Germination Improves the Polyphenolic Profile and Functional Value of Mung Bean (Vigna radiata L.)

This research was funded by the University of Granada through project PSE/17/002 of Plan Propio, as well as the Spanish Ministry of Science, Innovation and Universities and the European Union through projects RTC-2017-6540-1, and RTI-2018-100934-B-I00 and the FEDER program, respectively. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.The use of legumes as functional foods has gained increasing attention for the prevention and treatment of the so called non-communicable diseases that are highly prevalent worldwide. In this regard, biotechnological approaches for the enhancement of legumes’ nutritional and functional value have been extensively employed. In the present study, the process of germination increased several parameters of mung bean (Vigna radiata L.) functionality, including extract yield, total phenolic content and in vitro antioxidant capacity. In addition, 3-day-germinated mung bean proved to be an interesting source of dietary essential minerals and exhibited a greater variety of polyphenolic compounds compared to raw mung bean. These properties resulted in enhanced cytoprotective features of the 3-day mung bean extracts against radical oxygen species in human colorectal (HT29) and monocyte (U937) cell lines. Moreover, the antiproliferative effects were tested in different colon cancer cell lines, T84 and drug-resistant HCT-18, as well as in a non-tumor colon CCD-18 line. Altogether, our results demonstrate that the germination process improves the mung bean’s nutritional value and its potential as a functional food.University of Granada through Plan Propio PSE/17/002Spanish Ministry of Science, Innovation and UniversitiesEuropean Union (EU) RTC-2017-6540-1 RTI-2018-100934-B-I0

Pluripotency factors regulate the onset of Hox cluster activation in the early embryo

Pluripotent cells are a transient population of the mammalian embryo dependent on transcription factors, such as OCT4 and NANOG, which maintain pluripotency while suppressing lineage specification. However, these factors are also expressed during early phases of differentiation, and their role in the transition from pluripotency to lineage specification is largely unknown. We found that pluripotency factors play a dual role in regulating key lineage specifiers, initially repressing their expression and later being required for their proper activation. We show that Oct4 is necessary for activation of HoxB genes during differentiation of embryonic stem cells and in the embryo. In addition, we show that the HoxB cluster is coordinately regulated by OCT4 binding sites located at the 3′ end of the cluster. Our results show that core pluripotency factors are not limited to maintaining the precommitted epiblast but are also necessary for the proper deployment of subsequent developmental programs.This work was funded by the Spanish government (grants BFU2017-84914-P and PID2020-115755GB-I00 to M.M.; BFU2016-74961-P and BFU2016-81887-REDT to J.L.G.-S.), the Andalusian government (grant BIO-396 to J.L.G.-S.), and the European Research Council (ERC; grant agreement 740041 to J.L.G.-S.). M.T. held Juan de la Cierva fellowships from the Spanish government (FJCI-2017-31791 and IJC2019-038897-I), R.R. and R.D.A. held FPU fellowships from the government, and J.V. was the recipient of a “La Caixa” fellowship. Work in the laboratory of J.L.G.-S. was supported by a María de Maetzu Unit of Excellence Grant (MDM-2016-0687) to the Department of Gene Regulation and Morphogenesis of the CABD. The CBMSO is supported by an institutional grant from the Fundación Ramon Areces, and the CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN), and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033). : With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2020-001041-S)

["Good life is to be in peace and harmony with everything around us": a qualitative study on good living among the Kankuamo Indigenous people of Colombia].

The Kankuamo people are one of the 102 native peoples of Colombia, who are developing strategies for individual and collective health self-management. This article aims to investigate, identify and analyze, collaboratively and interculturally, the factors that influence the well-being of the Kankuamo people, using the Capabilities Approach proposed by Amartya Sen. To this end, three focus groups were conducted with the participation of 37 people from the 15 communities of the Kankuamo reservation. The transcripts were analyzed by means of a thematic analysis. Three central themes for the well-being of the Kankuamo emerged from the focus groups: (i) harmony between nature and human beings, (ii) social coexistence and (iii) self-determination. These themes reflect the fundamental principles and values that guide the community towards a good life, expansion of their capabilities, harmony and holistic development. The results suggest that material aspects play a secondary role in the Kankuamo community's concept of good life, and confirm that it is fundamental to consider a collective vision of capabilities, not only individual ones, in indigenous contexts. Studies such as this one can contribute to the development of more contextually appropriate approaches to assess and measure the quality of life and well-being of Indigenous communities, including the Kankuamo people

