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El conflicto armado ha marcado las diferentes dimensiones de vida de la población colombiana por lo que ha sido objeto de diversos estudios, generando la necesidad de evaluar el abordaje e instrumentos utilizados para medir indicadores de salud mental de población en contexto de conflicto armado. Esta investigación pretende analizar artículos científicos que aborden dichos indicadores y que utilicen instrumentos psicométricos para tal fin. Se realizó una revisión de alcance siguiendo la metodología PRISMA y utilizando el software CADIMA. La búsqueda bibliográfica se hizo en las bases de datos Web of Science, Scielo y Scopus, usando términos claves en inglés y español. Se analizaron 21 artículos en los que se identifica el uso de 53 instrumentos, siendo los más aplicados el AUDIT y la CIDI-CAPI. La mayoría de los artículos reportaron afectaciones relacionadas con estrés postraumático, ansiedad, depresión y consumo de sustancias. Se encontraron pocos estudios de validación o construcción de instrumentos. Es necesario fortalecer el trabajo en el desarrollo y validación de pruebas para evaluar indicadores de salud mental en poblaciones víctimas del conflicto armado colombiano, con las que se posibilite una mejor valoración de las afectaciones.

La presente investigación tiene como propósito describir la Responsabilidad Social Universitaria (RSU) de acuerdo a su conceptualización en la literatura. Se analizan las dimensiones de la Responsabilidad Social Universitaria, las subdimensiones, su la aplicación en los planes institucionales de desarrollo y la relación que existe entre la responsabilidad social universitaria con la competitividad en las instituciones de educación superior. Este trabajo realiza una revisión sistemática de la literatura, analizando sus principales autores. Así mismo, se explica que este trabajo corresponde a una primera etapa de un proyecto más amplio de investigación en donde se pretende una segunda etapa para determinar la gestión estratégica de la responsabilidad social universitaria y su relación con la competitividad académica de las instituciones de educación superior aplicando una metodología con enfoque cuantitativo y datos primarios y secundarios, colaborando con investigadores de otras instituciones en México y Latinoamérica, Los resultados obtenidos confirman lo estipulado en la revisión de la literatura, donde se comprueba que la responsabilidad social universitaria tiene relación la competitividad de las instituciones de educación superior de manera positiva lo cual indica la pauta para que las IES realicen una adecuada gestión de la responsabilidad social en beneficio a su desarrollo y competitividad.

La información genética y genómica requiere regulaciones estrictas para su manejo adecuado con el fin de evitar la divulgación inapropiada y la discriminación secundaria, pues tiene una relación directa con los derechos fundamentales y los principios bioéticos. De ahí la necesidad de evaluar la regulación colombiana existente, por lo que se realizó una revisión sistemática de la literatura en bases de datos del 2000 al 2020, sitios web del Congreso de la República de Colombia, la Comisión de Reforma de la Ley Australiana y la Corte Constitucional de Colombia, para identificar las falencias y los aciertos en la jurisprudencia actual del manejo, el control y la accesibilidad de la población colombiana a las pruebas e información genética. Se toma como referente Australia para comprender y plantear mejoras. Se encontró que en Colombia la información genética se cataloga como sensible (Sentencia C-334-10) con regulaciones inespecíficas sin norma legislativa. En contraste, Australia dispone de directrices bioéticas específicas, penalización y protocolos que abarcan las implicaciones individuales y colectivas descritas en el Privacy Legislation Amendment Act del 2006. Es necesario que en Colombia se cree una regulación jurídica específica para la información genética y genómica con énfasis en pautas de uso sobre la privacidad, la divulgación y la no discriminación.

Introduction: Mental health has been a concept frequently subjected to discussion and in the context of the COVID-19 pandemic it acquired broad relevance when its impact on the mental health of health workers was documented, which increases the need to study the triggers. And the preventive and mitigating strategies of these alterations, focusing specifically on the effectiveness of support groups for health workers.Methods: Quick review of the literature focused on support groups and their effectiveness in the context of the mental health of health personnel. Searches were made in PubMed, Embase, and Google Scholar, for the gray literature of articles published between 2013 and 2023. Relevant information was extracted about the realization of support groups, their effectiveness, facilities, and barriers.Results: 280 articles were identified, 150 from the indexed databases and 130 from gray literature, of which 16 were included in the final analysis. The results indicated differences between how the workers' mental health in the pre-pandemic health area was managed, during the pandemic and how this left different tools such as virtuality that facilitate access and increase assistance to them, where support groups strategies were implemented to support health personnel.Conclusion: The effectiveness of support groups and other interventions, both face-to-face and remote, have brought extensive benefits in the prevention and treatment of stressful triggers and for the maintenance of the mental health of health personnel, for which it is recommended the continuation of its implementation in this population and extrapolation to other contexts, people, and settings

Purpose: Bladder cancer is a current clinical and social problem. At diagnosis, most patients present with nonmuscle-invasive tumors, characterized by a high recurrence rate, which could progress to muscle-invasive disease and metastasis. Bone morphogenetic protein (BMP)–dependent signaling arising from stromal bladder tissue mediates urothelial homeostasis by promoting urothelial cell differentiation. However, the possible role of BMP ligands in bladder cancer is still unclear.Experimental Design: Tumor and normal tissue from 68 patients with urothelial cancer were prospectively collected and analyzed for expression of BMP and macrophage markers. The mechanism of action was assessed in vitro by experiments with bladder cancer cell lines and peripheral blood monocyte–derived macrophages.Results: We observed BMP4 expression is associated and favored type II macrophage differentiation. In vitro experiments showed that both recombinant BMP4 and BMP4-containing conditioned media from bladder cancer cell lines favored monocyte/macrophage polarization toward M2 phenotype macrophages, as shown by the expression and secretion of IL10. Using a series of human bladder cancer patient samples, we also observed increased expression of BMP4 in advanced and undifferentiated tumors in close correlation with epithelial–mesenchymal transition (EMT). However, the p-Smad 1,5,8 staining in tumors showing EMT signs was reduced, due to the increased miR-21 expression leading to reduced BMPR2 expression.Conclusions: These findings suggest that BMP4 secretion by bladder cancer cells provides the M2 signal necessary for a protumoral immune environment. In addition, the repression of BMPR2 by miR-21 makes the tumor cells refractory to the prodifferentiating actions mediated by BMP ligands, favoring tumor growth. Clin Cancer Res; 23(23); 7388–99. ©2017 AACR.

Purpose:Bladder cancer is a clinical and social problem due to its high incidence and recurrence rates. It frequently appears in elderly patients showing other medical comorbidities that hamper the use of standard chemotherapy. We evaluated the activity of CDK4/6 inhibitor as a new therapy for patients unfit for cisplatin (CDDP).Experimental Design:Bladder cancer cell lines were tested for in vitro sensitivity to CDK4/6 inhibition. A novel metastatic bladder cancer mouse model was developed and used to test its in vivo activity.Results:Cell lines tested were sensitive to CDK4/6 inhibition, independent on RB1 gene status. Transcriptome analyses and knockdown experiments revealed a major role for FOXM1 in this response. CDK4/6 inhibition resulted in reduced FOXM1 phosphorylation in vitro and in vivo and showed synergy with CDDP, allowing a significant tumor regression. FOXM1 exerted important oncogenic roles in bladder cancer.Conclusions:CDK4/6 inhibitors, alone or in combination, are a novel therapeutic strategy for patients with advanced bladder cancer previously classified as unfit for current treatment options.

Supplementary Table 4: Spreadsheet of transcriptomic data

Includes Supplementary Figures 1-13; Supplementary Tables 1, 2, 3, 7 and 8; and Supplementary References

Supplementary Table 1. Bladder Cancer cell lines. Supplementary Table 2. Primers and TaqMan probes used for qPCR. Supplementary Figure 1.Characterization of monocyte/macrophage polarization. Supplementary Figure 2. Resistance of BCCs to monocyte-induced apoptosis Supplementary Figure 3. Macrophage marker evaluation toward tumorigenesis and recurrence Supplementary Figure 4. Analyses of different factors that may influence time to recurrence Supplementary Figure 5.CD 163 expression in Tissue microarrays. Representative positive (A) and negative (B) tumors are shown. Supplementary Figure 6.BMP4 expression on NMIBC and MIBC

Introduction: Difficulties in adapting to university life are of vital importance at the individual level due to its influence on mental health and because university life can be seen as part of the development of the life cycle, but also at the public health level due to to its high prevalence and its possibility of impacting dropout rates through the development of a positive mental health intervention (. There is evidence that social support groups administered during the first weeks of university life function as buffers from stressful experiences, allow students to establish new social ties with peers who face the same adaptive difficulty, the same increase in academic demand and the same process of separation and independence from parents, therefore the objective of our study is to build a protocol that proposes a pilot on the intervention with support groups in students with difficulties in adapting to university life.Methods: A search of the literature was carried out in databases, snowball reviews and gray literature, obtaining articles that were used as a reference for the creation of the protocol. The participants are first-semester students from different faculties of the Pontificia Universidad Javeriana, not transferred, in whom the aim is to evaluate the adaptation to university life through the questionnaire of academic experiences (QVA-r) proposed to be applied as a pre-intervention and the presence of stress. academic through the SISCO questionnaire. Students who agree to participate will begin a series of interventions divided into modules and sessions that make up the protocol.

Supplementary Table 5: Spreadsheet of transcriptomic data

Introduction: Aging is a phenomenon that has increased worldwide as a result of a higher life expectancy, evidencing situations typical of this stage, which can impact the happiness of individuals, who deserve attention and approach from mental health and public health. Objective: to explore the association between sociodemographic characteristics, medical history and symptoms, emotional state, social support, cognitive performance, and functional dependence, in relation to happiness in older adults in a rural area of Túquerres, Nariño. Method: cross-sectional study of association. Results: There were 252 records in total, corresponding to the data of rural older adults. A multivariate linear regression was performed, finding an association with happiness in the variables of age (βa = .41; CI95% .09 - .73), socioeconomic level (βa = -.22; CI95% -.58 - .13), education level (βa = .41; CI95% .68 - 1.49), occupation (βa = .59; CI95% -.48 - 1.67), having chronic disease (βa = .42; CI95% .12 - .73), breathing difficulties (βa = -.25; CI95% -.51 - .02), joint pain (βa = .55; CI95% .26 - .83), depression symptoms (βa = -.21; CI95% -.48 - .06]) or anxiety (βa = .40; CI95% .72 - .07), and social support (βa = -.27; CI95% -.52 - -.02). Discussion: this population has unfavorable socioeconomic and health conditions that impact their perception of happiness. Conclusion: happiness is a multicausal phenomenon that in older adults is part of the result of the interaction of variables and historical decisions at a political, economic, and social level. Resumen. Introducción: El envejecimiento es un fenómeno que ha aumentado a nivel mundial como consecuencia de una mayor esperanza de vida, evidenciando situaciones propias de esta etapa, que pueden impactar en la felicidad de los individuos, quienes merecen la atención y el abordaje desde la salud mental y la salud pública. Objetivo: explorar la asociación entre las características sociodemográficas, los antecedentes y síntomas médicos, el estado emocional, el apoyo social, el desempeño cognitivo y la dependencia funcional, con la felicidad en los adultos mayores de una zona rural de Túquerres, Nariño. Método: estudio transversal de asociación, con análisis de datos secundarios. Resultados: Se contó con 252 registros en total, correspondientes a los datos de los adultos mayores rurales. Se realizó una regresión lineal multivariable, encontrando asociación con la felicidad de las variables nivel socioeconómico (βa = -.22; C95% -.58 - .13), nivel de escolaridad (βa = .41; IC95% -.68 - 1.49), ocupación (βa = .59; IC95% -.48 - 1.67), contar con enfermedad crónica (βa = .42; IC95% .12 - .73), dificultades para respirar (βa = -.25; IC95% -.51 - .02), presentar dolor en las coyunturas (βa = .55; IC95% .26 - .83), presentar síntomas de depresión (βa = -.21; IC95% -.48 - .06]) o de ansiedad (βa = .40; IC95% .72 - .07) y apoyo social (βa = -.27; IC95% -.52 - -.02). Discusión: esta población cuenta con condiciones socioeconómicas y de salud desfavorables que impactan en su percepción de felicidad. Conclusión: La felicidad es un fenómeno multicausal que en los adultos mayores hace parte del resultado de la interacción de variables y decisiones históricas, a nivel político, económico y social.

