Design of a Service for the Management of Heart Failure Patients Using Telemedicine

The tremendous prevalence and mortality of heart failure (HF), along with the social and economic impact of its consequences, make an appropriate disease management utmost important. In this context, telemedicine offers promising possibilities. Current clinical guidelines and technological solutions do not address the problem of monitoring at-risk patients and patients affected by mild HF for prevention purposes. The goal of this work is to design a service based on a telemedicine framework for the management of heart failure patients. The proposed service grounds the monitoring of the patient on a custom multi-sensor array that we designed and developed for the purpose. The description of the processes involved in the service was carried out by means of Process Modelling tools, and in particular through Swim Lane Activity Diagrams. The results look promising for the implementation of the service in a real-life scenario. The main strength of the service resides in a) the use of noninvasive monitoring technologies to include patients with a mild HF or at-risk patients; and b) the integration of hospital and territory services to grant continuity and coherence in the treatment

A Multi-Layered Study on Harmonic Oscillations in Mammalian Genomics and Proteomics

Cellular, organ, and whole animal physiology show temporal variation predominantly featuring 24-h (circadian) periodicity. Time-course mRNA gene expression profiling in mouse liver showed two subsets of genes oscillating at the second (12-h) and third (8-h) harmonic of the prime (24-h) frequency. The aim of our study was to identify specific genomic, proteomic, and functional properties of ultradian and circadian subsets. We found hallmarks of the three oscillating gene subsets, including different (i) functional annotation, (ii) proteomic and electrochemical features, and (iii) transcription factor binding motifs in upstream regions of 8-h and 12-h oscillating genes that seemingly allow the link of the ultradian gene sets to a known circadian network. Our multifaceted bioinformatics analysis of circadian and ultradian genes suggests that the different rhythmicity of gene expression impacts physiological outcomes and may be related to transcriptional, translational and post-translational dynamics, as well as to phylogenetic and evolutionary components

CACTO: Continuous Actor-Critic with Trajectory Optimization -- Towards global optimality

This paper presents a novel algorithm for the continuous control of dynamical systems that combines Trajectory Optimization (TO) and Reinforcement Learning (RL) in a single framework. The motivations behind this algorithm are the two main limitations of TO and RL when applied to continuous nonlinear systems to minimize a non-convex cost function. Specifically, TO can get stuck in poor local minima when the search is not initialized close to a "good" minimum. On the other hand, when dealing with continuous state and control spaces, the RL training process may be excessively long and strongly dependent on the exploration strategy. Thus, our algorithm learns a "good" control policy via TO-guided RL policy search that, when used as initial guess provider for TO, makes the trajectory optimization process less prone to converge to poor local optima. Our method is validated on several reaching problems featuring non-convex obstacle avoidance with different dynamical systems, including a car model with 6D state, and a 3-joint planar manipulator. Our results show the great capabilities of CACTO in escaping local minima, while being more computationally efficient than the Deep Deterministic Policy Gradient (DDPG) and Proximal Policy Optimization (PPO) RL algorithms.Comment: 8 pages, 8 figures. Submitted to IEEE RA-

Production and characterization of CSSI003 (2961) human induced pluripotent stem cells (iPSCs) carrying a novel puntiform mutation in RAI1 gene, Causative of Smith–Magenis syndrome

Smith-Magenis syndrome (SMS) is a complex genetic disorder characterized by developmental delay, behavioural problems and circadian rhythm dysregulation. About 90% of SMS cases are due to a 17p11.2 deletion containing retinoic acid induced1 (RAI1) gene, 10% are due to heterozygousmutations affecting RAI1 coding region. Little is known about RAI1 role

Copy number variations in healthy subjects. Case study: iPSC line CSSi005-A (3544) production from an individual with variation in 15q13.3 chromosome duplicating gene CHRNA7

CHRNA7, encoding the neuronal alpha7 nicotinic acetylcholine receptor (a7nAChR), is highly expressed in the brain, particularly in the hippocampus. It is situated in the 15q13.3 chromosome region, frequently associated with a Copy Number Variation (CNV), which causes its duplication or deletion. The clinical significance of CHRNA7 duplications is unknown so far, but there are several research data suggesting that they may be pathogenic, with reduced penetrance. We have produced an iPS cell line from a single healthy donor's fibroblasts carrying a 15q13.3 CNV, including CHRNA7 in order to study the exact role of this CNV during the neurodevelopment

Unbiased Characterization of Peptide-HLA Class II Interactions Based on Large-Scale Peptide Microarrays; Assessment of the Impact on HLA Class II Ligand and Epitope Prediction

Human Leukocyte Antigen class II (HLA-II) molecules present peptides to T lymphocytes and play an important role in adaptive immune responses. Characterizing the binding specificity of single HLA-II molecules has profound impacts for understanding cellular immunity, identifying the cause of autoimmune diseases, for immunotherapeutics, and vaccine development. Here, novel high-density peptide microarray technology combined with machine learning techniques were used to address this task at an unprecedented level of high-throughput. Microarrays with over 200,000 defined peptides were assayed with four exemplary HLA-II molecules. Machine learning was applied to mine the signals. The comparison of identified binding motifs, and power for predicting eluted ligands and CD4+ epitope datasets to that obtained using NetMHCIIpan-3.2, confirmed a high quality of the chip readout. These results suggest that the proposed microarray technology offers a novel and unique platform for large-scale unbiased interrogation of peptide binding preferences of HLA-II molecules

