Miracle-dz/UniFAR-FTUs huggingface dataset:
Symbolic Execution for Deep Neural Networks

Deep Neural Networks (DNN) are increasingly used in a variety of applications, many of them with substantial safety and security concerns. This paper introduces DeepCheck, a new approach for validating DNNs based on core ideas from program analysis, specifically from symbolic execution. The idea is to translate a DNN into an imperative program, thereby enabling program analysis to assist with DNN validation. A basic translation however creates programs that are very complex to analyze. DeepCheck introduces novel techniques for lightweight symbolic analysis of DNNs and applies them in the context of image classification to address two challenging problems in DNN analysis: 1) identification of important pixels (for attribution and adversarial generation); and 2) creation of 1-pixel and 2-pixel attacks. Experimental results using the MNIST data-set show that DeepCheck's lightweight symbolic analysis provides a valuable tool for DNN validation.
End-to-end Deep Learning from Raw Sensor Data: Atrial Fibrillation Detection using Wearables

We present a convolutional-recurrent neural network architecture with long short-term memory for real-time processing and classification of digital sensor data. The network implicitly performs typical signal processing tasks such as filtering and peak detection, and learns time-resolved embeddings of the input signal. We use a prototype multi-sensor wearable device to collect over 180h of photoplethysmography (PPG) data sampled at 20Hz, of which 36h are during atrial fibrillation (AFib). We use end-to-end learning to achieve state-of-the-art results in detecting AFib from raw PPG data. For classification labels output every 0.8s, we demonstrate an area under ROC curve of 0.9999, with false positive and false negative rates both below $2\times 10^{-3}$. This constitutes a significant improvement on previous results utilising domain-specific feature engineering, such as heart rate extraction, and brings large-scale atrial fibrillation screenings within imminent reach.
Aggressive Pituitary Tumors or Localized Pituitary Carcinomas: Defining Pituitary Tumors

ABSTRACT Pituitary tumors are common and exhibit a wide spectrum of hormonal, proliferative and invasive behaviors. Traditional classifications consider them malignant only when they exhibit metastasis. Patients who suffer morbidity and mortality from aggressive tumors classified as “adenomas” are denied support provided to patients with “cancers” and in many jurisdictions, these tumors are considered curiosities that do not warrant reporting in health registries. We propose use of the term “tumor” rather than “adenoma” to align with other neuroendocrine tumors. The features that can serve as diagnostic, prognostic and predictive markers are reviewed. Clinico-pathological and radiographic classifications provide important information and to date, no single biomarker has been able to offer valuable insight to guide the management of patients with pituitary tumors.
The role of RNA modifications in the regulation of tRNA cleavage

Transfer RNA (tRNA) have been harbingers of many paradigms in RNA biology. They are among the first recognized noncoding RNA (ncRNA) playing fundamental roles in RNA metabolism. Although mainly recognized for their role in decoding mRNA and delivering amino acids to the growing polypeptide chain, tRNA also serve as an abundant source of small ncRNA named tRNA fragments. The functional significance of these fragments is only beginning to be uncovered. Early on, tRNA were recognized as heavily post‐transcriptionally modified, which aids in proper folding and modulates the tRNA:mRNA anticodon–codon interactions. Emerging data suggest that these modifications play critical roles in the generation and activity of tRNA fragments. Modifications can both protect tRNA from cleavage or promote their cleavage. Modifications to individual fragments may be required for their activity. Recent work has shown that some modifications are critical for stem cell development and that failure to deposit certain modifications has profound effects on disease. This review will discuss how tRNA modifications regulate the generation and activity of tRNA fragments.
Stem cell colony interspacing effect on differentiation to neural cells

