Miracle-dz/UniFAR-FTUs huggingface dataset:
Motivation of Dutch high school students from various backgrounds for applying to study medicine: a qualitative study

Objective To explore high school students’ motivation for applying to study medicine and the factors that influence this. To find explanations for under-representation of minority students in medical education, descriptions of motivation of students with different background characteristics were compared. Design Qualitative phenomenological study using semistructured one-on-one interviews. Setting One predominantly white and one mixed high school in a large multicultural city in the Netherlands. The study was conducted in March–December 2015. Participants Twenty-four high school students, purposively sampled for demographic characteristics. Methods The analysis consisted of the coding of data using a template based on the motivation types (autonomous and controlled motivation) described by self-determination theory and open coding for factors that influence motivation. Results The main reasons for pursuing a medical career pertained to autonomous motivation (interest in science and helping people), but controlled motivation (eg, parental pressure, prestige) was also mentioned. Experiences with healthcare and patients positively influenced students’ autonomous motivation and served as a reality check for students’ expectations. Having to go through a selection process was an important demotivating factor, but did not prevent most students from applying. Having medical professionals in their network also sparked students’ interest, while facilitating easier access to healthcare experiences. Conclusions The findings showed a complex interplay between healthcare experiences, growing up in a medical family, selection processes and motivation. Healthcare experiences, often one of the selection criteria, help students to form autonomous motivation for studying medicine. However, such experiences as well as support in the selection process seem unequally accessible to students. As a result, under-represented students’ motivation decreases. Medical schools should be aware of this and could create opportunities to acquire healthcare experiences. High schools could incorporate internships as part of their study counselling programmes and offer tailor-made guidance to each individual student.
Two tarantula peptides inhibit activation of multiple sodium channels.

Two peptides, ProTx-I and ProTx-II, from the venom of the tarantula Thrixopelma pruriens, have been isolated and characterized. These peptides were purified on the basis of their ability to reversibly inhibit the tetrodotoxin-resistant Na channel, Na(V) 1.8, and are shown to belong to the inhibitory cystine knot (ICK) family of peptide toxins interacting with voltage-gated ion channels. The family has several hallmarks: cystine bridge connectivity, mechanism of channel inhibition, and promiscuity across channels within and across channel families. The cystine bridge connectivity of ProTx-II is very similar to that of other members of this family, i.e., C(2) to C(16), C(9) to C(21), and C(15) to C(25). These peptides are the first high-affinity ligands for tetrodotoxin-resistant peripheral nerve Na(V) channels, but also inhibit other Na(V) channels (IC(50)'s < 100 nM). ProTx-I and ProTx-II shift the voltage dependence of activation of Na(V) 1.5 to more positive voltages, similar to other gating-modifier ICK family members. ProTx-I also shifts the voltage dependence of activation of Ca(V) 3.1 (alpha(1G), T-type, IC(50) = 50 nM) without affecting the voltage dependence of inactivation. To enable further structural and functional studies, synthetic ProTx-II was made; it adopts the same structure and has the same functional properties as the native peptide. Synthetic ProTx-I was also made and exhibits the same potency as the native peptide. Synthetic ProTx-I, but not ProTx-II, also inhibits K(V) 2.1 channels with 10-fold less potency than its potency on Na(V) channels. These peptides represent novel tools for exploring the gating mechanisms of several Na(V) and Ca(V) channels.
Evaluation of DNA damage in Type 2 diabetes mellitus patients with and without peripheral neuropathy: A study in South Indian population