Clinical, pathological and PAM50 gene expression features of HER2-low breast cancer

Novel antibody-drug conjugates against HER2 are showing high activity in HER2-negative breast cancer (BC) with low HER2 expression (i.e., 1+ or 2+ and lack of ERBB2 amplification). However, the clinical and molecular features of HER2-low BC are yet to be elucidated. Here, we collected retrospective clinicopathological and PAM50 data from 3,689 patients with HER2-negative disease and made the following observations. First, the proportion of HER2-low was higher in HR-positive disease (65.4%) than triple-negative BC (TNBC, 36.6%). Second, within HR-positive disease, ERBB2 and luminal-related genes were more expressed in HER2-low than HER2 0. In contrast, no gene was found differentially expressed in TNBC according to HER2 expression. Third, within HER2-low, ERBB2 levels were higher in HR-positive disease than TNBC. Fourth, HER2-low was not associated with overall survival in HR-positive disease and TNBC. Finally, the reproducibility of HER2-low among pathologists was suboptimal. This study emphasizes the large biological heterogeneity of HER2-low BC, and the need to implement reproducible and sensitive assays to measure low HER2 expression

Universal mental health screening with a focus on suicidal behaviour using smartphones in a Mexican rural community: Protocol for the SMART-SCREEN population-based survey

Introduction Mental disorders represent the second cause of years lived with disability worldwide. Suicide mortality has been targeted as a key public health concern by the WHO. Smartphone technology provides a huge potential to develop massive and fast surveys. Given the vast cultural diversity of Mexico and its abrupt orography, smartphone-based resources are invaluable in order to adequately manage resources, services and preventive measures in the population. The objective of this study is to conduct a universal suicide risk screening in a rural area of Mexico, measuring also other mental health outcomes such as depression, anxiety and alcohol and substance use disorders. Methods and analysis A population-based cross-sectional study with a temporary sampling space of 9 months will be performed between September 2019 and June 2020. We expect to recruit a large percentage of the target population (at least 70%) in a short-term survey of Milpa Alta Delegation, which accounts for 137 927 inhabitants in a territorial extension of 288 km 2. They will be recruited via an institutional call and a massive public campaign to fill in an online questionnaire through mobile-assisted or computer-assisted web app. This questionnaire will include data on general health, validated questionnaires including Well-being Index 5, Patient Health Questionnaire-9, Generalized Anxiety Disorder Scale 2, Alcohol Use Disorders Identification Test, selected questions of the Drug Abuse Screening Test and Columbia-Suicide Severity Rating Scales and Diagnostic and statistical manual of mental disorders (DSM-5) questions about self-harm. We will take into account information regarding time to mobile app response and geo-spatial location, and aggregated data on social, demographical and environmental variables. Traditional regression modelling, multilevel mixed methods and data-driven machine learning approaches will be used to test hypotheses regarding suicide risk factors at the individual and the population level. Ethics and dissemination Ethical approval (002/2019) was granted by the Ethics Review Board of the Hospital Psiquiátrico Yucatán, Yucatán (Mexico). This protocol has been registered in ClinicalTrials.gov. The starting date of the study is 3 September 2019. Results will serve for the planning and healthcare of groups with greater mental health needs and will be disseminated via publications in peer-reviewed journal and presented at relevant mental health conferences. Trial registration number NCT04067063

Desafíos de las metrópolis: Efectos ambientales y sociales. Tendencias geográficas II

El libro está conformado de estudios realizados por profesores-investigadores de la Universidad Autónoma del Estado de México, de la Universidad de Varsovia, así como de la Universidad Pedagógica Comisión de Educación Nacional de Cracovia. En esta obra se exponen algunas investigaciones sobre los cambios en los factores sociales, naturales, económicos y ambientales como principales desafios que presentan las zonas de México, Polonia y de contextos de Sudamérica, tales como Sao Paulo, Quito y Bogotá y ciudades medias y pequeñas.Universidad Autónoma del Estado de Méxic

Orientaciones específicas para la incorporación de tecnología en procesos de formación de profesores de Ciencias Naturales, Lenguaje y Comunicación, y Matemáticas en contextos de diversidad para el diseño de secuencias de enseñanza aprendizaje

