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El objetivo de este estudio fue medir las conductas emprendedoras y su relación con el pensamiento empresarial en los estudiantes de la Universidad Politécnica del Carchi en Ecuador y la Universidad de San Buenaventura Cali en Colombia. Los procedimientos metodológicos probaron la teoría de McClelland, con una muestra de estudiantes universitarios (801 en Ecuador y 564 en Colombia). La recolección de datos se hizo en línea, en las dos universidades, aplicando un cuestionario con 50 preguntas y 5 de corrección mediante una escala de Likert, durante marzo de 2021. Usando el software SPSS y el método de extracción de factores con máxima verosimilitud y rotación Promax, para analizar el modelo de medida, así como, la invarianza configural y métrica, como paso previo para el desarrollo de un Modelo de Ecuaciones Estructurales (SEM). El ejercicio de modelo de medida aplicó el siguiente orden: 1) Verificar la fiabilidad y validez del modelo, 2) Validar la invarianza configural y métrica por país; en una futura entrega se podrá realizar un análisis SEM. Existen conductas orientadas a un vendedor exitoso: persistencia, búsqueda de oportunidades, persuasión y autoconfianza. Además, mediante el currículo desarrollado en la Upec se pretende modificar tales conductas que permitan incrementar la intención emprendedora con propensión a cerrar ventas. De igual manera, se encontraron conductas relacionadas con un gerente exitoso. Por ejemplo, toma de riesgos calculados, cumplimiento, planificación sistemática y búsqueda de información que pueden ser intervenidas para que los emprendedores aumenten su intención en la creación de empresas.

Prostate cancer (PrCa) is one of the most hereditable human cancers, however, only a small fraction of patients has been shown to carry deleterious variants in known cancer predisposition genes.Whole-exome sequencing was performed in multiple affected members of 45 PrCa families to select the best candidate genes behind part of the PrCa missing hereditability. Recurrently mutated genes were prioritised, and further investigated by targeted next-generation sequencing in the whole early-onset and/or familial PrCa series of 462 patients.PRUNE2 stood out from our analysis when also considering the available data on its association with PrCa development. Ten germline pathogenic/likely pathogenic variants in the PRUNE2 gene were identified in 13 patients. The most frequent variant was found in three unrelated patients and identical-by-descent analysis revealed that the haplotype associated with the variant is shared by all the variant carriers, supporting the existence of a common ancestor.This is the first report of pathogenic/likely pathogenic germline variants in PRUNE2 in PrCa patients, namely in those with early-onset/familial disease. Importantly, PRUNE2 was the most frequently mutated gene in the whole series, with a deleterious germline variant identified in 2.8% of the patients, representing a novel prostate cancer predisposition gene.

Helicobacter pylori have coevolved with mankind since its origins, adapting to different human groups. In America, H. pylori has evolved into several subpopulations. We analysed the genome of 154 Colombian strains along with 1,091 strains from worldwide populations to discern the ancestry and adaption to Colombian people. Population structure and ancestry was inferred with FineStructure and ChromoPainter. Phylogenetic relationship and the relative effect of recombination were analysing the core SNPs. Also, a Fst index was calculated to identify the gene variants with the strongest fixation in the Colombian subpopulations compared to their parent population hspSWEurope. FineStructure allowed the identification of two Colombian subpopulations, the previously described hspSWEuropeColombia and a novel subpopulation named hspColombia, that included three subgroups following their geographic origin. Colombian subpopulations represent an admixture of European, African and Indigenous ancestry; although some genomes showed a high proportion of self identity, suggesting an advanced adaption to these mestizo Colombian groups. We found that recombination is more important that punctual mutations in H. pylori genome diversity, 13.9 more important in hspSWEurope, 12.5 in hspSWEColombia and 10.5 in hspColombia, reflecting the divergence of these subpopulations. Fst analysis identified 82 SNPs fixed in 26 genes of the hspColombia subpopulation that encode for outer membrane and central metabolism proteins. Strongest fixation indexes were identified in genes encoding HofC, HopE, FrpB-4 and Sialidase A. These findings demonstrate that H. pylori has evolved in Colombia to give rise to subpopulations with a self identity ancestry, reflected in allele changes on genes encoding for outer membrane proteins.