We report the disparate clinical progression of a couple infected by SARS-CoV-2 based on their immune checkpoint (IC) levels and immune cell distribution in blood from admission to exitus in patient 1 and from admission to discharge and recovery in patient 2. A detailed clinical follow-up accompanied by a longitudinal analysis of immune phenotypes and IC levels is shown. The continuous increase in the soluble IC ligand galectin-9 (Gal-9) and the increment in T-cell immunoglobulin and mucin domain-containing 3 (TIM-3) protein in T cells in patient 1 suggests an activation of the Gal-9/TIM-3 axis and, subsequently, a potential cell exhaustion in this patient that did not occur in patient 2. Our data indicate that the Gal-9/TIM-3 axis could be a potential target in this clinical setting, along with a patent effector memory T-cell reduction.

espanolIntroduccion: Este articulo propone una revision critica de la categoria salud mental en relacion con los retos que implican los procesos migratorios. Objetivo: revisar la literatura cientifica reciente sobre la articulacion de las categorias de salud mental y migracion. Metodo: fueron revisados 36 articulos cientificos publicados entre 2016 y 2019. Las publicaciones fueron seleccionadas mediante un proceso sistematico de busqueda de literatura cientifica en las bases de datos Pubmed, Ebsco, Science Direct y Scielo. Se realizo un analisis cualitativo para caracterizar e identificar tendencias y particularidades en la investigacion. Resultados: la salud mental es abordada a partir de problemas, sintomas y enfermedades mentales. Los articulos son eminentemente cuantitativos y propios del area de la salud. Estos fueron realizados en paises de altos ingresos que son receptores de personas migrantes en situacion de vulnerabilidad. Se observan efectos diferenciales entre las situaciones previas a la migracion y las posteriores, asi como entre hombres y mujeres migrantes. Otros articulos hacen enfasis en las afectaciones particulares en la ninez y la adolescencia, o en el rol de los determinantes sociales en la migracion. Discusion y conclusiones: el fenomeno migratorio amerita una revision critica de la categoria de salud mental centrada exclusivamente en los problemas y trastornos mentales. Es importante promover tambien una comprension positiva de la salud mental en las intervenciones con la poblacion migrante. EnglishIntroduction: This paper proposes a critical review of the mental health category, given the challenges of migration. Objective: To review the recent scientific literature on the articulation of mental health and migration categories. Method: 36 scientific articles published between 2016 and 2019 were reviewed. They were selected through a systematic process of searching for scientific literature in the databases Pubmed, Ebsco, Science Direct and Scielo. It was made a qualitative analysis to characterized and identified trends and particularities in research. Results: the approach to mental health is mainly focused on problems, symptoms and mental illnesses. The articles are eminently quantitative and specific to the health area. They were carried out in high-income countries that receiving migrants in vulnerable situations. It is observed differential effects between pre-migration and postmigration, and between men and women migrants as well. Other papers studying the particular impact on children and adolescents, or the role of social determinants in migration. Discussion and conclusions: the migratory phenomenon merits a critical review of the mental health category centered exclusively on mental problems and disorders. It is important to promote also a positive understanding of mental health in interventions with the migrant population. portuguesIntroducao: este artigo propoe uma revisao critica da categoria saude mental face os desafios que implicam os processos migratorios. Objetivo: revisar a literatura cientifica recente sobre a articulacao das categorias de saude mental e migracao. Metodo: foram revisados 36 artigos cientificos publicados entre 2016 e 2019. As publicacoes foram selecionadas atraves de um processo sistematico de pesquisa de literatura cientifica nas bases de dados Pubmed, Ebsco, Science Direct y Scielo. Realizou-se uma analise qualitativa para caracterizar e identificar tendencias e particularidades na pesquisa. Resultados: a saude mental e abordada a partir de problemas, sintomas e doencas mentais. Os artigos sao eminentemente quantitativos e proprios da area da saude. Estes foram realizados em paises de altos ingressos que sao receptores de pessoas migrantes em situacao de vulnerabilidade. Observam-se efeitos diferenciais das situacoes previas a migracao e as posteriores, bem como entre homens e mulheres migrantes. Outros artigos fazem enfase nas afetacoes particulares nas criancas e adolescentes, ou no rol dos determinantes sociais na migracao. Discussoes e conclusoes: o fenomeno migratorio merece uma revisao critica da categoria de saude mental centrada exclusivamente nos problemas e transtornos mentais. E importante promover tambem uma compreensao positiva da saude mental nas intervencoes com a populacao migrante.