Background: The increasing incidence of Type 2 diabetes mellitus globally has collaterally increased the incidence of diabetes-associated complications such as neuropathy. Oxidative stress induced DNA damage is one of the mechanisms implicated in the pathogenesis of diabetic complications. Here we aimed to evaluate the extent of DNA damage in diabetes patients with and without clinical neuropathy using the Cytokinesis Block Micronucleus Cytome assay, in a group of South Indian population. Materials and Methods: The Cytokinesis Block Micronucleus Cytome assay was performed in lymphocyte cultures of 42 type 2 diabetes patients (22 with neuropathy and 20 without neuropathy) and 42 age and sex matched controls. Nuclear aberrations like Nuclear Buds, Nucleoplasmic Bridges and Micronuclei were analyzed. Results: The frequency of nuclear aberrations in diabetes patients with neuropathy was higher than compared to diabetes patients without neuropathy. The mean frequencies of nuclear aberrations per cell in diabetes patients with neuropathy and without neuropathy were 0.02 ± 0.02 and 0.01 ± 0.01, respectively. This was significantly higher than in the controls (0.002 ± 0.002) (P < 0.0001). An increasing trend of nuclear aberrations in correlation with the duration of diabetes was observed. Conclusion: This study highlights the use of the Cytokinesis Block Micronucleus Cytome assay as a potent tool for the identification of DNA damage, which may prove to be useful biomarker to assess the severity diabetes-associated complications such as neuropathy. Implementation of this technique at the clinical level would potentially enhance the quality of management of patients with diabetes and its complications like neuropathy.
Over the counter but no longer under the radar--pediatric cough and cold medications.

Dr. Joshua Sharfstein, Marisa North, and Dr. Janet Serwint write that, in October, an FDA advisory committee voted in favor of immediate action against the use of cough and cold medications in children under 6. After the meeting, the major manufacturers of these products announced that they would continue to market these preparations for children between 2 and 5 years of age.
An Overview of Interactive Medical Image Segmentation

Image segmentation is often described as partitioning an image into a ﬁnite number of semantically non-overlapping regions. In medical applications, it is a fundamental process in most systems that support medical diagnosis, surgical planning and treatments. Generally, this process is done manually by clinicians, which may be time-consuming and tedious. To alleviate the problem, a number of interactive segmentation methods have been proposed in the literature. These techniques take advantage of automatic segmentation and allow users to intervene the segmentation process by incorporating prior-knowledge, validating results and correcting errors, thus potentially lead to accurate segmentation results. In this paper, we present an overview on interactive segmentation techniques for medical images.
Education, income, occupation, and the 34-year incidence (1965-99) of Type 2 diabetes in the Alameda County Study.

BACKGROUND Lower socioeconomic position (SEP) is related to higher prevalence of Type 2 diabetes, yet little is known about the relationship of SEP with incident diabetes. METHODS The association between SEP, measured by self-reported education, income, and occupation, and Type 2 diabetes incidence was examined in a community sample of 6147 diabetes-free adults from Alameda County, CA. Cox proportional hazards models estimated the effect of baseline (1965) and time-dependent (value changes over time) measures of SEP on incident diabetes over a 34-year study period (1965-99). Demographic confounders (age, gender, race, and marital status) and potential components of the causal pathway (physical inactivity, smoking, alcohol consumption, body composition, hypertension, depression, and health care access) were included as fixed or time-dependent covariates. RESULTS Education, income, and occupation were associated with increased diabetes risk in unadjusted models. In baseline models adjusted for demographics, respondents with <12 years of education had 50% excess risk compared with those with more education [hazard ratio (HR) = 1.5, 95% confidence interval (95% CI) 1.11-2.04], but income and occupation were no longer significantly associated with increased risk. Further adjustment minimized the significance of all associations. Time-dependent effects were consistently elevated for low education and male blue-collar occupation, but non-significant after full adjustment (HR = 1.1, 95% CI 0.79-1.47 and HR = 1.3, 95% CI 0.91-1.89, respectively). CONCLUSIONS Socioeconomic disadvantage, especially with low educational attainment, is a significant predictor of incident Type 2 diabetes, although associations were largely eliminated after covariate adjustment. Obesity and overweight appear to mediate these associations.
Fair-efficient threshold parameters selection in call admission control for CDMA mobile multimedia communications using game theoretic framework