Dentro de las tecnologías multimedia, el uso de audios (como material de enseñanza) ha atraído la atención de los docentes debido a sus beneficios para el aprendizaje, tanto en términos de atención como de motivación de los estudiantes (Almobarraz, 2018; Brecht, 2012; Orús et al., 2016; entre otros). Entre los beneficios del aprendizaje, la literatura existente resalta los siguientes: 1) permite un proceso de aprendizaje más flexible temporal y espacial; 2) representa un ahorro en costes y tiempo tanto para los estudiantes como para las instituciones educativas; 3) mejora la autonomía del estudiante en el proceso de aprendizaje; y 4) promueve el aprendizaje colaborativo y bajo demanda. Actualmente se está realizando un testeo con el alumnado con disfunciones visuales de la Asignatura de Economía II del Grado de Turismo que culminará con una comparativa de las notas en el curso anterior a la puesta a disposición del mismo del material preparado. Se espera que las calificaciones sean superiores con el uso de esta locución.

Dentro de las tecnologías multimedia, el uso de audios (como material de enseñanza) ha atraído la atención de los docentes debido a sus beneficios para el aprendizaje, tanto en términos de atención como de motivación de los estudiantes (Almobarraz, 2018; Brecht, 2012; Orús et al., 2016; entre otros). Entre los beneficios del aprendizaje, la literatura existente resalta los siguientes: 1) permite un proceso de aprendizaje más flexible temporal y espacial; 2) representa un ahorro en costes y tiempo tanto para los estudiantes como para las instituciones educativas; 3) mejora la autonomía del estudiante en el proceso de aprendizaje; y 4) promueve el aprendizaje colaborativo y bajo demanda. Actualmente se está realizando un testeo con el alumnado con disfunciones visuales de la Asignatura de Economía II del Grado de Turismo que culminará con una comparativa de las notas en el curso anterior a la puesta a disposición del mismo del material preparado. Se espera que las calificaciones sean superiores con el uso de esta locución.

Dentro de las tecnologías multimedia, el uso de audios (como material de enseñanza) ha atraído la atención de los docentes debido a sus beneficios para el aprendizaje, tanto en términos de atención como de motivación de los estudiantes (Almobarraz, 2018; Brecht, 2012; Orús et al., 2016; entre otros). Entre los beneficios del aprendizaje, la literatura existente resalta los siguientes: 1) permite un proceso de aprendizaje más flexible temporal y espacial; 2) representa un ahorro en costes y tiempo tanto para los estudiantes como para las instituciones educativas; 3) mejora la autonomía del estudiante en el proceso de aprendizaje; y 4) promueve el aprendizaje colaborativo y bajo demanda. Actualmente se está realizando un testeo con el alumnado con disfunciones visuales de la Asignatura de Economía II del Grado de Turismo que culminará con una comparativa de las notas en el curso anterior a la puesta a disposición del mismo del material preparado. Se espera que las calificaciones sean superiores con el uso de esta locución.

PDF file of supplementary methods and materials, and supplementary figures and tables

