Dual-View Single-Shot Multibox Detector at Urban Intersections: Settings and Performance Evaluation

The explosion of artificial intelligence methods has paved the way for more sophisticated smart mobility solutions. In this work, we present a multi-camera video content analysis (VCA) system that exploits a single-shot multibox detector (SSD) network to detect vehicles, riders, and pedestrians and triggers alerts to drivers of public transportation vehicles approaching the surveilled area. The evaluation of the VCA system will address both detection and alert generation performance by combining visual and quantitative approaches. Starting from a SSD model trained for a single camera, we added a second one, under a different field of view (FOV) to improve the accuracy and reliability of the system. Due to real-time constraints, the complexity of the VCA system must be limited, thus calling for a simple multi-view fusion method. According to the experimental test-bed, the use of two cameras achieves a better balance between precision (68%) and recall (84%) with respect to the use of a single camera (i.e., 62% precision and 86% recall). In addition, a system evaluation in temporal terms is provided, showing that missed alerts (false negatives) and wrong alerts (false positives) are typically transitory events. Therefore, adding spatial and temporal redundancyincreases the overall reliability of the VCA system

A novel method to derive personalized minimum viable recommendations for type 2 diabetes prevention based on counterfactual explanations

Despite the growing availability of artificial intelligence models for predicting type 2 diabetes, there is still a lack of personalized approaches to quantify minimum viable changes in biomarkers that may help reduce the individual risk of developing disease. The aim of this article is to develop a new method, based on counterfactual explanations, to generate personalized recommendations to reduce the one-year risk of type 2 diabetes. Ten routinely collected biomarkers extracted from Electronic Medical Records of 2791 patients at low risk and 2791 patients at high risk of type 2 diabetes were analyzed. Two regions characterizing the two classes of patients were estimated using a Support Vector Data Description classifier. Counterfactual explanations (i.e., minimal changes in input features able to change the risk class) were generated for patients at high risk and evaluated using performance metrics (availability, validity, actionability, similarity, and discriminative power) and a qualitative survey administered to seven expert clinicians. Results showed that, on average, the requested minimum viable changes implied a significant reduction of fasting blood sugar, systolic blood pressure, and triglycerides and a significant increase of high-density lipoprotein in patients at risk of diabetes. A significant reduction in body mass index was also recommended in most of the patients at risk, except in females without hypertension. In general, greater changes were recommended in hypertensive patients compared to non-hypertensive ones. The experts were overall satisfied with the proposed approach although in some cases the proposed recommendations were deemed insufficient to reduce the risk in a clinically meaningful way. Future research will focus on a larger set of biomarkers and different comorbidities, also incorporating clinical guidelines whenever possible. Development of additional mathematical and clinical validation approaches will also be of paramount importance

The Dark That Matters: Long Non-coding RNAs as Master Regulators of Cellular Metabolism in Non-communicable Diseases

Non-coding RNAs are pivotal for many cellular functions, such as splicing, gene regulation, chromosome structure, and hormone-like activity. Here, we will report about the biology and the general molecular mechanisms associated with long non-coding RNAs (lncRNAs), a class of >200 nucleotides-long ribonucleic acid sequences, and their role in chronic non-transmissible diseases. In particular, we will summarize knowledge about some of the best-characterized lncRNAs, such as H19 and MALAT1, and how they regulate carbohydrate and lipid metabolism as well as protein synthesis and degradation. Evidence is discussed about how lncRNAs expression might affect cellular and organismal metabolism and whether their modulation could provide ground for the development of innovative treatments

Mitochondrial epigenetics in aging and cardiovascular diseases

Mitochondria are cellular organelles which generate adenosine triphosphate (ATP) molecules for the maintenance of cellular energy through the oxidative phosphorylation. They also regulate a variety of cellular processes including apoptosis and metabolism. Of interest, the inner part of mitochondria-the mitochondrial matrix-contains a circular molecule of DNA (mtDNA) characterised by its own transcriptional machinery. As with genomic DNA, mtDNA may also undergo nucleotide mutations that have been shown to be responsible for mitochondrial dysfunction. During physiological aging, the mitochondrial membrane potential declines and associates with enhanced mitophagy to avoid the accumulation of damaged organelles. Moreover, if the dysfunctional mitochondria are not properly cleared, this could lead to cellular dysfunction and subsequent development of several comorbidities such as cardiovascular diseases (CVDs), diabetes, respiratory and cardiovascular diseases as well as inflammatory disorders and psychiatric diseases. As reported for genomic DNA, mtDNA is also amenable to chemical modifications, namely DNA methylation. Changes in mtDNA methylation have shown to be associated with altered transcriptional programs and mitochondrial dysfunction during aging. In addition, other epigenetic signals have been observed in mitochondria, in particular the interaction between mtDNA methylation and non-coding RNAs. Mitoepigenetic modifications are also involved in the pathogenesis of CVDs where oxygen chain disruption, mitochondrial fission, and ROS formation alter cardiac energy metabolism leading to hypertrophy, hypertension, heart failure and ischemia/reperfusion injury. In the present review, we summarize current evidence on the growing importance of epigenetic changes as modulator of mitochondrial function in aging. A better understanding of the mitochondrial epigenetic landscape may pave the way for personalized therapies to prevent age-related diseases

