Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphodiesterase-5 Is Elevated in Failing Single Ventricle Myocardium and Affects Cardiomyocyte Remodeling In Vitro

Background Single ventricle (SV) congenital heart disease is fatal without intervention, and eventual heart failure is a major cause of morbidity and mortality. Although there are no proven medical therapies for the treatment or prevention of heart failure in the SV heart disease population, phosphodiesterase-5 inhibitors (PDE5i), such as sildenafil, are increasingly used. Although the pulmonary vasculature is the primary target of PDE5i therapy in patients with SV heart disease, the effects of PDE5i on the SV heart disease myocardium remain largely unknown. We sought to determine PDE5 expression and activity in the single right ventricle of SV heart disease patients relative to nonfailing controls and to determine whether PDE5 impacts cardiomyocyte remodeling using a novel serum-based in vitro model. Methods and Results PDE5 expression (n=9 nonfailing; n=7 SV heart disease), activity (n=8 nonfailing; n=9 SV heart disease), and localization (n=3 SV heart disease) were determined in explanted human right ventricle myocardium. PDE5 is expressed in SV heart disease cardiomyocytes, and PDE5 protein expression and activity are increased in SV heart disease right ventricle compared with nonfailing right ventricle. Isolated neonatal rat ventricular myocytes were treated for 72 hours with nonfailing or SV heart disease patient serum±sildenafil. Reverse transcription quantitative polymerase chain reaction (n=5 nonfailing; n=12 SV heart disease) and RNA sequencing (n=3 nonfailing; n=3 SV heart disease) were performed on serum-treated neonatal rat ventricular myocytes and demonstrated that treatment with SV heart disease sera results in pathological gene expression changes that are attenuated with PDE5i. Conclusions PDE5 is increased in failing SV heart disease myocardium, and pathological gene expression changes in SV heart disease serum-treated neonatal rat ventricular myocytes are abrogated by PDE5i. These results suggest that PDE5 represents an intriguing myocardial therapeutic target in this population.
Epidemiology, clinical presentation and respiratory sequelae of adenovirus pneumonia in children in Kuala Lumpur, Malaysia

Objectives To describe the severity, human adenovirus (HAdV) type and respiratory morbidity following adenovirus pneumonia in children. Methodology Retrospective review of children under 12 years of age, admitted with HAdV pneumonia, between January 2011 and July 2013, in a single centre in Malaysia. HAdV isolated from nasopharyngeal secretions were typed by sequencing hypervariable regions 1–6 of the hexon gene. Patients were reviewed for respiratory complications. Results HAdV was detected in 131 children of whom 92 fulfilled inclusion criteria. Median (range) age was 1.1 (0.1–8.0) years with 80% under 2 years. Twenty percent had severe disease with a case-fatality rate of 5.4%. Duration of admission (p = 0.02) was independently associated with severe illness. Twenty-two percent developed respiratory complications, the commonest being bronchiolitis obliterans (15.2%) and recurrent wheeze (5.4%). The predominant type shifted from HAdV1 and HAdV3 in 2011 to HAdV7 in 2013. The commonest types identified were types 7 (54.4%), 1(17.7%) and 3 (12.6%). Four out of the five patients who died were positive for HAdV7. Infection with type 7 (OR 8.90, 95% CI 1.32, 59.89), family history of asthma (OR 14.80, 95% CI 2.12–103.21) and need for invasive or non-invasive ventilation (OR 151.84, 95% CI 9.93–2.32E) were independent predictors of respiratory complications. Conclusions One in five children admitted with HAdV pneumonia had severe disease and 22% developed respiratory complications. Type 7 was commonly isolated in children with severe disease. Family history of asthma need for invasive or non-invasive ventilation and HAdV 7 were independent predictors of respiratory complications.
Worst outcomes according to RAS mutation variants: an analysis in patients with metastatic colorectal adenocarcinoma.