Spreadsheet of counts of patients with SNV/indel mutations in each gene

Spreadsheet of pan-cancer panel gene composition, with citation codes

Spreadsheet of sample mean sequencing depths

The tumor suppressor p53 (TP53) has a well-studied role in triggering cell-cycle checkpoint in response to DNA damage. Previous studies have suggested that functional p53 enhances chemosensitivity. In contrast, data are presented to show that p53 can be required for cell survival following DNA damage due to activation of reversible cell-cycle checkpoints. The cellular outcome to DNA damage is determined by the duration and extent of the stimulus in a p53-dependent manner. In response to transient or low levels of DNA damage, p53 triggers a reversible G2 arrest, whereas a sustained p53-dependent cell-cycle arrest and senescence follows prolonged or high levels of DNA damage. Regardless of the length of treatment, p53-null cells arrest in G2, but ultimately adapt and proceed into mitosis. Interestingly, they fail to undergo cytokinesis, become multinucleated, and then die from apoptosis. Upon transient treatment with DNA-damaging agents, wild-type p53 cells reversibly arrest and repair the damage, whereas p53-null cells fail to do so and die. These data indicate that p53 can promote cell survival by inducing reversible cell-cycle arrest, thereby allowing for DNA repair. Thus, transient treatments may exploit differences between wild-type p53 and p53-null cells.Implications: Although p53 status has been suggested as a clinical predictor of chemotherapeutic efficacy, studies to date have not always supported this. This study demonstrates that p53 is still an important determinant of cell fate in response to chemotherapy, under the appropriate treatment conditions. Mol Cancer Res; 13(1); 16–28. ©2014 AACR.

References for supplementary methods file

Supplemental Material. Supplemental Figure S1. A: Doxorubicin treatment leads to the concentration-dependent induction of p53 and p21 in parental U2OS cells. U2OS cells were treated with doxorubicin at concentrations ranging from 0.05 μg/ml to 0.2 μg/ml for 24 hours and harvested. Cell extracts were analyzed by immunoblotting for expression of p53, p21, and β-actin (loading control). B: Responses of control and p53-ablated cells to doxorubicin are not clonal in nature. U2OS derivatives expressing either a control shRNA (clone 1 and clone 4) or p53 shRNA (clone 7 and clone 8) were untreated or treated with 0.05 μg/ml doxorubicin for 1-6 days, and then analyzed by flow cytometry. The percentage of cells in each phase of the cell cycle or with a DNA content of less than 2N (

P53 CHIP-SEQ

The repression of repetitive elements is an important facet of p53's function as a guardian of the genome. Paradoxically, we found that p53 activated by MDM2 inhibitors induced the expression of endogenous retroviruses (ERV) via increased occupancy on ERV promoters and inhibition of two major ERV repressors, histone demethylase LSD1 and DNA methyltransferase DNMT1. Double-stranded RNA stress caused by ERVs triggered type I/III interferon expression and antigen processing and presentation. Pharmacologic activation of p53 in vivo unleashed the IFN program, promoted T-cell infiltration, and significantly enhanced the efficacy of checkpoint therapy in an allograft tumor model. Furthermore, the MDM2 inhibitor ALRN-6924 induced a viral mimicry pathway and tumor inflammation signature genes in patients with melanoma. Our results identify ERV expression as the central mechanism whereby p53 induction overcomes tumor immune evasion and transforms tumor microenvironment to a favorable phenotype, providing a rationale for the synergy of MDM2 inhibitors and immunotherapy.Significance:We found that p53 activated by MDM2 inhibitors induced the expression of ERVs, in part via epigenetic factors LSD1 and DNMT1. Induction of IFN response caused by ERV derepression upon p53-targeting therapies provides a possibility to overcome resistance to immune checkpoint blockade and potentially transform “cold” tumors into “hot.”This article is highlighted in the In This Issue feature, p. 2945