Las Tecnologías de la Información y de la Comunicación (TIC) se han transformado en un elemento de innovación dentro del conocimiento humano. Aplicadas directamente a la disciplina académica, las TIC se han ganado un espacio debido al creciente interés de este tipo de herramientas por parte de los docentes. No obstante, al día de hoy, en Latinoamérica el uso de TIC no es masivo. Su implementación aún está en una etapa inicial, y esto es debido a diversos factores. Algunos tienen que ver con el poco seguimiento que se realiza al implementar este tipo de tecnologías en las instituciones educativas; la limitada formación es una debilidad. En una escuela, el profesor que no ha sido preparado adecuadamente en el uso de TIC difícilmente logrará utilizarlas adecuadamente, y sus metodologías de aula serán, probablemente, idénticas a las que existían previas a su implementación. Existe una gran diferencia entre conocer una herramienta y dominarla; el dominio se logra, por ejemplo, al conocer las ventajas y desventajas que posee una herramienta determinada en conexión directa con los contenidos y las necesidades de los estudiantes. El dominio de las TIC otorga al docente de aula la posibilidad de tomar decisiones que tiendan a la efectividad del proceso educativo, puesto que las TIC no son solo un conjunto de herramientas, sino que, además, son orientables hacia un área u otra dependiendo de factores variables propios del proceso. Teniendo en cuenta el contexto anterior, este documento contiene algunas orientaciones para el uso del material desarrollado en el área de Ciencias Naturales, Lenguaje y Comunicación, y Matemáticas del Proyecto ALTER-NATIVA, el cual va dirigido a la formación de profesores que atienden poblaciones en contexto de diversidad con incorporación de las TIC. Es importante anotar que las actividades que se proponen son una posibilidad distinta de asumir la enseñanza de las ciencias naturales, lo cual a su vez implica reflexión y evaluación constante de la práctica de los docentes de esta área; que los compromete también con los desarrollos tecnológicos actuales, lo cual conlleva analizar y canalizar sus esfuerzos para diseñar y gestionar mecanismos que permitan la incorporación de las TIC en sus prácticas, pues se considera que estas posibilitan colaborar en la construcción de mundos posibles cercanos a los ideales de participación, igualdad y equidad (Alter -nativa , 2012). Estas orientaciones específicas tienen un doble propósito: primero, cobijan algunas recomendaciones, las cuales son una propuesta de uso para aprovechar al máximo el material que se propone en el estudio de las Ciencias Naturales, Lenguaje y Comunicación, y Matemáticas, para las poblaciones objeto de estudio. Para el desarrollo de las actividades planteadas es necesario que los estudiantes para profesor y profesores de escuelas, colegios y universidades de las áreas de Ciencias Naturales, Lenguaje y Comunicación, y Matemáticas, como posibles usuarios de este material, las perciban como un recurso que tiene un potencial y que, para su desarrollo, se hace necesario tener presente el diseño y estructura didáctica, los objetivos temáticos, la infraestructura, los recursos tecnológicos, las necesidades y características de las poblaciones con quien se vaya a utilizar, entre otros aspectos. Y segundo, estas orientaciones tienen como propósito ofrecer elementos para la formación de profesores de Ciencias Naturales, Lenguaje y Comunicación, y Matemáticas en su acción pedagógica y didáctica; se involucran las prácticas profesionales de diseño y elaboración de objetos didácticos y de los objetos virtuales de aprendizaje (OVA) como casos específicos de estos. Tomando como referencia lo anterior, se plantea como objetivos central de este texto el presentar algunas orientaciones que es necesario tener en cuenta a la hora incorporar TIC en la formación de profesores de Ciencias Naturales, Lenguaje y Comunicación, y Matemáticas. De igual forma, unos objetivos específicos serían los siguientes: a) Establecer unas orientaciones que sean consideradas a la hora de usar los recursos virtuales como los Objetos Virtuales de aprendizaje (OVA) que fueron diseñados como parte del proyecto ALTER-NATIVA en el área de ciencias naturales, lenguaje y matemáticas. b) Favorecer el aprendizaje de las ciencias naturales, lenguaje y matemáticas en las poblaciones objeto de estudio a través del uso de las TIC. c) Resaltar la importancia que tiene el uso de las TIC para concebir el aprendizaje como un sistema de interacción y no como transmisión de información solamente. d) Aportar a la reflexión y formación de docentes con una cultura tecnológica que les permita afrontar su labor pedagógica y didáctica en ámbitos de diversidad. e) Proporcionar unos elementos teóricos y de uso de las TIC que les admita la planeación, el diseño, desarrollo, uso y evaluación de objetos virtuales u OVA dentro de un ambiente virtual de aprendizaje

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation