Miracle-dz/UniFAR-FTUs huggingface dataset:
How do undergraduate medical students perceive social accountability?

Abstract Aim: The concept of social accountability within undergraduate training is embedded within the remit of medical schools. Little is known of how medical students perceive social accountability, recognize aspects of their training contributing to the development of this concept and cultivate the underpinning values. Methods: Students nearing graduation were recruited to participate in focus groups designed to explore their perceptions of social accountability, which curricular aspects had contributed to their understanding, and to investigate the implications of individual variations in training. Results: Students expressed limited appreciation of the concept of social accountability and acknowledged little explicit teaching around underpinning core concepts such as awareness of local health needs, advocacy and nurturing of altruism. However, participants recognized numerous aspects of the course and learning initiatives as impacting on their attitudes towards this concept implicitly. Conclusion: This study highlights areas of their undergraduate training that students recognize as having the greatest impact on their development into socially accountable professionals. It poses some significant challenges for health care educators in addressing unintended consequences, including an outcome-driven educational approach, in reducing students’ capacity or willingness to engage in curricular challenges often designed to embed this concept.
Children with genetic disorders undergoing open-heart surgery: Are they at increased risk for postoperative complications?*

Objectives: Children with congenital heart disease and genetic disorders may be at increased risk for postoperative mortality and morbidity compared with children with congenital heart disease alone. The aim of the present study was to determine differences in postcardiopulmonary bypass outcome between these two groups. Design: Prospective cohort study. Setting: Tertiary university children's hospital. Patients: We enrolled 211 infants (<1 yr) who underwent bypass surgery for congenital heart disease. Data on perioperative course were compared between infants with and without genetic disorders. Univariate analysis was followed by regression analysis to control for confounders. Interventions: None. Measurements and Main Results: We enrolled 148 infants without and 63 infants with a genetic disorder. The majority of infants with genetic disorders had trisomy 21 (n = 32), six had microdeletion 22q11, and 25 had other genetic disorders. There was no significant difference in mortality between infants with and without genetic disorders. An underlying genetic disorder was an independent risk factor for renal insufficiency (p = .003) and reintubation (p = .02). Trisomy 21 was an independent risk factor for chylothorax (p = .01) and sepsis (p = .05). The length of hospital stay was longer in infants with genetic disorders other than trisomy 21 compared with infants with trisomy 21 (p = .009). Conclusions: Infants with congenital heart disease and genetic disorders are not at increased risk for postoperative mortality. However, a genetic disorder is a risk factor for reintubation and renal insufficiency, whereas infants with trisomy 21 have a higher risk of chylothorax and sepsis. Intensive care providers need to be aware of these differences in morbidity to improve management decisions and parental counseling.
β-catenin-mediated adhesion is required for successful preimplantation mouse embryo development

β-catenin (CTNNB1) is integral to cell adhesion and to the canonical Wnt signaling pathway. The effects of maternal and zygotic CTNNB1 on embryogenesis have each been separately assessed, whereas the effect of its total absence has not. As the ‘traditional’ conditional Ctnnb1 knockout alleles give rise to truncated CTNNB1 fragments, we designed a new knockout allele incapable of CTNNB1 production. Mouse embryos lacking intact maternal/zygotic CTNNB1 from two knockout strains were examined in detail. Preimplantation embryos are formed, yet abnormalities in their size and shape were found throughout pre- and early postimplantation development. In the absence of the zona pellucida, embryos lacking CTNNB1 undergo fission and these separated blastomeres can become small trophoblastic vesicles, which in turn induce decidual reactions. Comparing the severity of this defective adhesion phenotype in embryos bearing the null allele with those carrying the ‘traditional’ knockout allele suggests a hypomorphic effect of the truncated CTNNB1 protein fragment, an important observation with possible impact on previous and future studies. Summary: Generation of a new targeted Ctnnb1 allele shows that maternal/zygotic Ctnnb1 null embryos cannot complete preimplantation development due to defective blastomere adhesion.
Early reduced liver graft survival in hepatitis C recipients identified by two combined genetic markers