Raw data for FACs profiling of immune cells on CT26

All Supplementary Figures

Primers, siRNAs and CRISPR guide RNAs

Background: Genome-wide association studies (GWAS) of multiple myeloma in populations of European ancestry (EA) identified and confirmed 24 susceptibility loci. For other cancers (e.g., colorectum and melanoma), risk loci have also been associated with patient survival. Methods: We explored the possible association of all the known risk variants and their polygenic risk score (PRS) with multiple myeloma overall survival (OS) in multiple populations of EA [the International Multiple Myeloma rESEarch (IMMEnSE) consortium, the International Lymphoma Epidemiology consortium, CoMMpass, and the German GWAS] for a total of 3,748 multiple myeloma cases. Cox proportional hazards regression was used to assess the association between each risk SNP with OS under the allelic and codominant models of inheritance. All analyses were adjusted for age, sex, country of origin (for IMMEnSE) or principal components (for the others) and disease stage (ISS). SNP associations were meta-analyzed. Results: SNP associations were meta-analyzed. From the meta-analysis, two multiple myeloma risk SNPs were associated with OS (P < 0.05), specifically POT1-AS1-rs2170352 [HR = 1.37; 95% confidence interval (CI) = 1.09–1.73; P = 0.007] and TNFRSF13B-rs4273077 (HR = 1.19; 95% CI = 1.01–1.41; P = 0.04). The association between the combined 24 SNP MM-PRS and OS, however, was not significant. Conclusions: Overall, our results did not support an association between the majority of multiple myeloma risk SNPs and OS. Impact: This is the first study to investigate the association between multiple myeloma PRS and OS in multiple myeloma.

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Purpose: Identification of single-nucleotide polymorphisms (SNP) associated with development of advanced colorectal adenomas.Experimental Design: Discovery phase: 1,406 Caucasian patients (139 advanced adenoma cases and 1,267 controls) from the Adenoma Prevention with Celecoxib (APC) trial were included in a genome-wide association study (GWAS) to identify variants associated with postpolypectomy disease recurrence. Genome-wide significance was defined as false discovery rate less than 0.05, unadjusted P = 7.4 × 10−7. Validation phase: results were further evaluated using 4,175 familial colorectal adenoma cases and 5,036 controls from patients of European ancestry [COloRectal Gene Identification consortium (CORGI), Scotland, Australia, and VQ58].Results: Our study identified eight SNPs associated with advanced-adenoma risk in the APC trial (rs2837156, rs7278863, rs2837237, rs2837241, rs2837254, rs741864 at 21q22.2, and rs1381392 and rs17651822 at 3p24.1, at P < 10−7 level with OR > 2). Five variants in strong pairwise linkage disequilibrium (rs7278863, rs2837237, rs741864, rs741864, and rs2837241; r2 = 0.8–1) are in or near the coding region for the tight junction adhesion protein, IGSF5. An additional variant associated with advanced adenomas, rs1535989 [minor allele frequency, 0.11; OR, 2.09; 95% confidence interval (CI), 1.50–2.91], also predicted colorectal cancer development in a validation analysis (P = 0.019) using a series of adenoma cases or colorectal cancer (CORGI study) and 3 sets of colorectal cancer cases and controls (Scotland, VQ58, and Australia; N = 9,211).Conclusions: Our results suggest that common polymorphisms contribute to the risk of developing advanced adenomas and might also contribute to the risk of developing colorectal cancer. The variant at rs1535989 may identify patients whose risk for neoplasia warrants increased colonoscopic surveillance. Clin Cancer Res; 19(23); 6430–7. ©2013 AACR.

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BackgroundBreast cancer is the most common cancer among women in the U.S. and the leading cause of cancer death among Hispanics/Latinas (H/L). H/L are less likely than Non-H/L White (NHW) women to be diagnosed in the early stages of this disease. Approximately 5-10% of breast cancer can be attributed to inherited genetic mutations in high penetrance genes such as BRCA1/2. Women with pathogenic variants in these genes have a 40-80% lifetime risk of breast cancer. Past studies have shown that genetic counseling can help women and their families make informed decisions about genetic testing and early cancer detection or risk-reduction strategies. However, H/L are 3.9-4.8 times less likely to undergo genetic testing than NHW women. We developed a program to outreach and educate the H/L community about hereditary breast cancer, targeting monolingual Spanish-speaking individuals in California. Through this program, we have assessed cancer screening behavior and identified women who might benefit from genetic counseling in a population that is usually excluded from cancer research and care.Materials and MethodsThe “Tu Historia Cuenta” program is a promotores-based virtual outreach and education program including the cities of San Francisco, Sacramento, and Los Angeles. Participants responded to three surveys: a demographic survey, a breast cancer family history survey, and a feedback survey. Survey responses were described for participants and compared by area where the program took place using chi-square, Fisher exact tests, and t tests. Multinomial logistic regression models were used for multivariate analyses.Results and ConclusionWe enrolled 1042 women, 892 completed the cancer family history survey and 62 (7%) provided responses compatible with referral to genetic counseling. We identified 272 women (42.8% ages 40 to 74 years) who were due for mammograms, 250 women (24.7% ages 25 to 65 years) due for Papanicolaou test, and 189 women (71.6% ages 50+) due for colorectal cancer screening. These results highlight the need of additional support for programs that spread awareness about cancer risk and facilitate access to resources, specifically within the H/L community.

