Conversational agent for supporting learners on a MOOC on programming with Java

One important problem in MOOCs is the lack of personalized support from teachers. Conversational agents arise as one possible solution to assist MOOC learners and help them to study. For example, conversational agents can help review key concepts of the MOOC by asking questions to the learners and providing examples. JavaPAL, a voice-based conversational agent for supporting learners on a MOOC on programming with Java offered on edX. This paper evaluates JavaPAL from different perspectives. First, the usability of JavaPAL is analyzed, obtaining a score of 74.41 according to a System Usability Scale (SUS). Second, learners’ performance is compared when answering questions directly through JavaPAL and through the equivalent web interface on edX, getting similar results in terms of performance. Finally, interviews with JavaPAL users reveal that this conversational agent can be helpful as a complementary tool for the MOOC due to its portability and flexibility compared to accessing the MOOC contents through the web interface.This work was supported in part by the FEDER/Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación, through the Smartlet and H2O Learning projects under Grant TIN2017-85179-C3-1-R and PID2020-112584RB-C31, and in part by the Madrid Regional Government through the e-Madrid-CM Project under Grant S2018/TCS-4307 and under the Multiannual Agreement with UC3M in the line of Excellence of University Professors (EPUC3M21), and in the context of the V PRICIT (Regional Programme of Research and Technological Innovation), a project which is co-funded by the European Structural Funds (FSE and FEDER). Partial support has also been received from the European Commission through Erasmus+ Capacity Building in the Field of Higher Education projects, more specifically through projects LALA, InnovaT, and PROF-XXI (586120-EPP-1-2017-1-ES-EPPKA2-CBHE-JP), (598758-EPP-1-2018-1-AT-EPPKA2-CBHE-JP), (609767-EPP-1-2019-1-ES-EPPKA2-CBHE-JP). This publication reflects the views only of the authors and funders cannot be held responsible for any use which may be made of the information contained therein

Antioxidant activity of fractions from Quercus sideroxyla bark and identifi cation of proanthocyanidins by HPLC-DAD and HPLC-MS

The most active phenolics in Quercus sideroxyla Humb. & Bonpl. residual bark were identified and evaluated following a chromatographic fractionation. Bark powder was defatted with hexane and crude extract (CE) was obtained by extraction with aqueous acetone (70%). A liquid partition with ethyl acetate was performed to produce an organic extract (OE), which was subsequently purified by column chromatography (Toyopearl HW-40F, methanol), and resulted in six methanolic fractions (MF1 to MF6) and an oligomeric fraction (OLF) eluted with acetone 67%. Extraction yields, total phenolic and flavanol contents were determined. The antioxidant activity of bark extracts was measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH), Trolox (6-hydroxy-2,5,7,8-tetramethyl-chroman-2-carboxylic-acid)-equivalent antioxidant capacity (TEAC), and ferric ion reducing antioxidant power (FRAP) assays. Their median effective concentration (EC₅₀) data and rate constants for DPPH radical scavenging were also estimated. Identification of major phenolics was carried out by high performance liquid chromatography with diode array detection (HPLC-DAD) and high performance liquid chromatography with electrospray ionization coupled to mass spectrometry (HPLC-ESI-MS) instruments. Bioactive gallic acid, catechin, epicatechin, gallocatechin, catechin gallate, dimeric procyanidins, galloylated dimeric proanthocyanidins, trimeric procyanidins, and tetrameric proanthocyanidins were detected and identified in Q. sideroxyla bark extracts. MF2 was the most active fraction containing gallocatechin as its major compound; MF5 and OLF contain galloylated procyanidins, which may explain their higher antiradical activity. OLF besides galloylated procyanidins has gallocatechin, which presumably contributes to its higher antiradical activity. Consequently, Q. sideroxyla bark could be a good source of therapeutic health products or nutraceutical ingredients that may exert a potential prevention or treatment action against diseases in biological systems.This is the publisher’s final pdf. The published article is copyrighted by Walter de Gruyter and can be found at: http://www.degruyter.com/view/j/hfsg.Keywords: proanthocyanidins, Quercus sideroxyla ., bark, antiradical activity, HPL

Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics

A better understanding of the molecular mechanisms that participate in the development and clinical manifestations of schizophrenia can lead to improve our ability to diagnose and treat this disease. Previous data strongly associated the levels of deregulated ADAMTS2 expression in peripheral blood mononuclear cells (PBMCs) from patients at first episode of psychosis (up) as well as in clinical responders to treatment with antipsychotic drugs (down). In this current work, we performed an independent validation of such data and studied the mechanisms implicated in the control of ADAMTS2 gene expression. Using a new cohort of drug-naïve schizophrenia patients with clinical follow-up, we confirmed that the expression of ADAMTS2 was highly upregulated in PBMCs at the onset (drug-naïve patients) and downregulated, in clinical responders, after treatment with antipsychotics. Mechanistically, ADAMTS2 expression was activated by dopaminergic signalling (D1-class receptors) and downstream by cAMP/CREB and mitogen-activated protein kinase (MAPK)/ERK signalling. Incubation with antipsychotic drugs and selective PKA and MEK inhibitors abrogated D1-mediated activation of ADAMTS2 in neuronal-like cells. Thus, D1 receptors signalling towards CREB activation might participate in the onset and clinical responses to therapy in schizophrenia patients, by controlling ADAMTS2 expression and activity. The unbiased investigation of molecular mechanisms triggered by antipsychotic drugs may provide a new landscape of novel targets potentially associated with clinical efficacy.Acknowledgements: We are highly indebted to the participants and their families for their cooperation in this study. We also thank IDIVAL biobank (Inés Santiuste and Jana Arozamena) for clinical samples and data as well as the PAFIP members (Marga Corredera) for the data collection. This work was supported by: SAF2016-76046-R and SAF2013-46292-R (MINECO and FEDER) to B.C.F., PI16/00156 (isciii and FEDER) to J.P.V., LUCHAMOS POR LA VIDA project to F.R.J. and J.P.V., SAF2017-83702-R (MINECO and FEDER), Red TERCEL RD12/0019/0024 (ISCIII) and GVA-PROMETEO 2018/041 (Generalitat Valenciana) to S.M. J.P.V. is supported by the RyC research programme (RYC-2013-14097) and F.R.J. by the predoctoral research programme (BES-2014-070615), from MINECO and FEDER

Multicenter study of brain volume abnormalities in children and adolescent-onset psychosis

The goal of the study is to determine the extent of structural brain abnormalities in a multicenter sample of children and adolescents with a recent-onset first episode of psychosis (FEP), compared with a sample of healthy controls. Total brain and lobar volumes and those of gray matter (GM), white matter, and cerebrospinal fluid (CSF) were measured in 92 patients with a FEP and in 94 controls, matched for age, gender, and years of education. Male patients (n = 64) showed several significant differences when compared with controls (n = 61). GM volume in male patients was reduced in the whole brain and in frontal and parietal lobes compared with controls. Total CSF volume and frontal, temporal, and right parietal CSF volumes were also increased in male patients. Within patients, those with a further diagnosis of "schizophrenia" or "other psychosis" showed a pattern similar to the group of all patients relative to controls. However, bipolar patients showed fewer differences relative to controls. In female patients, only the schizophrenia group showed differences relative to controls, in frontal CSF. GM deficit in male patients with a first episode correlated with negative symptoms. Our study suggests that at least part of the GM deficit in children and adolescent-onset schizophrenia and in other psychosis occurs before onset of the first positive symptoms and that, contrary to what has been shown in children-onset schizophrenia, frontal GM deficits are probably present from the first appearance of positive symptoms in children and adolescents

Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: a real-life multicentre analysis of 162 patients