Efforts to enhance the efficiency of neural differentiation of stem cells are primarily focused on exogenous modulation of physical niche parameters such as surface topography and extracellular matrix proteins, or addition of certain growth factors or small molecules to culture media. We report a novel neurogenic niche to enhance the neural differentiation of embryonic stem cells (ESCs) without any external intervention by micropatterning ESCs into spatially organized colonies of controlled size and interspacing. Using an aqueous two‐phase system cell microprinting technology, we generated pairs of uniformly sized isolated ESC colonies at defined interspacing distances over a layer of differentiation‐inducing stromal cells. Our comprehensive analysis of temporal expression of neural genes and proteins of cells in colony pairs showed that interspacing two colonies at approximately 0.66 times the colony diameter (0.66D) significantly enhanced neural differentiation of ESCs. Cells in these colonies displayed higher expression of neural genes and proteins and formed thick neurite bundles between the two colonies. A computational model of spatial distribution of soluble factors of cells in interspaced colony pairs showed that the enhanced neural differentiation is due to the presence of stable concentration gradients of soluble signalling factors between the two colonies. Our results indicate that culturing ESCs in colony pairs with defined interspacing is a promising approach to efficiently derive neural cells. Additionally, this approach provides a platform for quantitative studies of molecular mechanisms that regulate neurogenesis of stem cells.
Pathway enrichment and protein interaction network analysis for milk yield, fat yield and age at first calving in a Thai multibreed dairy population

Objective This research aimed to determine biological pathways and protein-protein interaction (PPI) networks for 305-d milk yield (MY), 305-d fat yield (FY), and age at first calving (AFC) in the Thai multibreed dairy population. Methods Genotypic information contained 75,776 imputed and actual single nucleotide polymorphisms (SNP) from 2,661 animals. Single-step genomic best linear unbiased predictions were utilized to estimate SNP genetic variances for MY, FY, and AFC. Fixed effects included herd-year-season, breed regression and heterosis regression effects. Random effects were animal additive genetic and residual. Individual SNP explaining at least 0.001% of the genetic variance for each trait were used to identify nearby genes in the National Center for Biotechnology Information database. Pathway enrichment analysis was performed. The PPI of genes were identified and visualized of the PPI network. Results Identified genes were involved in 16 enriched pathways related to MY, FY, and AFC. Most genes had two or more connections with other genes in the PPI network. Genes associated with MY, FY, and AFC based on the biological pathways and PPI were primarily involved in cellular processes. The percent of the genetic variance explained by genes in enriched pathways (303) was 2.63% for MY, 2.59% for FY, and 2.49% for AFC. Genes in the PPI network (265) explained 2.28% of the genetic variance for MY, 2.26% for FY, and 2.12% for AFC. Conclusion These sets of SNP associated with genes in the set enriched pathways and the PPI network could be used as genomic selection targets in the Thai multibreed dairy population. This study should be continued both in this and other populations subject to a variety of environmental conditions because predicted SNP values will likely differ across populations subject to different environmental conditions and changes over time.
Greening Cloud-Enabled Big Data Storage Forensics: Syncany as a Case Study

The pervasive nature of cloud-enabled big data storage solutions introduces new challenges in the identification, collection, analysis, preservation, and archiving of digital evidences. Investigation of such complex platforms to locate and recover traces of criminal activities is a time-consuming process. Hence, cyber forensics researchers are moving towards streamlining the investigation process by locating and documenting residual artefacts (evidences) of forensic value of users’ activities on cloud-enabled big data platforms in order to reduce the investigation time and resources involved in a real-world investigation. In this paper, we seek to determine the data remnants of forensic value from Syncany private cloud storage service, a popular storage engine for big data platforms. We demonstrate the types and the locations of the artifacts that can be forensically recovered. Findings from this research contribute to an in-depth understanding of cloud-enabled big data storage forensics, which can result in reduced time and resources spent in real-world investigations involving Syncany-based cloud platforms.
Obesity and energy balance: What is the role of physical activity?

