Search results for: brain activation

Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Kawasaki disease (KD) is the primary cause of acquired pediatric heart disease as an acute vasculitis. In children with prolonged fever, rash, and inflammation of the mucosa KD must be considered as a clinical diagnosis. There is a persuasive suggestion of immune-mediated damage as the pathophysiologic cascade of KD. For example, the invasion of cytotoxic T-cells supports a viral etiology and the inflammasome of the innate immune system is a critical component in the vasculitis formation in KD. Animal models of KD propose the cytokine profiles, such as increased IL-1 and GM-CSF, which cause vascular damage. CRP and IFN-γ elevated expression and the upregulation of IL-6, and IL-10 production are also described in previous studies. Untreated KD is a critical risk factor for coronary artery diseases and myocardial infarction. Vascular damage may encompass amplified T-cell activity. SMAD3 is an essential molecule in down-regulating T-cells and increasing expression of FoxP3. It has a critical effect in the differentiation of regulatory T-cells. The discrepancy of regulatory T-cells and pro-inflammatory Th17 has been studied in acute coronary syndrome during KD. However in the coronary artery damaged lymphocytes and IgA plasma cells are seen at the lesion locations, the major immune cells in the coronary lesions are monocytes/macrophages and neutrophils. These cells secrete TNF-α, and activates matrix metalloprotease (MMP)-9, reducing the integrity of vessels and prompting patients to arise aneurysm. MMPs can break down the components of the extracellular matrix and assist immune cell movement. IVIG as an effective form of treatment clarified the role of the immune system, which may target pathogenic antigens and regulate cytokine production. Several reports have revealed that in the coronary arteries, high expression of MMP-9 in monocyte/macrophage results in pathologic cascades. Curcumin is a potent antioxidant and anti-inflammatory molecule. Curcumin decreases the production of reactive oxygen and nitrogen species and inhibits transcription factors like AP-1 and NF-κB. Curcumin also contains the characteristics of inhibitory effects on MMPs, especially MMP-9. The upregulation of MMP-9 is an important cellular response. Curcumin treatment caused a reverse effect and down-regulates MMP-9 gene expression which may fund the anti-inflammatory effect. Curcumin inhibits MMP-9 expression via PKC and AMPK-dependent pathways in Human monocytes cells. Elevated expression and activity of MMP-9 are correlated with advanced vascular lesions. AMPK controls lipid metabolism and oxidation, and protein synthesis. AMPK is also necessary for the MMP-9 activity and THP-1 cell adhesion to endothelial cells. Curcumin was shown to inhibit the activation of AMPKα. Compound C (AMPK inhibitor) inhibits MMP-9 expression level. Therefore, through inactivating AMPKs and PKC, curcumin decreases the MMP-9 level, which results in inhibiting monocyte/macrophage differentiation. Compound C also suppress the phosphorylation of three major classes of MAP kinase signaling, suggesting that curcumin may suppress MMP-9 level by inactivation of MAPK pathways. MAPK cascades are activated to induce the expression of MMP-9. Curcumin inhibits MAPKs phosphorylation, which contributes to the down-regulation of MMP-9. This study demonstrated that the potential inhibitory properties of curcumin over MMP-9 lead to a therapeutic strategy to reduce the risk of coronary artery involvement during KD.

Keywords: MMP-9, coronary artery aneurysm, Kawasaki’s disease, curcumin, AMPK, immune system, NF-κB, MAPK

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Authors: Rajeswari Raguraman, Sowmya Parameswaran, Krishnakumar Subramanian, Jagat Kanwar, Rupinder Kanwar

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Background: Tumor microenvironment has been implicated in several cancers to regulate cell growth, invasion and metastasis culminating in outcome of therapy. Tumor stroma consists of multiple cell types that are in constant cross-talk with the tumor cells to favour a pro-tumorigenic environment. Not much is known about the existence of tumor microenvironment in the pediatric intraocular malignancy, Retinoblastoma (RB). In the present study, we aim to understand the multiple stromal cellular subtypes and tumor stromal interactions expressed in RB tumors. Materials and Methods: Immunohistochemistry for stromal cell markers CD31, CD68, alpha-smooth muscle (α-SMA), vimentin and glial fibrillary acidic protein (GFAP) was performed on formalin fixed paraffin embedded tissues sections of RB (n=12). The differential expression of stromal target molecules; fibroblast activation protein (FAP), tenascin-C (TNC), osteopontin (SPP1), bone marrow stromal antigen 2 (BST2), stromal derived factor 2 and 4 (SDF2 and SDF4) in primary RB tumors (n=20) and normal retina (n=5) was studied by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. The differential expression was correlated with the histopathological features of RB. The interaction between RB cell lines (Weri-Rb-1, NCC-RbC-51) and Bone marrow stromal cells (BMSC) was also studied using direct co-culture and indirect co-culture methods. The functional effect of the co-culture methods on the RB cells was evaluated by invasion and proliferation assays. Global gene expression was studied by using Affymetrix 3’ IVT microarray. Pathway prediction was performed using KEGG and the key molecules were validated using qRT-PCR. Results: The immunohistochemistry revealed the presence of several stromal cell types such as endothelial cells (CD31+;Vim+/-); macrophages (CD68+;Vim+/-); Fibroblasts (Vim+; CD31-;CD68- );myofibroblasts (α-SMA+/ Vim+) and invading retinal astrocytes/ differentiated retinal glia (GFAP+; Vim+). A characteristic distribution of these stromal cell types was observed in the tumor microenvironment, with endothelial cells predominantly seen in blood vessels and macrophages near actively proliferating tumor or necrotic areas. Retinal astrocytes and glia were predominant near the optic nerve regions in invasive tumors with sparse distribution in tumor foci. Fibroblasts were widely distributed with rare evidence of myofibroblasts in the tumor. Both gene and protein expression revealed statistically significant (P<0.05) up-regulation of FAP, TNC and BST2 in primary RB tumors compared to the normal retina. Co-culture of BMSC with RB cells promoted invasion and proliferation of RB cells in direct and indirect contact methods respectively. Direct co-culture of RB cell lines with BMSC resulted in gene expression changes in ECM-receptor interaction, focal adhesion, IL-8 and TGF-β signaling pathways associated with cancer. In contrast, various metabolic pathways such a glucose, fructose and amino acid metabolism were significantly altered under the indirect co-culture condition. Conclusion: The study suggests that the close interaction between RB cells and the stroma might be involved in RB tumor invasion and progression which is likely to be mediated by ECM-receptor interactions and secretory factors. Targeting the tumor stroma would be an attractive option for redesigning treatment strategies for RB.

Keywords: gene expression profiles, retinoblastoma, stromal cells, tumor microenvironment

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Authors: Ho Yin Wickson Cheung, Liora Malki-Epshtein

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Outdoor air pollution presents a significant challenge for public health globally, especially in urban areas, with road traffic acting as the primary contributor to air pollution. Several studies have documented the antagonistic relation between traffic-related air pollution (TRAP) and the impact on health, especially to the vulnerable group of population, particularly young pupils. Generally, TRAP could cause damage to their brain, restricting the ability of children to learn and, more importantly, causing detrimental respiratory issues in later life. Butlittle is known about the specific exposure of children at school during the school day and the impact this may have on their overall exposure to pollution at a crucial time in their development. This project has set out to examine the air quality across primary schools in South-East London and assesses the variability of data found based on their geographic location and surroundings. Nitrogen dioxide, PM contaminants, and carbon dioxide were collected with diffusion tubes and portable monitoring equipment for eight schools across three local areas, that are Greenwich, Lewisham, and Tower Hamlets. This study first examines the geographical features of the schools surrounding (E.g., coverage of urban road structure and green infrastructure), then utilize three different methods to capture pollutants data. Moreover, comparing the obtained results with existing data from monitoring stations to understand the differences in air quality before and during the pandemic. Furthermore, most studies in this field have unfortunately neglected human exposure to pollutants and calculated based on values from fixed monitoring stations. Therefore, this paper introduces an alternative approach by calculating human exposure to air pollution from real-time data obtained when commuting within related areas (Driving routes and field walking). It is found that schools located highly close to motorways are generally not suffering from the most air pollution contaminants. Instead, one with the worst traffic congested routes nearby might also result in poor air quality. Monitored results also indicate that the annual air pollution values have slightly decreased during the pandemic. However, the majority of the data is currently still exceeding the WHO guidelines. Finally, the total human exposures for NO2 during commuting in the two selected routes were calculated. Results illustrated the total exposure for route 1 were 21,730 μm/m3 and 28,378.32 μm/m3, and for route 2 were 30,672 μm/m3 and 16,473 μm/m3. The variance that occurred might be due to the difference in traffic volume that requires further research. Exposure for NO2 during commuting was plotted with detailed timesteps that have shown their peak usually occurred while commuting. These have consolidated the initial assumption to the extremeness of TRAP. To conclude, this paper has yielded significant benefits to understanding air quality across schools in London with the new approach of capturing human exposure (Driving routes). Confirming the severity of air pollution and promoting the necessity of considering environmental sustainability for policymakers during decision making to protect society's future pillars.

Keywords: air pollution, schools, pupils, congestion

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Authors: Bruno Biagianti, Angela Tseng, Kathy Wannaviroj, Allison Corlett, Megan DuBois, Kyu Lee, Suma Jacob

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Background: ASD is characterized by pervasive Sensory Processing Abnormalities (SPA) and social cognitive deficits that persist throughout the course of the illness and have been linked to functional abnormalities in specific neural systems that underlie the perception, processing, and representation of sensory information. SPA and social cognitive deficits are associated with difficulties in interpersonal relationships, poor development of social skills, reduced social interactions and lower academic performance. Importantly, they can hamper the effects of established evidence-based psychological treatments—including PEERS (Program for the Education and Enrichment of Relationship Skills), a parent/caregiver-assisted, 16-weeks social skills intervention—which nonetheless requires a functional brain capable of assimilating and retaining information and skills. As a matter of fact, some adolescents benefit from PEERS more than others, calling for strategies to increase treatment response rates. Objective: We will present interim data on CICADAS (Care Improving Cognition for ADolescents on the Autism Spectrum)—a clinician-assisted, closed-loop technology mobile application for adolescents with ASD. Via ten mobile assessments, CICADAS captures data on sensory processing abnormalities and associated cognitive deficits. These data populate a machine learning algorithm that tailors the delivery of ten neuroplasticity-based social cognitive training (NB-SCT) exercises targeting sensory processing abnormalities. Methods: In collaboration with the Autism Spectrum and Neurodevelopmental Disorders Clinic at the University of Minnesota, we conducted a fully remote, three-arm, randomized crossover trial with adolescents with ASD to document the acceptability of CICADAS and evaluate its potential as a stand-alone treatment or as a treatment enhancer of PEERS. Twenty-four adolescents with ASD (ages 11-18) have been initially randomized to 16 weeks of PEERS + CICADAS (Arm A) vs. 16 weeks of PEERS + computer games vs. 16 weeks of CICADAS alone (Arm C). After 16 weeks, the full battery of assessments has been remotely administered. Results: We have evaluated the acceptability of CICADAS by examining adherence rates, engagement patterns, and exit survey data. We found that: 1) CICADAS is able to serve as a treatment enhancer for PEERS, inducing greater improvements in sensory processing, cognition, symptom reduction, social skills and behaviors, as well as the quality of life compared to computer games; 2) the concurrent delivery of PEERS and CICADAS induces greater improvements in study outcomes compared to CICADAS only. Conclusion: While preliminary, our results indicate that the individualized assessment and treatment approach designed in CICADAS seems effective in inducing adaptive long-term learning about social-emotional events. CICADAS-induced enhancement of processing and cognition facilitates the application of PEERS skills in the environment of adolescents with ASD, thus improving their real-world functioning.

Keywords: ASD, social skills, cognitive training, mobile app

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Authors: Berengere Vire, Nicolas Salvetat, Yoann Lannay, Guillaume Marcellin, Siem Van Der Laan, Franck Molina, Dinah Weissmann

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Predicting suicidal behaviors is one of the most complex challenges of daily psychiatric practices. Today, suicide risk prediction using biological tools is not validated and is only based on subjective clinical reports of the at-risk individual. Therefore, there is a great need to identify biomarkers that would allow early identification of individuals at risk of suicide. Alterations of adenosine-to-inosine (A-to-I) RNA editing of neurotransmitter receptors and other proteins have been shown to be involved in etiology of different psychiatric disorders and linked to suicidal behavior. RNA editing is a co- or post-transcriptional process leading to a site-specific alteration in RNA sequences. It plays an important role in the epi transcriptomic regulation of RNA metabolism. On postmortem human brain tissue (prefrontal cortex) of depressed suicide victims, Alcediag found specific alterations of RNA editing activity on the mRNA coding for the serotonin 2C receptor (5-HT2cR). Additionally, an increase in expression levels of ADARs, the RNA editing enzymes, and modifications of RNA editing profiles of prime targets, such as phosphodiesterase 8A (PDE8A) mRNA, have also been observed. Interestingly, the PDE8A gene is located on chromosome 15q25.3, a genomic region that has recurrently been associated with the early-onset major depressive disorder (MDD). In the current study, we examined whether modifications in RNA editing profile of prime targets allow identifying disease-relevant blood biomarkers and evaluating suicide risk in patients. To address this question, we performed a clinical study to identify an RNA editing signature in blood of depressed patients with and without the history of suicide attempts. Patient’s samples were drawn in PAXgene tubes and analyzed on Alcediag’s proprietary RNA editing platform using next generation sequencing technology. In addition, gene expression analysis by quantitative PCR was performed. We generated a multivariate algorithm comprising various selected biomarkers to detect patients with a high risk to attempt suicide. We evaluated the diagnostic performance using the relative proportion of PDE8A mRNA editing at different sites and/or isoforms as well as the expression of PDE8A and the ADARs. The significance of these biomarkers for suicidality was evaluated using the area under the receiver-operating characteristic curve (AUC). The generated algorithm comprising the biomarkers was found to have strong diagnostic performances with high specificity and sensitivity. In conclusion, we developed tools to measure disease-specific biomarkers in blood samples of patients for identifying individuals at the greatest risk for future suicide attempts. This technology not only fosters patient management but is also suitable to predict the risk of drug-induced psychiatric side effects such as iatrogenic increase of suicidal ideas/behaviors.

Keywords: blood biomarker, next-generation-sequencing, RNA editing, suicide

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Authors: Jessica M. Black

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Although much of natural and social science research aims to enhance human flourishing and address social problems, the training within the two fields is significantly different across theory, methodology, and implementation of results. Social scientists are trained in social, psychological, and to the extent that it is relevant to their discipline, spiritual development, theory, and accompanying methodologies. They tend not to receive training or learn about accompanying methodology related to interrogating human development and social problems from a biological perspective. On the other hand, those in the natural sciences, and for the purpose of this work, human biological sciences specifically – biology, neuroscience, genetics, epigenetics, and physiology – are often trained first to consider cellular development and related methodologies, and may not have opportunity to receive formal training in many of the foundational principles that guide human development, such as systems theory or person-in-environment framework, methodology related to tapping both proximal and distal psycho-social-spiritual influences on human development, and foundational principles of equity, justice and inclusion in research design. There is a need for disciplines heretofore siloed to know one another, to receive streamlined, easy to access training in theory and methods from one another and to learn how to build interdisciplinary teams that can speak and act upon a shared research language. Team science is more essential than ever, as are transdisciplinary approaches to training and research design. This study explores the use of a methodological toolbox that natural and social scientists can use by employing a decision-making tree regarding project aims, costs, and participants, among other important study variables. The decision tree begins with a decision about whether the researcher wants to learn more about social sciences approaches or biological approaches to study design. The toolbox and platform are flexible, such that users could also choose among modules, for instance, reviewing epigenetics or community-based participatory research even if those are aspects already a part of their home field. To start, both natural and social scientists would receive training on systems science, team science, transdisciplinary approaches, and translational science. Next, social scientists would receive training on grounding biological theory and the following methodological approaches and tools: physiology, (epi)genetics, non-invasive neuroimaging, invasive neuroimaging, endocrinology, and the gut-brain connection. Natural scientists would receive training on grounding social science theory, and measurement including variables, assessment and surveys on human development as related to the developing person (e.g., temperament and identity), microsystems (e.g., systems that directly interact with the person such as family and peers), mesosystems (e.g., systems that interact with one another but do not directly interact with the individual person, such as parent and teacher relationships with one another), exosystems (e.g., spaces and settings that may come back to affect the individual person, such as a parent’s work environment, but within which the individual does not directly interact, macrosystems (e.g., wider culture and policy), and the chronosystem (e.g., historical time, such as the generational impact of trauma). Participants will be able to engage with the toolbox and one another to foster increased transdisciplinary work

Keywords: methodology, natural science, social science, transdisciplinary

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Authors: Hyohun Kim, Dongwha Shin, Yeonseok Kim, Ji-Su Ahn, Kensuke Nakamura, Dongeun Choi, Byung-Woo Hong

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Artefacts are commonly encountered in the imaging process of clinical computed tomography (CT) where the artefact refers to any systematic discrepancy between the reconstructed observation and the true attenuation coefficient of the object. It is known that CT images are inherently more prone to artefacts due to its image formation process where a large number of independent detectors are involved, and they are assumed to yield consistent measurements. There are a number of different artefact types including noise, beam hardening, scatter, pseudo-enhancement, motion, helical, ring, and metal artefacts, which cause serious difficulties in reading images. Thus, it is desired to remove nuisance factors from the degraded image leaving the fundamental intrinsic information that can provide better interpretation of the anatomical and pathological characteristics. However, it is considered as a difficult task due to the high dimensionality and variability of data to be recovered, which naturally motivates the use of machine learning techniques. We propose an image restoration algorithm based on the deep neural network framework where the denoising auto-encoders are stacked building multiple layers. The denoising auto-encoder is a variant of a classical auto-encoder that takes an input data and maps it to a hidden representation through a deterministic mapping using a non-linear activation function. The latent representation is then mapped back into a reconstruction the size of which is the same as the size of the input data. The reconstruction error can be measured by the traditional squared error assuming the residual follows a normal distribution. In addition to the designed loss function, an effective regularization scheme using residual-driven dropout determined based on the gradient at each layer. The optimal weights are computed by the classical stochastic gradient descent algorithm combined with the back-propagation algorithm. In our algorithm, we initially decompose an input image into its intrinsic representation and the nuisance factors including artefacts based on the classical Total Variation problem that can be efficiently optimized by the convex optimization algorithm such as primal-dual method. The intrinsic forms of the input images are provided to the deep denosing auto-encoders with their original forms in the training phase. In the testing phase, a given image is first decomposed into the intrinsic form and then provided to the trained network to obtain its reconstruction. We apply our algorithm to the restoration of the corrupted CT images by the artefacts. It is shown that our algorithm improves the readability and enhances the anatomical and pathological properties of the object. The quantitative evaluation is performed in terms of the PSNR, and the qualitative evaluation provides significant improvement in reading images despite degrading artefacts. The experimental results indicate the potential of our algorithm as a prior solution to the image interpretation tasks in a variety of medical imaging applications. This work was supported by the MISP(Ministry of Science and ICT), Korea, under the National Program for Excellence in SW (20170001000011001) supervised by the IITP(Institute for Information and Communications Technology Promotion).

Keywords: auto-encoder neural network, CT image artefact, deep learning, intrinsic image representation, noise reduction, total variation

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Authors: Michelle Maurer, Antonia Last, Mark S. Gresnigt, Bernhard Hube, Alexander S. Mosig

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The intestinal epithelium forms an essential barrier to prevent translocation of microorganisms, toxins or other potentially harmful molecules into the bloodstream. In particular, dendritic cells of the intestinal epithelium orchestrate an adapted response of immune tolerance to commensals and immune defense against invading pathogens. Systemic inflammation is typically associated with a dysregulation of this adapted immune response and is accompanied by a disruption of the epithelial and endothelial gut barrier which enables dissemination of pathogens within the human body. To understand the pathophysiological mechanisms underlying the inflammation-associated gut barrier breakdown, it is crucial to elucidate the complex interplay of the host and the intestinal microbiome. A microfluidically perfused three-dimensional intestine-on-chip model was established to emulate these processes in the presence of immune cells, commensal bacteria, and facultative pathogens. Multi-organ tissue flow (MOTiF) biochips made from polystyrene were used for microfluidic perfusion of the intestinal tissue model. The biochips are composed of two chambers separated by a microporous membrane. Each chamber is connected to inlet and outlet channels allowing independent perfusion of the individual channels and application of microfluidic shear stress. Human umbilical vein endothelial cells (HUVECs), monocyte-derived macrophages and intestinal epithelial cells (Caco-2) were assembled on the biochip membrane. Following 7 – 14 days of growth in the presence of physiological flow conditions, the epithelium was colonized with the commensal bacterium Lactobacillus rhamnosus, while the endothelium was perfused with peripheral blood mononuclear cells (PBMCs). Additionally, L. rhamnosus was co-cultivated with the opportunistic fungal pathogen Candida albicans. Within one week of perfusion, the epithelial cells formed self-organized and well-polarized villus- and crypt-like structures that resemble essential morphological characteristics of the human intestine. Dendritic cells were differentiated in the epithelial tissue that specifically responds to bacterial lipopolysaccharide (LPS) challenge. LPS is well-tolerated at the luminal epithelial side of the intestinal model without signs of tissue damage or induction of an inflammatory response, even in the presence of circulating PBMC at the endothelial lining. In contrast, LPS stimulation at the endothelial side of the intestinal model triggered the release of pro-inflammatory cytokines such as TNF, IL-1β, IL-6, and IL-8 via activation of macrophages residing in the endothelium. Perfusion of the endothelium with PBMCs led to an enhanced cytokine release. L. rhamnosus colonization of the model was tolerated in the immune competent tissue model and was demonstrated to reduce damage induced by C. albicans infection. A microfluidic intestine-on-chip model was developed to mimic a systemic infection with a dysregulated immune response under physiological conditions. The model facilitates the colonization of commensal bacteria and co-cultivation with facultative pathogenic microorganisms. Both, commensal bacteria alone and facultative pathogens controlled by commensals, are tolerated by the host and contribute to cell signaling. The human intestine-on-chip model represents a promising tool to mimic microphysiological conditions of the human intestine and paves the way for more detailed in vitro studies of host-microbiota interactions under physiologically relevant conditions.