Background Anti-CGRP monoclonal antibodies have shown notable effectiveness and tolerability in migraine patients; however, data on their use in elderly patients is still lacking, as clinical trials have implicit age restrictions and real-world evidence is scarce. In this study, we aimed to describe the safety and effectiveness of erenumab, galcanezumab and fremanezumab in migraine patients over 65 years old in real-life. Methods In this observational real-life study, a retrospective analysis of prospectively collected data from 18 different headache units in Spain was performed. Migraine patients who started treatment with any anti-CGRP monoclonal antibody after the age of 65 years were included. Primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and medication intake frequencies by months 3 and 6, response rates, changes in patient-reported outcomes and reasons for discontinuation. As a subanalysis, reduction in monthly migraine days and proportion of adverse effects were also compared among the three monoclonal antibodies. Results A total of 162 patients were included, median age 68 years (range 65-87), 74.1% women. 42% had dyslipidaemia, 40.3% hypertension, 8% diabetes, and 6.2% previous cardiovascular ischaemic disease. The reduction in monthly migraine days at month 6 was 10.17.3 days. A total of 25.3% of patients presented adverse effects, all of them mild, with only two cases of blood pressure increase. Headache and medication intake frequencies were significantly reduced, and patient-reported outcomes were improved. The proportions of responders were 68%, 57%, 33% and 9% for reductions in monthly migraine days >= 30%,>= 50%,>= 75% and 100%, respectively. A total of 72.8% of patients continued with the treatment after 6 months. The reduction in migraine days was similar for the different anti-CGRP treatments, but fewer adverse effects were detected with fremanezumab (7.7%). Conclusions Anti-CGRP mAbs are safe and effective treatments in migraine patients over 65 years old in real-life clinical practice

Differential body composition effects of protease inhibitors recommended for initial treatment of HIV infection: A randomized clinical trial

This article has been accepted for publication in Clinical Infectious Diseases ©2014 The Authors .Published by Oxford University Press on Clinical Infectious Disease 60.5. DOI: 10.1093/cid/ciu898Background. It is unclear whether metabolic or body composition effects may differ between protease inhibitor-based regimens recommended for initial treatment of HIV infection. Methods. ATADAR is a phase IV, open-label, multicenter randomized clinical trial. Stable antiretroviral-naive HIV-infected adults were randomly assigned to atazanavir/ritonavir 300/100 mg or darunavir/ritonavir 800/100 mg in combination with tenofovir/emtricitabine daily. Pre-defined end-points were treatment or virological failure, drug discontinuation due to adverse effects, and laboratory and body composition changes at 96 weeks. Results. At 96 weeks, 56 (62%) atazanavir/ritonavir and 62 (71%) darunavir/ritonavir patients remained free of treatment failure (estimated difference 8.2%; 95%CI -0.6 to 21.6); and 71 (79%) atazanavir/ritonavir and 75 (85%) darunavir/ritonavir patients remained free of virological failure (estimated difference 6.3%; 95%CI -0.5 to 17.6). Seven vs. five patients discontinued atazanavir/ritonavir or darunavir/ritonavir due to adverse effects. Total and HDL cholesterol similarly increased in both arms, but triglycerides increased more in atazanavir/ritonavir arm. At 96 weeks, body fat (estimated difference 2862.2 gr; 95%CI 726.7 to 4997.7; P=0.0090), limb fat (estimated difference 1403.3 gr; 95%CI 388.4 to 2418.2; P=0.0071), and subcutaneous abdominal adipose tissue (estimated difference 28.4 cm2; 95%CI 1.9 to 55.0; P=0.0362) increased more in atazanavir/ritonavir than in darunavir/ritonavir arm. Body fat changes in atazanavir/ritonavir arm were associated with higher insulin resistance. Conclusions. We found no major differences between atazanavir/ritonavir and darunavir/ritonavir in efficacy, clinically-relevant side effects, or plasma cholesterol fractions. However, atazanavir/ritonavir led to higher triglycerides and total and subcutaneous fat than darunavir/ritonavir and fat gains with atazanavir/ritonavir were associated with insulin resistanceThis is an Investigator Sponsored Research study. It was supported in part by research grants from Bristol‐Myers Squibb and Janssen‐Cilag; Instituto de Salud Carlos III (PI12/01217) and Red Temática Cooperativa de Investigación en SIDA G03/173 (RIS‐EST11), Ministerio de Ciencia e Innovación, Spain. (Registration number: NCT01274780; registry name: ATADAR; EUDRACT; 2010‐021002‐38)