HLA and IL‐28B genes were independently associated with severity of HCV‐related liver disease. We investigated the effects of these combined genetic factors on post‐transplant survival in HCV‐infected recipients, aiming to provide new data to define the optimal timing of novel antiviral therapies in the transplant setting. HLA‐A/B/DRB1 alleles and IL‐28B rs12979860 (C > T) polymorphism frequencies were determined in 449 HCV viremic recipients and in their donors. Median follow‐up was 10 years; study outcome was graft survival. HLA‐DRB1*11 phenotype and IL‐28B C/C genotype were significantly less frequent in recipients than donors (27.8% vs. 45.9% and 27.4% vs. 44.9%, respectively, P < 0.00001). Ten‐year graft survival was better in patients with HLA‐DRB1*11 (P = 0.0183) or IL‐28B C/C (P = 0.0436). Conversely, concomitant absence of HLA‐DRB1*11 and IL‐28B C/C in 228 (50.8%) predicted worse survival (P = 0.0006), which was already evident at the first post‐transplant year (P = 0.0370). In multivariable Cox analysis, absence of both markers ranked second as risk factor for survival (HR = 1.74), following donor age ≥ 70 years (HR = 1.77). In the current era of direct‐acting antiviral agents, the negative effects of this common immunogenetic profile in HCV‐infected recipients could be most effectively neutralized by peri‐transplant treatment. This should be particularly relevant in countries where elderly donors represent an unavoidable resource.
Material Characterization of Woven Fabrics for Thermoforming of Composites

Proper material characterization of woven fabric reinforcement is important for accurate modeling of thermoforming. Thermoforming of commingled thermoplastic/glass fabric relies strictly on material deformation at temperatures above the matrix melting temperature. As the temperature increases, the viscosity decreases allowing for the resin to flow. The yarns are freer to rotate, reducing shear loads in the material. The resistance to deformation depends not only on the matrix viscosity, but also on the fabric architecture. The two types of materials used in this study are a plain weave and a 4-harness satin weave structure. An interesting characteristic of these woven materials is that they exhibit shear deformation with concomitant area changes, enabling them to take on shapes of double curvature. This makes them a great candidate for thermoforming of structural parts. To improve the viability of this manufacturing process, simulations and design tools are needed. A standardized test method must be devised to ensure an accurate material characterization for finite element models. Therefore, extensive testing with the use of a trellis shear frame is discussed. Testing shows significant non-repeatability, introducing great concern for modeling purposes. Possible reasons for inconsistency addressed in this paper are fiber tension, alignment and manufacturing. Although all of these may contribute to the inconsistencies seen, yarn misalignment is discussed in greater detail. Correlation between test fixtures of different sizes was established by normalizing the data with respect to area. These results suggest that the number of crossovers, as represented by the area, within the material is critical. Two distinct areas of concern addressed in this paper include: the change in fabric temperature during stamping and the material response at these temperatures.
Therapeutic potential of proteasome inhibitors in congenital erythropoietic porphyria