The call admission control (CAC) for code-division multiple-access (CDMA) mobile multimedia communications is one of the most important engineering issues since it belongs to the category of resource management and the radio spectrum is a very scarce resource. As efficiency is an important performance issue of CAC in the mobile networks with multimedia services, the concept of fairness among services should also be considered. Game theory provides an appropriate framework for formulating such fair and efficient CAC problem. Thus, in this paper, a selection method of fair-efficient threshold parameters of the CAC scheme for the asymmetrical traffic case in CDMA mobile multimedia communications based on the framework of game theory (both of noncooperative and cooperative games) is proposed. The proposed scheme provides fair and efficient resource allocation for multiple classes of traffic, and also guarantees the proper priority mechanism. Call classes are viewed as the players of a game. Utility function of the player is defined as the bandwidth utilization. The numerical results show that there is a unique equilibrium point of the noncooperative game for any given offered load. The results also indicate that, for the cooperative game, the Nash solution with the origin (0,0) as the starting point of the bargaining problem can achieve higher total utilization compared with the previous control method while at the same time providing fairness by satisfying a set of fairness axioms.
Festival 2 - build your own general purpose unit selection speech synthesiser

This paper describes version 2 of the Festival speech synthesis system. Festival 2 provides a development environment for concatenative speech synthesis, and now includes a general purpose unit selection speech synthesis engine. We discuss various aspects of unit selection speech synthesis, focusing on the research issues that relate to voice design and the automation of the voice development process.
Locating depots for capacitated vehicle routing

We study a location‐routing problem in the context of capacitated vehicle routing. The input to the k‐location capacitated vehicle routing problem (k‐LocVRP) consists of a set of demand locations in a metric space and a fleet of k identical vehicles, each of capacity Q. The objective is to locate k depots, one for each vehicle, and compute routes for the vehicles so that all demands are satisfied and the total cost is minimized. Our main result is a constant‐factor approximation algorithm for k‐LocVRP. In obtaining this result, we introduce a common generalization of the k‐median and minimum spanning tree problems (called k median forest), which might be of independent interest. We give a local‐search based ( 3 + ε ) ‐approximation algorithm for k median forest, which leads to a ( 12 + ε ) ‐approximation algorithm for k‐LocVRP, for any constant ε > 0 . © 2016 Wiley Periodicals, Inc. NETWORKS, Vol. 68(2), 94–103 2016
Structure of a Light-Activated LOV Protein Dimer That Regulates Transcription

Light-induced conformational changes in a blue-light sensor facilitate its dimerization. Coming Together in the Light The filamentous fungus Neurospora crassa uses two blue-light sensors, white collar-1 (WC-1) and VIVID (VVD), both of which contain light, oxygen, or voltage (LOV) domains, to regulate its responses to light. WC-1 and WC-2 form a complex (WCC) to drive expression of light-induced genes, including vvd, whereas VVD tunes responses to light by directly interacting with and antagonizing the function of WCC. Vaidya et al. solved the crystal structure of the light-induced dimer of VVD and compared it to previously determined structures of the dark-state, monomeric protein. This analysis revealed that light not only induced a conformational change in the positioning of the N-terminal cap of one subunit of VVD but also triggered the opening of a binding pocket in the opposing subunit, into which the N-terminal cap could dock. Determining the structure explained the functional responses observed in vvd-deficient Neurospora that expressed variant VVD proteins and may inform mechanisms by which LOV-containing proteins interact. Light, oxygen, or voltage (LOV) protein domains are present in many signaling proteins in bacteria, archaea, protists, plants, and fungi. The LOV protein VIVID (VVD) of the filamentous fungus Neurospora crassa enables the organism to adapt to constant or increasing amounts of light and facilitates proper entrainment of circadian rhythms. Here, we determined the crystal structure of the fully light-adapted VVD dimer and reveal the mechanism by which light-driven conformational change alters the oligomeric state of the protein. Light-induced formation of a cysteinyl-flavin adduct generated a new hydrogen bond network that released the amino (N) terminus from the protein core and restructured an acceptor pocket for binding of the N terminus on the opposite subunit of the dimer. Substitution of residues critical for the switch between the monomeric and the dimeric states of the protein had profound effects on light adaptation in Neurospora. The mechanism of dimerization of VVD provides molecular details that explain how members of a large family of photoreceptors convert light responses to alterations in protein-protein interactions.
Early initiation of antiretroviral therapy in HIV-infected adults and adolescents: a systematic review

