Miracle-dz/UniFAR-FTUs huggingface dataset:
Association Between ABCB1 Polymorphism and Stable Warfarin Dose Requirements in Brazilian Patients

The ideal dose of the oral anticoagulant warfarin varies widely among patients, mainly due to genetic factors. Genetic variations that impact warfarin pharmacokinetics and the vitamin K cycle are plausible candidates for being associated with warfarin dose requirements. Therefore, the aim of this study was to assess whether polymorphisms in the ABCB1 and CYP4F2 genes were associated with stable warfarin dose requirements in Brazilian patients. This retrospective study included samples from 309 individuals. Genotyping of ABCB1 c.3435C>T and CYP4F2 c.1297G>A were performed by polymerase chain reaction followed by melting curve analysis (HRM-PCR) and TaqMan® genotyping assay, respectively. Stable doses were adjusted in a linear multiple regression model for age, gender, body mass index, self-reported race, use of amiodarone, CYP2C9 (*2 and *3), VKORC1 c.1639G>A, and ABCB1 c.3435C>T or CYP4F2 c.1297G>A. By performing a univariate analysis of variance, we found that the warfarin patients who carry ABCB1 c.3435T variant alleles (CT and TT genotypes) need fewer warfarin stable doses in comparison with the individuals that are CC wild-type: 2.5 (p = 0.003) and 4.3 (p < 0.001) mg/week less, respectively, for the overall group of patients on stable anticoagulation therapeutics (n = 309); and 5.5 (p = 0.006) and 10.2 (p < 0.001) mg/week less, respectively, for the self-declared non-white stable subgroup (n = 76). No statistically significant differences in dose requirements were observed according to CYP4F2 genotypes. In conclusion, our results suggest ABCB1 c.3435C>T variant may influence warfarin dose requirements in Brazilian patients, when associated with other genotypic, demographic and clinical factors.
Sensor Fault Tolerance Enhancement of DFIG-WTs via Perturbation Observer-Based DPC and Two-Stage Kalman Filters

This paper presents a sensor fault-tolerant control (SFTC) strategy, combining perturbation observer-based direct power control (PODPC) and two-stage Kalman filter (TSKF) to enhance the fault tolerance of a doubly fed induction generator-based wind turbine (DFIG-WT) subject to rotor and stator current sensor faults. In the PODPC scheme, the interactions between active and reactive power control loops are represented by newly introduced perturbation states, and the feedback linearization control is realized with the state estimations derived from perturbation observers to achieve the decoupled power control. No rotor current sensors nor parameters of DFIG-WT are required in the implementation of PODPC. Stator current TSKFs are designed to generate residuals for fault detection and isolation, and provide current estimations to replace the faulty current measurements for system reconfiguration under stator current sensor faults. Simulation studies undertaken on a grid-connected DFIG-WT system reveal that the proposed SFTC strategy is immune to rotor current sensor faults, and it provides strong fault tolerance to stator current sensor faults.
PheProb: probabilistic phenotyping using diagnosis codes to improve power for genetic association studies

Objective Standard approaches for large scale phenotypic screens using electronic health record (EHR) data apply thresholds, such as ≥2 diagnosis codes, to define subjects as having a phenotype. However, the variation in the accuracy of diagnosis codes can impair the power of such screens. Our objective was to develop and evaluate an approach which converts diagnosis codes into a probability of a phenotype (PheProb). We hypothesized that this alternate approach for defining phenotypes would improve power for genetic association studies. Methods The PheProb approach employs unsupervised clustering to separate patients into 2 groups based on diagnosis codes. Subjects are assigned a probability of having the phenotype based on the number of diagnosis codes. This approach was developed using simulated EHR data and tested in a real world EHR cohort. In the latter, we tested the association between low density lipoprotein cholesterol (LDL-C) genetic risk alleles known for association with hyperlipidemia and hyperlipidemia codes (ICD-9 272.x). PheProb and thresholding approaches were compared. Results Among n = 1462 subjects in the real world EHR cohort, the threshold-based p-values for association between the genetic risk score (GRS) and hyperlipidemia were 0.126 (≥1 code), 0.123 (≥2 codes), and 0.142 (≥3 codes). The PheProb approach produced the expected significant association between the GRS and hyperlipidemia: p = . 001. Conclusions PheProb improves statistical power for association studies relative to standard thresholding approaches by leveraging information about the phenotype in the billing code counts. The PheProb approach has direct applications where efficient approaches are required, such as in Phenome-Wide Association Studies.
Repairing Crashes in Android Apps