Significance The genetic disease congenital erythropoietic porphyria (CEP) results from the accumulation of toxic porphyrins owing to an enzymatic uroporphyrinogen III synthase (UROS) defect. We have already shown that the UROSC73R and UROSP248Q mutants, usually associated with a severe phenotype, conserve partial intrinsic enzymatic activity but suffer from kinetic instability and premature degradation by the proteasome pathway. We now demonstrate that treatment with a clinically approved proteasome inhibitor could rescue UROS mutant expression in human erythroid cells and reverse the skin photosensitivity in homozygous UrosP248Q CEP mice. Based on our understanding of the biochemical mechanism of UROS enzymatic deficiency, these innovative results open the way for a pharmacologic treatment of CEP disease as an alternative to bone marrow transplantation. Congenital erythropoietic porphyria (CEP) is a rare autosomal recessive disorder characterized by uroporphyrinogen III synthase (UROS) deficiency resulting in massive porphyrin accumulation in blood cells, which is responsible for hemolytic anemia and skin photosensitivity. Among the missense mutations actually described up to now in CEP patients, the C73R and the P248Q mutations lead to a profound UROS deficiency and are usually associated with a severe clinical phenotype. We previously demonstrated that the UROSC73R mutant protein conserves intrinsic enzymatic activity but triggers premature degradation in cellular systems that could be prevented by proteasome inhibitors. We show evidence that the reduced kinetic stability of the UROSP248Q mutant is also responsible for increased protein turnover in human erythroid cells. Through the analysis of EGFP-tagged versions of UROS enzyme, we demonstrate that both UROSC73R and UROSP248Q are equally destabilized in mammalian cells and targeted to the proteasomal pathway for degradation. We show that a treatment with proteasomal inhibitors, but not with lysosomal inhibitors, could rescue the expression of both EGFP-UROS mutants. Finally, in CEP mice (UrosP248Q/P248Q) treated with bortezomib (Velcade), a clinically approved proteasome inhibitor, we observed reduced porphyrin accumulation in circulating RBCs and urine, as well as reversion of skin photosensitivity on bortezomib treatment. These results of medical importance pave the way for pharmacologic treatment of CEP disease by preventing certain enzymatically active UROS mutants from early degradation by using proteasome inhibitors or chemical chaperones.
Changes in Phosphoinositide Turnover in Isolated Guinea Pig Hearts Stimulated With Isoproterenol

The incorporation of 32P1 into phospholamban, troponin I, phosphatidylinositols, and inositol trisphosphates was studied in Langendorff-perfused guinea pig hearts stimulated with isoproterenol. Hearts were perfused with Krebs-Henseleit buffer containing [32P]P| and freezeclamped at different times during the positive inotropic response. Exposure of the hearts to 0.1 μM isoproterenol for up to 1 minute was associated with significant (up to threefold) increases in phospholamban and troponin I phosphorylation, but there was no significant increase in 32P incorporation into phospholipids. However, longer exposure (2 minutes or more) to isoproterenol was associated with increases in the degree of P labeling of phosphatidylinositols and phosphatidic acid. Examination of 32P labeling of Inositol trisphosphates in the same hearts revealed that the radioactivity associated with these compounds decreased with time. The decreases were significant at times of exposure of 2 minutes or longer to β-adrenergic stimulation. The tissue levels of the inositol 1,4,5-trisphosphate isoform were also measured in hearts perfused with isoproterenol for 3 minutes, and they were found to be significantly lower compared with values obtained in control hearts. The effects of isoproterenol on 32P incorporation into phospholipids and proteins were observed in the presence of prazosin, and they were completely abolished by the β-receptor blocker propranolol. Examination of the phosphoinositldespecific phosphoUpase C activity in the perfused hearts revealed that isoproterenol stimulation was associated with a decrease in the membrane-associated enzymatic activity at physiological calcium concentrations. These findings indicate that β-adrenergic stimulation of isolated hearts is associated with changes in basal phosphatidylinositol turnover that may be mediated, at least in part, by inhibition of the phosphoUpase C enzymatic activity specific for phosphatidylinositols.
Preparation and properties of extruded thermoplastic starch/polymer blends

This article examines the starch gelatinization and the blend morphology development in blends of thermoplastic starch (TPS) with high-density polyethylene, polypropylene, polystyrene, poly(lactic acid), and polycaprolactone. The TPS gelatinization and mixing with the second polymer was carried out on a twin-screw extrusion process, where the starch was sequentially gelatinized, devolatilized, and then mixed in the molten state with a synthetic polymer. The role of excess water and process temperature on starch gelatinization was assessed by measuring the X-ray scattering. All prepared blends included 25 % TPS that was dispersed in the synthetic polymer matrix. Compatibilized versions of these same blends were obtained by partially substituting the polymer matrices with maleated analogs. The blend morphology was probed by scanning electron microscopy. Complete starch gelatinization was obtained when the gelatinization process was carried out over 100°C regardless of amount of water used as co-plasticizer. The blend morphologies were greatly improved when a maleated compatibilizer was added. Only TPS/PCL blends exhibited a finely dispersed TPS phase without the use of a compatibilizer. In general, the addition of the TPS reduced slightly the tensile modulus and strength of the different polymers and more importantly the elongation at break. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Systematically Differentiating Functions for Alternatively Spliced Isoforms through Integrating RNA-seq Data