PURPOSE Over 50% of metastatic colorectal cancers harbor RAS mutations. It is unclear if different mutation variants have an impact on survival. The purpose of this study was to evaluate the impact of these mutations on colorectal cancer survival. METHODS The charts of all cases of metastatic colorectal cancer diagnosed between January 2005 and January 2016 in a tertiary hospital in Brazil were reviewed. Inclusion criteria were complete data on clinical staging, treatments received and all-RAS testing. Multivariate Cox proportional survival models were used to evaluate the impact of specific RAS variants on survival. RESULTS There were 151 eligible patients and 61.6% had RAS alterations, the most common G12D (11.9%) and G12A (8.6%). Most patients received chemotherapy, including oxaliplatin (79%), irinotecan (53%) and bevacizumab (59%). Among RAS-wild type patients, 46% received anti-EGFR therapy. Median survival was 39.2 months for RAS-wildtype, 18.8 months for RAS G12A and 34.6 for other RASmutant patients (multivariate analysis for G12A vs RASwild type HR 1.94; 95% CI 0.83-5.51; p=0.12). CONCLUSION Patients with metastatic colorectal cancer who have RAS mutations have shorter overall survival. Regarding the impact of specific KRAS alterations, G12A mutations have a worse prognosis.
Imaging the Effects of &bgr;-Hydroxybutyrate on Peri-Infarct Neurovascular Function and Metabolism

Background and Purpose— Recent evidence suggests great potential of metabolically targeted interventions for treating neurological disorders. We investigated the use of the endogenous ketone body &bgr;-hydroxybutyrate (BHB) as an alternate metabolic substrate for the brain in the acute phase of ischemia because postischemic hyperglycemia and brain glucose metabolism elevation compromise functional recovery. Methods— We delivered BHB (or vehicle) 1 hour after ischemic insult induced by cortical microinjection of endothelin-1 in sensorimotor cortex of rats. Two days after ischemic insult, the rats underwent multimodal characterization of the BHB effects. We examined glucose uptake on 2-Deoxy-D-glucose chemical exchange saturation transfer magnetic resonance imaging, cerebral hemodynamics on continuous arterial spin labeling magnetic resonance imaging, resting-state field potentials by intracerebral multielectrode arrays, Neurological Deficit Score, reactive oxygen species production, and astrogliosis and neuronal death. Results— When compared with vehicle-administered animals, BHB-treated cohort showed decreased peri-infarct neuronal glucose uptake which was associated with reduced oxidative stress, diminished astrogliosis and neuronal death. Functional examination revealed ameliorated neuronal functioning, normalized perilesional resting perfusion, and ameliorated cerebrovascular reactivity to hypercapnia, suggesting improved functioning. Cellular and functional recovery of the neurogliovascular unit in the BHB-treated animals was associated with improved performance on the withdrawal test. Conclusions— We characterize the effects of the ketone body BHB administration at cellular and system levels after focal cortical stroke. The results demonstrate that BHB curbs the peri-infarct glucose-metabolism driven production of reactive oxygen species and astrogliosis, culminating in improved neurogliovascular and functional recovery.
Older Adult Internet Use and eHealth Literacy

We examine Internet use and eHealth literacy among older adults (aged 55+ years) who were patients at clinics serving low-income populations. Participants included 200 minority and White adults who completed interviews based on a technology acceptance conceptual model. A total of 106 participants (53.0%) used the Internet; utilization was associated with personal characteristics (age, ethnicity, education, poverty), computer characteristics (number of e-devices, computer stress), social support (marital status), and health knowledge and attitudes (health literacy, medical decision making, health information sources), but not health status. Of the 106 participants who used the Internet, 52 (49.1%) had high eHealth literacy; eHealth literacy was associated with computer characteristics (number of e-devices, computer stress), and health knowledge and attitudes (medical decision making, health information sources). In multivariate analysis, computer stress maintained a significant inverse association with eHealth literacy. Educational interventions to help older adults successfully use technology and improve eHealth literacy must be identified.
MARVEL: Enabling Mobile Augmented Reality with Low Energy and Low Latency

