Informe final del proyecto: Creación de algoritmos utilizando técnicas de clasificación supervisada y no supervisada para el diagnóstico de enfermedades cardiovasculares en una población de adultos mayores de bajos recursos en Uruguay

El avance de los algoritmos de aprendizaje automático ha posibilitado la aplicación de nuevos métodos con capacidad diagnóstica igual a su contraparte humana, permitiendo el alcance a una mayor cantidad de usuarios, superando las restricciones de recursos limitados, en menor tiempo y garantizando la reproducibilidad de los resultados. Los algoritmos de aprendizaje automático son susceptibles a los datos con que se los entrena y sus resultados pueden variar si los datos a los que se los aplica no provienen de la misma población que se utilizó para entrenar los algoritmos. Ésta es una de las razones de relevancia para la generación de capacidades locales en la creación y evaluación de las nuevas técnicas, especialmente en el área de la salud donde importa tanto el resultado como la interpretación del método por el que se llegó al mismo. La presente investigación tiene como propósito la generación de algoritmos de aprendizaje automático para la identificación de la patología cardíaca, fibrilación auricular, a partir de datos de la señal electrocardiográfica de una sola derivación con un dispositivo móvil de tecnología electrónica. La fibrilación auricular (FA) es la arritmia sostenida más frecuente en el adulto, y su prevalencia aumenta con la edad. Según el informe “Global Burden of Diseases, Injuries, and Risk Factors Study” de 2010 se estimó que en este año 33,5 millones de individuos presentaban FA, constituyendo aproximadamente el 0,5% de la población mundial. Su incidencia y prevalencia van en aumento. Esto puede explicarse en gran medida por el envejecimiento de la población y el aumento de la comorbilidad. La FA es la primera causa de internación por arritmia cardíaca y existe evidencia de que se viene incrementando como causa de internación. Las múltiples internaciones generan deterioro en la calidad de vida en una población especialmente vulnerable, aumentando los costos en salud.Agencia Nacional de Investigación e Innovació

Informe final del proyecto: Creación de algoritmos utilizando técnicas de clasificación supervisada y no supervisada para el diagnóstico de enfermedades cardiovasculares en una población de adultos mayores de bajos recursos en Uruguay

El avance de los algoritmos de aprendizaje automático ha posibilitado la aplicación de nuevos métodos con capacidad diagnóstica igual a su contraparte humana, permitiendo el alcance a una mayor cantidad de usuarios, superando las restricciones de recursos limitados, en menor tiempo y garantizando la reproducibilidad de los resultados. Los algoritmos de aprendizaje automático son susceptibles a los datos con que se los entrena y sus resultados pueden variar si los datos a los que se los aplica no provienen de la misma población que se utilizó para entrenar los algoritmos. Ésta es una de las razones de relevancia para la generación de capacidades locales en la creación y evaluación de las nuevas técnicas, especialmente en el área de la salud donde importa tanto el resultado como la interpretación del método por el que se llegó al mismo. La presente investigación tiene como propósito la generación de algoritmos de aprendizaje automático para la identificación de la patología cardíaca, fibrilación auricular, a partir de datos de la señal electrocardiográfica de una sola derivación con un dispositivo móvil de tecnología electrónica. La fibrilación auricular (FA) es la arritmia sostenida más frecuente en el adulto, y su prevalencia aumenta con la edad. Según el informe “Global Burden of Diseases, Injuries, and Risk Factors Study” de 2010 se estimó que en este año 33,5 millones de individuos presentaban FA, constituyendo aproximadamente el 0,5% de la población mundial. Su incidencia y prevalencia van en aumento. Esto puede explicarse en gran medida por el envejecimiento de la población y el aumento de la comorbilidad. La FA es la primera causa de internación por arritmia cardíaca y existe evidencia de que se viene incrementando como causa de internación. Las múltiples internaciones generan deterioro en la calidad de vida en una población especialmente vulnerable, aumentando los costos en salud.Agencia Nacional de Investigación e Innovació

Temozolomide treatment alters mismatch repair and boosts mutational burden in tumor and blood of colorectal cancer patients

The majority of metastatic colorectal cancers (mCRC) are mismatch repair (MMR) proficient and unresponsive to immunotherapy, while MMR-deficient (MMRd) tumors often respond to immune-checkpoint-blockade. We previously reported that treatment of CRC preclinical models with temozolomide (TMZ) leads to MMR-deficiency, increased tumor mutational burden (TMB) and sensitization to immunotherapy. To clinically translate these findings, we designed the ARETHUSA clinical trial whereby O6-Methylguanine-DNA-methyltransferase (MGMT) deficient, MMR-proficient, RAS mutant mCRC patients received priming therapy with TMZ. Analysis of tissue biopsies and circulating tumor DNA (ctDNA) revealed the emergence of a distinct mutational signature and increased TMB after TMZ treatment. Multiple alterations in the nucleotide context favored by the TMZ signature emerged in MMR genes and the p.T1219I MSH6 variant was detected in ctDNA and tissue of 94% (16/17) of the cases. A patient's subset whose tumors displayed the MSH6 mutation, the TMZ mutational signature and increased TMB, achieved disease stabilization upon pembrolizumab treatment

Synthetic Glycolipids as Molecular Vaccine Adjuvants: Mechanism of Action in Human Cells and In Vivo Activity