Simple Summary Bladder cancer (BC) is the second most frequent cancer of the genitourinary system. More than 500,000 patients per year are diagnosed with BC, a disease which additionally results in more than 200,000 annual deaths. One of the major problems in BC treatment is that many patients cannot receive appropriate treatment due to comorbidities and the severe inflammatory side effects of therapy. The aim of our study was to assess the effect of butyrate derivatives, demonstrating that they could be beneficial for treating the tumor and also to modify the tumor microenvironment. Upon treatment with butyrate derivatives, we particularly saw increased PD-L1 surface expression and reduced pluripotency molecular markers in a hybrid BC–macrophage cell population. This is a cell population known to display an increased capacity to migrate and evade immunity. Treatment with butyrate derivatives may also provide a better chance of immunotherapy success for BC patients. Abstract Bladder cancer (BC) is the second most frequent cancer of the genitourinary system. The most successful therapy since the 1970s has consisted of intravesical instillations of Bacillus Calmette–Guérin (BCG) in which the tumor microenvironment (TME), including macrophages, plays an important role. However, some patients cannot be treated with this therapy due to comorbidities and severe inflammatory side effects. The overexpression of histone deacetylases (HDACs) in BC has been correlated with macrophage polarization together with higher tumor grades and poor prognosis. Herein we demonstrated that phenylbutyrate acid (PBA), a HDAC inhibitor, acts as an antitumoral compound and immunomodulator. In BC cell lines, PBA induced significant cell cycle arrest in G1, reduced stemness markers and increased PD-L1 expression with a corresponding reduction in histone 3 and 4 acetylation patterns. Concerning its role as an immunomodulator, we found that PBA reduced macrophage IL-6 and IL-10 production as well as CD14 downregulation and the upregulation of both PD-L1 and IL-1β. Along this line, PBA showed a reduction in IL-4-induced M2 polarization in human macrophages. In co-cultures of BC cell lines with human macrophages, a double-positive myeloid–tumoral hybrid population (CD11b+EPCAM+) was detected after 48 h, which indicates BC cell–macrophage fusions known as tumor hybrid cells (THC). These THC were characterized by high PD-L1 and stemness markers (SOX2, NANOG, miR-302) as compared with non-fused (CD11b−EPCAM+) cancer cells. Eventually, PBA reduced stemness markers along with BMP4 and IL-10. Our data indicate that PBA could have beneficial properties for BC management, affecting not only tumor cells but also the TME.

Simple Summary Few metastatic urothelial cancer patients achieve durable clinical benefit with vinflunine. Predictive biomarkers to help to identify better treatment strategies are extremely needed. The objective of this study was to identify molecular differences between extreme responders to vinflunine in urothelial cancer. Genomic and immune markers are potentially useful identifying patients that may achieve greater benefit with vinflunine. Abstract Background and Aims: Metastatic urothelial carcinoma (mUC) remains an incurable disease with limited treatment options after platinum-based chemotherapy and immune checkpoint blockade (ICB). Vinflunine has shown a modest increase in overall survival and remains a therapeutic option for chemo- and immunotherapy refractory tumours. However, biomarkers that could identify responding patients to vinflunine and possible alternative therapies after failure to treatment are still missing. In this study, we aimed to identify potential genomic biomarkers of vinflunine response in mUC patient samples and potential management alternatives. Methods: Formalin-fixed paraffin-embedded samples of mUC patients (n = 23) from three university hospitals in Spain were used for genomic targeted-sequencing and transcriptome (using the Immune Profile panel by NanoString) analyses. Patients who received vinflunine after platinum-based chemotherapy failure were classified in non-responders (NR: progressive disease ≤ 3 months; n= 11) or responders (R: response ≥ 6 months; n = 12). Results: Genomic characterization revealed that the most common alteration, TP53 mutations, had comparable frequency in R (6/12; 50%) and NR (4/11; 36%). Non-synonymous mutations in KTM2C (4/12; 33.3%), PIK3CA (3/12; 25%) and ARID2 (3/12; 25%) were predominantly associated with response. No significant difference was observed in tumour mutational burden (TMB) between R and NR patients. The NR tumours showed increased expression of diverse immune-related genes and pathways, including various interferon gamma-related genes. We also identified increased MAGEA4 expression as a potential biomarker of non-responding tumours to vinflunine treatment. Conclusions: Our data may help to identify potential genomic biomarkers of response to vinflunine. Moreover, tumours refractory to vinflunine showed immune signatures potentially associated with response to ICB. Extensive validation studies, including longitudinal series, are needed to corroborate these findings.