Keywords: host-microbiota interaction, immune tolerance, microfluidics, organ-on-chip

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Authors: Eduardo Rodrigues, Gisela Mendes, José M. Torres, José E. Sousa

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In the sequence of the liberalisation of the electricity sector a progressive engagement of consumers has been considered and targeted by sector regulatory policies. With the objective of promoting market competition while protecting consumers interests, by transferring some of the upstream benefits to the end users while reaching a fair distribution of system costs, different market models to value consumers’ demand flexibility at the energy community level are envisioned. Local Energy and Flexibility Markets (LEFM) involve stakeholders interested in providing or procure local flexibility for community, services and markets’ value. Under the scope of DOMINOES, a European research project supported by Horizon 2020, the local market concept developed is expected to: • Enable consumers/prosumers empowerment, by allowing them to value their demand flexibility and Distributed Energy Resources (DER); • Value local liquid flexibility to support innovative distribution grid management, e.g., local balancing and congestion management, voltage control and grid restoration; • Ease the wholesale market uptake of DER, namely small-scale flexible loads aggregation as Virtual Power Plants (VPPs), facilitating Demand Response (DR) service provision; • Optimise the management and local sharing of Renewable Energy Sources (RES) in Medium Voltage (MV) and Low Voltage (LV) grids, trough energy transactions within an energy community; • Enhance the development of energy markets through innovative business models, compatible with ongoing policy developments, that promote the easy access of retailers and other service providers to the local markets, allowing them to take advantage of communities’ flexibility to optimise their portfolio and subsequently their participation in external markets. The general concept proposed foresees a flow of market actions, technical validations, subsequent deliveries of energy and/or flexibility and balance settlements. Since the market operation should be dynamic and capable of addressing different requests, either prioritising balancing and prosumer services or system’s operation, direct procurement of flexibility within the local market must also be considered. This paper aims to highlight the research on the definition of suitable DR models to be used by the Distribution System Operator (DSO), in case of technical needs, and by the retailer, mainly for portfolio optimisation and solve unbalances. The models to be proposed and implemented within relevant smart distribution grid and microgrid validation environments, are focused on day-ahead and intraday operation scenarios, for predictive management and near-real-time control respectively under the DSO’s perspective. At local level, the DSO will be able to procure flexibility in advance to tackle different grid constrains (e.g., demand peaks, forecasted voltage and current problems and maintenance works), or during the operating day-to-day, to answer unpredictable constraints (e.g., outages, frequency deviations and voltage problems). Due to the inherent risks of their active market participation retailers may resort to DR models to manage their portfolio, by optimising their market actions and solve unbalances. The interaction among the market actors involved in the DR activation and in flexibility exchange is explained by a set of sequence diagrams for the DR modes of use from the DSO and the energy provider perspectives. • DR for DSO’s predictive management – before the operating day; • DR for DSO’s real-time control – during the operating day; • DR for retailer’s day-ahead operation; • DR for retailer’s intraday operation.

Keywords: demand response, energy communities, flexible demand, local energy and flexibility markets

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Authors: Nilam Bano, Uzma Iram

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Globally, the dilemma of undernutrition has become a notable concern for the researchers, academicians, and policymakers because of its severe consequences for many centuries. The nutritional deficiencies create hurdles for the people to achieve goals related to live a better lifestyle. Not only at micro level but also at the macro level, the consequences of undernutrition affect the economic progress of the country. The initial five years of a child’s life are considered critical for the physical growth and brain development. In this regard, children require special care and good quality food (nutrient intake) to fulfill their nutritional demand of the growing body. Having the sensitive stature and health, children specially under the age of 5 years are more vulnerable to the poor economic, housing, environmental and other social conditions. Beside confronting economic challenges and political upheavals, Pakistan is also going through from a rough patch in the context of social development. Majority of the children are facing serious health problems in the absence of required nutrition. The complexity of this issue is getting severe day by day and specially children are left behind with different type of immune problems and vitamins and mineral deficiencies. It is noted that children from the well-off background are less likely affected by the undernutrition. In order to underline this issue, the present study aims to highlight the existing nutritional inequalities among the children of under five years in Pakistan. Moreover, this study strives to decompose those factors that severely affect the existing nutritional inequality and standing in the queue to capture the consideration of concerned authorities. Pakistan Demographic and Health Survey 2012-13 was employed to assess the relevant indicators of undernutrition such as stunting, wasting, underweight and associated socioeconomic factors. The objectives were executed through the utilization of the relevant empirical techniques. Concentration indices were constructed to measure the nutritional inequalities by utilizing three measures of undernutrition; stunting, wasting and underweight. In addition to it, the decomposition analysis following the logistic regression was made to unfold the determinants that severely affect the nutritional inequalities. The negative values of concentration indices illustrate that children from the marginalized background are affected by the undernutrition more than their counterparts who belong from rich households. Furthermore, the result of decomposition analysis indicates that child age, size of a child at birth, wealth index, household size, parents’ education, mother’s health and place of residence are the most contributing factors in the prevalence of existing nutritional inequalities. Considering the result of the study, it is suggested to the policymakers to design policies in a way so that the health sector of Pakistan can stimulate in a productive manner. Increasing the number of effective health awareness programs for mothers would create a notable difference. Moreover, the education of the parents must be concerned by the policymakers as it has a significant association with the present research in terms of eradicating the nutritional inequalities among children.

Keywords: concentration index, decomposition analysis, inequalities, undernutrition, Pakistan

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Authors: Reggie Chandra

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Trafficaccidents and traffic signal optimization are correlated. However, 70-90% of the traffic signals across the USA are not synchronized. The reason behind that is insufficient resources to create and implement timing plans. In this work, we will discuss the use of a breakthrough Artificial Intelligence (AI) technology to optimize traffic flow and collect 24/7/365 accurate traffic data using a vehicle detection system. We will discuss what are recent advances in Artificial Intelligence technology, how does AI work in vehicles, pedestrians, and bike data collection, creating timing plans, and what is the best workflow for that. Apart from that, this paper will showcase how Artificial Intelligence makes signal timing affordable. We will introduce a technology that uses Convolutional Neural Networks (CNN) and deep learning algorithms to detect, collect data, develop timing plans and deploy them in the field. Convolutional Neural Networks are a class of deep learning networks inspired by the biological processes in the visual cortex. A neural net is modeled after the human brain. It consists of millions of densely connected processing nodes. It is a form of machine learning where the neural net learns to recognize vehicles through training - which is called Deep Learning. The well-trained algorithm overcomes most of the issues faced by other detection methods and provides nearly 100% traffic data accuracy. Through this continuous learning-based method, we can constantly update traffic patterns, generate an unlimited number of timing plans and thus improve vehicle flow. Convolutional Neural Networks not only outperform other detection algorithms but also, in cases such as classifying objects into fine-grained categories, outperform humans. Safety is of primary importance to traffic professionals, but they don't have the studies or data to support their decisions. Currently, one-third of transportation agencies do not collect pedestrian and bike data. We will discuss how the use of Artificial Intelligence for data collection can help reduce pedestrian fatalities and enhance the safety of all vulnerable road users. Moreover, it provides traffic engineers with tools that allow them to unleash their potential, instead of dealing with constant complaints, a snapshot of limited handpicked data, dealing with multiple systems requiring additional work for adaptation. The methodologies used and proposed in the research contain a camera model identification method based on deep Convolutional Neural Networks. The proposed application was evaluated on our data sets acquired through a variety of daily real-world road conditions and compared with the performance of the commonly used methods requiring data collection by counting, evaluating, and adapting it, and running it through well-established algorithms, and then deploying it to the field. This work explores themes such as how technologies powered by Artificial Intelligence can benefit your community and how to translate the complex and often overwhelming benefits into a language accessible to elected officials, community leaders, and the public. Exploring such topics empowers citizens with insider knowledge about the potential of better traffic technology to save lives and improve communities. The synergies that Artificial Intelligence brings to traffic signal control and data collection are unsurpassed.

Keywords: artificial intelligence, convolutional neural networks, data collection, signal control, traffic signal

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Authors: Saule Balmagambetova, Zhenisgul Tlegenova, Saule Madinova

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Cardiotoxicity associated with anticancer treatment, now defined as cancer therapy-related cardiac dysfunction (CTRCD), accompanies cancer patients and negatively impacts their survivorship. Currently, a cardio-oncological service is being created in Kazakhstan based on the provisions of the European Society of Cardio-oncology (ESC) Guidelines. In the frames of a pilot project, a cohort study on CTRCD conditions was initiated at the Aktobe Cancer center. One hundred twenty-eight newly diagnosed breast cancer patients started on doxorubicin and/or trastuzumab were recruited. Echocardiography with global longitudinal strain (GLS) assessment, biomarkers panel (cardiac troponin (cTnI), brain natriuretic peptide (BNP), myeloperoxidase (MPO), galectin-3 (Gal-3), D-dimers, C-reactive protein (CRP)), and other tests were performed at baseline and every three months. Patients were stratified by the cardiovascular risks according to the ESC recommendations and allocated into the risk groups during the pre-treatment visit. Of them, 10 (7.8%) patients were assigned to the high-risk group, 48 (37.5%) to the medium-risk group, and 70 (54.7%) to the low-risk group, respectively. High-risk patients have been receiving their cardioprotective treatment from the outset. Patients were also divided by treatment - in the anthracycline-based 83 (64.8%), in trastuzumab- only 13 (10.2%), and in the mixed anthracycline/trastuzumab group 32 individuals (25%), respectively. Mild symptomatic CTRCD was revealed and treated in 2 (1.6%) participants, and a mild asymptomatic variant in 26 (20.5%). Mild asymptomatic conditions are defined as left ventricular ejection fraction (LVEF) ≥50% and further relative reduction in GLS by >15% from baseline and/or a further rise in cardiac biomarkers. The listed biomarkers were assessed longitudinally in repeated-measures linear regression models during 12 months of observation. The associations between changes in biomarkers and CTRCD and between changes in biomarkers and LVEF were evaluated. Analysis by risk groups revealed statistically significant differences in baseline LVEF scores (p 0.001), BNP (p 0.0075), and Gal-3 (p 0.0073). Treatment groups found no statistically significant differences at baseline. After 12 months of follow-up, only LVEF values showed a statistically significant difference by risk groups (p 0.0011). When assessing the temporal changes in the studied parameters for all treatment groups, there were statistically significant changes from visit to visit for LVEF (p 0.003); GLS (p 0.0001); BNP (p<0.00001); MPO (p<0.0001); and Gal-3 (p<0.0001). No moderate or strong correlations were found between the biomarkers values and LVEF, between biomarkers and GLS. Between the biomarkers themselves, a moderate, close to strong correlation was established between cTnI and D-dimer (r 0.65, p<0.05). The dose-dependent effect of anthracyclines has been confirmed: the summary dose has a moderate negative impact on GLS values: -r 0.31 for all treatment groups (p<0.05). The present study found myeloperoxidase as a promising biomarker of cardiac dysfunction in the mixed anthracycline/trastuzumab treatment group. The hazard of CTRCD increased by 24% (HR 1.21; 95% CI 1.01;1.73) per doubling in baseline MPO value (p 0.041). Increases in BNP were also associated with CTRCD (HR per doubling, 1.22; 95% CI 1.12;1.69). No cases of chemotherapy discontinuation due to cardiotoxic complications have been recorded. Further observations are needed to gain insight into the ability of biomarkers to predict CTRCD onset.