This paper presents MARVEL, a mobile augmented reality (MAR) system which provides a notation display service with imperceptible latency (<100 ms) and low energy consumption on regular mobile devices. In contrast to conventional MAR systems, which recognize objects using image-based computations performed in the cloud, MARVEL mainly utilizes a mobile device's local inertial sensors for recognizing and tracking multiple objects, while computing local optical flow and offloading images only when necessary. We propose a system architecture which uses local inertial tracking, local optical flow, and visual tracking in the cloud synergistically. On top of that, we investigate how to minimize the overhead for image computation and offloading. We have implemented and deployed a holistic prototype system in a commercial building and evaluate MARVEL's performance. The efficient use of a mobile device's capabilities lowers latency and energy consumption without sacrificing accuracy.
In-season eccentric-overload training in elite soccer players: Effects on body composition, strength and sprint performance

The aim of this study was to describe the changes in body composition, strength and sprint performance in response to an entire competitive season of football training supplemented with 2 inertial eccentric-overload training sessions a week in young male professional soccer players. Whole body and regional composition (assessed using dual-energy X-ray absorptiometry), power output in half-squat and 40-m sprinting performance were evaluated in fourteen players. The eccentric-overload training consisted of training sessions a week of 1–2 sets of 10 exercises of upper-body and core (Day 1) and lower-body (Day 2), during the entire competitive season (27 weeks). Whole body fat mass decreased (-6.3 ± 3.6%, ES = -0.99 ± 0.54) substantially while lean mass increased (2.5 ± 0.8%, ES = 0.25 ± 0.09), with some regional differences. There was a substantial increase in half-squat power output (from 3% to 14%, ES from 0.45 to 1.73) and sprint performance (from 1.1% to 1.8%, ES from -0.33 to -0.44), however performance changes were not correlated with changes in body composition. A combined soccer and eccentric-overload training program was able to promote positive changes in body composition and physical factors relevant to both on-field performance and injury prevention in elite soccer players.
Irritable Bowel Syndrome and Depression: A Shared Pathogenesis

It is common knowledge that dysfunction of the immune and neuroendocrine systems, in addition to neuroplasticity, is among the pathways that underlie irritable bowel syndrome (IBS) and depression. From as early as the 1950s, the association of IBS with psychiatric disease was postulated; however, the exact mechanism remains elusive. There has been considerable research into the association of IBS and depression over the last years; research into the gut-brain axis and alterations in gut microbes have gained momentum to spell out the relationship between depression and IBS. Evidence from these researchers indicate the dysfunction of homeostatic coping mechanisms; corticotropin-releasing factor appears to be at the core of this dysfunction. The multifactorial etiology of both depression and IBS hinders a universal, one-strategy-fits-all treatment approach to patients with comorbid depression and IBS. This review analyzes the pathophysiology that associates these two conditions; it explores the bidirectional communication between the brain and the gastrointestinal tract, and how these influence the endocrine and immune systems. Review articles, clinical trials and randomized controlled trials that analyzed the association of depression and IBS were identified by searching PubMed, Google Scholar, and articles in PMC databases. Full texts written in English and available via these search engines were selected for the synthesis of this review. Alterations to the gut-brain axis, intestinal microbiota, and the neuro-immune system may be the cornerstone to the association of IBS and depression. This literature review opens alternate therapeutic approaches to comorbid IBS and depression and encourages further research into this topic.
From G2 to G3 Continuity: Continuous Curvature Rate Steering Functions for Sampling-Based Nonholonomic Motion Planning

Motion planning for car-like robots is one of the major challenges in automated driving. It requires to solve a two-point boundary value problem (BVP) in real time while taking into account the nonholonomic constraints of the vehicle and the obstacles in the non-convex environment. This paper introduces Hybrid Curvature Rate (HCR) and Continuous Curvature Rate (CCR) Steer: Two novel steering functions for car-like robots that compute a curvature rate continuous solution of the two-point BVP. Hard constraints on the maximum curvature, maximum curvature rate, and maximum curvature acceleration are satisfied resulting in directly driveable $\mathrm{G^{3}}$ continuous paths. The presented steering functions are bench-marked in terms of computation time and path length against its $\mathrm{G^{1}}$ and $\mathrm{G^{2}}$ continuous counterparts, namely Dubins, Reeds-Shepp, Hybrid Curvature, and Continuous Curvature Steer. It is shown that curvature rate continuity can be achieved with only small computational overhead. The generic motion planner Bidirectional $\mathrm{RRT^{\ast}}$ is finally used to present the effectiveness of HCR and CCR Steer in three challenging automated driving scenarios.
Vision-Based Recognition of Road Regulation for Intelligent Vehicle