Android apps are omnipresent, and frequently suffer from crashes — leading to poor user experience and economic loss. Past work focused on automated test generation to detect crashes in Android apps. However, automated repair of crashes has not been studied. In this paper, we propose the first approach to automatically repair Android apps, specifically we propose a technique for fixing crashes in Android apps. Unlike most test-based repair approaches, we do not need a test-suite; instead a single failing test is meticulously analyzed for crash locations and reasons behind these crashes. Our approach hinges on a careful empirical study which seeks to establish common root-causes for crashes in Android apps, and then distills the remedy of these root-causes in the form of eight generic transformation operators. These operators are applied using a search-based repair framework embodied in our repair tool Droix. We also prepare a benchmark DroixBench capturing reproducible crashes in Android apps. Our evaluation of Droix on DroixBench reveals that the automatically produced patches are often syntactically identical to the human patch, and on some rare occasion even better than the human patch (in terms of avoiding regressions). These results confirm our intuition that our proposed transformations form a sufficient set of operators to patch crashes in Android.
Density-functional calculations of defect formation energies using supercell methods: Defects in diamond

Density-functional theory combined with periodic boundary conditions is used to systematically study the dependence of defect formation energy on supercell size for diamond containing vacancy and self-interstitial defects. We investigate the effect of the electrostatic energy due to the neutralization of charged supercells and the effect of the alignment of the valence band maximum sVBMd on the formation energy. For negatively charged vacancies and positively charged interstitials, the formation energies show a clear dependence on supercell size, and the electrostatic corrections agree with the trend given by the Makov-Payne scheme sRef. 28d. For positively charged vacancies and negatively charged interstitials, the size dependence and the electrostatic corrections are quite weak. An analysis of the spatial charge density distributions reveals that these large variations in electrostatic terms with defect type originate from differences in the screening of the defect-localized charge, as explained by using a simple electron-gas model. Several VBM alignment schemes are also tested. The best agreement between the calculated and asymptotically exact ionization levels is obtained when the levels are based on the formation energies referenced to the VBM of the defect-containing supercell.
The Impact of Nutrition and Health Claims on Consumer Perceptions and Portion Size Selection: Results from a Nationally Representative Survey

Nutrition and health claims on foods can help consumers make healthier food choices. However, claims may have a ‘halo’ effect, influencing consumer perceptions of foods and increasing consumption. Evidence for these effects are typically demonstrated in experiments with small samples, limiting generalisability. The current study aimed to overcome this limitation through the use of a nationally representative survey. In a cross-sectional survey of 1039 adults across the island of Ireland, respondents were presented with three different claims (nutrition claim = “Low in fat”; health claim = “With plant sterols. Proven to lower cholesterol”; satiety claim = “Fuller for longer”) on four different foods (cereal, soup, lasagne, and yoghurt). Participants answered questions on perceived healthiness, tastiness, and fillingness of the products with different claims and also selected a portion size they would consume. Claims influenced fillingness perceptions of some of the foods. However, there was little influence of claims on tastiness or healthiness perceptions or the portion size selected. Psychological factors such as consumers’ familiarity with foods carrying claims and belief in the claims were the most consistent predictors of perceptions and portion size selection. Future research should identify additional consumer factors that may moderate the relationships between claims, perceptions, and consumption.
Regulation of the heat shock transcription factor Hsf1 in fungi: implications for temperature-dependent virulence traits