Modern adjuvants for vaccine formulations are immunostimulating agents whose action is based on the activation of pattern recognition receptors (PRRs) by well-defined ligands to boost innate and adaptive immune responses. Monophosphoryl lipid A (MPLA), a detoxified analogue of lipid A, is a clinically approved adjuvant that stimulates toll-like receptor 4 (TLR4). The synthesis of MPLA poses manufacturing and quality assessment challenges. Bridging this gap, we report here the development and preclinical testing of chemically simplified TLR4 agonists that could sustainably be produced in high purity and on a large scale. Underpinned by computational and biological experiments, we show that synthetic monosaccharide-based molecules (FP compounds) bind to the TLR4/MD-2 dimer with submicromolar affinities stabilizing the active receptor conformation. This results in the activation of MyD88- and TRIF-dependent TLR4 signaling and the NLRP3 inflammasome. FP compounds lack in vivo toxicity and exhibit adjuvant activity by stimulating antibody responses with a potency comparable to MPLA

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Diachronic Treebanks for Historical Linguistics

Over the last few decades, the widespread diffusion of digital technology has increased availability of primary textual sources, radically changing the everyday life of scholars in the humanities, who are now able to access, query and process a wealth of empirical evidence in ways not possible before. Also for ancient languages, corpora enhanced with increasingly complex layers of metalinguistic information, such as part-of-speech tagging and syntactic annotation (called 'treebanks') are now available. In particular, diachronic treebanks, which provide data for a language across several historical stages of a given language, allow for a new approach to diachronic studies of syntactic phenomena where scholars previously had to content themselves with empirical work on a much smaller scale. This volume brings together a set of papers that report research on various diachronic matters supported by evidence from diachronic treebanks. The contents of the papers cover a wide range of languages, including English, French, Russian, Old Church Slavonic, Latin and Ancient Greek

Diachronic treebanks for historical linguistics Benjamins current topics ;, v. 113./ edited by Hanne Martine Eckhoff, Silvia Luraghi, Marco Passarotti.

Includes bibliographical references and index."Over the last few decades, the widespread diffusion of digital technology has increased availability of primary textual sources, radically changing the everyday life of scholars in the humanities, who are now able to access, query and process a wealth of empirical evidence in ways not possible before. Also for ancient languages, corpora enhanced with increasingly complex layers of metalinguistic information, such as part-of-speech tagging and syntactic annotation (called 'treebanks') are now available. In particular, diachronic treebanks, which provide data for a language across several historical stages of a given language, allow for a new approach to diachronic studies of syntactic phenomena where scholars previously had to content themselves with empirical work on a much smaller scale. This volume brings together a set of papers that report research on various diachronic matters supported by evidence from diachronic treebanks. The contents of the papers cover a wide range of languages, including English, French, Russian, Old Church Slavonic, Latin and Ancient Greek. Originally published as special issue of Diachronica 35:3 (2018)"--Introduction: The added value of diachronic treebanks for historical linguistics / Hanne Martine Eckhoff, Silvia Luraghi and Marco Passarotti -- Split coordination in English : why we need parsed corpora / Ann Taylor and Susan Pintzuk -- A corpus approach to the history of Russian po delimitatives / Hanne Martine Eckhoff -- Non-configurationality in diachrony : correlations in local and global networks of Ancient Greek and Latin / Edoardo Maria Ponti and Silvia Luraghi -- Text form and grammatical changes in Medieval French : a treebank-based diachronic study / Alexandra Simonenko, Benoît Crabbé and Sophie Prévost -- Spoken Latin behind written texts : formulaicity and salience in medieval documentary texts / Timo Korkiakangas.1 online resource (154 pages)

Editorial: Special Issue of the Italian Chapter of the European Society of Biomechanics dedicated to \u201cBiomechanics for in silico clinical trials\u201d

The 9th Meeting of the Italian Chapter of the European Society of Biomechanics (Bologna, 30 September - 1 October 2019) included a Thematic Symposium on \u201cBiomechanics for in silico clinical trials\u201d. Despite being a meeting of the National Chapter, it always has an international audience. This edition, also thanks to the Thematic Symposium, had a high number of papers with international authors (more than 20 papers out of 72), and international keynote speakers. We felt it was the right time to have a Thematic symposium on in silico trials, as this is definitely an emerging field, not quite mature yet for extensive deployment, and for this reason posing every day new challenges to scientists and to engineers. The choice of the topic is linked to the growing reliability and improved performance of computational models that are changing the approach to clinical tests. New pharmacological treatments, new devices and new surgical techniques can be tested through virtual models by means of numerical simulations. In this context, the understanding of the biomechanical mechanisms plays a fundamental role, since tissue mechanics is linked in a direct and indirect way to the evolution of physiological and pathological conditions. Although the road seems to be marked to favour the exit of the in silico world from laboratories to the clinical side, still a number of open challenges in the field of basic research, industrial developments and regulatory needs remain. The scientific community is then called for applied and interdisciplinary research efforts. The aim of this Special Issue is to collect to-date and advanced results in the field. Interestingly, this is collecting the effort not only of groups working in the field of numerical simulations, but also experimental ones, for the possible synergies. In particular, this Special Issue collect the best papers that were shortlisted by the Scientific Committee and by the Award Committees for the different awards assigned during the meeting