Keywords: breast cancer, chemotherapy, cardiotoxicity, Kazakhstan

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Authors: Soumia Hammadi, Imane Nouacer, Lamine Hamida, Younes A. Hammadi, Rachid Chaibi

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Aims and objective: In the present work, we investigate the impact of both acute and chronic diabetes mellitus induced by streptozotocin (STZ) on the hypothalamus of the small gerbil (Gerbillus gerbillus). In this purpose, we aimed to study the histologic structure of the gerbil’s hypothalamic supraoptic (NSO) and paraventricular nucleus (NPV) at two distinct time points: two days and 30 days after diabetes onset. Methods: We conducted our investigation using 19 adult male gerbils weighing 25 to 28 g, divided into three groups as follow: Group I: Control gerbils (n=6) received an intraperitoneal injection of citrate buffer. Group II: STZ-diabetic gerbils (n=8) received a single intraperitoneal injection of STZ at a dose of 165 mg/kg of body weight. Diabetes onset (D0) is considered with the first hyperglycemia level exceeding 2,5 g/L. This group was further divided into two subgroups: Group II-1: Experimental Gerbils, at acute state of diabetes (n=8) sacrificed after 02 days of diabetes onset, Group II-2: Experimental Gerbils at chronic state of diabetes (n=7) sacrificed after 30 days of diabetes onset. Two and 30 days after diabetes onset, gerbils had blood drawn from the retro-orbital sinus into EDTA tubes. After centrifugation at -4°C, plasma was frozen at -80°C for later measurement of Cortisol, ACTH, and insulin. Afterward, animals were decapitated; their brain was removed, weighed, fixed in aqueous bouin, and processed and stained with Toluidine Bleu stain for histo-stereological analysis. A comparison was done with control gerbils treated with citrate buffer. Results: Compared to control gerbils, at 02 Days post diabetes onset, the neuronal somata of the paraventricular (NPV) and supraoptic nuclei (NSO) expressed numerous vacuoles of various sizes, we distinct also a neuronal juxtaposition and several unidentifiable vacuolated profiles were also seen in the neuropile. At the same time, we revealed the presence of à shrunken and condensed nuclei, which seem to touch the parvocellular neurons ( NPV); this leads us to suggest the presence of an apoptotic process in the early stage of diabetes. At 30 days of diabetes mellitus, the NPV manifests a few neurons with a distant appearance, in addition the magnocellular neurons in both NPV and NSO were hypertrophied with a rich euchromatin nucleus, a well-defined nucleolus, and a granular cytoplasm. Despite the neuronal degeneration at this stage, unexpectedly, ACTH registers a continuous significant high level compared to the early stage of diabetes mellitus and to control gerbils. Conclusion: The results suggest that the induction of diabetes mellitus using STZ in the small gerbils lead to alterations in the structure and morphology of the hypothalamus and hyper-secretion of ACTH and cortisol, possibly indicating hyperactivity of the hypothalamo-pituitary adrenal axis (HPA) during both the early and later stages of the disease. The subsequent quantitative evaluation of CRH, immunehistochemical evaluation of apoptosis, and oxidative stress assessment could corroborate our results.

Keywords: diabetes type 1., streptozotocin., small gerbil., hypothalamus., paraventricular nucleus., supraoptic nucleus.

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Authors: Michael Brave, Mark Kroll, Steven Karch, Charles Wetli, Michael Graham, Sebastian Kunz, Dorin Panescu

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Background: Conducted electrical weapons (CEW) are now used in 107 countries and are a common law enforcement less-lethal force practice in the United Kingdom (UK), United States of America (USA), Canada, Australia, New Zealand, and others. Use of these devices is rarely temporally associated with the occurrence of sudden arrest-related deaths (ARD). Because such deaths are uncommon, few Medical Examiners (MEs) ever encounter one, and even fewer offices have established comprehensive investigative protocols. Without sufficient scientific data, the role, if any, played by a CEW in a given case is largely supplanted by conjecture often defaulting to a CEW-induced fatal cardiac arrhythmia. In addition to the difficulty in investigating individual deaths, the lack of information also detrimentally affects being able to define and evaluate the ARD cohort generally. More comprehensive, better information leads to better interpretation in individual cases and also to better research. The purpose of this presentation is to provide MEs with a comprehensive evidence-based checklist to assist in the assessment of CEW-ARD cases. Methods: PUBMED and Sociology/Criminology data bases were queried to find all medical, scientific, electrical, modeling, engineering, and sociology/criminology peer-reviewed literature for mentions of CEW or synonymous terms. Each paper was then individually reviewed to identify those that discussed possible bioelectrical mechanisms relating CEW to ARD. A Naranjo-type pharmacovigilance algorithm was also employed, when relevant, to identify and quantify possible direct CEW electrical myocardial stimulation. Additionally, CEW operational manuals and training materials were reviewed to allow incorporation of CEW-specific technical parameters. Results: Total relevant PUBMED citations of CEWs were less than 250, and reports of death extremely rare. Much relevant information was available from Sociology/Criminology data bases. Once the relevant published papers were identified, and reviewed, we compiled an annotated checklist of data that we consider critical to a thorough CEW-involved ARD investigation. Conclusion: We have developed an evidenced-based checklist that can be used by MEs and their staffs to assist them in identifying, collecting, documenting, maintaining, and objectively analyzing the role, if any, played by a CEW in any specific case of sudden death temporally associated with the use of a CEW. Even in cases where the collected information is deemed by the ME as insufficient for formulating an opinion or diagnosis to a reasonable degree of medical certainty, information collected as per the checklist will often be adequate for other stakeholders to use as a basis for informed decisions. Having reviewed the appropriate materials in a significant number of cases careful examination of the heart and brain is likely adequate. Channelopathy testing should be considered in some cases, however it may be considered cost prohibitive (aprox $3000). Law enforcement agencies may want to consider establishing a reserve fund to help manage such rare cases. The expense may stay the enormous costs associated with incident-precipitated litigation.

Keywords: ARD, CEW, police, TASER

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Authors: Asma Ben Hmidene, Mizuho Hanaki, Kazuma Murakami, Kazuhiro Irie, Hiroko Isoda, Hideyuki Shigemori

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Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) are characterized as a peripheral metabolic disorder and a degenerative disease of the central nervous system, respectively. It is now widely recognized that T2DM and AD share many pathophysiological features including glucose metabolism, increased oxidative stress and amyloid aggregation. Amyloid beta (Aβ) is the components of the amyloid deposits in the AD brain and while the component of the amyloidogenic peptide deposit in the pancreatic islets of Langerhans is identified as human islet amyloid polypeptide (hIAPP). These two proteins are originated from the amyloid precursor protein and have a high sequence similarity. Although the amino acid sequences of amyloidogenic proteins are diverse, they all adopt a similar structure in aggregates called cross-beta-spine. Add at that, extensive studies in the past years have found that like Aβ1-42, IAPP forms early intermediate assemblies as spherical oligomers, implicating that these oligomers possess a common folding pattern or conformation. These similarities can be used in the search for effective pharmacotherapy for DM, since potent therapeutic agents such as antioxidants with a catechol moiety, proved to inhibit Aβ aggregation, may play a key role in the inhibit the aggregation of hIAPP treatment of patients with DM. Tamarix gallica is one of the halophyte species having a powerful antioxidant system. Although it was traditionally used for the treatment of various liver metabolic disorders, there is no report about the use of this plant for the treatment or prevention of T2DM and AD. Therefore, the aim of this work is to investigate their protective effect towards T2DM and AD by isolation and identification of α-glucosidase inhibitors, with antioxidant potential, that play an important role in the glucose metabolism in diabetic patient, as well as, the polymerization of hIAPP and Aβ aggregation inhibitors. Structure-activity relationship study was conducted for both assays. And as for α-glucosidase inhibitors, their mechanism of action and their synergistic potential when applied with a very low concentration of acarbose were also suggesting that they can be used not only as α-glucosidase inhibitors but also be combined with established α-glucosidase inhibitors to reduce their adverse effect. The antioxidant potential of the purified substances was evaluated by DPPH and SOD assays. Th-T assay using 42-mer amyloid β-protein (Aβ42) for AD and hIAPP which is a 37-residue peptide secreted by the pancreatic β –cells for T2DM and Transmission electronic microscopy (TEM) were conducted to evaluate the amyloid aggragation of the actives substances. For α-glucosidase, p-NPG and glucose oxidase assays were performed for determining the inhibition potential and structure-activity relationship study. The Enzyme kinetic protocol was used to study the mechanism of action. From this research, it was concluded that polyphenols playing a role in the glucose metabolism and oxidative stress can also inhibit the amyloid aggregation, and that substances with a catechol and glucuronide moieties inhibiting amyloid-β aggregation, might be used to inhibit the aggregation of hIAPP.