Study question Can major de novo genetic and chromosomal abnormalities (i.e., ploidy, microdeletions) be effectively tested on a single embryo biopsy specimen using an integrated NGS approach? Summary answer The integrated NGS workflow provided high accuracy for multilevel chromosome and genetic abnormalities analysis based on single biopsies expanding PGT informativity to de novo conditions. What is known already Current NGS-based methodologies employed in PGT for aneuploidy (PGT-A) do not detect embryo ploidy level nor frequent pathogenic de novo microdeletions below resolution limits. Moreover, despite their considerable incidence and adverse pregnancy outcomes, de novo mutations causing severe dominant monogenic fetal structural defects (FSD) are not investigated during PGT. The development of a single biopsy specimen-based PGT-A sequencing strategy that integrates ploidy and de novo microdeletions/mutations assessment would significantly widen PGT-A diagnostic scope and technical capabilities. This comprehensive approach would provide additional valuable genetic information of unquestionable clinical utility to further refine embryo selection process among those showing euploid profiles. Study design, size, duration Chromosomal conditions were validated using 24 embryo rebiopsies and 5 cell lines with both known ploidy level and known microdeletions (–4p; –8q; –1p; –22q; –5p; –15q; –11q). Genotyping for monogenic conditions was validated using 5 genomic DNA samples (33pg/µl) carrying known pathogenic Single Nucleotide Variants (SNVs) in COL1A1, SOS1, PTPN11, TSC2 and FGFR2 genes. To assess technical performance across identified SNPs, genotyping accuracy was evaluated on 17 samples from 5 embryos and 2 cell lines. Participants/materials, setting, methods Thirty-two de novo dominant monogenic conditions with FSD and strong gene-disease relationship were tested using a multiplex PCR panel with sequencing for the genes’ whole coding region. Eight common microdeletions ( Main results and the role of chance Blinded NGS data analysis confirmed the ploidy status in all (19) samples with known constitution (8 diploids, 7 polyploids, 4 haploids). Specifically, the proportion of heterozygote calls (BAF 40%–60%) was 60.9% (95%CI:47.6–72.8) for diploid samples and Limitations, reasons for caution Positive controls were not available for all genes and microdeletions included in the panel. Moreover, inefficient amplification has affected some target regions and further optimization will be required. However, analytical performance on technical and biological replicates were highly promising for the tested conditions both cell lines and trophectoderm biopsies. Wider implications of the findings: This study demonstrates that the integration of genotyping and chromosomal analyses can be efficiently achieved in the same NGS workflow. This approach can be employed to expand PGT diagnostic scope to conditions undetectable in parents due to their de novo onset, or that are below the standard PGT-A resolution. Trial registration number N/A

Study question Can major de novo genetic and chromosomal abnormalities (i.e., ploidy, microdeletions) be effectively tested on a single embryo biopsy specimen using an integrated NGS approach? Summary answer The integrated NGS workflow provided high accuracy for multilevel chromosome and genetic abnormalities analysis based on single biopsies expanding PGT informativity to de novo conditions. What is known already Current NGS-based methodologies employed in PGT for aneuploidy (PGT-A) do not detect embryo ploidy level nor frequent pathogenic de novo microdeletions below resolution limits. Moreover, despite their considerable incidence and adverse pregnancy outcomes, de novo mutations causing severe dominant monogenic fetal structural defects (FSD) are not investigated during PGT. The development of a single biopsy specimen-based PGT-A sequencing strategy that integrates ploidy and de novo microdeletions/mutations assessment would significantly widen PGT-A diagnostic scope and technical capabilities. This comprehensive approach would provide additional valuable genetic information of unquestionable clinical utility to further refine embryo selection process among those showing euploid profiles. Study design, size, duration Chromosomal conditions were validated using 24 embryo rebiopsies and 5 cell lines with both known ploidy level and known microdeletions (-4p; -8q; -1p; -22q; -5p; -15q; -11q). Genotyping for monogenic conditions was validated using 5 genomic DNA samples (33pg/µl) carrying known pathogenic Single Nucleotide Variants (SNVs) in COL1A1, SOS1, PTPN11, TSC2 and FGFR2 genes. To assess technical performance across identified SNPs, genotyping accuracy was evaluated on 17 samples from 5 embryos and 2 cell lines. Participants/materials, setting, methods Thirty-two de novo dominant monogenic conditions with FSD and strong gene-disease relationship were tested using a multiplex PCR panel with sequencing for the genes’ whole coding region. Eight common microdeletions ( < 10Mb) syndromes (Wolf-Hirshorn, Langer-Geidion, 1p36 deletion, De George, Cri-du-Chat, Prader-Willy/Angelman, Jacobsen) were tested using B-allelic frequency (BAF) of 356 highly polymorphic Single Nucleotide Polymorphisms (SNPs). These SNPs were also used for ploidy assessment. Library preparation and sequencing were performed on the IonTorrent S5 (ThermoFisher). Main results and the role of chance Blinded NGS data analysis confirmed the ploidy status in all (19) samples with known constitution (8 diploids, 7 polyploids, 4 haploids). Specifically, the proportion of heterozygote calls (BAF 40%-60%) was 60.9% (95%CI:47.6-72.8) for diploid samples and < 1% for haploid samples(P Limitations, reasons for caution Positive controls were not available for all genes and microdeletions included in the panel. Moreover, inefficient amplification has affected some target regions and further optimization will be required. However, analytical performance on technical and biological replicates were highly promising for the tested conditions both cell lines and trophectoderm biopsies. Wider implications of the findings This study demonstrates that the integration of genotyping and chromosomal analyses can be efficiently achieved in the same NGS workflow. This approach can be employed to expand PGT diagnostic scope to conditions undetectable in parents due to their de novo onset, or that are below the standard PGT-A resolution. Trial registration number N/A