ABSTRACT Introduction: Despite billions of dollars spent over decades of research, debate remains over the causes and solutions of the obesity epidemic. The specific role of physical activity in the prevention or treatment of obesity seems a particularly contentious issue, with opposing views put forth in both academic and popular media. In an attempt to provide context and clarity to the specific question of the role of physical activity in determination of body weight, we have attempted to identify evidence or lack thereof in the scientific literature and provide a summary of our findings. Areas covered: Topics included in this narrative review are an overview of energy balance, the relationship between physical activity and energy expenditure, compensatory responses in non-exercise energy expenditure and energy intake, and the relationship between physical activity and obesity. Expert commentary: Based on a review of the existing literature, daily physical activity and structured exercise has beneficial effects on an individual’s body weight. In most instances, exercise occurring in adequate amounts will increase total daily energy expenditure and create an acute energy deficit, without compensatory decreases in non-exercise physical activity or energy expenditure nor compensatory increases in energy intake. Several gaps in the literature exist, both in terms of the number of adequately powered clinical trials with rigorous assessments of both energy intake and expenditure, and with a variety of study populations (by age, sex, race, etc.) and with varying exercise volumes and intensities.
The clinical heterogeneity of Parkinson's disease and its therapeutic implications

Although Parkinson's disease (PD) is primarily a movement disorder, there are a range of associated nonmotor symptoms, including cognitive impairment, depression and sleep disturbance. These can occur throughout the disease course, even predating the motor syndrome. However, both motor and nonmotor symptoms are variable between individual patients. Rate of disease progression is also heterogenous: although 50% have reached key milestones of either postural instability or dementia within 4 years from diagnosis, almost a quarter have a good prognosis at 10 years. In this review we discuss how a range of different factors including clinical features, pathology and genetics, have been used to describe the heterogeneity of PD. We explore the value of longitudinal studies of incident PD cohorts, based on our own experience in Cambridgeshire, to define differences in rates of disease progression and predictors of outcome, including how such studies have informed the development of prognostic models which can be used at an individual patient level. Finally, we discuss the benefits of better understanding the basis of heterogeneity of PD in terms of implications for the development and trialling of more targeted therapies for different subgroups of patients, including regenerative approaches.
In Standing, Corticospinal Excitability Is Proportional to COP Velocity Whereas M1 Excitability Is Participant-Specific

Reductions in the base of support (BOS) make standing difficult and require adjustments in the neural control of sway. In healthy young adults, we determined the effects of reductions in mediolateral (ML) BOS on peroneus longus (PL) motor evoked potential (MEP), intracortical facilitation (ICF), short interval intracortical inhibition (SICI) and long interval intracortical inhibition (LICI) using transcranial magnetic stimulation (TMS). We also examined whether participant-specific neural excitability influences the responses to increasing standing difficulty. Repeated measures ANOVA revealed that with increasing standing difficulty MEP size increased, SICI decreased (both p < 0.05) and ICF trended to decrease (p = 0.07). LICI decreased only in a sub-set of participants, demonstrating atypical facilitation. Spearman’s Rank Correlation showed a relationship of ρ = 0.50 (p = 0.001) between MEP size and ML center of pressure (COP) velocity. Measures of M1 excitability did not correlate with COP velocity. LICI and ICF measured in the control task correlated with changes in LICI and ICF, i.e., the magnitude of response to increasing standing difficulty. Therefore, corticospinal excitability as measured by MEP size contributes to ML sway control while cortical facilitation and inhibition are likely involved in other aspects of sway control while standing. Additionally, neural excitability in standing is determined by an interaction between task difficulty and participant-specific neural excitability.
Immune Effects of Corticosteroids in Sepsis

Sepsis, a life-threatening organ dysfunction, results from a dysregulated host response to invading pathogens that may be characterized by overwhelming systemic inflammation or some sort of immune paralysis. Sepsis remains a major cause of morbidity and mortality. Treatment is nonspecific and relies on source control and organ support. Septic shock, the most severe form of sepsis is associated with the highest rate of mortality. Two large multicentre trials, undertaken 15 years apart, found that the combination of hydrocortisone and fludrocortisone significantly reduces mortality in septic shock. The corticosteroids family is composed of several molecules that are usually characterized according to their glucocorticoid and mineralocorticoid power, relative to hydrocortisone. While the immune effects of glucocorticoids whether mediated or not by the intracellular glucocorticoid receptor have been investigated for several decades, it is only very recently that potential immune effects of mineralocorticoids via non-renal mineralocorticoid receptors have gained popularity. We reviewed the respective role of glucocorticoids and mineralocorticoids in counteracting sepsis-associated dysregulated immune systems.
Recent intimate partner violence against women and health: a systematic review and meta-analysis of cohort studies