Integrating large-scale functional genomic data has significantly accelerated our understanding of gene functions. However, no algorithm has been developed to differentiate functions for isoforms of the same gene using high-throughput genomic data. This is because standard supervised learning requires ‘ground-truth’ functional annotations, which are lacking at the isoform level. To address this challenge, we developed a generic framework that interrogates public RNA-seq data at the transcript level to differentiate functions for alternatively spliced isoforms. For a specific function, our algorithm identifies the ‘responsible’ isoform(s) of a gene and generates classifying models at the isoform level instead of at the gene level. Through cross-validation, we demonstrated that our algorithm is effective in assigning functions to genes, especially the ones with multiple isoforms, and robust to gene expression levels and removal of homologous gene pairs. We identified genes in the mouse whose isoforms are predicted to have disparate functionalities and experimentally validated the ‘responsible’ isoforms using data from mammary tissue. With protein structure modeling and experimental evidence, we further validated the predicted isoform functional differences for the genes Cdkn2a and Anxa6. Our generic framework is the first to predict and differentiate functions for alternatively spliced isoforms, instead of genes, using genomic data. It is extendable to any base machine learner and other species with alternatively spliced isoforms, and shifts the current gene-centered function prediction to isoform-level predictions.
Respiratory Depression after Epidural Morphine—An Experimental and Clinical Study

This study was comprised of an experimental part (20 volunteers) and a clinical part (10 surgical patients). In the experimental part, the effects of either 2-, 4-, or 10-mg doses of epidural morphine on ventilatory responses to a standardized CO2 challenge were studied in healthy volunteers. In the clinical part, ventilatory responses to CO2 were evaluated in patients receiving 4 mg of epidural morphine for pain relief after gall bladder surgery. Naloxone infusion was given to five volunteers to determine whether ventilatory changes due to epidural morphine could be prevented. Using a nonrebreathing method, end-tidal Pco2 (PETCO2) and minute ventilation (tidal volume × frequency) were measured before and 1, 5, 8, 13, and 22 hr after epidural morphine injection. Ventilation was stimulated by 4% CO2 in 21 % O2 and 75% N2. In the experimental study, a dose-related depression of ventilatory drive was seen after epidural morphine. After 2− and 4-mg doses, increases in PETCO2 were present up to 5 hr after injection with a corresponding reduction in minute ventilation. Ten mg of epidural morphine was followed by a significant reduction in minute ventilation and an increase in PETco2 that started 1 hr after injection, peaked at 5 hr, and then remained almost unchanged for the next 17 hr. PETco2 was higher and remained elevated longer in surgical patients than in volunteers given the same amount of epidural morphine (4 mg). Naloxone infusion (5 μg·kg−1·hr−1), prevented the reduction of minute volume and decreased the elevation of PETco2 due to epidural morphine. After larger doses (10 μg·kg−1·hr−1), minute volume and respiratory frequency were well above control levels, and PETco2 was restored to near control values. Thus infusion of naloxone could prevent the respiratory changes after 4 mg of epidural morphine.
Endocardial and Epicardial Epithelial to Mesenchymal Transitions in Heart Development and Disease

Epithelial to mesenchymal transition (EMT) converts epithelial cells to mobile and developmentally plastic mesenchymal cells. All cells in the heart arise from one or more EMTs. Endocardial and epicardial EMTs produce most of the noncardiomyocyte lineages of the mature heart. Endocardial EMT generates valve progenitor cells and is necessary for formation of the cardiac valves and for complete cardiac septation. Epicardial EMT is required for myocardial growth and coronary vessel formation, and it generates cardiac fibroblasts, vascular smooth muscle cells, a subset of coronary endothelial cells, and possibly a subset of cardiomyocytes. Emerging studies suggest that these developmental mechanisms are redeployed in adult heart valve disease, in cardiac fibrosis, and in myocardial responses to ischemic injury. Redirection and amplification of disease-related EMTs offer potential new therapeutic strategies and approaches for treatment of heart disease. Here, we review the role and molecular regulation of endocardial and epicardial EMT in fetal heart development, and we summarize key literature implicating reactivation of endocardial and epicardial EMT in adult heart disease.
NRF2 Regulates PINK1 Expression under Oxidative Stress Conditions