The impact of fungal pathogens on human health is devastating. For fungi and other pathogens, a key determinant of virulence is the capacity to thrive at host temperatures, with elevated temperature in the form of fever as a ubiquitous host response to defend against infection. A prominent feature of cells experiencing heat stress is the increased expression of heat shock proteins (Hsps) that play pivotal roles in the refolding of misfolded proteins in order to restore cellular homeostasis. Transcriptional activation of this heat shock response is orchestrated by the essential heat shock transcription factor, Hsf1. Although the influence of Hsf1 on cellular stress responses has been studied for decades, many aspects of its regulation and function remain largely enigmatic. In this review, we highlight our current understanding of how Hsf1 is regulated and activated in the model yeast Saccharomyces cerevisiae, and highlight exciting recent discoveries related to its diverse functions under both basal and stress conditions. Given that thermal adaption is a fundamental requirement for growth and virulence in fungal pathogens, we also compare and contrast Hsf1 activation and function in other fungal species with an emphasis on its role as a critical regulator of virulence traits.
Learning to cope with mirror movements in unilateral spastic cerebral palsy: a brief report

ABSTRACT Purpose: Mirror movements (MM) in unilateral spastic cerebral palsy (USCP) interfere with many bimanual activities of daily living. Methods: Here, we developed a specific bimanual therapeutic regimen, focusing on asymmetric simultaneous movements of the two hands. Twelve children (6-17 years old; complete data available in ten children) with USCP and MM were included. Results: After three weeks of inpatient rehabilitation, we observed significant improvements for two self-defined bimanual goal activities (Goal Attainment Scaling, Canadian Occupational Performance Measure) and for bimanual performance in general (Assisting Hand Assessment). These improvements were still present 6 months later. In contrast, even immediately after therapy, the severity of MM had not changed. Conclusions: Hence, targeted bimanual therapy improved bimanual performance, but did not lead to a reduction of MM. The results of this pilot study might suggest that children with MM benefit more from acquiring strategies to cope with MM than by an active training which aimed to reduce MM.
Joint Detection and Localization of an Unknown Number of Sources Using the Algebraic Structure of the Noise Subspace

Source localization and spectral estimation are among the most fundamental problems in statistical and array signal processing. Methods that rely on the orthogonality of the signal and noise subspaces, such as Pisarenko's method, MUSIC, and root-MUSIC, are some of the most widely used algorithms to solve these problems. As a common feature, these methods require both a priori knowledge of the number of sources and an estimate of the noise subspace. Both requirements are complicating factors to the practical implementation of the algorithms and, when not satisfied exactly, can potentially lead to severe errors. In this paper, we propose a new localization criterion based on the algebraic structure of the noise subspace that is described for the first time to the best of our knowledge. Using this criterion and the relationship between the source localization problem and the problem of computing the greatest common divisor (GCD), or more practically approximate GCD, for polynomials, we propose two algorithms, which adaptively learn the number of sources and estimate their locations. Simulation results show a significant improvement over root-MUSIC in challenging scenarios such as closely located sources, both in terms of detection of the number of sources and their localization over a broad and practical range of signal-to-noise ratios. Furthermore, no performance sacrifice in simple scenarios is observed.
MicroRNAs as potential regulators of platelet function and bleeding diatheses

Abstract Although a growing number of studies suggest that microRNAs (miRNAs) play a relevant role in platelet biology, their implications in bleeding diatheses are starting to be investigated. Indeed, several studies have shown that alterations in the intracellular levels of highly expressed platelet miRNAs provoke a thrombotic phenotype. On the other hand, primary immune thrombocytopenia (ITP), which is considered the hallmark of acquired bleeding disorders, has been recently associated with altered levels of miRNAs in peripheral blood mononuclear cells, plasma, and platelets. In this review, we will focus on miRNAs that may affect the hemostatic and thrombotic functions of platelets, and we will discuss the different studies that have attempted to associate miRNAs with regulatory mechanisms of ITP.
Training Effects of Alternated and Pulsed Currents on the Quadriceps Muscles of Athletes