Temperature dependence of plankton community metabolism in the subtropical and tropical oceans

Here we assess the temperature dependence of the metabolic rates (gross primary production (GPP), community respiration (CR), and the ratio GPP/CR) of oceanic plankton communities. We compile data from 133 stations of the Malaspina 2010 Expedition, distributed among the subtropical and tropical Atlantic, Pacific, and Indian oceans. We used the in vitro technique to measured metabolic rates during 24 h incubations at three different sampled depths: surface, 20%, and 1% of the photosynthetically active radiation measured at surface. We also measured the % of ultraviolet B radiation (UVB) penetrating at surface waters. GPP and CR rates increased with warming, albeit different responses were observed for each sampled depth. The overall GPP/CR ratio declined with warming. Higher activation energies (Ea) were derived for both processes (GPPChla = 0.97; CRChla = 1.26; CRHPA = 0.95 eV) compared to those previously reported. The Indian Ocean showed the highest Ea (GPPChla = 1.70; CRChla = 1.48; CRHPA = 0.57 eV), while the Atlantic Ocean showed the lowest (GPPChla = 0.86; CRChla = 0.77; CRHPA = 0.13 eV). We believe that the difference between previous assessments and the ones presented here can be explained by the overrepresentation of Atlantic communities in the previous data sets. We found that UVB radiation also affects the temperature dependence of surface GPP, which decreased rather than increased under high levels of UVB. Ocean warming, which causes stratification and oligotrophication of the subtropical and tropical oceans, may lead to reduced surface GPP as a result of increased penetration of UVB radiation.En prens

The COMT Val158 Met polymorphism as an associated risk factor for Alzheimer disease and mild cognitive impairment in APOE 4 carriers

<p>Abstract</p> <p>Background</p> <p>The aim of this study is to examine the influence of the <it>catechol-O-methyltranferase (COMT) </it>gene (polymorphism Val158 Met) as a risk factor for Alzheimer's disease (AD) and mild cognitive impairment of amnesic type (MCI), and its synergistic effect with the <it>apolipoprotein E gene (APOE)</it>.</p> <p>A total of 223 MCI patients, 345 AD and 253 healthy controls were analyzed. Clinical criteria and neuropsychological tests were used to establish diagnostic groups.</p> <p>The DNA Bank of the University of the Basque Country (UPV-EHU) (Spain) determined <it>COMT </it>Val158 Met and <it>APOE </it>genotypes using real time polymerase chain reaction (rtPCR) and polymerase chain reaction (PCR), and restriction fragment length polymorphism (RFLPs), respectively. Multinomial logistic regression models were used to determine the risk of AD and MCI.</p> <p>Results</p> <p>Neither <it>COMT </it>alleles nor genotypes were independent risk factors for AD or MCI. The high activity genotypes (GG and AG) showed a synergistic effect with <it>APOE ε4 </it>allele, increasing the risk of AD (OR = 5.96, 95%CI 2.74-12.94, p < 0.001 and OR = 6.71, 95%CI 3.36-13.41, p < 0.001 respectivily). In AD patients this effect was greater in women.</p> <p>In MCI patients such as synergistic effect was only found between AG and <it>APOE ε4 </it>allele (OR = 3.21 95%CI 1.56-6.63, p = 0.02) and was greater in men (OR = 5.88 95%CI 1.69-20.42, p < 0.01).</p> <p>Conclusion</p> <p><it>COMT </it>(Val158 Met) polymorphism is not an independent risk factor for AD or MCI, but shows a synergistic effect with <it>APOE ε4 </it>allele that proves greater in women with AD.</p

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.info:eu-repo/semantics/publishedVersio