text Study question Which are the trends shown in data collection XXI of the European Society of Human Reproduction and Embryology (ESHRE) PGT Consortium compared with previous years? Summary answer Data collection XXI, year 2019, represents valuable data on PGT activity in (mainly) Europe and reports on the main trends observed, being the further expansion of comprehensive testing technology in PGT-SR and PGT-A. What is known already The ESHRE PGT Consortium was set up in 1997 and from that time has been collecting data on PGT and PGT-A. The PGT database comprises the world’s largest collection of PGT / PGT-A data providing a valuable resource for data mining and for following trends in PGT practice. So far, up to the year 2015, data collections were carried out in a retrospective data way, from 2016 onwards a prospective data collection was in place. Study design, size, duration As the nature of PGT/ PGT-A treatments has changed significantly over the last years and IVF cycle management and genetic analysis techniques are getting more complex, ESHRE uses an online data collection system in which data are collected prospectively from oocyte retrieval to analysis, embryo transfer and pregnancy / live birth. Data are collected cycle by cycle on a voluntary basis. Participants/materials, settings, method For the 2019 data, individual centres (31) from 19 countries directly entered the data into the PGT database through software developed by ESHRE. Data were analysed at ESHRE headquarters and include all aspects of PGT/PGT-A cycles. Main results and the role of chance The Consortium has analysed the PGT analyses (n = 2735) performed in 2019. The indications for PGT included inherited chromosomal abnormalities (n = 253 analyses), monogenic disorders (n = 1105 analyses), aneuploidy testing for infertility (n = 1111 analyses) or combinations of the above (n = 266 analyses). In addition, 662 clinical pregnancies and 216 deliveries have been analysed in detail. The methods used for biopsy were polar body (2%), cleavage stage biopsy (35%) and blastocyst biopsy (61%; comparable with data from 2018). The methodology used for diagnosis is what is evolving most over the last years, with data set XXI (2019) showing around 7% of FISH, 37% of PCR and 55% of WGA. Within WGA 90.6% of the analysis were done using NGS, in 4.4% cases SNP arrays were used and in 2.4% array-CGH was used. The overall clinical pregnancy rate is about 24% per analysis. The baby data show that it is difficult for most centres to have a detailed follow-up. Limitations, reasons for caution The findings apply to the 31 participating centres and may not represent worldwide trends in PGT. Data were collected prospectively, but details of the follow-up on PGT pregnancies and babies born were limited. Wider implications of the findings The ESHRE PGD Consortium continues its activities as an important forum for PGT practitioners to share data and exchange experiences. The information extracted from the data collections helps to monitor quality issues in PGT and survey the introduction and effectiveness of new PGT technologies and methods.

Study question Is maternal cell-free DNA (cfDNA) testing a feasible alternative to the analysis of the product of conception (POC) in clinical miscarriages? Summary answer This study demonstrates that genome-wide cfDNA testing in the maternal bloodstream constitutes a reliable tool to analyse chromosome aneuploidies in clinical miscarriages. What is known already It is well established that 50-70% of clinical miscarriages are caused by numerical chromosomal anomalies (aneuploidies), mostly trisomies. To date, conventional cytogenetic and advanced molecular techniques are used for the analysis of POC to identify the genetic cause of miscarriage, providing valuable information for genetic counselling. However, both approaches are based in the direct analysis of the abortive tissue, which entails several limitations due to the risk of culture failure and/or maternal cell contamination. To solve these drawbacks, maternal cfDNA testing emerges as a promising alternative due to the accumulated evidence. Study design, size, duration This was a retrospective study conducted in a reference genetic laboratory from January to December 2020. Before carrying out the foetal tissues collection that precludes the POC analysis, a blood sample was drawn to evaluate possible aneuploidies by cfDNA testing. Using NGS+STR POC results as the gold standard, results derived from both studies were compared to assess the percentage of concordance and the cases of non-informativeness (foetal fraction (FF) Participants/materials, setting, methods A total of 12 cases were included in the study. cfDNA testing in the mother’s blood was performed by using Illumina’s technology platform. Genetic testing for POC was done using an NGS technology (Thermo Fisher Scientific, USA) for 24 chromosome aneuploidy screening. Short-tandem repeat (STR) analysis allowed us to detect or rule out maternal cell contamination (MCC) and some types of polyploidies. Main results and the role of chance The non-informative rate for both analysis techniques was 9.1% (1 out of 12 cases: 1 low FF for cfDNA testing and maternal cell contamination for POC analysis). The median cfDNA FF was 9.0%. Using the molecular POC analysis as gold standard, the concordance rate between both studies was 90.0% (9 out of 10 cases;1 monosomy X, 1 trisomy (T) 21, 1 T22, 1 T11 and 5 patients with no alteration detected). No mosaics or structural rearrangements were identified by either of the two analysis techniques. The only discordant result was a case in which cytogenetics of POCs identified a triploidy. This discordancy is expected since triploidies are outside the scope of cfDNA testing. Also, foetal sex was correctly assigned in all informative cases. The sensibility and specificity of the study were estimated at 80.0 (4/5) and 100.0% (6/6), respectively. Statistics analysis suggested that no significant difference was found between both techniques regarding the aneuploidy detection ability (P=0.5). These promising results indicate that genome-wide cfDNA-based screening provides a non-invasive approach for determining whether foetal aneuploidy could explain the loss in patients experiencing early o recurrent pregnancy loss (RPL). Limitations, reasons for caution The sample size prevents drawing more significant conclusions regarding the diagnosis power similarity between both testing techniques. Therefore, a larger cohort will be essential to improve confirm the cfDNA testing performance. Current cfDNA testing technology fails in polyploidy identification, which is a potential cause of pregnancy loss. Wider implications of the findings CfDNA testing could be an alternative to POC analysis in clinical miscarriage. If optimized, cfDNA testing could be used contingently with the molecular POC analysis in cases where maternal cell contamination is present. As a result, the overall success rate in the POC program could be substantially improved. Trial registration number NA

Bladder cancer is lethal in its advanced, muscle-invasive phase with very limited therapeutic advances1,2. Recent molecular characterization has defined new (epi)genetic drivers and potential targets for bladder cancer3,4. The immune checkpoint inhibitors have shown remarkable efficacy but only in a limited fraction of bladder cancer patients5–8. Here, we show that high G9a (EHMT2) expression is associated with poor clinical outcome in bladder cancer and that targeting G9a/DNMT methyltransferase activity with a novel inhibitor (CM-272) induces apoptosis and immunogenic cell death. Using an immunocompetent quadruple-knockout (PtenloxP/loxP; Trp53loxP/loxP; Rb1loxP/loxP; Rbl1−/−) transgenic mouse model of aggressive metastatic, muscle-invasive bladder cancer, we demonstrate that CM-272 + cisplatin treatment results in statistically significant regression of established tumors and metastases. The antitumor effect is significantly improved when CM-272 is combined with anti-programmed cell death ligand 1, even in the absence of cisplatin. These effects are associated with an endogenous antitumor immune response and immunogenic cell death with the conversion of a cold immune tumor into a hot tumor. Finally, increased G9a expression was associated with resistance to programmed cell death protein 1 inhibition in a cohort of patients with bladder cancer. In summary, these findings support new and promising opportunities for the treatment of bladder cancer using a combination of epigenetic inhibitors and immune checkpoint blockade. Inhibition of histone and DNA methyltransferase activity enhances sensitivity to platinum-based and immunotherapy in a novel transgenic mouse model of metastatic bladder cancer.

