A Virtual Conversational Agent for Teens with Autism: Experimental Results and Design Lessons

We present the design of an online social skills development interface for teenagers with autism spectrum disorder (ASD). The interface is intended to enable private conversation practice anywhere, anytime using a web-browser. Users converse informally with a virtual agent, receiving feedback on nonverbal cues in real-time, and summary feedback. The prototype was developed in consultation with an expert UX designer, two psychologists, and a pediatrician. Using the data from 47 individuals, feedback and dialogue generation were automated using a hidden Markov model and a schema-driven dialogue manager capable of handling multi-topic conversations. We conducted a study with nine high-functioning ASD teenagers. Through a thematic analysis of post-experiment interviews, identified several key design considerations, notably: 1) Users should be fully briefed at the outset about the purpose and limitations of the system, to avoid unrealistic expectations. 2) An interface should incorporate positive acknowledgment of behavior change. 3) Realistic appearance of a virtual agent and responsiveness are important in engaging users. 4) Conversation personalization, for instance in prompting laconic users for more input and reciprocal questions, would help the teenagers engage for longer terms and increase the system's utility

new morphologic variants of the hand motor cortex as seen with mr imaging in a large study population

BACKGROUND AND PURPOSE: The hand motor cortex (HMC) has been classically described as having an omega or epsilon shape in axial-plane images obtained with CT and MR imaging. The aim of this study was to use MR imaging and Talairach normalization in a large sample population that was homogeneous for age and handedness to evaluate in a sex model a new classification with 5 morphologic variants of the HMC in the axial plane (omega, medially asymmetric epsilon, epsilon, laterally asymmetric epsilon, and null). MATERIALS AND METHODS: Structural brain MR images were obtained from 257 right-handed healthy subjects (143 men and 114 women; mean age, 23.1 ± 1.1 years) via a Talairach space transformed 3D magnetization-prepared rapid acquisition of gradient echo sequence. The frequencies of the different HMC variants were reported for hemisphere and sex. RESULTS: The new variants of the HMC (medially asymmetric epsilon, laterally asymmetric epsilon, and null) were observed in 2.9%, 7.0%, and 1.8% of the hemispheres, respectively. Statistically significant sex differences were observed: The epsilon variant was twice as frequent in men, and an interhemispheric concordance for morphologic variants was observed only for women. CONCLUSION: The large study population permitted the description of a new morphologic classification that included 3 new variants of the HMC. This new morphologic classification should facilitate the identification of the precentral gyrus in subsequent studies and in everyday practice

Redistribution of CD8+ T cell subsets in metastatic renal cell carcinoma patients treated with anti-PD-1 therapy

Renal-cell carcinoma (RCC) is responsible for the majority of tumors arising from the kidney parenchyma. Although a progressive improvement in median overall survival has been observed after the introduction of anti-PD-1 therapy, many patients do not benefit from this treatment. Therefore, we have investigated T cell dynamics to find immune modification induced by anti-PD-1 therapy. Here, we show that, after therapy, RCC patients (5 responders and 14 nonresponders) are characterized by a redistribution of different subsets across the memory T cell compartment

LonP1 Differently Modulates Mitochondrial Function and Bioenergetics of Primary Versus Metastatic Colon Cancer Cells

Mitochondrial Lon protease (LonP1) is a multi-function enzyme that regulates mitochondrial functions in several human malignancies, including colorectal cancer (CRC). The mechanism(s) by which LonP1 contributes to colorectal carcinogenesis is not fully understood. We found that silencing LonP1 leads to severe mitochondrial impairment and apoptosis in colon cancer cells. Here, we investigate the role of LonP1 in mitochondrial functions, metabolism, and epithelial-mesenchymal transition (EMT) in colon tumor cells and in metastasis. LonP1 was almost absent in normal mucosa, gradually increased from aberrant crypt foci to adenoma, and was most abundant in CRC. Moreover, LonP1 was preferentially upregulated in colorectal samples with mutated p53 or nuclear \u3b2-catenin, and its overexpression led to increased levels of \u3b2-catenin and decreased levels of E-cadherin, key proteins in EMT, in vitro. LonP1 upregulation also induced opposite changes in oxidative phosphorylation, glycolysis, and pentose pathway in SW480 primary colon tumor cells when compared to SW620 metastatic colon cancer cells. In conclusion, basal LonP1 expression is essential for normal mitochondrial function, and increased LonP1 levels in SW480 and SW620 cells induce a metabolic shift toward glycolysis, leading to EMT

Plasma Cytokine Atlas Reveals the Importance of TH2 Polarization and Interferons in Predicting COVID-19 Severity and Survival

Although it is now widely accepted that host inflammatory response contributes to COVID-19 immunopathogenesis, the pathways and mechanisms driving disease severity and clinical outcome remain poorly understood. In the effort to identify key soluble mediators that characterize life-threatening COVID-19, we quantified 62 cytokines, chemokines and other factors involved in inflammation and immunity in plasma samples, collected at hospital admission, from 80 hospitalized patients with severe COVID-19 disease who were stratified on the basis of clinical outcome (mechanical ventilation or death by day 28). Our data confirm that age, as well as neutrophilia, lymphocytopenia, procalcitonin, D-dimer and lactate dehydrogenase are strongly associated with the risk of fatal COVID-19. In addition, we found that cytokines related to TH2 regulations (IL-4, IL-13, IL-33), cell metabolism (lep, lep-R) and interferons (IFNα, IFNβ, IFNγ) were also predictive of life-threatening COVID-19