Mutations of the PTEN-induced putative kinase 1 (PINK1) gene are a cause of autosomal recessive forms of Parkinson’s disease. Recent studies have revealed that PINK1 is an essential factor for controlling mitochondrial quality, and that it protects cells from oxidative stresses. Although there has been considerable progress in the elucidation of various aspects of PINK1 protein regulation such as activation, stability and degradation, the transcriptional regulation of PINK1 mRNA under stress conditions remains unclear. In this study, we found that nuclear factor (erythroid-derived 2)-like 2 (NRF2), an antioxidant transcription factor, regulates PINK1 expression under oxidative stress conditions. Damaged mitochondria arising from stress conditions induced NRF2-dependent transcription of the PINK1 gene through production of reactive oxygen species (ROS). Either an ROS scavenger or forced expression of KEAP1, a potent inhibitory partner to NRF2, restricted PINK1 expression induced by activated NRF2. Transcriptionally up-regulated PINK1 diminished oxidative stress-associated cell death. The results indicate that PINK1 expression is positively regulated by NRF2 and that the NRF2-PINK1 signaling axis is deeply involved in cell survival.
The attack on universal health coverage in Europe: recession, austerity and unmet needs

More than 1.5 million extra people have unmet need for healthcare since the beginning of the economic crisis in Europe. The advent of the Great Recession has placed Europe’s health systems under severe pressure, with real terms cuts to funding in many countries.1 Accounts in the peer-reviewed literature and popular media have catalogued examples of vulnerable groups and individuals unable to access necessary care.2 Although there have been case-studies of Spain, Greece and other individual nations,3 to our knowledge there has been no systematic attempt to quantify changes in unmet need for medical care across the European Union. Here, using data from the EU-wide Statistics of Income and Living Conditions (EU-SILC), we quantify the increase in self-reported unmet need, a comparative measure of healthcare access defined as being unable to obtain care when people believed it to be medically necessary, in association with the Great Recession.4 From 2005 to 2008, prior to the Great Recession, the proportion of the EU population (a population-weighted average of individual national figures) reporting unmet need was falling, as shown in the figure 1. Between 2005 and 2008 self-reported unmet medical need fell by 2% points, from 5 to 3.1%. Then, coinciding with the onset of the recession in 2008, this trend reversed, to …
Thermodynamic analysis of selective reduction of nickeliferous limonitic laterite ore by carbon monoxide

The nickel sulphide ore deposits are becoming more expensive to mine, and increasing attention is being paid to the recovery of the nickel from the nickeliferous laterite ore deposits. In contrast to the sulphide ores, these oxide ores cannot be beneficiated by flotation or other conventional mineral processing techniques. One potential concentrating method would be the solid state pyrometallurgical reduction of the ore followed by upgrading using magnetic separation. In this research, a thermodynamic model has been developed in order to investigate the solid state reduction of a nickeliferous limonitic laterite ore by carbon monoxide. The objective was to recover all of the nickel as a high grade ferronickel and convert the goethite (FeO·OH) to wüstite (FeO), so that the ferronickel could be recovered by subsequent magnetic separation. For the calcined ore, at the stoichiometric carbon monoxide/ore ratio of 0.558 kmol/100 kg, nickel recoveries of ∼98% and nickel grades of ∼65% were possible at an optimum reduction temperature of 660°C. The results showed that the nickel recovery and the grade of the ferronickel depended on the reduction temperature and the reductant/ore ratio. For the uncalcined ore, the recoveries were slightly lower and the grades slightly higher due to the increased oxidation potential.