Objectives:The objective of this review was to update evidence on when to initiate antiretroviral therapy (ART) to inform revision of the 2013 WHO guidelines for ART in low and middle-income countries. Design:A systematic review and meta-analysis. Methods:We comprehensively searchescohorts. Outcomes were mortality, clinical progression, virologic failure, immunologic recover, and severe adverse events. We pooled data across studies and estimated summary effect sizes. We graded the quality of evidence from the literature for each outcome. Results:We identified 24 studies; 3 were RCTs. Studies found reduced risk of mortality [1 RCT: hazard ratio 0.77, 95% confidence interval (CI) 0.34–1.76; 13 cohorts: relative risk (RR) 0.66, 95% CI 0.55–0.79], progression to AIDS or death (2 RCTs: RR 0.48, 95% CI 0.26–0.91; 9 cohorts: RR 0.70, 95% CI 0.40–1.24) and diagnosis of a non-AIDS-defining illness (1 RCT: RR 0.14, 95% CI 0.03–0.64; 1 cohort: RR 0.47, 95% CI 0.23–0.98), and an increased risk of grade 3/4 laboratory abnormalities in patients initiating ART at at least 350 cells/&mgr;l (1 RCT: RR 1.49, 95% CI 1.25–1.77). The quality of evidence was low or very low for clinical outcomes due to few events and imprecision, and high for adverse events. Conclusions:Our findings contributed to the evidence base for the revised 2013 WHO guidelines on ART, which recommend initiating ART at CD4+ T-cell counts of 350–500 cells/&mgr;l, but not above 500 cells/&mgr;l compared to initiating it later when CD4+ T-cell counts fall below 350 cells/&mgr;l.
The third component of complement protects against Escherichia coli endotoxin-induced shock and multiple organ failure

We investigated whether the third component of complement (C3) is involved in the pathophysiology of endotoxic shock, and if it is involved, whether it plays a protective role or whether it mediates shock and multiple organ failure. In a prospective, controlled investigation, six Brittany spaniels that were homozygous for a genetically determined deficiency of C3 (C3 deficient, < 0.003% of normal serum C3 levels) and six heterozygous littermates (controls, approximately 50% of mean normal serum C3 level) were given 2 mg/kg of reconstituted Escherichia coli 026:B6 acetone powder as a source of endotoxin, intravenously. All animals were given similar fluid and prophylactic antibiotic therapy, and had serial hemodynamic variables obtained. After E. coli endotoxin infusion, C3-deficient animals had higher peak levels of endotoxin and less of a rise in temperature than controls (P < 0.05). During the first 4 h after E. coli endotoxin infusion, C3-deficient animals had significantly greater decreases in mean central venous pressure and mean pulmonary artery pressure than controls (P < 0.02). During the first 48 h after E. coli endotoxin infusion, C3-deficient animals had significantly greater decreases in mean arterial pH, left ventricular ejection fraction, and mean pulmonary capillary wedge pressure, and greater increases in mean arterial lactate, arterial-alveolar O2 gradient, and transaminases (aspartate aminotransferase and alanine aminotransferase) than controls, (all P < 0.05). After E. coli endotoxin infusion, C3- deficient animals compared to controls had significantly less of a decrease in mean C5 levels (P < 0.01), but similar (P = NS) increases in circulating tumor necrosis factor levels, bronchoalveolar lavage neutrophils, and protein, and similar (P = NS) decreases in blood leukocytes and platelets. Two of six C3-deficient animals and two of six controls died. In summary, after intravenous infusion of E. coli endotoxin, canines with C3 deficiency have decreased endotoxin clearance and worse E. coli endotoxin-induced shock and organ damage. Thus, the third component of the complement system plays a beneficial role in the host defense against E. coli endotoxic shock.
Diagram Method in Stratified Institutions

