Factors associated with the perceived impact of the Peruvian hospital internship during COVID-19

"Introducción: La pandemia afectó el internado de estudiantes de salud en su asistencia hospitalaria, en la cual realizan las prácticas. Objetivo: Determinar los factores asociados a la percepción de repercusiones del internado hospitalario peruano durante la COVID-19. Métodos: Estudio transversal; se obtuvo estadística descriptiva, analítica bivariada y multivariada basado en una encuesta realizada de forma exploratoria, como parte de otra investigación mayor, a la cual se le asoció variables como edad, sexo, tipo de universidad, estrés, ansiedad, depresión y repercusiones del internado. Resultados: De los 121 encuestados, la mayoría pensó que su familia le hubiese apoyado si se enfermaba de gravedad, que pudo haber infectado a sus familiares o alguna amistad/conocido si acudían al hospital. Muchos estuvieron en desacuerdo con que el hospital o la universidad les darían los implementos de seguridad, por la falta de apoyo de estas entidades. Hubo asociación entre el pensar que se habría contagiado de la COVID-19 si iba al hospital versus el puntaje de ansiedad (p= 0,030), el sexo masculino, según la percepción de que la universidad les daría los materiales para cuidarse (p= 0,029) y el provenir de una universidad privada según el percibir que el hospital no le hubiese apoyado, si se enfermaba de gravedad (p= 0,049). Conclusión: Los factores asociados a la percepción de repercusiones del internado son el apoyo familiar, el poder contagiar a sus familiares, falta de materiales dados por las universidades y hospitales, la ansiedad, el sexo masculino y provenir de universidades privadas.

Factors associated with the perceived impact of the Peruvian hospital internship during COVID-19

"Introducción: La pandemia afectó el internado de estudiantes de salud en su asistencia hospitalaria, en la cual realizan las prácticas. Objetivo: Determinar los factores asociados a la percepción de repercusiones del internado hospitalario peruano durante la COVID-19. Métodos: Estudio transversal; se obtuvo estadística descriptiva, analítica bivariada y multivariada basado en una encuesta realizada de forma exploratoria, como parte de otra investigación mayor, a la cual se le asoció variables como edad, sexo, tipo de universidad, estrés, ansiedad, depresión y repercusiones del internado. Resultados: De los 121 encuestados, la mayoría pensó que su familia le hubiese apoyado si se enfermaba de gravedad, que pudo haber infectado a sus familiares o alguna amistad/conocido si acudían al hospital. Muchos estuvieron en desacuerdo con que el hospital o la universidad les darían los implementos de seguridad, por la falta de apoyo de estas entidades. Hubo asociación entre el pensar que se habría contagiado de la COVID-19 si iba al hospital versus el puntaje de ansiedad (p= 0,030), el sexo masculino, según la percepción de que la universidad les daría los materiales para cuidarse (p= 0,029) y el provenir de una universidad privada según el percibir que el hospital no le hubiese apoyado, si se enfermaba de gravedad (p= 0,049). Conclusión: Los factores asociados a la percepción de repercusiones del internado son el apoyo familiar, el poder contagiar a sus familiares, falta de materiales dados por las universidades y hospitales, la ansiedad, el sexo masculino y provenir de universidades privadas.

Identification of FAM111A as an SV40 Host Range Restriction and Adenovirus Helper Factor

The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT) contains several discrete functional domains including the LXCXE or RB-binding motif, the DNA binding and helicase domains that contribute to the viral life cycle. In addition, the LT C-terminal region contains the host range and adenovirus helper functions required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells, identified interacting host proteins and carried out expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes. Affinity purification of LT followed by mass spectrometry revealed a specific interaction between the LT C-terminal region and FAM111A, a previously uncharacterized protein. Depletion of FAM111A recapitulated the effects of heterologous expression of the LT C-terminal region, including increased viral gene expression and lytic infection of SV40 host range mutants and adenovirus replication in restrictive cells. FAM111A functions as a host range restriction factor that is specifically targeted by SV40 LT

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Simian Virus 40 and Human Polyomavirus Oncogenic Perturbations

Polyomaviruses have widespread prevalence across many animal species. Polyomaviruses are small DNA tumor viruses that endow their host cells with proliferative signals through interactions between their small T (ST) and large T (LT) antigens and host cell proteins. For example, simian virus 40 (SV40) LT can simultaneously bind and inhibit the retinoblastoma (pRb) and p53 tumor suppressor pathways, while ST binds to and perturbs protein phosphatase 2A (PP2A). In this dissertation, we sought to characterize the oncogenic properties of T antigens from several polyomaviruses, including Malawi polyomavirus (MWPyV), Merkel cell polyomavirus (MCPyV) and SV40, and determine whether they had shared or unique growth-promoting mechanisms. MWPyV is a recently identified human polyomavirus with unknown transforming potential. We found that its T antigens, although capable of binding to pRb, p53 and PP2A, were not as transforming as T antigens from SV40. In contrast, Merkel cell polyomavirus (MCPyV) ST is required for maintenance of Merkel cell carcinoma (MCC), a highly aggressive skin cancer. To gain insights into its transforming function, we performed transcriptome profiling of normal human cells expressing MCPyV ST and identified significant perturbations in glycolysis-related genes. Furthermore, targeting aerobic glycolysis inhibited MCPyV-induced transformation as well as MCC growth. To gain further insight into MCPyV virus-host interactions in a relevant cell type, we pursued the development of a system to isolate and characterize primary Merkel cells and investigate their response to MCPyV T antigens. Co-expression of SV40 ST and LT together with the telomerase catalytic subunit (hTERT) and oncogenic Ras is sufficient to fully transform normal human fibroblasts. SV40 ST is known to bind to the A and C subunits of PP2A, displacing B subunits and altering PP2A-mediated regulation of numerous cancer-associated pathways. We were interested in pursuing SV40 STs recently described association with a PP2A A, B and C subunit-containing complex known as the striatin-interacting phosphatase and kinase (STRIPAK) complex. We determined that the STRIPAK complex was required for SV40 STs transforming ability and this was due, at least in part, to inhibition of the STRIPAK associated-MAP4K4 kinase activity. The results presented in this dissertation highlight the striking distinctions in the transforming mechanisms of three divergent polyomaviruses. While each polyomavirus targets some of the same cancer pathways such as pRb, full transformation is achieved through non-overlapping mechanisms specific to each virus. Such an analysis of the polyomavirus tumor virus family provides insight into the heterogeneity of their oncogenic activity, thereby facilitating the discovery of novel cancer targets and therapeutic opportunities.Medical Science

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Sex differences in oncogenic mutational processes

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Peer reviewe