Keywords: α-glucosidase inhibitors, amyloid aggregation inhibition, mechanism of action, polyphenols, structure activity relationship, synergistic potential, tamarix gallica

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Authors: V. K. Tewari, M. Hussain, H. K. D. Gupta

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Background: Nitric Oxide Donars (NODs) (intrathecal sodium nitroprusside (ITSNP) and oral tadalafil 20mg post ITSNP) has been studied in this context in cerebral palsy patients for fast recovery. This work proposes two mechanisms for acute cases and one mechanism for chronic cases, which are interrelated, for physiological recovery. a) Retrograde Neurotransmission (acute cases): 1) Normal excitatory impulse: at the synaptic level, glutamate activates NMDA receptors, with nitric oxide synthetase (NOS) on the postsynaptic membrane, for further propagation by the calcium-calmodulin complex. Nitric oxide (NO, produced by NOS) travels backward across the chemical synapse and binds the axon-terminal NO receptor/sGC of a presynaptic neuron, regulating anterograde neurotransmission (ANT) via retrograde neurotransmission (RNT). Heme is the ligand-binding site of the NO receptor/sGC. Heme exhibits > 10,000-fold higher affinity for NO than for oxygen (the 10,000-fold effect) and is completed in 20 msec. 2) Pathological conditions: normal synaptic activity, including both ANT and RNT, is absent. A NO donor (SNP) releases NO from NOS in the postsynaptic region. NO travels backward across a chemical synapse to bind to the heme of a NO receptor in the axon terminal of a presynaptic neuron, generating an impulse, as under normal conditions. b) Vasopasm: (acute cases) Perforators show vasospastic activity. NO vasodilates the perforators via the NO-cAMP pathway. c) Long-Term Potentiation (LTP): (chronic cases) The NO–cGMP-pathway plays a role in LTP at many synapses throughout the CNS and at the neuromuscular junction. LTP has been reviewed both generally and with respect to brain regions specific for memory/learning. Aims/Study Design: The principles of “generation of impulses from the presynaptic region to the postsynaptic region by very potent RNT (10,000-fold effect)” and “vasodilation of arteriolar perforators” are the basis of the authors’ hypothesis to treat cerebral palsy cases. Case-control prospective study. Materials and Methods: The experimental population included 82 cerebral palsy patients (10 patients were given control treatments without NOD or with 5% dextrose superfusion, and 72 patients comprised the NOD group). The mean time for superfusion was 5 months post-cerebral palsy. Pre- and post-NOD status was monitored by Gross Motor Function Classification System for Cerebral Palsy (GMFCS), MRI, and TCD studies. Results: After 7 days in the NOD group, the mean change in the GMFCS score was an increase of 1.2 points mean; after 3 months, there was an increase of 3.4 points mean, compared to the control-group increase of 0.1 points at 3 months. MRI and TCD documented the improvements. Conclusions: NOD (ITSNP boosts up the recovery and oral tadalafil maintains the recovery to a well-desired level) acts swiftly in the treatment of CP, acting within 7 days on 5 months post-cerebral palsy either of the three mechanisms.

Keywords: cerebral palsy, intrathecal sodium nitroprusside, oral tadalafil, perforators, vasodilations, retrograde transmission, the 10, 000-fold effect, long-term potantiation

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Authors: Alok Bapatla, Pamela Lutting, Mariastella Serrano

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Background: Irritable Bowel Syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain associated with altered bowel habits in the absence of an underlying organic cause. Although the exact etiology of IBS is not fully understood, one of the leading theories postulates a pathology within the Brain-Gut Axis that leads to an overall increase in gastrointestinal sensitivity and pejorative changes in gastrointestinal motility. Research and clinical practice have shown that Gut Directed Hypnotherapy (GDH) has a beneficial clinical role in improving Mind-Gut control and thereby comorbid conditions such as anxiety, abdominal pain, constipation, and diarrhea. Aims: This study presents a 17-year old male with underlying anxiety and a one-year history of IBS-Constipation Predominant Subtype (IBS-C), who has demonstrated impressive improvement of symptoms following GDH treatment following refractory trials with medications including bisacodyl, senna, docusate, magnesium citrate, lubiprostone, linaclotide. Method: The patient was referred to a licensed clinical psychologist specializing in clinical hypnosis and cognitive-behavioral therapy (CBT), who implemented “The Standardized Hypnosis Protocol for IBS” developed by Dr. Olafur S. Palsson, Psy.D at the University of North Carolina at Chapel Hill. The hypnotherapy protocol consisted of a total of seven weekly 45-minute sessions supplemented with a 20-minute audio recording to be listened to once daily. Outcome variables included the GAD-7, PHQ-9 and DCI-2, as well as self-ratings (ranging 0-10) for pain (intensity and frequency), emotional distress about IBS symptoms, and overall emotional distress. All variables were measured at intake prior to administration of the hypnosis protocol and at the conclusion of the hypnosis treatment. A retrospective IBS Questionnaire (IBS Severity Scoring System) was also completed at the conclusion of the GDH treatment for pre-and post-test ratings of clinical symptoms. Results: The patient showed improvement in all outcome variables and self-ratings, including abdominal pain intensity, frequency of abdominal pain episodes, emotional distress relating to gut issues, depression, and anxiety. The IBS Questionnaire showed a significant improvement from a severity score of 400 (defined as severe) prior to GDH intervention compared to 55 (defined as complete resolution) at four months after the last session. IBS Questionnaire subset questions that showed a significant score improvement included abdominal pain intensity, days of pain experienced per 10 days, satisfaction with bowel habits, and overall interference of life affected by IBS symptoms. Conclusion: This case supports the existing research literature that GDH has a significantly beneficial role in improving symptoms in patients with IBS. Emphasis is placed on the numerical results of the IBS Questionnaire scoring, which reflects a patient who initially suffered from severe IBS with failed response to multiple medications, who subsequently showed full and sustained resolution

Keywords: pediatrics, constipation, irritable bowel syndrome, hypnotherapy, gut-directed hypnosis

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Authors: Vladimir Smirnov, Roman Tominov, Vadim Avilov, Oleg Ageev

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The creation of a new generation micro- and nanoelectronics elements opens up unlimited possibilities for electronic devices parameters improving, as well as developing neuromorphic computing systems. Interest in the latter is growing up every year, which is explained by the need to solve problems related to the unstructured classification of data, the construction of self-adaptive systems, and pattern recognition. However, for its technical implementation, it is necessary to fulfill a number of conditions for the basic parameters of electronic memory, such as the presence of non-volatility, the presence of multi-bitness, high integration density, and low power consumption. Several types of memory are presented in the electronics industry (MRAM, FeRAM, PRAM, ReRAM), among which non-volatile resistive memory (ReRAM) is especially distinguished due to the presence of multi-bit property, which is necessary for neuromorphic systems manufacturing. ReRAM is based on the effect of resistive switching – a change in the resistance of the oxide film between low-resistance state (LRS) and high-resistance state (HRS) under an applied electric field. One of the methods for the technical implementation of neuromorphic systems is cross-bar structures, which are ReRAM cells, interconnected by cross data buses. Such a structure imitates the architecture of the biological brain, which contains a low power computing elements - neurons, connected by special channels - synapses. The choice of the ReRAM oxide film material is an important task that determines the characteristics of the future neuromorphic system. An analysis of literature showed that many metal oxides (TiO2, ZnO, NiO, ZrO2, HfO2) have a resistive switching effect. It is worth noting that the manufacture of nanocomposites based on these materials allows highlighting the advantages and hiding the disadvantages of each material. Therefore, as a basis for the neuromorphic structures manufacturing, it was decided to use ZnₓTiᵧHfzOᵢ nanocomposite. It is also worth noting that the ZnₓTiᵧHfzOᵢ nanocomposite does not need an electroforming, which degrades the parameters of the formed ReRAM elements. Currently, this material is not well studied, therefore, the study of the effect of resistive switching in forming-free ZnₓTiᵧHfzOᵢ nanocomposite is an important task and the goal of this work. Forming-free nanocomposite ZnₓTiᵧHfzOᵢ thin film was grown by pulsed laser deposition (Pioneer 180, Neocera Co., USA) on the SiO2/TiN (40 nm) substrate. Electrical measurements were carried out using a semiconductor characterization system (Keithley 4200-SCS, USA) with W probes. During measurements, TiN film was grounded. The analysis of the obtained current-voltage characteristics showed a resistive switching from HRS to LRS resistance states at +1.87±0.12 V, and from LRS to HRS at -2.71±0.28 V. Endurance test shown that HRS was 283.21±32.12 kΩ, LRS was 1.32±0.21 kΩ during 100 measurements. It was shown that HRS/LRS ratio was about 214.55 at reading voltage of 0.6 V. The results can be useful for forming-free nanocomposite ZnₓTiᵧHfzOᵢ films in neuromorphic systems manufacturing. This work was supported by RFBR, according to the research project № 19-29-03041 mk. The results were obtained using the equipment of the Research and Education Center «Nanotechnologies» of Southern Federal University.

Keywords: nanotechnology, nanocomposites, neuromorphic systems, RRAM, pulsed laser deposition, resistive switching effect

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Authors: Michael R. Shurin, Galina Shurin, Vladimir A. Kirichenko

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Background. Visibility of hepatic malignancies is poor on non-contrast imaging for daily verification of liver malignancies prior to radiation therapy on MRI-guided Linear Accelerators (MR-Linac). Ferumoxytol® (Feraheme, AMAG Pharmaceuticals, Waltham, MA) is a SPION agent that is increasingly utilized off-label as hepatic MRI contrast. This agent has the advantage of providing a functional assessment of the liver based upon its uptake by hepatic Kupffer cells proportionate to vascular perfusion, resulting in strong T1, T2 and T2* relaxation effects and enhanced contrast of malignant tumors, which lack Kupffer cells. The latter characteristic has been recently utilized for MRI-guided radiotherapy planning with precision targeting of liver malignancies. However potential radiotoxicity of SPION has never been addressed for its safe use as an MRI-contrast agent during liver radiotherapy on MRI-Linac. This study defines the radiomodulating properties of SPIONs in vitro on human monocyte and macrophage cell lines exposed to 60Go gamma-rays within clinical radiotherapy dose range. Methods. Human monocyte and macrophages cell line in cultures were loaded with a clinically relevant concentration of Ferumoxytol (30µg/ml) for 2 and 24 h and irradiated to 3Gy, 5Gy and 10Gy. Cells were washed and cultured for additional 24 and 48 h prior to assessing their phenotypic activation by flow cytometry and function, including viability (Annexin V/PI assay), proliferation (MTT assay) and cytokine expression (Luminex assay). Results. Our results reveled that SPION affected both human monocytes and macrophages in vitro. Specifically, iron oxide nanoparticles decreased radiation-induced apoptosis and prevented radiation-induced inhibition of human monocyte proliferative activity. Furthermore, Ferumoxytol protected monocytes from radiation-induced modulation of phenotype. For instance, while irradiation decreased polarization of monocytes to CD11b+CD14+ and CD11bnegCD14neg phenotype, Ferumoxytol prevented these effects. In macrophages, Ferumoxytol counteracted the ability of radiation to up-regulate cell polarization to CD11b+CD14+ phenotype and prevented radiation-induced down-regulation of expression of HLA-DR and CD86 molecules. Finally, Ferumoxytol uptake by human monocytes down-regulated expression of pro-inflammatory chemokines MIP-1α (Macrophage inflammatory protein 1α), MIP-1β (CCL4) and RANTES (CCL5). In macrophages, Ferumoxytol reversed the expression of IL-1RA, IL-8, IP-10 (CXCL10) and TNF-α, and up-regulates expression of MCP-1 (CCL2) and MIP-1α in irradiated macrophages. Conclusion. SPION agent Ferumoxytol increases resistance of human monocytes to radiation-induced cell death in vitro and supports anti-inflammatory phenotype of human macrophages under radiation. The effect is radiation dose-dependent and depends on the duration of Feraheme uptake. This study also finds strong evidence that SPIONs reversed the effect of radiation on the expression of pro-inflammatory cytokines involved in initiation and development of radiation-induced liver damage. Correlative translational work at our institution will directly assess the cyto-protective effects of Ferumoxytol on human Kupfer cells in vitro and ex vivo analysis of explanted liver specimens in a subset of patients receiving Feraheme-enhanced MRI-guided radiotherapy to the primary liver tumors as a bridge to liver transplant.