Abstract The aim of the study was to evaluate the effects of 6 weeks training with different neuromuscular electrical stimulation (NMES) currents (medium alternated and low-frequency pulsed current) on muscle architecture and neuromuscular performance of competitive athletes. A double-blind controlled and randomized experimental study was carried out with 33 athletes (22.2±2.6 yrs, 74.7±9.8 kg, 176.8±6.0 cm), divided into 3 groups: mid-frequency current (MF, n=12), pulsed current (PC, n=11) and the control group (CG, n=10). Quadriceps maximal voluntary peak torque (PT) and corresponding vastus lateralis electromyographic activity, evoked torque (PT-NMES), vastus lateralis muscle thickness, fascicle length, pennation angle, and level of discomfort were assessed before and after the interventions. NMES training was performed 3 times per week and consisted of 18 sessions, 15 min/session, 6 s duration in each contraction interspersed with 18 s rest. After the training period, muscle thickness increased in the MF and PC groups (p<0.05). PT-NMES increased only in the PC group (p<0.05). All currents produced similar levels of discomfort (p>0.05). Quadriceps NMES training applied through alternated or pulsed currents produced similar effects in architecture and neuromuscular performance in competitive athletes.
Morphological Proximity Priors: Spatial Relationships for Semantic Segmentation

The introduction of prior knowledge into image analysis algorithms is a central challenge in computer vision. In this paper, we introduce the concept of proximity priors into semantic segmentation methods in order to penalize the proximity of certain object classes. Proximity priors are a generalization of purely global and purely local co-occurrence priors which have been introduced recently. The key idea is to consider pixels as adjacent if they are within a specified neighborhood of arbitrary size and shape. Respective penalties for the adjacency of various label pairs (the labels ’sheep’ and ’lion’ for example) can be learned statistically from a set of segmented images. We propose a variational approach which integrates morphological operators and derive an exact convex relaxation which can be minimized globally. Extensive numerical validations on an established semantic segmentation benchmark demonstrate that the proposed proximity priors compare favorably to existing approaches.
Pallister‐Killian syndrome: Review of fetal phenotype

Pallister‐Killian syndrome is a multi‐system sporadic disorder with developmental delay. It is a rare chromosomal abnormality involving supernumerary isochormosome 12p. The disorder exhibits tissue specific mosaicism. The first prenatal diagnosis of PKS was reported in 1985 after ultrasound detection of fetal anomalies. Since this observation, there have been about 62 reports of fetuses with PKS. In this review, we cover the prenatal aspects of PKS.
PA0833 Is an OmpA C-Like Protein That Confers Protection Against Pseudomonas aeruginosa Infection

Pseudomonas aeruginosa is a formidable pathogen that causes infections with high mortality rates. Because of its ability to form biofilms and rapidly acquire resistance to many first-line antibiotics, P. aeruginosa-related infections are typically difficult to cure by traditional antibiotic treatment regimes. Thus, new strategies to prevent and treat such infections are urgently required. PA0833 is a newly identified protective antigen of P. aeruginosa that was identified in a screen using a reverse vaccine strategy in our laboratory. In this study, we further confirmed its protective efficacy in murine sepsis and pneumonia models. Immunization with PA0833 induced strong immune responses and resulted in reduced bacterial loads; decreased pathology, inflammatory cytokine expression and inflammatory cell infiltration; and improved survival. Furthermore, PA0833 was identified as an OmpA C-like protein by bioinformatics analysis and biochemical characterization and shown to contribute to bacterial environmental stress resistance and virulence. These results demonstrate that PA0833 is an OmpA C-like protein that induces a protective immune response in mice, indicating that PA0833 is a promising antigen for vaccine development.
Proximal pulmonary vascular stiffness as a prognostic factor in children with pulmonary arterial hypertension