Objective We reviewed cohort studies to determine the magnitude and temporal direction of the association between recent intimate partner violence (IPV) and a range of adverse health outcomes or health risk behaviours. Design Systematic review and meta-analysis. Methods Medline, EMBASE and PsycINFO were searched from the first record to November 2016. Recent IPV was defined as occurring up to and including the last 12 months; all health outcomes were eligible for inclusion. Results were combined using random-effects meta-analysis. Results 35 separate cohort studies were retrieved. Eight studies showed evidence of a positive association between recent IPV and subsequent depressive symptoms, with a pooled OR from five estimates of 1.76 (95% CI 1.26 to 2.44, I2=37.5%, p=0.172). Five studies demonstrated a positive, statistically significant relationship between depressive symptoms and subsequent IPV; the pooled OR from two studies was 1.72 (95% CI 1.28 to 2.31, I2=0.0%, p=0.752). Recent IPV was also associated with increased symptoms of subsequent postpartum depression in five studies (OR=2.19, 95% CI 1.39 to 3.45, p=0.000), although there was substantial heterogeneity. There was some evidence of a bidirectional relationship between recent IPV and hard drug use and marijuana use, although studies were limited. There was no evidence of an association between recent IPV and alcohol use or sexually transmitted infections (STIs), although there were few studies and inconsistent measurement of alcohol and STIs. Conclusions Exposure to violence has significant impacts. Longitudinal studies are needed to understand the temporal relationship between recent IPV and different health issues, while considering the differential effects of recent versus past exposure to IPV. Improved measurement will enable an understanding of the immediate and longer term health needs of women exposed to IPV. Healthcare providers and IPV organisations should be aware of the bidirectional relationship between recent IPV and depressive symptoms. PROSPERO registration number CRD42016033372.
Combining Restricted Boltzmann Machines with Neural Networks for Latent Truth Discovery

Latent truth discovery, LTD for short, refers to the problem of aggregating ltiple claims from various sources in order to estimate the plausibility of atements about entities. In the absence of a ground truth, this problem is highly challenging, when some sources provide conflicting claims and others no claims at all. In this work we provide an unsupervised stochastic inference procedure on top of a model that combines restricted Boltzmann machines with feed-forward neural networks to accurately infer the reliability of sources as well as the plausibility of statements about entities. In comparison to prior work our approach stands out (1) by allowing the incorporation of arbitrary features about sources and claims, (2) by generalizing from reliability per source towards a reliability function, and thus (3) enabling the estimation of source reliability even for sources that have provided no or very few claims, (4) by building on efficient and scalable stochastic inference algorithms, and (5) by outperforming the state-of-the-art by a considerable margin.
Nutrición y Rendimiento Deportivo

Academia: Sports, Cardiovascular and Wellness Nutrition dietetic practice group (Jackie Buell, PhD, RD, CSSD, ATC Ohio State University, Columbus, OH); Amanda Carlson-Phillips, MS, RD, CSSD (EXOS Phoenix, AZ); Sharon Denny, MS, RD (Academy Knowledge Center, Chicago, IL); D. Enette Larson-Meyer, PhD, RD, FACSM (University of Wyoming, Laramie, WY); Mary Pat Raimondi, MS, RD (Academy Policy Initiatives & Advocacy, Washington DC);
Healthy obesity as an intermediate state of risk: a critical review