In this paper, we present a new framework to detect and recognize entire lanes and symbolic marks on high resolution road images. The first part of the framework utilizes local threshold to overcome the limitations of fixed threshold determination in road marking segmentation. The second part of the framework handles false detections caused by nearby objects on the roads such as vehicles and buildings by re-moving the areas that are not related to road surface using semantic segmentation. It also boosts recognition performance with a cascaded classifier structure that combines CNN for symbolic mark recognition and SVM for lane verification. The proposed lane detection achieves average Fl-score of 0.96 and symbol recognition achieves average Fl-score of 0.91. The proposed method is expected to advance the vehicle industry; with a GPU device, the proposed method can easily be embedded in smart vehicles.
The Epidemiology of Hepatitis D Virus in North Africa: A Systematic Review and Meta-Analysis

Background Hepatitis D virus (HDV) infection has been considered a serious neglected pandemic, particularly in developing countries. The virus causes a more severe disease than mono infection with hepatitis B virus (HBV). The epidemiology of HDV is not well documented in North Africa, which is known to be endemic for HBV. In this study, we explored the prevalence of HDV infection and also attempted to identify factors associated with hepatitis D positive status among chronic hepatitis B patients in North Africa. Methods The electronic databases PubMed, Embase, Scopus, Science Direct, Web of Science, and Google Scholar were comprehensively searched for all papers published between January 1, 1998, and December 31, 2017, using appropriate strategies containing all related keywords, including North Africa, names of countries in the region, and all permutations of hepatitis D virus. The estimated prevalence of HDV in North Africa was calculated as an average of the pooled infection prevalence in each country weighted by the ratio of the country's hepatitis D virus population to the study's sample size in the survey data analysis. Findings A total of 312 studies were identified and 32 were included in this study, with a total sample of 4907 individuals screened for HDV. There was considerable variability in the prevalence estimates of HDV within the countries of the region. The overall prevalence of HDV in the general population of North Africa was 5·01% (95% CI: 1·25–8·27) and in liver disease patients it was 20.7% (95% CI:9.87–44.53). Genotype-1 was the most prominent genotype reported in five published studies. Ten studies reported on HDV RNA in participants who were seropositive for HDV, and four studies highlighted the impact of demographic factors (sex and age). No study showed the impact of risk factors on the prevalence of HDV in North Africa. Interpretation This review provides a comprehensive assessment of the burden of HDV in Northern Africa. There were significant differences in seroprevalence, study population, and diagnostic testing between the countries in the region. The results presented here will alert health professionals to implement clear policies based on evidence to diminish the burden of HDV infection. Such measures may include but are not restricted to improving the laboratory diagnostic tests and initiating patient data registries and blood screening. Further epidemiological and research studies are needed to explore the risk factors, coinfections, and approaches to increase testing for HDV, particularly in high-risk subpopulations, such as intravenous drug users and immigrants, and to define the consequences of HDV infection in North Africa.
Genome-wide Identification, Classification, Molecular Evolution and Expression Analysis of Malate Dehydrogenases in Apple

Malate dehydrogenase plays crucial roles in energy homeostasis, plant development and cold and salt tolerance, as it mediates the reversible conversion of malate to oxaloacetate. However, the evolutionary pattern of MDH genes in apple remains elusive. In this study, a total of 20 MDH genes were identified from the “Golden Delicious” apple draft genome. We revealed the physiological and biochemical properties, gene structure, and conserved motifs of MdMDH genes. Chromosomal localization and Ka/Ks ratio analysis of MdMDH genes revealed different selective pressures acted on duplicated MdMDH genes. Exploration of the phylogenetic relationships revealed six clades and similar frequencies between old and recent duplications, and significant differences in the evolutionary rates of the MDH gene family were observed. One MdMDH gene, MDP0000807458, which was highly expressed during apple fruit development and flower bud differentiation, was under positive selection. Thus, we speculated that MDP0000807458 is a likely candidate gene involved in regulation of flower bud differentiation and organic acid metabolism in apple fruits. This study provides a foundation for improved understanding of the molecular evolution of MdMDH genes and further facilitates the functional analysis of MDP0000807458 to unravel its exact role in flower bud differentiation and organic acid metabolism.
Primary care in Germany: access and utilisation—a cross-sectional study with data from the German Socio-Economic Panel (SOEP)