Keywords: superparamagnetic iron oxide nanoparticles, radioprotection, magnetic resonance imaging, liver

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Authors: Jacqueline Eleonora Ek, Michael Spiteri, Chris Giordimaina, Pierre Agius

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Background: Malta is known for being a key player as a frontline country with regard to irregular immigration from Africa to Europe. Every year the island experiences an influx of migrants as boat movement across the Mediterranean continues to be a humanitarian challenge. Irregular immigration and applying for asylum is both a lengthy and mentally demanding process. Those doing so are often faced with multiple challenges, which can adversely affect their mental health. Between January and August 2020, Malta disembarked 2 162 people rescued at sea, 463 of them between July & August. Given the small size of the Maltese islands, this regulation places a disproportionately large burden on the country, creating a backlog in the processing of asylum applications resulting in increased time periods of detention. These delays reverberate throughout multiple management pathways resulting in prolonged periods of detention and challenging access to health services. Objectives: To better understand the spatial dimensions of this humanitarian crisis, this study aims to assess disparities in the acute medical management of migrants presenting to the emergency department (ED) with acute mental health presentations as compared to that of local and non-local residents. Method: In this retrospective study, 17795 consecutive ED attendances were reviewed to look for acute mental health presentations. These were further evaluated to assess discrepancies in transportation routes to hospital, nature of presenting complaint, effects of language barriers, use of CT brain, treatment given at ED, availability of psychiatric reviews, and final admission/discharge plans. Results: Of the ED attendances, 92.3% were local residents, and 7.7% were non-locals. Of the non-locals, 13.8% were migrants, and 86.2% were other-non-locals. Acute mental health presentations were seen in 1% of local residents; this increased to 20.6% in migrants. 56.4% of migrants attended with deliberate self-harm; this was lower in local residents, 28.9%. Contrastingly, in local residents, the most common presenting complaint was suicidal thought/ low mood 37.3%, the incidence was similar in migrants at 33.3%. The main differences included 12.8% of migrants presenting with refused oral intake while only 0.6% of local residents presented with the same complaints. 7.7% of migrants presented with a reduced level of consciousness, no local residents presented with this same issue. Physicians documented a language barrier in 74.4% of migrants. 25.6% were noted to be completely uncommunicative. Further investigations included the use of a CT scan in 12% of local residents and in 35.9% of migrants. The most common treatment administered to migrants was supportive fluids 15.4%, the most common in local residents was benzodiazepines 15.1%. Voluntary psychiatric admissions were seen in 33.3% of migrants and 24.7% of locals. Involuntary admissions were seen in 23% of migrants and 13.3% of locals. Conclusion: Results showed multiple disparities in health management. A meeting was held between entities responsible for migrant health in Malta, including the emergency department, primary health care, migrant detention services, and Malta Red Cross. Currently, national quality-improvement initiatives are underway to form new pathways to improve patient-centered care. These include an interpreter unit, centralized handover sheets, and a dedicated migrant health service.

Keywords: emergency department, communication, health, migration

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Authors: Michael Josef Schwerer, Oliver Peschel

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Background: The sense and purpose of forensic postmortem examinations are undoubtedly the same in Institutes of Legal Medicine all over the world. Cause and manner of death must be determined, persons responsible for unnatural death must be brought to justice, and accidents demand changes in the respective scenarios to avoid future mishaps. The latter particularly concerns aircraft accidents, not only regarding consequences from criminal or civil law but also in pursuance of the International Civil Aviation Authority’s regulations, which demand lessons from mishap investigations to improve flight safety. Irrespective of the distinct circumstances of a given casualty or the respective questions in subsequent death investigations, a forensic autopsy is the basis for all further casework, the clue to otherwise hidden solutions, and the crucial limitation for final success when not all possible findings have been properly collected. This also implies that the targeted work of police forces and expert witnesses strongly depends on the quality of forensic pathology practice. Deadly events in foreign countries, which lead to investigations not only abroad but also in Germany, can be challenging in this context. Frequently, second-look autopsies after the repatriation of the deceased to Germany are requested by the legal authorities to ensure proper and profound documentation of all relevant findings. Aims and Methods: To validate forensic postmortem practice abroad, a retrospective study using the findings in the corresponding second-look autopsies in the Institute of Legal Medicine Munich over the last 20 years was carried out. New findings unreported in the previous autopsy were recorded and judged for their relevance to solving the respective case. Further, the condition of the corpse at the time of the second autopsy was rated to discuss artifacts mimicking evidence or the possibility of lost findings resulting from, e.g., decomposition. Recommendations for future handling of death cases abroad and efficient autopsy practice were pursued. Results and Discussion: Our re-evaluation confirmed a high quality of autopsy practice abroad in the vast majority of cases. However, in some casework, incomplete documentation of pathology findings was revealed along with either insufficient or misconducted dissection of organs. Further, some of the bodies showed missing parts of some organs, most probably resulting from sampling for histology studies during the first postmortem. For the aeromedical evaluation of a decedent’s health status prior to an aviation mishap, particularly lost or obscured findings in the heart, lungs, and brain impeded expert testimony. Moreover, incomplete fixation of the body or body parts for repatriation was seen in several cases. This particularly involved previously dissected organs deposited back into the body cavities at the end of the first autopsy. Conclusions and Recommendations: Detailed preparation in the first forensic autopsy avoids the necessity of a second-look postmortem in the majority of cases. To limit decomposition changes during repatriation from abroad, special care must be taken to include pre-dissected organs in the chemical fixation process, particularly when they are separated from the blood vessels and just deposited back into the body cavities.

Keywords: autopsy practice, second-look autopsy, retrospective study, quality standards, decomposition changes, repatriation

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Authors: Yi-Hao Wong, Li-Li Chan, Chee-Onn Leong, Stephen Ambu, Joon-Wah Mak, Priyasashi Sahu

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Background: Acanthamoeba is a genus of amoebae which lives as a free-living in nature or as a human pathogen that causes severe brain and eye infections. Virulence potential of Acanthamoeba is not constant and can change with growth conditions. DNA methylation, an epigenetic process which adds methyl groups to DNA, is used by eukaryotic cells, including several human parasites to control their gene expression. We used qPCR, siRNA gene silencing, and RNA sequencing (RNA-Seq) to study DNA-methyltransferase gene family (DNMT) in order to indicate the possibility of its involvement in programming Acanthamoeba virulence potential. Methods: A virulence-attenuated Acanthamoeba isolate (designation: ATCC; original isolate: ATCC 50492) was subjected to mouse passages to restore its pathogenicity; a virulence-reactivated isolate (designation: AC/5) was generated. Several established factors associated with Acanthamoeba virulence phenotype were examined to confirm the succession of reactivation process. Differential gene expression of DNMT between ATCC and AC/5 isolates was performed by qPCR. Silencing on DNMT gene expression in AC/5 isolate was achieved by siRNA duplex. Total RNAs extracted from ATCC, AC/5, and siRNA-treated (designation: si-146) were subjected to RNA-Seq for comparative transcriptomic analysis in order to identify the genome-wide effect of DNMT in regulating Acanthamoeba gene expression. qPCR was performed to validate the RNA-Seq results. Results: Physiological and cytophatic assays demonstrated an increased in virulence potential of AC/5 isolate after mouse passages. DNMT gene expression was significantly higher in AC/5 compared to ATCC isolate (p ≤ 0.01) by qPCR. si-146 duplex reduced DNMT gene expression in AC/5 isolate by 30%. Comparative transcriptome analysis identified the differentially expressed genes, with 3768 genes in AC/5 vs ATCC isolate; 2102 genes in si-146 vs AC/5 isolate and 3422 genes in si-146 vs ATCC isolate, respectively (fold-change of ≥ 2 or ≤ 0.5, p-value adjusted (padj) < 0.05). Of these, 840 and 1262 genes were upregulated and downregulated, respectively, in si-146 vs AC/5 isolate. Eukaryotic orthologous group (KOG) assignments revealed a higher percentage of downregulated gene expression in si-146 compared to AC/5 isolate, were related to posttranslational modification, signal transduction and energy production. Gene Ontology (GO) terms for those downregulated genes shown were associated with transport activity, oxidation-reduction process, and metabolic process. Among these downregulated genes were putative genes encoded for heat shock proteins, transporters, ubiquitin-related proteins, proteins for vesicular trafficking (small GTPases), and oxidoreductases. Functional analysis of similar predicted proteins had been described in other parasitic protozoa for their survival and pathogenicity. Decreased expression of these genes in si146-treated isolate may account in part for Acanthamoeba reduced pathogenicity. qPCR on 6 selected genes upregulated in AC/5 compared to ATCC isolate corroborated the RNA sequencing findings, indicating a good concordance between these two analyses. Conclusion: To the best of our knowledge, this study represents the first genome-wide analysis of DNA methylation and its effects on gene expression in Acanthamoeba spp. The present data indicate that DNA methylation has substantial effect on global gene expression, allowing further dissection of the genome-wide effects of DNA-methyltransferase gene in regulating Acanthamoeba pathogenicity.

Keywords: Acanthamoeba, DNA methylation, RNA sequencing, virulence

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Authors: Stephanie J. Sedberry, William J. Gerace, Ian D. Beatty, Michael J. Kane

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Increasing the number of US university students who attain degrees in STEM and enter the STEM workforce is a national priority. Demographic groups vary in their rates of participation in STEM, and the US produces just 10% of the world’s science and engineering degrees (2014 figures). To address these gaps, we have developed and tested a practical, 30-minute, single-session classroom-based intervention to improve students’ self-efficacy and academic performance in University STEM courses. Self-efficacy is a psychosocial construct that strongly correlates with academic success. Self-efficacy is a construct that is internal and relates to the social, emotional, and psychological aspects of student motivation and performance. A compelling body of research demonstrates that university students’ self-efficacy beliefs are strongly related to their selection of STEM as a major, aspirations for STEM-related careers, and persistence in science. The development of an intervention to increase students’ self-efficacy is motivated by research showing that short, social-psychological interventions in education can lead to large gains in student achievement. Our intervention addresses STEM self-efficacy via two strong, but previously separate, lines of research into attitudinal/affect variables that influence student success. The first is ‘attributional retraining,’ in which students learn to attribute their successes and failures to internal rather than external factors. The second is ‘mindset’ about fixed vs. growable intelligence, in which students learn that the brain remains plastic throughout life and that they can, with conscious effort and attention to thinking skills and strategies, become smarter. Extant interventions for both of these constructs have significantly increased academic performance in the classroom. We developed a 34-item questionnaire (Likert scale) to measure STEM Self-efficacy, Perceived Academic Control, and Growth Mindset in a University STEM context, and validated it with exploratory factor analysis, Rasch analysis, and multi-trait multi-method comparison to coded interviews. Four iterations of our 42-week research protocol were conducted across two academic years (2017-2018) at three different Universities in North Carolina, USA (UNC-G, NC A&T SU, and NCSU) with varied student demographics. We utilized a quasi-experimental prospective multiple-group time series research design with both experimental and control groups, and we are employing linear modeling to estimate the impact of the intervention on Self-Efficacy,wth-Mindset, Perceived Academic Control, and final course grades (performance measure). Preliminary results indicate statistically significant effects of treatment vs. control on Self-Efficacy, Growth-Mindset, Perceived Academic Control. Analyses are ongoing and final results pending. This intervention may have the potential to increase student success in the STEM classroom—and ownership of that success—to continue in a STEM career. Additionally, we have learned a great deal about the complex components and dynamics of self-efficacy, their link to performance, and the ways they can be impacted to improve students’ academic performance.

