Miracle-dz/UniFAR-FTUs huggingface dataset:
Syndromic surveillance: two decades experience of sustainable systems – its people not just data!

Abstract Syndromic surveillance is a form of surveillance that generates information for public health action by collecting, analysing and interpreting routine health-related data on symptoms and clinical signs reported by patients and clinicians rather than being based on microbiologically or clinically confirmed cases. In England, a suite of national real-time syndromic surveillance systems (SSS) have been developed over the last 20 years, utilising data from a variety of health care settings (a telehealth triage system, general practice and emergency departments). The real-time systems in England have been used for early detection (e.g. seasonal influenza), for situational awareness (e.g. describing the size and demographics of the impact of a heatwave) and for reassurance of lack of impact on population health of mass gatherings (e.g. the London 2012 Olympic and Paralympic Games). We highlight the lessons learnt from running SSS, for nearly two decades, and propose questions and issues still to be addressed. We feel that syndromic surveillance is an example of the use of ‘big data’, but contend that the focus for sustainable and useful systems should be on the added value of such systems and the importance of people working together to maximise the value for the public health of syndromic surveillance services.
Homochiral and racemic MicroED structures of a peptide repeat from the ice-nucleation protein InaZ

The atomic asymmetry, left- or right-handedness, that is present in macromolecules and that was first described by Pasteur in his experiments with tartaric acid is evident even in complex molecular assemblies such as amyloid fibrils. Here, using the cryo-EM method MicroED, it is shown that a segment from the ice-nucleation protein InaZ assembles into homochiral and racemic water-binding amyloid protofibrils.
Acquired von Willebrand Syndrome Associated with Cardiovascular Diseases

The blood glycoprotein von Willebrand factor (VWF) plays an important role in hemostasis and thrombosis. VWF is produced and secreted as large multimers by endothelial cells and megakaryocytes. It is then cleaved in a sheer-stress dependent manner by a specific protease, ADAMTS13, into multimers consisting of 2–80 subunits. Among VWF multimers, high molecular weight (HMW) multimers play important roles in platelet aggregation. Therefore, their loss induces a hemostatic disorder known as von Willebrand disease (VWD) type 2A. Various cardiovascular diseases, such as aortic stenosis, hypertrophic obstructive cardiomyopathy (HOCM), and several congenital structural diseases, as well as mechanical circulatory support systems, generate excessive high shear stress in the bloodstream. These cause excessive cleavage of VWF multimers resulting in a loss of HMW multimers, known as acquired von Willebrand syndrome (AVWS), a hemostatic disorder similar to VWD type 2A. Bleeding often occurs in the gastrointestinal tract since a fragile angiodysplasia develops associated with these diseases. Radical treatment for AVWS is to remove the pathological high shear causing AVWS.
Preparation of magnetic molecularly imprinted polymers for the rapid detection of diethylstilbestrol in milk samples.

BACKGROUND Diethylstilbestrol (DES) residues are harmful to human health because of their potential carcinogenic properties. Therefore, it is important to develop a fast and efficient pretreatment method to prevent their harmful effects on human health and the environment. RESULTS In this paper, two types of magnetic molecularly imprinted polymers (MMIPs) of DES were prepared by bulk polymerization and the sol-gel method, respectively. The synthetic materials were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy and thermogravimetric analysis. Adsorption capacities of the bulk and sol-gel MMIPs were investigated. A rapid detection method was developed using the two types of MMIPs as sorbents, coupled to high-performance liquid chromatography, for the determination of DES residues in milk samples. Under optimized conditions, the limit of detection (S/N = 3) of both methods for DES was 2.0 μg L-1 ; and the linear response range to DES was 0.1-500 mg L-1 . The milk samples were analyzed according to this method with good recoveries of 88.3-97.6 and 90.5-103.5% for the two types of MMIPs, respectively. CONCLUSIONS The method described had high sensitivity and high selectivity, and could prove to be a new method for the rapid determination of DES residues in milk samples. © 2019 Society of Chemical Industry.
Identification of bloodmeal sources of triatomines captured in the Paraguayan Chaco region of South America by means of molecular biology analysis

ABSTRACT The Paraguayan Chaco is an isolated environment with its own unique ecosystem. In this region, Chagas disease remains a health problem. Chagas disease is caused by the parasite Trypanosoma cruzi, and it is primarily transmitted by triatomines. In order to identify the blood meal sources of triatomines, specimens of the vector were collected in domestic and peridomestic areas and the PCR-RFLP method was implemented. Cytochrome b was amplified from the samples and later subjected to digestion with two restriction enzymes: Hae III and Xho I.It was possible to generate distinct restriction patterns on the amplified material to identify several blood meal sources for the vectors. We employed the blood from several species as positive controls: human, chicken, canine, feline, and armadillo blood. However, we identified only 3 sources for the blood meals of the insect vectors: human, chicken and canine blood. In total, 76 triatomines were captured. T. cruzi was not found in any of them. In 61% of the captured specimens, the blood meal sources for the vectors could be identified. In 30% of these cases, the presence of DNA from more than one vertebrate was detected in the same triatomine. The most common blood meal source found was chicken blood. The presence of human and chicken blood in triatomines captured in domestic and peridomestic areas strongly suggests that the parasite can freely move amongst both areas regardless of food availability. Free vector movement in these areas constitutes an epidemiological threat for the inhabitants of the community under study.
VRKitchen: an Interactive 3D Virtual Environment for Task-oriented Learning