Aims Main pulmonary artery (MPA) stiffness and abnormal flow haemodynamics in pulmonary arterial hypertension (PAH) are strongly associated with elevated right ventricular (RV) afterload and associated with disease severity and poor clinical outcomes in adults with PAH. However, the long-term effects of MPA stiffness on RV function in children with PAH remain poorly understood. This study is the first comprehensive evaluation of MPA stiffness in children with PAH, delineating the mechanistic relationship between flow haemodynamics and MPA stiffness as well as the prognostic ability of these measures regarding clinical outcomes. Methods and results Fifty-six children diagnosed with PAH underwent baseline cardiac magnetic resonance (CMR) acquisition and were compared with 23 control subjects. MPA stiffness and wall shear stress (WSS) were evaluated using phase contrast CMR and were evaluated for prognostic potential along with standard RV volumetric and functional indices. Pulse wave velocity (PWV) was significantly increased (2.8 m/s vs. 1.4 m/s, P < 0.0001) and relative area change (RAC) was decreased (25% vs. 37%, P < 0.0001) in the PAH group, correlating with metrics of RV performance. Decreased WSS was associated with a decrease in RAC over time (r = 0.679, P < 0.001). For each unit increase in PWV, there was approximately a 3.2-fold increase in having a moderate clinical event. Conclusion MPA stiffness assessed by non-invasive CMR was increased in children with PAH and correlated with RV performance, suggesting that MPA stiffness is a major contribution to RV dysfunction. PWV is predictive of moderate clinical outcomes, and may be a useful prognostic marker of disease activity in children with PAH.
Frailty, Neurocognitive Impairment, or Both in Predicting Poor Health Outcomes Among Adults Living With Human Immunodeficiency Virus

Background Neurocognitive impairment (NCI) is strongly associated with frailty in people living with human immunodeficiency virus (PLWH); the overlap of frailty and NCI and the impact on health outcomes in PLWH are unknown. Methods PLWH in a longitudinal, observational study of aging completed entry evaluations for frailty and NCI. Outcomes of falls (recurrent) increased limitations in independent activities of daily living (IADL), or mortality were combined. Poisson regression models estimated prevalence ratios (PR) for ≥1 outcome over 2 years. Results Among 987 participants, the median age at entry was 51 years; 19% were female; the median CD4 count was 616 cells/µL; and HIV-1 RNA was <200 copies/mL in 94%. Most (79%) participants had neither frailty nor NCI; 2% had both; 4% frailty only; and 15% NCI only. Over 2 years of observation, 100 (10%) participants experienced recurrent falls; 175 (18%) had worsening IADL limitations; 17 (2%) died; and 254 (26%) experienced ≥1 poor health outcome. In adjusted models, frailty with NCI was associated with more than double the risk of a poor health outcome (PR 2.65; 95% CI 1.98, 3.54); a significant association was also seen with frailty alone (PR 2.26; 95%CI 1.71, 2.99) and NCI alone (PR 1.73; 95% CI 1.36, 2.20). Conclusions The presence of frailty with NCI was associated with a greater risk of falls, disability, or death in PLWH than NCI alone. Interventions that target prevention or reversal of both frailty and NCI (such as increased physical activity) may significantly limit poor health outcomes among PLWH.
Intraindividual Variation of Meiotic Recombination Parameters in Pig Spermatocytes: A Preliminary Study

Meiotic recombination parameters like crossover (CO) rate or synaptonemal complex (SC) length are known to vary strongly between individuals and between cells from the same individual. The origins of this variability remain elusive, and little is known about the variations that might occur between different samples and/or over time within the same individual. To document this question, pachytene cells from 3 boars of the Large White breed were analyzed twice, at a 1-year interval, using immunocytological techniques. CO rate, SC length, and MLH1 inter-foci distances varied significantly between the 3 individuals. CO rate and SC length differed significantly between the 2 sampling periods for 1 individual. However, no significant differences were observed between the 2 samples for CO distribution and inter-foci distances in the 3 boars studied.