El desarrollo de esta investigación busca determinar el perfil del cliente que visita los jardines de orquídeas de la provincia del Carchi para establecer estrategias de comercialización. Mediante un análisis cualitativo y cuantitativo del perfil turístico de los clientes se logró establecer las estrategias de comercialización que se pueden implementar en los jardines de orquídeas para fomentar el crecimiento turístico en la provincia. Además, se identificó mayor presencia de los segmentos de mercado turístico ecuatoriano provenientes de Ibarra y turistas de Colombia. En conclusión, se destaca que los jardines de orquídeas quieren posicionarse en el mercado turístico, mientras se busca la conservación y protección de las especies de orquídeas, mientras más raras son, mayor es su valor.

Las cuencas hidrográficas se constituyen en unidades fundamentales de análisis para el desarrollo de procesos de planificación y gestión. La comprensión de su dinámica, estructura y funcionamiento constituyen el soporte para la planificación del territorio y la toma de decisiones. Sin embargo, la funcionalidad y aprovechamiento sostenible son dependientes de la información y el conocimiento de estos ecosistemas, así como de sus regímenes y capacidades de respuesta frente a las intervenciones antrópicas, variabilidad y cambio climático. Este libro brinda instrumentos y metodologías para la planificación y evaluación del recurso hídrico, así como en la formulación e implementación de mecanismos de adaptación al cambio climático y la gestión integrada de cuencas hidrográficas. La publicación denominada: “Gestión integrada de la cuenca alta del río Magdalena: instrumentos para su evaluación y planificación” es producto de investigaciones realizadas por estudiantes, docentes y egresados de la Escuela de Ciencias Agrícolas, Pecuarias y del Medio Ambiente (ECAPMA) de la UNAD y el grupo de investigación Inyumacizo, categorizado en A por MinCiencias.

Gastric cancer is a leading cause of cancer mortality and health disparities in Latinos. We evaluated gastric intratumoral heterogeneity using multiregional sequencing of >700 cancer genes in 115 tumor biopsies from 32 patients, 29 who were Latinos. Analyses focused on comparisons with The Cancer Genome Atlas (TCGA) and on mutation clonality, druggability, and signatures. We found that only approximately 30% of all mutations were clonal and that only 61% of the known TCGA gastric cancer drivers harbored clonal mutations. Multiple clonal mutations were found in new candidate gastric cancer drivers such as EYS, FAT4, PCDHA1, RAD50, EXO1, RECQL4, and FSIP2. The genomically stable (GS) molecular subtype, which has the worse prognosis, was identified in 48% of our Latino patients, a fraction that was >2.3-fold higher than in TCGA Asian and White patients. Only a third of all tumors harbored clonal pathogenic mutations in druggable genes, with most (93%) GS tumors lacking actionable clonal mutations. Mutation signature analyses revealed that, in microsatellite-stable (MSS) tumors, DNA repair mutations were common for both tumor initiation and progression, while tobacco, POLE, and inflammation signatures likely initiate carcinogenesis. MSS tumor progression was likely driven by aging- and aflatoxin-associated mutations, as these latter changes were usually nonclonal. In microsatellite-unstable tumors, nonclonal tobacco-associated mutations were common. Our study, therefore, contributed to advancing gastric cancer molecular diagnostics and suggests clonal status is important to understanding gastric tumorigenesis. Our findings of a higher frequency of a poor prognosis associated molecular subtype in Latinos and a possible new aflatoxin gastric cancer etiology also advance cancer disparities research. Significance: Our study contributes to advancing our knowledge of gastric carcinogenesis, diagnostics, and cancer health disparities.