One of the main challenges of advancing task-oriented learning such as visual task planning and reinforcement learning is the lack of realistic and standardized environments for training and testing AI agents. Previously, researchers often relied on ad-hoc lab environments. There have been recent advances in virtual systems built with 3D physics engines and photo-realistic rendering for indoor and outdoor environments, but the embodied agents in those systems can only conduct simple interactions with the world (e.g., walking around, moving objects, etc.). Most of the existing systems also do not allow human participation in their simulated environments. In this work, we design and implement a virtual reality (VR) system, VRKitchen, with integrated functions which i) enable embodied agents powered by modern AI methods (e.g., planning, reinforcement learning, etc.) to perform complex tasks involving a wide range of fine-grained object manipulations in a realistic environment, and ii) allow human teachers to perform demonstrations to train agents (i.e., learning from demonstration). We also provide standardized evaluation benchmarks and data collection tools to facilitate a broad use in research on task-oriented learning and beyond.
Diabetes-Induced DUSP4 Reduction Promotes Podocyte Dysfunction and Progression of Diabetic Nephropathy

Diabetic nephropathy (DN) remains the leading cause of end-stage renal disease. Hyperglycemia-induced podocyte dysfunction is a major contributor of renal function impairment in DN. Previous studies showed that activation of mitogen-activated protein kinase (MAPK) in diabetes promotes podocyte dysfunction and cell death. Dual specificity phosphatases (DUSPs) are a family of phosphatases mainly responsible for MAPK inhibition. In this study, we demonstrated that diabetes and high glucose exposure decreased DUSP4 expression in cultured podocytes and glomeruli. Diabetes-induced DUSP4 reduction enhanced p38 and c-Jun N-terminal kinase (JNK) activity and podocyte dysfunction. The overexpression of DUSP4 prevented the activation of p38, JNK, caspase 3/7 activity, and NADPH oxidase 4 expression induced by high glucose level exposure. Deletion of DUSP4 exacerbated albuminuria and increased mesangial expansion and glomerular fibrosis in diabetic mice. These morphological changes were associated with profound podocyte foot process effacement, cell death, and sustained p38 and JNK activation. Moreover, inhibition of protein kinase C-δ prevented DUSP4 expression decline and p38/JNK activation in the podocytes and renal cortex of diabetic mice. Analysis of DUSP4 expression in the renal cortex of patients with diabetes revealed that decreased DUSP4 mRNA expression correlated with reduced estimated glomerular filtration rate (<60 mL/min/1.73 m2). Thus, this study demonstrates that preserving DUSP4 expression could protect against podocyte dysfunction and preserve glomerular function in DN.
Non-invasive home telemonitoring system for heart failure patients: A randomized clinical trial

Introduction The low quality of life in heart failure patients is related to low self-care and treatment adherence. Consequently, innovative strategies are needed to improve them. The objective of this work is to determine the effectiveness of the use of a home telemonitoring system to improve the self-care and treatment adherence of heart failure patients. Methods A randomized clinical trial that compares the efficacy of a home telemonitoring system –intervention group versus usual care control group – among heart failure outpatients over a 90-day monitoring period was carried out. The home telemonitoring system consists of an application that collects measurements of different parameters on a daily basis and provides health education to patients. The home telemonitoring system processes data gathered and generates an alert if a risky situation arises. The outcomes observed were significant changes in patients’ self-care (European Heart Failure Self-care Behaviour Scale), treatment adherence (Morisky Modified Scale) and re-hospitalizations over the follow-up period. Results 104 heart failure patients were screened; 40 met the inclusion criteria; only 30 completed the study. After the follow-up, intragroup analysis of the control group indicated a decrease in treatment adherence (p = 0.02). The mean European Heart Failure Self-care Behaviour Scale overall score indicated an improved self-care in the intervention group patients (p = 0.03) and a worsened self-care in the control group (p = 0.04) with a p value of 0.004 in the intergroup analysis. Thanks to the home telemonitoring system alerts, two re-hospitalizations were avoided. Discussion This study demonstrated that the proposed home telemonitoring system improves patient self-care when compared to usual care and has the potential to avoid re-hospitalizations, even considering patients with low literacy levels. Trial Registration: Home Telemonitoring System for Patients with Heart Failure. clinicaltrials.gov Identifier: NCT04071093
On the Pitfalls of Measuring Emergent Communication