Plasma Cytokine Atlas Reveals the Importance of TH2 Polarization and Interferons in Predicting COVID-19 Severity and Survival

Although it is now widely accepted that host inflammatory response contributes to COVID-19 immunopathogenesis, the pathways and mechanisms driving disease severity and clinical outcome remain poorly understood. In the effort to identify key soluble mediators that characterize life-threatening COVID-19, we quantified 62 cytokines, chemokines and other factors involved in inflammation and immunity in plasma samples, collected at hospital admission, from 80 hospitalized patients with severe COVID-19 disease who were stratified on the basis of clinical outcome (mechanical ventilation or death by day 28). Our data confirm that age, as well as neutrophilia, lymphocytopenia, procalcitonin, D-dimer and lactate dehydrogenase are strongly associated with the risk of fatal COVID-19. In addition, we found that cytokines related to TH2 regulations (IL-4, IL-13, IL-33), cell metabolism (lep, lep-R) and interferons (IFNα, IFNβ, IFNγ) were also predictive of life-threatening COVID-19

Altered pathways of keratinization, extracellular matrix generation, angiogenesis, and stromal stem cells proliferation in patients with systemic sclerosis

Objective: Systemic sclerosis is characterized by endothelial dysfunction, autoimmunity abnormalities, and fibrosis of the skin and internal organs. The pathogenetic mechanisms underlying systemic sclerosis vasculopathy are still not clarified. A complex cellular and extracellular network of interactions has been studied, but it is currently unclear what drives the activation of fibroblasts/myofibroblasts and the extracellular matrix deposition. Methods: Using RNA sequencing, the aim of the work was to identify potential functional pathways implied in systemic sclerosis pathogenesis and markers of endothelial dysfunction and fibrosis in systemic sclerosis patients. RNA-sequencing analysis was performed on RNA obtained from biopsies from three systemic sclerosis patients and three healthy controls enrolled in our University Hospital. RNA was used to generate sequencing libraries that were sequenced according to proper transcriptomic analyses. Subsequently, we performed gene set enrichment analysis of differentially expressed genes on the entire list of genes that compose the RNA-sequencing expression matrix. Results: Gene set enrichment analysis revealed that healthy controls were characterized by gene signatures related to stromal stem cells proliferation, cytokine–cytokine receptor interaction, macrophage-enriched metabolic network, whereas systemic sclerosis tissues were enriched in signatures associated with keratinization, cornification, retinoblastoma 1 and tumor suppressor 53 signaling. Conclusion: According to our data, RNA-sequencing and pathway analysis revealed that systemic sclerosis subjects display a discrete pattern of gene expression associated with keratinization, extracellular matrix generation, and negative regulation of angiogenesis and stromal stem cells proliferation. Further analysis on larger numbers of patients is needed; however, our findings provide an interesting framework for the development of biomarkers useful to explore potential future therapeutic approaches

Implementación de la gestión de energía en el sistema operativo didáctico utilizando el modelo APM

El presente trabajo de investigación se centra en el manejo de los estados de energía por parte del sistema operativo utilizando la norma The Advanced Power Management Standard APM, como introducción a la norma ACPI, que es la que aceptan las notebooks y las netbooks, para manejo de la energía en sistemas de computación y su respectiva implementación en el sistema operativo de características didácticas SODIUM. Informamos también sobre los problemas encontrados en la utilización de diferentes sistemas, especialmente con herramientas de máquinas virtuales y los desvíos que se produjeron por el uso de las mismas, que retrasaron la construcción de la base de investigación. Por último hacemos constar los alcances establecidos y se explica hacia dónde apuntaremos nuestra atención en la definición de las líneas de investigación que dejamos abiertas para las futuras investigaciones relacionadas. Finalmente en las conclusiones expresamos nuestra visión y opinión refiriéndonos en normas generales a la forma de trabajo adoptadas.Eje: Arquitectura, redes y sistemas operativosRed de Universidades con Carreras en Informática (RedUNCI

Innate immunity changes in soccer players after whole-body cryotherapy

Whole-body cryotherapy (WBC) consists of short exposure (up to 2–3 min) to dry air at cryogenic temperatures (up to -190 °C) and has recently been applied for muscle recovery after injury to reduce the inflammation process. We aimed to determine the impact of cryotherapy on immunological, hormonal, and metabolic responses in non-professional soccer players (NPSPs). Nine male NPSPs (age: 20 ± 2 years) who trained regularly over 5 consecutive days, immediately before and after each training session, were subjected to WBC treatment (WBC-t). Blood samples were collected for the evaluation of fifty analytes including hematologic parameters, serum chemistry, and hormone profiles. Monocytes phenotyping (Mo) was performed and plasmatic markers, usually increased during inflammation [CCL2, IL-18, free mitochondrial (mt)DNA] or with anti-inflammatory effects (IL2RA, IL1RN), were quantified. After WBC-t, we observed reduced levels of ferritin, mean corpuscular hemoglobin, mean platelet volume, testosterone, and estradiol, which however remain within the normal ranges. The percentage of the total, intermediates and non-classical Mo increased, while classical Mo decreased. CXCR4 expression decreased in each Mo subset. Plasma IL18 and IL2RA levels decreased, while IL1RN only exhibited a tendency to decrease and CCL2 showed a tendency to increase. Circulating mtDNA levels were not altered following WBC-t. The differences observed in monocyte subsets after WBC-t may be attributable to their redistribution into the surrounding tissue. Moreover, the decrease of CXCR4 in Mo subpopulations could be coherent with their differentiation process. Thus, WBC through yet unknown mechanisms could promote their differentiation having a role in tissue repair