Generation of an induced pluripotent stem cell line (CSS012-A (7672)) carrying the p.G376D heterozygous mutation in the TARDBP protein

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative condition with phenotypic and genetic heterogeneity. It is characterized by the selective vulnerability and the progressive loss of the neural population. Here, an induced pluripotent stem cell (iPSC) line was generated from dermal fibroblasts of an individual carrying the p.G376D mutation in the TDP-43 protein. Fibroblasts were reprogrammed using nonintegrating episomal plasmids. There were no karyotype abnormalities, and iPSCs successfully differentiated into all three germ layers. This cell line may prove useful in the study of the pathogenic mechanisms that underpin ALS syndrome

Increase in newly diagnosed type 1 diabetes and serological evidence of recent SARS-CoV-2 infection: Is there a connection?

Several studies have investigated the correlation between the COVID-19 pandemic and the onset of type 1 diabetes (T1D) in children, reporting an increased incidence of T1D and severe diabetic ketoacidosis (DKA). This study aimed to investigate the infection by SARS-CoV-2 in children with newly-diagnosed T1D to explore a possible link between SARS-CoV-2 infection, T1D and DKA. Thirty-nine children with a T1D new onset between October 15, 2020, and April 15, 2021, were enrolled. SARS-CoV-2 infection was investigated through a polymerase chain reaction on the nasal swab, dosage of specific antibodies, and an anamnestic question form. Nine (23%) of them had antibodies directed toward SARS-CoV-2, and five (12%) had a history of recent SARS-CoV-2 infection in themselves or in their family. No molecular swabs were positive. Compared to the general pediatric population, the overall incidence of COVID-19 was 5.6 times higher in the T1D patients' group (p < 0.00001). Referring only to the cases in the metropolitan area, we find a net increase in the incidence of T1D compared to the 5 years preceding our study, by 50% compared to the same months in 2016/2017 and 2017/2018, by 69% compared to 2018/2019 and by 77% compared to 2019/2020. The same trend was observed regarding DKA cases. The attributable risk of the pandemic cohort compared to the previous year is 44%. The abnormal disproportion of SARS-CoV-2 infection between children with T1D and the pediatric reference population, with a ratio of 5.6, appears to support the causative role of SARS-CoV-2 in triggering the immune response underlying diabetes, as often described for other viral infections. The difficulty accessing care services during the pandemic, with a consequent diagnosis delay, does not justify the increase in observed T1D cases, which could to be directly linked to the pandemic. The acceleration of the immune process provoked by SARS-CoV-2 may play a suggestive role in the development of T1D with DKA. Multicenter studies are needed to deepen and fully understand the pathophysiological link between SARS-CoV-2 and the onset of T1D in children

Determining Breast Implant Prevalence. A Population Study of Italian Chest Radiographs

Background Current breast implant prevalence within the general population remains elusive. An accurate prevalence is critical to serve as the denominator for any assessment of breast implant-related complication. The purpose of this manuscript is to assess this prevalence in women aged 20-70 years in Italy.Materials and Methods Eight reviewers, demonstrating a mean sensitivity of 87.0% and specificity of 97.0%, were recruited for retrospective identification of implants on chest radiographs from a tertiary academic hospital in a major urban setting. Three final reviewers were selected, and they assessed all eligible chest radiographs collected between January and December 2019. The hospital-based population was compared to epidemiological data at a local, regional and national level to demonstrate homogeneity of age structures using the phi correlation coefficient.Results We identified 3,448 chest X-rays which yielded 140 implants, with an overall prevalence of 4.1% for women aged 20-70. Implants were bilateral in 76% of cases and unilateral in 24%. They were placed cosmetically in 47.1% cases and used for reconstruction in 52.9% cases. Phi correlation coefficient found no differences across hospital-based, local, regional and national populations.Conclusion A validated method was performed to estimate implant prevalence from an academic hospital in a major urban setting at 4.1% and was used to estimate national prevalence in Italy. The implications of this epidemiologic study may reach across national borders for improved understanding of breast implant epidemiology and in predicting the total number of patients within a given population that may be affected by device complications

Production and characterization of human induced pluripotent stem cells (iPSCs) from Joubert Syndrome: CSSi001-A (2850)

Abstract Joubert Syndrome (JS) is a rare autosomal recessive or X-linked condition characterized by a peculiar cerebellar malformation, known as the molar tooth sign (MTS), associated with other neurological phenotypes and multiorgan involvement. JS is a ciliopathy, a spectrum of disorders whose causative genes encode proteins involved in the primary cilium apparatus. In order to elucidate ciliopathy-associated molecular mechanisms, human induced pluripotent stem cells (hiPSCs) were derived from a patient affected by JS carrying a homozygous missense mutation in the AHI1 gene (p.H896R) that encodes a protein named Jouberin