Development of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established the genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cancer types, together with mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared with human tumors, PDXs typically have higher purity and fit to investigate dynamic driver events and molecular properties via multiple time points from same case PDXs. Here, we report on dynamic genomic landscapes and pharmacogenomic associations, including associations between activating oncogenic events and drugs, correlations between whole-genome duplications and subclone events, and the potential PDX models for NCI-MATCH trials. Lastly, we provide a web portal having comprehensive pan-cancer PDX genomic profiles and source code to facilitate identification of more druggable events and further insights into PDXs’ recapitulation of human tumors., Patient-derived xenograft models (PDX) have been extensively used to study the molecular and clinical features of cancers. Here the authors present a cohort of 536 PDX models from 25 cancers, as well as their genomic and evolutionary profiles and their suitability for clinical trials.

BackgroundCancer is the leading cause of death among Latinos, the largest minority population in the United States (US). To address cancer challenges experienced by Latinos, we conducted a catchment area population assessment (CAPA) using validated questions from the National Cancer Institute (NCI) population health assessment supplement at our NCI-designated cancer center in California.MethodsA mixed-methods CAPA was administered by bilingual-bicultural staff, with a focus on understanding the differences between foreign-born and US-born Latinos.Results255 Latinos responded to the survey conducted between August 2019 and May 2020. Most respondents were foreign-born (63.9%), female (78.2%), and monolingual Spanish speakers (63.2%). Results showed that compared to US-born Latinos, foreign-born individuals were older, had lower educational attainment, were most likely to be monolingual Spanish speakers, were low-income, and were more likely to be uninsured. Foreign-born Latinos had lower levels of alcohol consumption and higher consumption of fruits and vegetables. The rate of preventive cancer screenings for breast, cervical and colorectal cancer did not differ by birthplace, although a low fraction (35.3%) of foreign-born Latinas who were up-to-date compared to US-born Latinas (83.3%) with colorectal cancer screening was observed. Time since the last routine check-up for all preventable cancers (cervical p=0.0002, breast p=0.0039, and colorectal p=0.0196) is significantly associated with being up to date with cancer screening. Individuals who had a check-up of two or more years ago are 84% less likely to be up to date with pap smears than those who had a check-up within the year (p=0.0060). Individuals without health insurance are 94% less likely to be up to date with mammograms and colonoscopy/FIT tests (p=0.0016 and p=0.0133, respectively) than those who are insured. There is no significant association between screening and nativity.ConclusionsConsiderable differences in socio-economic and environmental determinants of health and colorectal cancer screening rates were observed between US-born and foreign-born Latinos. The present study represents the foundation for future targeted intervention among immigrant populations at our cancer center’s catchment area.

Population stratification (PS) is a confounding factor in genome-wide association studies (GWASs) and also an interesting process itself. Latin American populations have mixed genetic ancestry, which may account for PS. We have analyzed the relatedness, by means of the identity-by-descent (IBD) estimations, in a sample of 1805 individuals and 1.006.703 autosomal mutations from a case-control study of colorectal cancer in Mexico. When using the recommended protocol for quality control assessment, 402 should have been removed due to relatedness. Our purpose was to analyze this value in the context of an admixed population. For that aim, we reanalyzed the sample using two software designed for admixed populations, obtaining estimates of 110 and 70 related individuals to remove. The results showed that the first estimation of relatedness was an effect of the higher Native American contribution in part of the data samples, being a confounding factor for IBD estimations. We conclude in the importance of considering PS and genetic ancestry in order to avoid spurious results, not only in GWAS but also in relatedness analysis.