Objectives (1) To describe the accessibility of general practitioners (GPs) by the German population; (2) to determine factors on individual and area level, such as settlement structure and area deprivation, which are associated with the walking distance to a GP; and (3) to identify factors that may cause differences in the utilisation of any doctors. Design Cross-sectional study using individual survey data from the representative German Socio-Economic Panel (SOEP) linked with area deprivation data from the German Index of Multiple Deprivation for 2010 (GIMD 2010) and official data for settlement structure (urban/rural areas) at district level. Logistic regression models were estimated to determine the relationship of individual and area factors with the distance to a GP. Negative binomial regressions were used to analyse the association with utilisation. Setting Germany. Population n=20 601 respondents from the SOEP survey data 2009. Primary outcome measure Walking distance to a GP. Secondary outcome measure Doctor visits. Results Nearly 70% of the sample lives within a 20 min walk to a GP. People living in the most deprived areas have a 1.4-fold (95% CI 1.3 to 1.6) increased probability of a greater walking distance compared with the least deprived quintile, even after controlling for settlement structure and individual factors. In rural districts, people have a 3.1-fold (95% CI 2.8 to 3.4) higher probability of a greater walking distance compared with those in cities. Both area deprivation and rurality have a negative relationship with the utilisation of physicians, whereas the distance to a GP is not associated with the utilisation of physicians. Conclusion Walking distance to a GP depends on individual and area factors. In Germany, area deprivation is negatively correlated with the accessibility of GPs while controlling for settlement structure and individual factors. Both area factors are negatively associated with the utilisation of doctors. This knowledge could be used for future GP requirement plans.
Peyer’s patch myeloid cells infection by Listeria signals through gp38+ stromal cells and locks intestinal villus invasion

The foodborne pathogen Listeria monocytogenes (Lm) crosses the intestinal villus epithelium via goblet cells (GCs) upon the interaction of Lm surface protein InlA with its receptor E-cadherin. Here, we show that Lm infection accelerates intestinal villus epithelium renewal while decreasing the number of GCs expressing luminally accessible E-cadherin, thereby locking Lm portal of entry. This novel innate immune response to an enteropathogen is triggered by the infection of Peyer’s patch CX3CR1+ cells and the ensuing production of IL-23. It requires STAT3 phosphorylation in epithelial cells in response to IL-22 and IL-11 expressed by lamina propria gp38+ stromal cells. Lm-induced IFN-&ggr; signaling and STAT1 phosphorylation in epithelial cells is also critical for Lm-associated intestinal epithelium response. GC depletion also leads to a decrease in colon mucus barrier thickness, thereby increasing host susceptibility to colitis. This study unveils a novel innate immune response to an enteropathogen, which implicates gp38+ stromal cells and locks intestinal villus invasion, but favors colitis.
Reversible Recurrent Neural Networks

Recurrent neural networks (RNNs) provide state-of-the-art performance in processing sequential data but are memory intensive to train, limiting the flexibility of RNN models which can be trained. Reversible RNNs---RNNs for which the hidden-to-hidden transition can be reversed---offer a path to reduce the memory requirements of training, as hidden states need not be stored and instead can be recomputed during backpropagation. We first show that perfectly reversible RNNs, which require no storage of the hidden activations, are fundamentally limited because they cannot forget information from their hidden state. We then provide a scheme for storing a small number of bits in order to allow perfect reversal with forgetting. Our method achieves comparable performance to traditional models while reducing the activation memory cost by a factor of 10--15. We extend our technique to attention-based sequence-to-sequence models, where it maintains performance while reducing activation memory cost by a factor of 5--10 in the encoder, and a factor of 10--15 in the decoder.