Keywords: academic performance, affect variables, growth mindset, intervention, perceived academic control, psycho-social variables, self-efficacy, STEM, university classrooms

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Authors: Adriana De Serio, Donato Forenza

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Aims. In this experimental research the Authors present the methodological plan “Musictherapy and Gardentherapy” that they created interconnected with the garden landscape ecosystems and aimed at PsychoPhysical Disability (MusGarPPhyD). In the context of the environmental education aimed at spreading the landscape culture and its values, it’s necessary to develop a solid perception of the environment sustainability to implement a multidimensional approach that pays attention to the conservation and enhancement of gardens and natural environments. The result is an improvement in the life quality also in compliance with the objectives of the European Agenda 2030. The MusGarPPhyD can help professionals such as musictherapists and environmental and landscape researchers strengthen subjects' motivation to learn to deal with the psychophysical discomfort associated with disability and to cope with the distress and the psychological fragility and the loneliness and the social seclusion and to promote productive social relationships. Materials and Methods. The MusGarPPhyD was implemented in multiple spaces. The musictherapy treatments took place first inside residential therapeutic centres and then in the garden landscape ecosystem. Patients: twenty, set in two groups. Weekly-sessions (50’) for three months. Methodological phases: - Phase P1. MusicTherapy treatments for each group in the indoor spaces. - Phase P2. MusicTherapy sessions inside the gardens. After each Phase, P1 and P2: - a Questionnaire for each patient (ten items / liking-indices) was administrated at t0 time, during the treatment and at tn time at the end of the treatment. - Monitoring of patients' behavioral responses through assessment scales, matrix, table and graph system. MusicTherapy methodology: pazient Sonorous-Musical Anamnesis, Musictherapy Assessment Document, Observation Protocols, Bodily-Environmental-Rhythmical-Sonorous-Vocal-Energy production first indoors and then outside, sonorous-musical instruments and edible instruments made by the Author/musictherapist with some foods; Administration of Patient-Environment-Music Index at time to and tn, to estimate the patient’s behavior evolution, Musictherapeutic Advancement Index. Results. The MusGarPPhyD can strengthen the individual sense of identity and improve the psychophysical skills and the resilience to face and to overcome the difficulties caused by the congenital /acquired disability. The multi-sensory perceptions deriving from contact with the plants in the gardens improve the psychological well-being and regulate the physiological parameters such as blood pressure, cardiac and respiratory rhythm, reducing the cholesterol levels. The secretions of the peptide hormones endorphins and the endogenous opioids enkephalins increase and bring a state of patient’s tranquillity and a better mood. The subjects showed a preference for musictherapy treatments within a setting made up of gardens and peculiar landscape systems. This resulted in greater health benefits. Conclusions. The MusGarPPhyD contributes to reduce psychophysical tensions, anxiety, depression and stress, facilitating the connections between the cerebral hemispheres, thus also improving intellectual performances, self-confidence, motor skills and social interactions. Therefore it is necessary to design hospitals, rehabilitation centers, nursing homes, surrounded by gardens. Ecosystems of natural and urban parks and gardens create fascinating skyline and mosaics of landscapes rich in beauty and biodiversity. The MusGarPPhyD is useful for the health management promoting patient’s psychophysical activation, better mood/affective-tone and relastionships and contributing significantly to improving the life quality.

Keywords: musictherapy, gardentherapy, disability, life quality

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Authors: Valerie Porr, Sydney A. DeCaro

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TARA for borderline personality disorder (BPD), an education and advocacy organization, helps families to compassionately and effectively deal with troubling BPD behaviors. Our psychoeducational programs focus on understanding underlying neurobiological features of BPD and evidence-based methodology integrating dialectical behavior therapy (DBT) and mentalization based therapy (MBT,) clarifying the inherent misunderstanding of BPD behaviors and improving family communication. TARA4BPD conducts online surveys, workshops, and topical webinars. For over 25 years, we have collected data from BPD helpline callers. This data drew our attention to particular childhood idiosyncrasies that seem to characterize many of the children who later met the criteria for BPD. The idiosyncrasies we observed, heightened sensory sensitivity and hypervigilance, were included in Adolf Stern’s 1938 definition of “Borderline.” This aspect of BPD has not been prioritized by personality disorder researchers, presently focused on emotion processing and social cognition in BPD. Parents described sleep reversal problems in infants who, early on, seem to exhibit dysregulation in circadian rhythm. Families describe children as supersensitive to sensory sensations, such as specific sounds, heightened sense of smell, taste, textures of foods, and an inability to tolerate various fabrics textures (i.e., seams in socks). They also exhibit high sensitivity to particular words and voice tones. Many have alexithymia and dyslexia. These children are either hypo- or hypersensitive to sensory sensations, including pain. Many suffer from fibromyalgia. BPD reactions to pain have been studied (C. Schmahl) and confirm the existence of hyper and hypo-reactions to pain stimuli in people with BPD. To date, there is little or no data regarding what comprises a normative range of sensitivity in infants and children. Many parents reported that their children were tested or treated for sensory processing disorder (SPD), learning disorders, and ADHD. SPD is not included in the DSM and is treated by occupational therapists. The overwhelming anecdotal data from thousands of parents of children who later met criteria for BPD led TARA4BPD to develop a sensitivity survey to develop evidence of the possible role of early sensory perception problems as a pre-cursor to BPD, hopefully initiating new directions in BPD research. At present, the research community seems unaware of the role supersensory sensitivity might play as an early indicator of BPD. Parents' observations of childhood sensitivity obtained through family interviews and results of an extensive online survey on sensory responses across various ages of development will be presented. People with BPD suffer from a sense of isolation and otherness that often results in later interpersonal difficulties. Early identification of supersensitive children while brain circuits are developing might decrease the development of social interaction deficits such as rejection sensitivity, self-referential processes, and negative bias, hallmarks of BPD, ultimately minimizing the maladaptive methods of coping with distress that characterizes BPD. Family experiences are an untapped resource for BPD research. It is hoped that this data will give family observations the critical credibility to inform future treatment and research directions.

Keywords: alexithymia, dyslexia, hypersensitivity, sensory processing disorder

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Authors: Artem Kim, Clara Savary, Christele Dubourg, Wilfrid Carre, Houda Hamdi-Roze, Valerie Dupé, Sylvie Odent, Marie De Tayrac, Veronique David

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Holoprosencephaly (HPE) is a rare congenital brain malformation resulting from the incomplete separation of the two cerebral hemispheres. It is characterized by a wide phenotypic spectrum and a high degree of locus heterogeneity. Genetic defects in 16 genes have already been implicated in HPE, but account for only 30% of cases, suggesting that a large part of genetic factors remains to be discovered. HPE has been recently redefined as a complex multigenic disorder, requiring the joint effect of multiple mutational events in genes belonging to one or several developmental pathways. The onset of HPE may result from accumulation of the effects of multiple rare variants in functionally-related genes, each conferring a moderate increase in the risk of HPE onset. In order to decipher the genetic basis of HPE, unconventional patterns of inheritance involving multiple genetic factors need to be considered. The primary objective of this study was to uncover possible disease causing combinations of multiple rare variants underlying HPE by performing trio-based Whole Exome Sequencing (WES) of familial cases where no molecular diagnosis could be established. 39 families were selected with no fully-penetrant causal mutation in known HPE gene, no chromosomic aberrations/copy number variants and without any implication of environmental factors. As the main challenge was to identify disease-related variants among a large number of nonpathogenic polymorphisms detected by WES classical scheme, a novel variant prioritization approach was established. It combined WES filtering with complementary gene-level approaches: transcriptome-driven (RNA-Seq data) and clinically-driven (public clinical data) strategies. Briefly, a filtering approach was performed to select variants compatible with disease segregation, population frequency and pathogenicity prediction to identify an exhaustive list of rare deleterious variants. The exome search space was then reduced by restricting the analysis to candidate genes identified by either transcriptome-driven strategy (genes sharing highly similar expression patterns with known HPE genes during cerebral development) or clinically-driven strategy (genes associated to phenotypes of interest overlapping with HPE). Deeper analyses of candidate variants were then performed on a family-by-family basis. These included the exploration of clinical information, expression studies, variant characteristics, recurrence of mutated genes and available biological knowledge. A novel bioinformatics pipeline was designed. Applied to the 39 families, this final integrated workflow identified an average of 11 candidate variants per family. Most of candidate variants were inherited from asymptomatic parents suggesting a multigenic inheritance pattern requiring the association of multiple mutational events. The manual analysis highlighted 5 new strong HPE candidate genes showing recurrences in distinct families. Functional validations of these genes are foreseen.