Personalized medicine holds great promise for improving cancer outcomes, yet there is a large inequity in the demographics of patients from whom genomic data and models, including patient derived xenografts (PDX), are developed and for whom treatments are optimized. In this study we develop a genetic ancestry pipeline for the Cancer Genomics Cloud, which we use to assess the diversity of models currently available in the National Cancer Institute (NCI) supported PDX Development and Trial Centers Research Network (PDXNet). We show that there is an over-representation of models derived from patients of European ancestry, which is consistent with other cancer model resources. We discuss these findings in the context of disparities in cancer incidence and outcomes among demographic groups in the US. For example, for the top cancer health disparities affecting African Americans and Latinos, there is a significant lack of ethnic/race appropriate models needed to advance pre-clinical research and personalized clinical treatment. For stomach and liver tumors, which represent disparities in these two minority populations, there are only three available models derived from patients from such backgrounds. Fortunately, ongoing NCI-funded efforts in minority focused PDXNet centers are actively addressing these gaps. We further discuss these results in the context of power analyses to highlight the immediate need for the development of models from minority populations to address cancer health equity in personalized medicine. Citation Format: Brian J. Sanderson, Paul Lott, Katherine Chiu, Juanita Elizabeth Quino, April Pangia Vang, Michael W. Lloyd, PDXNet Consortium, Anuj Srivastava, Jeffrey H. Chuang, Luis G. Carvajal-Carmona. Development and application of genetic ancestry reconstruction methods to study diversity of patient-derived models in the NCI PDXNet Consortium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1946.

Patient-derived xenografts (PDXs) model human intra-tumoral heterogeneity in the context of the intact tissue of immunocompromised mice. Histological imaging via hematoxylin and eosin (H&E) staining is performed on PDX samples for routine assessment and, in principle, captures the complex interplay between tumor and stromal cells. Deep learning (DL)-based analysis of large human H&E image repositories has extracted inter-cellular and morphological signals correlated with disease phenotype and therapeutic response. Here, we present an extensive, pan-cancer repository of nearly 1,000 PDX and paired human progenitor H&E images. These images, curated from the PDXNet consortium, are associated with genomic and transcriptomic data, clinical metadata, pathological assessment of cell composition, and, in several cases, detailed pathological annotation of tumor, stroma, and necrotic regions. We demonstrate that DL can be applied to these images to classify tumor regions with an accuracy of 0.87. Further, we show that DL can predict xenograft-transplant lymphoproliferative disorder, the unintended outgrowth of human lymphocytes at the transplantation site, with an accuracy of 0.97. This repository enables PDX-specific investigations of cancer biology through histopathological analysis and contributes important model system data that expand on existing human histology repositories. We expect the PDXNet Image Repository to be valuable for controlled digital pathology analysis, both for the evaluation of technical issues such as stain normalization and for development of novel computational methods based on spatial behaviors within cancer tissues. Citation Format: Brian S. White, Xing Yi Woo, Soner Koc, Todd Sheridan, Steven B. Neuhauser, Shidan Wang, Yvonne A. Evrard, John David Landua, R Jay Mashl, Sherri R. Davies, Bingliang Fang, Maria Gabriela Raso, Kurt W. Evans, Matthew H. Bailey, Yeqing Chen, Min Xiao, Jill Rubinstein, Ali Foroughi pour, Lacey Elizabeth Dobrolecki, Maihi Fujita, Junya Fujimoto, Guanghua Xiao, Ryan C. Fields, Jacqueline L. Mudd, Xiaowei Xu, Melinda G. Hollingshead, Shahanawaz Jiwani, PDXNet consortium, Tiffany A. Wallace, Jeffrey A. Moscow, James H. Doroshow, Nicholas Mitsiades, Salma Kaochar, Chong-xian Pan, Moon S. Chen, Luis G. Carvajal-Carmona, Alana L. Welm, Bryan E. Welm, Ramaswamy Govindan, Shunqiang Li, Michael A. Davies, Jack A. Roth, Funda Meric-Bernstam, Yang Xie, Meenhard Herlyn, Li Ding, Michael T. Lewis, Carol J. Bolt, Dennis A. Dean, Jeffrey H. Chuang. A pan-cancer PDX histology image repository with genomic and pathological annotations for deep learning analysis. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5407.