ABSTRACT Introduction: Obesity is a top public health priority but interventions to reverse the condition have had limited success. About one-in-three obese adults are free of metabolic risk factor clustering and are considered ‘healthy’, and much attention has focused on the implications of this state for obesity management. Areas covered: We searched for individual studies, systematic reviews, and meta-analyses which examined correlates and outcomes of metabolically healthy obesity. We discuss the key roles of fat distribution and physical activity in determining healthy vs. unhealthy obesity and report a greatly increased risk of incident type 2 diabetes associated with healthy obesity vs. healthy normal weight, among other outcomes. We argue that despite inconsistencies in the definition, patterns across studies clearly show that healthy obesity is a state of intermediate disease risk. Expert commentary: Given the current state of population-level evidence, we conclude that obesity and metabolic dysfunction are inseparable and that healthy obesity is best viewed only as a state of relative health but not of absolute health. We recommend that weight loss through energy restriction be a stand-alone target in addition to increased physical activity for minimising risk of future disease.
Advancing Predictions of Tissue and Intracellular Drug Concentrations Using In Vitro, Imaging and Physiologically Based Pharmacokinetic Modeling Approaches

This white paper examines recent progress, applications, and challenges in predicting unbound and total tissue and intra/subcellular drug concentrations using in vitro and preclinical models, imaging techniques, and physiologically based pharmacokinetic (PBPK) modeling. Published examples, regulatory submissions, and case studies illustrate the application of different types of data in drug development to support modeling and decision making for compounds with transporter‐mediated disposition, and likely disconnects between tissue and systemic drug exposure. The goals of this article are to illustrate current best practices and outline practical strategies for selecting appropriate in vitro and in vivo experimental methods to estimate or predict tissue and plasma concentrations, and to use these data in the application of PBPK modeling for human pharmacokinetic (PK), efficacy, and safety assessment in drug development.
Characterization of a bafinivirus exoribonuclease activity.

White bream virus (WBV), a poorly characterized plus-strand RNA virus infecting freshwater fish of the Cyprinidae family, is the prototype species of the genus Bafinivirus in the subfamily Torovirinae (family Coronaviridae, order Nidovirales). In common with other nidoviruses featuring >20 kilobase genomes, bafiniviruses have been predicted to encode an exoribonuclease (ExoN) in their replicase gene. Here, we used information on the substrate specificity of bafinivirus 3C-like proteases to express WBV ExoN in an active form in Escherichia coli. The 374-residue protein displayed robust 3'-to-5' exoribonuclease activity in the presence of Mg2+ ions and, unlike its coronavirus homologues, did not require a protein cofactor for activity. Characterization of mutant forms of ExoN provided support for predictions on putative active-site and conserved zinc-binding residues. WBV ExoN was revealed to be most active on double-stranded RNA substrates containing one or two non-paired 3'-terminal nucleotides, supporting its presumed role in increasing the fidelity of the bafinivirus RNA-dependent RNA polymerase.
Investigational drugs in phase I and phase II clinical trials targeting interleukin 23 (IL23) for the treatment of Crohn’s disease

ABSTRACT Introduction: Medical therapy for Crohn’s disease (CD) is directed at controlling intestinal inflammation to prevent development of disease-related complications. Not all patients will respond to currently available treatments and thus, novel therapies are needed. The interleukin (IL)-23 cytokine axis is implicated in CD pathogenesis and so targeting this pathway has become an important focus for drug development. Areas covered: This review summarizes the role of the IL23 cytokine pathway in CD pathogenesis and appraises phase I and II clinical trial data for novel IL23p19 specific monoclonal antibodies for the treatment of CD. The evidence for risankizumab (BI655066/ABBV066), brazikumab (MEDI2070, formerly AMG139), guselkumab (CNTO1959), tildrakizumab (MK3222), and mirikizumab (LY3074828) is reviewed; moreover, future applications for these agents are considered. Expert opinion: Targeting the specific p19 subunit of IL23 is a promising strategy in CD. Two multicenter, randomized, placebo-controlled phase II clinical trials have evaluated risankizumab and brazikumab. Both studies indicate that IL23-specific blockade is likely to be a safe and effective alternative to current biologics, including the TNF antagonists vedolizumab and ustekinumab. Confirmatory Phase 3 studies are underway. Ultimately, comparative effectiveness trials will be necessary to define the role of IL23-specific antagonists in CD treatment algorithms.