How do we know if communication is emerging in a multi-agent system? The vast majority of recent papers on emergent communication show that adding a communication channel leads to an increase in reward or task success. This is a useful indicator, but provides only a coarse measure of the agent's learned communication abilities. As we move towards more complex environments, it becomes imperative to have a set of finer tools that allow qualitative and quantitative insights into the emergence of communication. This may be especially useful to allow humans to monitor agents' behaviour, whether for fault detection, assessing performance, or even building trust. In this paper, we examine a few intuitive existing metrics for measuring communication, and show that they can be misleading. Specifically, by training deep reinforcement learning agents to play simple matrix games augmented with a communication channel, we find a scenario where agents appear to communicate (their messages provide information about their subsequent action), and yet the messages do not impact the environment or other agent in any way. We explain this phenomenon using ablation studies and by visualizing the representations of the learned policies. We also survey some commonly used metrics for measuring emergent communication, and provide recommendations as to when these metrics should be used.
100 years of modelling ligand–receptor binding and response: A focus on GPCRs

Experimental pharmacologists rely on the application of models to describe biological observations in order to learn about a drug's effective concentration, the strength with which it binds its target and drives a response (at either molecular or system level), and the nature of more complex drug actions (allosterism/functional selectivity). Models in current use build upon decades of basic principles, going back to the beginning of the last century. Yet often, researchers are only partially familiar with these underlying principles, creating the potential for confusion due to failure to recognise the underpinning assumptions of the models that are used. Here, we describe the history of receptor theory as it underpins receptor stimulus–response models in use today, emphasising particularly attributes and models relevant to GPCRs—and point to some current aims of model development.
Nutrigenetics, epigenetics and gestational diabetes: consequences in mother and child

ABSTRACT Gestational Diabetes Mellitus (GDM) is the most common metabolic condition during pregnancy and may result in short- and long-term complications for both mother and offspring. The complexity of phenotypic outcomes seems influenced by genetic susceptibility, nutrient-gene interactions and lifestyle interacting with clinical factors. There is strong evidence that not only the adverse genetic background but also the epigenetic modifications in response to nutritional and environmental factors could influence the maternal hyperglycemia in pregnancy and the foetal metabolic programming. In this view, the correlation between epigenetic modifications and their transgenerational effects represents a very interesting field of study. The present review gives insight into the role of gene variants and their interactions with nutrients in GDM. In addition, we provide an overview of the epigenetic changes and their role in the maternal-foetal transmission of chronic diseases. Overall, the knowledge of epigenetic modifications induced by an adverse intrauterine and perinatal environment could shed light on the potential pathophysiological mechanisms of long-term disease development in the offspring and provide useful tools for their prevention.
Advances in Delayed-Onset Muscle Soreness (DOMS) – Part II: Treatment and Prevention

Abstract Delayed-onset muscle soreness (DOMS) describes an entity of ultrastructural muscle damage. The manifestation of DOMS is caused by eccentric muscle contractions or unaccustomed forms of exercise. Clinical signs include impaired muscular force capacities, painful restriction of movement, stiffness, swelling, and altered biomechanics in adjacent joints. Although DOMS is categorised as a mild type of muscle damage, it is one of the most common reasons for compromised sportive performance. In the last decade, many hypotheses have been developed to explain the aetiology of DOMS, and there are a wide range of different interventions aiming to prevent or alleviate the symptoms. Many studies have evaluated various types of cold or heat therapy, compression, massage, physical therapy or nutritional interventions. Treatment considerations focus on the primary prevention of ultrastructural lesions during exercise, the treatment of the inflammatory response that leads to DOMS, and recovery strategies for manifest DOMS. This narrative review aims to present an overview of the current treatment and preventive strategies in the field of DOMS.
Region- and Cell Type-Specific Facilitation of Synaptic Function at Destination Synapses Induced by Oligodendrocyte Depolarization