The well-known diagram method is one of the powerful tools offered by classical model theory to build models of a certain kind. In order to make it available for a large number of logics, we consider its generalization at the level of the institutions. To be more precise we consider an extension of the institutional framework called stratified institutions. To illustrate the power of the method, we apply this generalization of the diagram method to two of its classic applications: Löwenheim-Skolem’s theorems and Lòs-Vaught’s test.
Evaluation of the Clinical and Procedural Predictive Factors of no-Reflow Phenomenon Following Primary Percutaneous Coronary Intervention

Background: The no-reflow phenomenon is an uncommon and critical occurrence which myocardial reperfusion does not restore to its optimal level. Several predisposing factors of the no-reflow phenomenon have been identified. However, at present we know little about clinical predictors of no-reflow after percutaneous coronary intervention (PCI). Objectives: In this study, we evaluated clinical predictors of no-reflow phenomenon after PCI in patients with acute STEMI, to plan a better treatment of these patients. Patients and Methods: During an 18-month period, from 2013 to 2014, 438 patients with acute myocardial infarction (AMI) presenting within the first 24 hours from symptoms onset were treated with primary PCI in the Rajaie Cardiovascular Medical and Research Center. Thrombolysis in myocardial infarction (TIMI) flow was measured in all patients on the first angiography, following stenting. A total of 49 patients were allocated to the case group, based on the no-reflow phenomenon occurred during primary PCI (TIMI grade 0 and 1) and 50 patients without the no-reflow phenomenon (TIMI grades 3) were randomly selected, as the control group. They were evaluated from the point of demographic variables and also infarction territory, pain duration, maximal ST-change, left ventricle (LV) function, laboratory data, coronary anatomy, culprit vessel, location of lesion, target vessel diameter, lesion length, eccentricity, thrombus grade, tortuosity, lesion angulation, bifurcation, predilation, postdilation, thrombus aspiration, number of stent, in stent thrombosis. Data were then analyzed with the SPSS statistical software. Results: Mean age of patients was 59.47 (SD = 12.48) years, of which 75 (75.8%) were male and 24 (24.2%) were female. Based on univariable analysis, white blood cell (WBC) count, pain duration, LV function, maximal ST-change, thrombus grade and eccentricity were identified as predictors of the no-reflow phenomenon. After multivariable logistic regression: WBC count and thrombus grade remained the significant independent predictors of the no-reflow phenomenon (P < 0.05). In case group, slow-flow was seen in 42 (9.5%), while no-reflow was seen in seven (1.6%) patients. Conclusions: The WBC count and thrombus grade are strong, independent predictive factors of developing the no-reflow phenomenon, in AMI patients undergoing primary PCI. There is also an association between the no-reflow phenomenon and pain duration, maximal ST-change, LV function, high sensitivity C-reactive protein (hs-CRP), bifurcation, eccentricity and coronary anatomy.
Patient preferences for stopping tyrosine kinase inhibitors in chronic myeloid leukemia.

BACKGROUND We used an interview-assisted survey of patients with chronic myeloid leukemia (cml) at a single tertiary care centre to explore patient reactions to and preferences for, and the risk-acceptability of, stopping tyrosine kinase inhibitor (tki) treatment. METHODS The study included patients with confirmed cml currently being treated with a tki. The survey was conducted by structured interview using a standard form. Patient preferences were explored in a case-based scenario using 0%-100% visual analog scales and 5-point Likert scales. Data were analyzed using proportions for dichotomous variables and medians and interquartile ranges for continuous variables. RESULTS Of 63 patients approached, 56 completed the survey. Participant responses suggest that the idea of stopping tki use is appealing to many patients if there is a chance of long-term stable disease and a high probability of response upon restarting a tki. Participants were more likely to stop their tki as the risk of relapse decreased. Participants reported loss of disease control and failure of disease to respond to treatment as important concerns if they chose to stop their tki. CONCLUSIONS Given the current 60% estimated rate of relapse after discontinuation of tki therapy, most patients with cml chose to continue with tki. However, at the lower relapse rates reported with second-generation tkis, participants were more undecided, demonstrating a basic understanding of risk. Contrary to our hypothesis, neither compliance nor occurrence of side effects significantly affected patient willingness to stop their tki.