A partir del análisis de dieciocho estudios realizados por científicos sociales de América Latina, el presente trabajo busca poner en el escenario la “violencia obstétrica” y suscitar reflexión en torno a su conceptualización y sus orígenes, además de retomar las recomendaciones propuestas por las y los autores para un cambio de situación y de proponer nuevas rutas de indagación. Un cambio de paradigmas en los sistemas de salud, en los procedimientos y en la formación de los profesionales con miras a la humanización de la atención en el campo de la salud de las mujeres y la erradicación de todas las formas de la violencia obstétrica son requeridos para que sea posible hablar de ejercicio de ciudadanía en ese ámbito; en la investigación social se requiere incluir la perspectiva del personal de salud y profundizar en realidades como la vulnerabilidad social de las mujeres y el aborto.

The ‘cancer cell fusion’ theory is controversial due to the lack of methods available to identify hybrid cells and to follow the phenomenon in patients. However, it seems to be one of the best explanations for both the origin and metastasis of primary tumors. Herein, we co-cultured lung cancer stem cells with human monocytes and analyzed the dynamics and properties of tumor-hybrid cells (THC), as well as the molecular mechanisms beneath this fusion process by several techniques: electron-microscopy, karyotyping, CRISPR-Cas9, RNA-seq, immunostaining, signaling blockage, among others. Moreover, mice models were assessed for in vivo characterization of hybrids colonization and invasiveness. Then, the presence of THCs in bloodstream and samples from primary and metastatic lesions were detected by FACS and immunofluorescence protocols, and their correlations with TNM stages established. Our data indicate that the generation of THCs depends on the expression of CD36 on tumor stem cells and the oxidative state and polarization of monocytes, the latter being strongly influenced by microenvironmental fluctuations. Highly oxidized M2-like monocytes show the strongest affinity to fuse with tumor stem cells. THCs are able to proliferate, colonize and invade organs. THC-specific cell surface signature CD36+CD14+PANK+ allows identifying them in matched primary tumor tissues and metastases as well as in bloodstream from patients with lung cancer, thus functioning as a biomarker. THCs levels in circulation correlate with TNM classification. Our results suggest that THCs are involved in both origin and spread of metastatic cells. Furthermore, they might set the bases for future therapies to avoid or eradicate lung cancer metastasis., Research in the laboratory of EL-C was supported by “Fundación para la Investigación Biomédica La Paz Hospital” ((FIBHULP) and “Fundación Familia Alonso”.

Resumen Introducción La atención humanizada del parto observa atributos en el cuidado a la gestante, orientados a hacer satisfactoria la experiencia reproductiva. Objetivos Recoger, a partir de la voz de las mujeres, y analizar, desde una perspectiva de humanización, experiencias con la atención del embarazo y parto y sugerencias para fortalecer el parto humanizado en una subred integrada de servicios de salud de Bogotá. Materiales y Métodos Estudio cualitativo fenomenológico, basado en entrevistas semiestructuradas y grupos focales, que exploraron experiencias de embarazo y parto con 16 participantes. Se implementó un análisis temático. Resultados La falta de oportunidad y falencias en la coordinación, información y trato a las usuarias afectan la atención del embarazo. En el trabajo de parto y parto, se relatan experiencias de desconocimiento de la privacidad, sentirse “conejillos de indias”, intervenciones no informadas y ejercicio autoritario de las relaciones de poder profesionales-usuarias. Discusión Se evidencia la necesidad de garantizar la atención prioritaria a las gestantes, eliminando barreras y mejorando la información y trato a las usuarias. En el parto, se reconoce la existencia de prácticas de deshumanización, naturalizadas en la atención reproductiva, que deben ser erradicadas. Conclusiones Se requiere romper paradigmas culturales y de género que afectan la humanización en la atención al embarazo y parto mediante formación al personal, reconociendo las necesidades de las usuarias y cualificando la organización institucional para la atención del parto. El respeto a los derechos de las gestantes debe primar en procesos formativos con estudiantes. El acompañamiento permanente a las usuarias es crucial. Summary Introduction Humanized care at childbirth observes attributes in the care of pregnant women aimed at making the reproductive experience satisfactory. Objectives This study is aimed to hear the experiences related to pregnancy and childbirth care as well as the suggestions to strengthen humanized childbirth in an integrated healthcare subnetwork in Bogotá from the voice of women and to analyze them from a humanization perspective. Materials and Methods A qualitative phenomenological study was conducted based on semi-structured interviews and focus groups in 16 participants to explore the experiences of pregnancy and childbirth. A thematic analysis was implemented. Results Lack of opportunities and deficiencies in the coordination, information and treatment of patients affect pregnancy care. In labor and delivery, experiences related to the lack of knowledge of patient privacy, feeling like "guinea pigs", uninformed interventions, and authoritarian exercise of healthcare professional-patient power relations are reported. Discussion The need to ensure priority attention to pregnant women, eliminating barriers and improving information and treatment of patients is evident. In childbirth, the existence of dehumanizing practices, which have been naturalized in reproductive healthcare, is recognized and must be eradicated. Conclusions It is necessary to break cultural and gender paradigms that affect the humanization of pregnancy and childbirth care by providing staff training, recognizing the needs of patients and qualifying the institutional organization for childbirth care. Respect for the rights of pregnant women should be a priority in student training. Permanent support to patients is crucial. Resumo Introdução O cuidado humanizado ao parto observa atributos no cuidado à gestante, orientados a tornar satisfatória a experiência reprodutiva. Objetivos Reunir, a partir da voz das mulheres, e analisar, do ponto de vista da humanização, experiências com os cuidados com a gravidez e o parto e sugestões para fortalecer o parto humanizado em uma sub-rede integrada de serviços de saúde em Bogotá. Materiais e Métodos Estudo fenomenológico qualitativo, baseado em entrevistas semiestruturadas e grupos focais, que explorou experiências de gravidez e parto com 16 participantes. Uma análise temática foi implementada. Resultados A falta de oportunidade e falhas na coordenação, informação e tratamento das usuárias afetam o cuidado da gravidez. No trabalho de parto e parto, são relatadas experiências de ignorância da privacidade, sentimento de "cobaias", intervenções desinformadas e exercício autoritário de relações de poder entre usuários profissionais. Discussão É evidente a necessidade de garantir atendimento prioritário às gestantes, removendo barreiras e melhorando as informações e o tratamento para as usuárias. No parto, é reconhecida a existência de práticas de desumanização, naturalizadas no cuidado reprodutivo, que devem ser erradicadas. Conclusões É necessário romper os paradigmas culturais e de gênero que afetam a humanização no cuidado com a gravidez e o parto, por meio da capacitação da equipe, reconhecendo as necessidades das usuárias e qualificando a organização institucional para o cuidado ao parto. O respeito pelos direitos das mulheres grávidas deve ter precedência nos processos de treinamento com as estudantes. O acompanhamento permanente dos usuários é crucial.