The axonal conduction of action potentials affects the absolute time it takes to transmit nerve impulses as well as temporal summation at destination synapses. At the physiological level, oligodendrocyte depolarization facilitates axonal conduction along myelinated fibers in the hippocampus; however, the functional significance of this facilitation is largely unknown. In this study, we examined the physiology of the facilitation of axonal conduction by investigating the changes in synaptic responses at destination synapses using male and female mice in which channelrhodopsin-2 expression was restricted to oligodendrocytes. The subiculum, one of the projection areas of the examined axons at the alveus of the hippocampus, is divided into three regions (proximal, mid, and distal) and contains two types of principal neurons: regular firing and bursting pyramidal cells. We found a significant increase in excitatory synaptic responses following optogenetic oligodendrocyte depolarization in bursting neurons at two of the three regions, but not in regular firing neurons at any region. The long-term potentiation (LTP) induced by theta burst stimulation at the synapses showing a significant increase was also enhanced after oligodendrocyte depolarization. Conversely, the reduction of oligodendrocyte depolarization during theta burst stimulation, which was achieved by photostimulation of archaerhodopsin-T expressed selectively on oligodendrocytes, reduced the magnitude of LTP. These results show that oligodendrocyte depolarization contributes to the fine control of synaptic activity between the axons they myelinate and targets subicular cells in a region- and cell type-specific manner, and suggest that oligodendrocyte depolarization during conditioning of stimuli is involved in the induction of LTP. SIGNIFICANCE STATEMENT All activity in the nervous system depends on the propagation of action potentials. Changes in the axonal conduction of action potentials influence the timing of synaptic transmission and information processing in neural circuits. At the physiological level, oligodendrocyte depolarization facilitates axonal conduction along myelinated fibers. In this study, we investigated the functional significance of the facilitation of axonal conduction induced by physiological oligodendrocyte depolarization. Using optogenetics and electrophysiological recordings, we demonstrated that oligodendrocyte depolarization in mice expressing channelrhodopsin-2 on oligodendrocytes increased excitatory synaptic responses and enhanced the induction of long-term potentiation at destination synapses in a region- and cell type-specific manner. This facilitation may have a hitherto unappreciated influence on the transfer of information between regions in the nervous system.
Association between clinical risk scores and mortality in atrial fibrillation: Systematic review and network meta-regression of 669,000 patients

Aims Many clinical scores for risk stratification in patients with atrial fibrillation have been proposed, and some have been useful in predicting all-cause mortality. We aim to analyse the relationship between clinical risk score and all-cause death occurrence in atrial fibrillation patients. Methods We performed a systematic search in PubMed and Scopus from inception to 22 July 2017. We considered the following scores: ATRIA-Stroke, ATRIA-Bleeding, CHADS2, CHA2DS2-VASc, HAS-BLED, HATCH and ORBIT. Papers reporting data about scores and all-cause death rates were considered. Results Fifty studies and 71 scores groups were included in the analysis, with 669,217 patients. Data on ATRIA-Bleeding, CHADS2, CHA2DS2-VASc and HAS-BLED were available. All the scores were significantly associated with an increased risk for all-cause death. All the scores showed modest predictive ability at five years (c-indexes (95% confidence interval) CHADS2: 0.64 (0.63–0.65), CHA2DS2-VASc: 0.62 (0.61–0.64), HAS-BLED: 0.62 (0.58–0.66)). Network meta-regression found no significant differences in predictive ability. CHA2DS2-VASc score had consistently high negative predictive value (≥94%) at one, three and five years of follow-up; conversely it showed the highest probability of being the best performing score (63% at one year, 60% at three years, 68% at five years). Conclusion In atrial fibrillation patients, contemporary clinical risk scores are associated with an increased risk of all-cause death. Use of these scores for death prediction in atrial fibrillation patients could be considered as part of holistic clinical assessment. The CHA2DS2-VASc score had consistently high negative predictive value during follow-up and the highest probability of being the best performing clinical score.
Lower circulating adiponectin is associated with higher risk of renal cell carcinoma: A meta-analysis

Background: Changes in circulating adiponectin have been related to the risks of various cancers. However, the association between circulating adiponectin and the risk of renal cell carcinoma has not been fully determined. A meta-analysis was performed to evaluate the relationship between circulating adiponectin and renal cell carcinoma risk. Methods: Observational studies that evaluated the association between circulating adiponectin and renal cell carcinoma risk were identified via a systematic search of PubMed and Embase databases. The difference between circulating adiponectin in renal cell carcinoma cases and healthy controls, and the multivariable adjusted association between circulating adiponectin and renal cell carcinoma risk were evaluated. A random effects model was used if significant heterogeneity existed; otherwise a fixed effects model was applied. Results: Eight case-control studies with 2624 renal cell carcinoma cases and 2904 healthy controls were included. Pooled results showed that circulating adiponectin was significantly lower in renal cell carcinoma cases than in healthy controls (mean difference = −1.08 ug/mL; 95% confidence interval (CI) −1.62, −0.54; P < 0.001). Higher circulating adiponectin was independently associated with a significantly lowered risk of renal cell carcinoma (adjusted odds ratio for 1 SD increment of adiponectin = 0.78; 95% CI: 0.63, 0.96; P = 0.02). Subgroup analyses according to characteristics including study design, ethnics of participants, blood samples, numbers of participants, mean ages of participants, and study quality showed consistent results. Conclusions: Lower circulating adiponectin is associated with increased risk of renal cell carcinoma. The potential pathophysiological mechanisms underlying the role of circulating adiponectin in the pathogenesis of renal cell carcinoma deserve further investigation.