Keywords: complex genetic disorder, holoprosencephaly, multiple rare variants, whole exome sequencing

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Authors: Alexandria Carey, Angela Starkweather, Ann Horgas, Hwayoung Cho, Jason Beneciuk

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Background/Significance: Over 3.4 million acute axial low back pain (aLBP) cases are treated annually in the United States (US) emergency departments (ED). ED patients with aLBP receive varying verbal and written discharge routine care (RC), leading to ineffective patient self-management. Ineffective self-management increase chronic low back pain (cLPB) transition risks, a chief cause of worldwide disability, with associated costs >$60 million annually. This research addresses this significant problem by evaluating an ED digital pain self-management intervention (EDPSI) focused on improving self-management through improved knowledge retainment, skills, and self-efficacy (confidence) (KSC) thus reducing aLBP to cLBP transition in ED patients discharged with aLBP. The research has significant potential to increase self-efficacy, one of the most potent mechanisms of behavior change and improve health outcomes. Focusing on accessibility and usability, the intervention may reduce discharge disparities in aLBP self-management, especially with low health literacy. Study Questions: This research will answer the following questions: 1) Will an EDPSI focused on improving KSC progress patient self-management behaviors and health status?; 2) Is the EDPSI sustainable to improve pain severity, interference, and pain recurrence?; 3) Will an EDPSI reduce aLBP to cLBP transition in patients discharged with aLBP? Aims: The pilot randomized-controlled trial (RCT) study’s objectives assess the effects of a 12-week digital self-management discharge tool in patients with aLBP. We aim to 1) Primarily assess the feasibility [recruitment, enrollment, and retention], and [intervention] acceptability, and sustainability of EDPSI on participant’s pain self-management; 2) Determine the effectiveness and sustainability of EDPSI on pain severity/interference among participants. 3) Explore patient preferences, health literacy, and changes among participants experiencing the transition to cLBP. We anticipate that EDPSI intervention will increase likelihood of achieving self-management milestones and significantly improve pain-related symptoms in aLBP. Methods: The study uses a two-group pilot RCT to enroll 30 individuals who have been seen in the ED with aLBP. Participants are randomized into RC (n=15) or RC + EDPSI (n=15) and receive follow-up surveys for 12-weeks post-intervention. EDPSI innovative content focuses on 1) highlighting discharge education; 2) provides self-management treatment options; 3) actor demonstration of ergonomics, range of motion movements, safety, and sleep; 4) complementary alternative medicine (CAM) options including acupuncture, yoga, and Pilates; 5) combination therapies including thermal application, spinal manipulation, and PT treatments. The intervention group receives Booster sessions via Zoom to assess and reinforce their knowledge retention of techniques and provide return demonstration reinforcing ergonomics, in weeks two and eight. Outcome Measures: All participants are followed for 12-weeks, assessing pain severity/ interference using the Brief Pain Inventory short-form (BPI-sf) survey, self-management (measuring KSC) using the short 13-item Patient Activation Measure (PAM), and self-efficacy using the Pain Self-Efficacy Questionnaire (PSEQ) weeks 1, 6, and 12. Feasibility is measured by recruitment, enrollment, and retention percentages. Acceptability and education satisfaction are measured using the Education-Preference and Satisfaction Questionnaire (EPSQ) post-intervention. Self-management sustainment is measured including PSEQ, PAM, and patient satisfaction and healthcare utilization (PSHU) requesting patient overall satisfaction, additional healthcare utilization, and pain management related to continued back pain or complications post-injury.

Keywords: digital, pain self-management, education, tool

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Authors: Melina Kopke, Jelle Van Dijk

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Persons with cognitive disabilities, such as Autism Spectrum Disorder (ASD) are often dependent on some form of professional support. Recent transformations in Dutch healthcare have spurred institutions to apply new, empowering methods and tools to enable their clients to cope (more) independently in daily life. Assistive Technologies (ATs) seem promising as empowering tools. While ATs can, functionally speaking, help people to perform certain activities without human assistance, we hold that, from a design-theoretical perspective, such technologies often fail to empower in a deeper sense. Most technologies serve either to prescribe or to monitor users’ actions, which in some sense objectifies them, rather than strengthening their agency. This paper proposes that theories of embodied interaction could help formulating a design vision in which interactive assistive devices augment, rather than replace, human agency and thereby add to a persons’ empowerment in daily life settings. It aims to close the gap between empowerment theory and the opportunities provided by assistive technologies, by showing how embodiment and empowerment theory can be applied in practice in the design of new, interactive assistive devices. Taking a Research-through-Design approach, we conducted a case study of designing to support independently living people with ASD with structuring daily activities. In three iterations we interlaced design action, active involvement and prototype evaluations with future end-users and healthcare professionals, and theoretical reflection. Our co-design sessions revealed the issue of handling daily activities being multidimensional. Not having the ability to self-manage one’s daily life has immense consequences on one’s self-image, and also has major effects on the relationship with professional caregivers. Over the course of the project relevant theoretical principles of both embodiment and empowerment theory together with user-insights, informed our design decisions. This resulted in a system of wireless light units that users can program as a reminder for tasks, but also to record and reflect on their actions. The iterative process helped to gradually refine and reframe our growing understanding of what it concretely means for a technology to empower a person in daily life. Drawing on the case study insights we propose a set of concrete design principles that together form what we call the embodied empowerment design framework. The framework includes four main principles: Enabling ‘reflection-in-action’; making information ‘publicly available’ in order to enable co-reflection and social coupling; enabling the implementation of shared reflections into an ‘endurable-external feedback loop’ embedded in the persons familiar ’lifeworld’; and nudging situated actions with self-created action-affordances. In essence, the framework aims for the self-development of a suitable routine, or ‘situated practice’, by building on a growing shared insight of what works for the person. The framework, we propose, may serve as a starting point for AT designers to create truly empowering interactive products. In a set of follow-up projects involving the participation of persons with ASD, Intellectual Disabilities, Dementia and Acquired Brain Injury, the framework will be applied, evaluated and further refined.

Keywords: assistive technology, design, embodiment, empowerment

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Authors: Pejman Salimi, Sebastiano Tieuli, Somayeh Taghavi, Michela Signoretto, Remo Proietti Zaccaria

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Increasing the growth of industrial waste due to the large quantities of production leads to numerous environmental and economic challenges, such as climate change, soil and water contamination, human disease, etc. Energy recovery of waste can be applied to produce heat or electricity. This strategy allows for the reduction of energy produced using coal or other fuels and directly reduces greenhouse gas emissions. Among different factories, leather manufacturing plays a very important role in the whole world from the socio-economic point of view. The leather industry plays a very important role in our society from a socio-economic point of view. Even though the leather industry uses a by-product from the meat industry as raw material, it is considered as an activity demanding integrated prevention and control of pollution. Along the entire process from raw skins/hides to finished leather, a huge amount of solid and water waste is generated. Solid wastes include fleshings, raw trimmings, shavings, buffing dust, etc. One of the most abundant solid wastes generated throughout leather tanning is shaving waste. Leather shaving is a mechanical process that aims at reducing the tanned skin to a specific thickness before tanning and finishing. This product consists mainly of collagen and tanning agent. At present, most of the world's leather processing is chrome-tanned based. Consequently, large amounts of chromium-containing shaving wastes need to be treated. The major concern about the management of this kind of solid waste is ascribed to chrome content, which makes the conventional disposal methods, such as landfilling and incineration, not practicable. Therefore, many efforts have been developed in recent decades to promote eco-friendly/alternative leather production and more effective waste management. Herein, shaving waste resulting from metal-free tanning technology is proposed as low-cost precursors for the preparation of carbon material as anodes for lithium-ion batteries (LIBs). In line with the philosophy of a reduced environmental impact, for preparing fully sustainable and environmentally friendly LIBs anodes, deionized water and carboxymethyl cellulose (CMC) have been used as alternatives to toxic/teratogen N-methyl-2- pyrrolidone (NMP) and to biologically hazardous Polyvinylidene fluoride (PVdF), respectively. Furthermore, going towards the reduced cost, we employed water solvent and fluoride-free bio-derived CMC binder (as an alternative to NMP and PVdF, respectively) together with LiFePO₄ (LFP) when a full cell was considered. These actions make closer to the 2030 goal of having green LIBs at 100 $ kW h⁻¹. Besides, the preparation of the water-based electrodes does not need a controlled environment and due to the higher vapour pressure of water in comparison with NMP, the water-based electrode drying is much faster. This aspect determines an important consequence, namely a reduced energy consumption for the electrode preparation. The electrode derived from leather waste demonstrated a discharge capacity of 735 mAh g⁻¹ after 1000 charge and discharge cycles at 0.5 A g⁻¹. This promising performance is ascribed to the synergistic effect of defects, interlayer spacing, heteroatoms-doped (N, O, and S), high specific surface area, and hierarchical micro/mesopore structure of the biochar. Interestingly, these features of activated biochars derived from the leather industry open the way for possible applications in other EESDs as well.

Keywords: biowaste, lithium-ion batteries, physical activation, waste management, leather industry

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Authors: V. Saccà, A. Sarica, F. Novellino, S. Barone, T. Tallarico, E. Filippelli, A. Granata, P. Valentino, A. Quattrone

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The work aim was to evaluate how well Random Forest (RF) and Support Vector Machine (SVM) algorithms could support the early diagnosis of Multiple Sclerosis (MS) from resting-state functional connectivity data. In particular, we wanted to explore the ability in distinguishing between controls and patients of mean signals extracted from ICA components corresponding to 15 well-known networks. Eighteen patients with early-MS (mean-age 37.42±8.11, 9 females) were recruited according to McDonald and Polman, and matched for demographic variables with 19 healthy controls (mean-age 37.55±14.76, 10 females). MRI was acquired by a 3T scanner with 8-channel head coil: (a)whole-brain T1-weighted; (b)conventional T2-weighted; (c)resting-state functional MRI (rsFMRI), 200 volumes. Estimated total lesion load (ml) and number of lesions were calculated using LST-toolbox from the corrected T1 and FLAIR. All rsFMRIs were pre-processed using tools from the FMRIB's Software Library as follows: (1) discarding of the first 5 volumes to remove T1 equilibrium effects, (2) skull-stripping of images, (3) motion and slice-time correction, (4) denoising with high-pass temporal filter (128s), (5) spatial smoothing with a Gaussian kernel of FWHM 8mm. No statistical significant differences (t-test, p < 0.05) were found between the two groups in the mean Euclidian distance and the mean Euler angle. WM and CSF signal together with 6 motion parameters were regressed out from the time series. We applied an independent component analysis (ICA) with the GIFT-toolbox using the Infomax approach with number of components=21. Fifteen mean components were visually identified by two experts. The resulting z-score maps were thresholded and binarized to extract the mean signal of the 15 networks for each subject. Statistical and machine learning analysis were then conducted on this dataset composed of 37 rows (subjects) and 15 features (mean signal in the network) with R language. The dataset was randomly splitted into training (75%) and test sets and two different classifiers were trained: RF and RBF-SVM. We used the intrinsic feature selection of RF, based on the Gini index, and recursive feature elimination (rfe) for the SVM, to obtain a rank of the most predictive variables. Thus, we built two new classifiers only on the most important features and we evaluated the accuracies (with and without feature selection) on test-set. The classifiers, trained on all the features, showed very poor accuracies on training (RF:58.62%, SVM:65.52%) and test sets (RF:62.5%, SVM:50%). Interestingly, when feature selection by RF and rfe-SVM were performed, the most important variable was the sensori-motor network I in both cases. Indeed, with only this network, RF and SVM classifiers reached an accuracy of 87.5% on test-set. More interestingly, the only misclassified patient resulted to have the lowest value of lesion volume. We showed that, with two different classification algorithms and feature selection approaches, the best discriminant network between controls and early MS, was the sensori-motor I. Similar importance values were obtained for the sensori-motor II, cerebellum and working memory networks. These findings, in according to the early manifestation of motor/sensorial deficits in MS, could represent an encouraging step toward the translation to the clinical diagnosis and prognosis.

Keywords: feature selection, machine learning, multiple sclerosis, random forest, support vector machine

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