STUDY QUESTION What are the trends and developments in preimplantation genetic testing (PGT) in 2013–2015 as compared to previous years? SUMMARY ANSWER The main trends observed in the retrospective data collections 2013–2015, representing valuable data on PGT activity in (mainly) Europe, are the increased application of trophectoderm biopsy at the cost of cleavage stage biopsy and the continuing expansion of comprehensive testing technology in PGT for chromosomal structural rearrangements and for aneuploidies (PGT-SR and PGT-A). WHAT IS KNOWN ALREADY Since it was established in 1997, the ESHRE PGT Consortium has been collecting data from international PGT centres. To date, 15 data sets and an overview of the first 10 years of data collections have been published. STUDY DESIGN, SIZE, DURATION Collection of (mainly) European data by the PGT Consortium for ESHRE. The data for PGT cycles performed between 1 January 2013 and 31 December 2015 were provided by participating centres on a voluntary basis. For the collection of cycle, pregnancy and baby data, separate, pre-designed MS Excel tables were used. PARTICIPANTS/MATERIALS, SETTING, METHODS Data were submitted by 59, 60 and 59 centres respectively for 2013, 2014 and 2015 (full PGT Consortium members). Records with incomplete or inconsistent data were excluded from the calculations. Corrections, calculations, figures and tables were made by expert co-authors. MAIN RESULTS AND THE ROLE OF CHANCE For data collection XVI/XVII/XVIII, 59/60/59 centres reported data on 8164/9769/11 120 cycles with oocyte retrieval: 5020/6278/7155 cycles for PGT-A, 2026/2243/2661 cycles for PGT for monogenic/single gene defects, 1039/1189/1231 cycles for PGT-SR and 79/59/73 cycles for sexing for X-linked diseases. From 2013 until 2015, the uptake of biopsy at the blastocyst stage was mainly observed in cycles for PGT-A (from 23% to 36%) and PGT-SR (from 22% to 36%), alongside the increased application of comprehensive testing technology (from 66% to 75% in PGT-A and from 36% to 58% in PGT-SR). LIMITATIONS, REASONS FOR CAUTION The findings apply to the 59/60/59 participating centres and may not represent worldwide trends in PGT. Data were collected retrospectively and no details of the follow-up on PGT pregnancies and babies born were provided. WIDER IMPLICATIONS OF THE FINDINGS Being the largest data collection on PGT worldwide, detailed information about ongoing developments in the field is provided. STUDY FUNDING/COMPETING INTEREST(S) The study has no external funding and all costs are covered by ESHRE. There are no competing interests declared. TRIAL REGISTRATION NUMBER N/A.

En el sistema colombiano actual existen diferentes variables que pueden afectar la prestación de los servicios públicos domiciliarios por parte de las empresas constituidas para tal fin. Tanto así, que su mal funcionamiento genera grandes pérdidas comerciales, las cuales resultan siendo asumidas por los usuarios. El estudio realizó un planteamiento sobre las falencias ocasionadas en esta materia, incluyendo factores de responsabilidad social empresarial, con el único objetivo de proponer una estrategia para mejorar el procedimiento que realizan las empresas de servicios públicos domiciliarios.

The purpose of the study was to explore variables of the health belief model in relation to the follow-up of abnormal Pap smear among low-income women in Medellín, Colombia. Eight focus groups (62 women) were conducted according to age groups (25-45 and 46-69 years). The data were analyzed using content analysis. The participants perceived themselves as vulnerable, recognized the severity of the disease in terms of both its emotional and physical consequences, perceived the benefits of the follow-up, and mentioned cues to action, such as social support and the support of health entities. Perceived self-efficacy was compromised by health system barriers and by personal barriers, such as placing the needs of their children ahead of their own, fear, neglect, and the pain caused by the diagnostic and therapeutic procedures. Health education activities aimed at increasing the follow-up of abnormal Pap smears should consider psychological factors.