, since inhibition of MLCK suppressed MyoD expression but inhibition of ROCK did not. Inhibition of contractility suppressed MyoD but did not reduce actin polymer levels. However, actin depolymerization with latrunculin B inhibited MyoD expression. Taken together, our observations indicate that actin polymer status and contractility regulate MyoD expression. We suggest that in myoblasts, the Rho pathway and regulation of acto-myosin contractility may define a control point for conditional uncoupling of differentiation and the cell cycle.
Treatment of Poor-Grade Subarachnoid Hemorrhage Trial

BACKGROUND AND PURPOSE: Management of poor-grade subarachnoid hemorrhage is based on limited evidence from small single-center retrospective observational studies. The purpose of this study was to undertake a single-center randomized controlled feasibility trial comparing a strategy of early endovascular aneurysm treatment with treatment after neurologic recovery in this group of patients. MATERIALS AND METHODS: Patients with poor-grade SAH were randomized within 24 hours of admission to early treatment or treatment after neurologic recovery. If a patient was randomized to early treatment, the aneurysm was treated endovascularly within 24 hours of randomization. Recruitment rate, safety profile, and functional outcome at the time of discharge and at 6 months were assessed. RESULTS: Fourteen of 51 patients screened were eligible for the trial. Of these 14, 8 patients were randomized (57%). All patients in the early coiling arm received treatment within 24 hours of randomization. There was no treatment-related complication. Overall, good outcome occurred in 25% of patients; the mortality rate was 75%. Patients in the early treatment arm (n = 5) had a good outcome rate of 20%, while those in treatment after neurologic recovery arm (n = 3) had a good outcome rate of 33.3%. CONCLUSIONS: This was a feasibility study that demonstrated that recruitment and randomization for comparing management strategies in poor-grade SAH are feasible. The recruitment rate among eligible patients was encouraging (57%), though a number of patients had to be excluded due to ineligibility. A multicenter study is necessary to recruit the numbers required to compare the clinical outcomes of these management strategies.
Role of serum carbohydrate antigen 19‐9 and carcinoembryonic antigen in distinguishing between benign and invasive intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has malignant potential. Although serum levels of carbohydrate antigen (CA) 19‐9 and carcinoembryonic antigen (CEA) are known to be raised in pancreatic ductal adenocarcinoma, little has been reported about their significance in IPMN.