Epigenetic Network in Immunometabolic Disease

Although a large amount of data consistently shows that genes affect immunometabolic characteristics and outcomes, epigenetic mechanisms are also heavily implicated. Epigenetic changes, including DNA methylation, histone modification, and noncoding RNA, determine gene activity by altering the accessibility of chromatin to transcription factors. Various factors influence these alterations, including genetics, lifestyle, and environmental cues. Moreover, acquired epigenetic signals can be transmitted across generations, thus contributing to early disease traits in the offspring. A closer investigation is critical in this aspect as it can help to understand the underlying molecular mechanisms further and gain insights into potential therapeutic targets for preventing and treating diseases arising from immuno-metabolic dysregulation. In this review, the role of chromatin alterations in the transcriptional modulation of genes involved in insulin resistance, systemic inflammation, macrophage polarization, endothelial dysfunction, metabolic cardiomyopathy, and nonalcoholic fatty liver disease (NAFLD), is discussed. An overview of emerging chromatin-modifying drugs and the importance of the individual epigenetic profile for personalized therapeutic approaches in patients with immuno-metabolic disorders is also presented

Epigenetic Signatures in Arterial Hypertension: Focus on the Microvasculature

Systemic arterial hypertension (AH) is a multifaceted disease characterized by accelerated vascular aging and high cardiometabolic morbidity and mortality. Despite extensive work in the field, the pathogenesis of AH is still incompletely understood, and its treatment remains challenging. Recent evidence has shown a deep involvement of epigenetic signals in the regulation of transcriptional programs underpinning maladaptive vascular remodeling, sympathetic activation and cardiometabolic alterations, all factors predisposing to AH. After occurring, these epigenetic changes have a long-lasting effect on gene dysregulation and do not seem to be reversible upon intensive treatment or the control of cardiovascular risk factors. Among the factors involved in arterial hypertension, microvascular dysfunction plays a central role. This review will focus on the emerging role of epigenetic changes in hypertensive-related microvascular disease, including the different cell types and tissues (endothelial cells, vascular smooth muscle cells and perivascular adipose tissue) as well as the involvement of mechanical/hemodynamic factors, namely, shear stress

An RNA-seq study in Friedreich ataxia patients identified hsa-miR-148a-3p as a putative prognostic biomarker of the disease

friedreich ataxia (FRDA) is a life-threatening hereditary ataxia; its incidence is 1:50,000 individuals in the caucasian population. a unique therapeutic drug for FRDA, the antioxidant omaveloxolone, has been recently approved by the US food and drug administration (FDA). FRDA is a multi-systemic neurodegenerative disease; in addition to a progressive neurodegeneration, FRDA is characterized by hypertrophic cardiomyopathy, diabetes mellitus and musculoskeletal deformities. cardiomyopathy is the predominant cause of premature death. the onset of FRDA typically occurs between the ages of 5 and 15. given the complexity and heterogeneity of clinical features and the variability of their onset, the identification of biomarkers capable of assessing disease progression and monitoring the efficacy of treatments is essential to facilitate decision making in clinical practice. we conducted an RNA-seq analysis in peripheral blood mononuclear cells from FRDA patients and healthy donors, identifying a signature of small non-coding RNAs (sncRNAs) capable of distinguishing healthy individuals from the majority of FRDA patients. among the differentially expressed sncRNAs, microRNAs are a class of small non-coding endogenous RNAs that regulate posttranscriptional silencing of target genes. In FRDA plasma samples, hsa-miR-148a-3p resulted significantly upregulated. the analysis of the receiver operating characteristic (ROC) curve, combining the circulating expression levels of hsa-miR-148a-3p and hsa-miR-223-3p (previously identified by our group), revealed an area under the curve (AUC) of 0.86 (95%, confidence Interval 0.77-0.95; p-value < 0.0001). an in silico prediction analysis indicated that the IL6ST gene, an interesting marker of neuroinflammation in FRDA, is a common target gene of both miRNAs. our findings support the evaluation of combined expression levels of different circulating miRNAs as potent epi-biomarkers in FRDA. moreover, we found hsa-miR-148a-3p significantly over-expressed in Intermediate and late-onset friedreich ataxia patients' group (IOG and LOG, respectively) compared to healthy individuals, indicating it as a putative prognostic biomarker in this pathology

Mitochondrial epigenetics in aging and cardiovascular diseases

Mitochondria are cellular organelles which generate adenosine triphosphate (ATP) molecules for the maintenance of cellular energy through the oxidative phosphorylation. They also regulate a variety of cellular processes including apoptosis and metabolism. Of interest, the inner part of mitochondria—the mitochondrial matrix—contains a circular molecule of DNA (mtDNA) characterised by its own transcriptional machinery. As with genomic DNA, mtDNA may also undergo nucleotide mutations that have been shown to be responsible for mitochondrial dysfunction. During physiological aging, the mitochondrial membrane potential declines and associates with enhanced mitophagy to avoid the accumulation of damaged organelles. Moreover, if the dysfunctional mitochondria are not properly cleared, this could lead to cellular dysfunction and subsequent development of several comorbidities such as cardiovascular diseases (CVDs), diabetes, respiratory and cardiovascular diseases as well as inflammatory disorders and psychiatric diseases. As reported for genomic DNA, mtDNA is also amenable to chemical modifications, namely DNA methylation. Changes in mtDNA methylation have shown to be associated with altered transcriptional programs and mitochondrial dysfunction during aging. In addition, other epigenetic signals have been observed in mitochondria, in particular the interaction between mtDNA methylation and non-coding RNAs. Mitoepigenetic modifications are also involved in the pathogenesis of CVDs where oxygen chain disruption, mitochondrial fission, and ROS formation alter cardiac energy metabolism leading to hypertrophy, hypertension, heart failure and ischemia/reperfusion injury. In the present review, we summarize current evidence on the growing importance of epigenetic changes as modulator of mitochondrial function in aging. A better understanding of the mitochondrial epigenetic landscape may pave the way for personalized therapies to prevent age-related diseases