Background MDM2/MDMX proteins are frequently elevated in hormone receptor-positive (ER+) breast cancer. We sought to determine the antitumor efficacy of the combination of ALRN-6924, a dual inhibitor of MDM2/MDMX, with chemotherapy in ER+ breast cancer models. Methods Three hundred two cell lines representing multiple tumor types were screened to confirm the role of TP53 status in ALRN-6924 efficacy. ER+ breast cancer cell lines (MCF-7 and ZR-75-1) were used to investigate the antitumor efficacy of ALRN-6924 combination. In vitro cell proliferation, cell cycle, and apoptosis assays were performed. Xenograft tumor volumes were measured, and reverse-phase protein array (RPPA), immunohistochemistry (IHC), and TUNEL assay of tumor tissues were performed to evaluate the in vivo pharmacodynamic effects of ALRN-6924 with paclitaxel. Results ALRN-6924 was active in wild-type TP53 (WT-TP53) cancer cell lines, but not mutant TP53. On ER+ breast cancer cell lines, it was synergistic in vitro and had enhanced in vivo antitumor activity with both paclitaxel and eribulin. Flow cytometry revealed signs of mitotic crisis in all treatment groups; however, S phase was only decreased in MCF-7 single agent and combinatorial ALRN-6924 arms. RPPA and IHC demonstrated an increase in p21 expression in both combinatorial and single agent ALRN-6924 in vivo treatment groups. Apoptotic assays revealed a significantly enhanced in vivo apoptotic rate in ALRN-6924 combined with paclitaxel treatment arm compared to either single agent. Conclusion The significant synergy observed with ALRN-6924 in combination with chemotherapeutic agents supports further evaluation in patients with hormone receptor-positive breast cancer.

El presente trabajo ofrece un panorama de la manera en que, ante la contingencia de covid-19, las pequeñas y medianas empresas (pymes) dentro de los Altos de Jalisco, México, lograron mantener un equilibrio en la mayor medida posible. Se revisaron técnicas y herramientas para que las empresas pudieran detectar cuáles son las fortalezas y debilidades tanto internas y externas para prevenir o corregir desajustes en sus diferentes sectores. Asimismo, se presentan algunas de las herramientas más utilizadas por estas empresas, con las cuales lograron construir métodos eficientes para mitigar el impacto económico dentro de las mismas.

El ensayo expone, desde un enfoque social, científico y técnico, los aspectos y consecuencias más relevantes relacionadas con la incidencia de los factores climáticos en los agrosistemas lecheros en la provincia del Carchi. En esta zona la producción lechera, es de primera importancia como actividad generadora de alimentos básicos y de recursos económicos. Sin embargo, el mal uso de los recursos naturales ha generado una degradación de estos y causado efectos negativos en la vida del hombre. La biodiversidad, el agua, el suelo y las poblaciones humanas están estrechamente relacionados, de manera que un cambio en uno de ellos genera cambios en los otros, la responsabilidad de esto recae en las prácticas de administración defectuosas en los agrosistemas. El objetivo es: proponer una metodología para analizar la influencia de los factores climáticos en los agronegocios de producción lechera. Con estos elementos se obtendrá un modelo económico matemático de valoración que proporcione información con la cual las autoridades definan políticas públicas para convertir a esta actividad, en una alternativa de desarrollo económico sostenible y consecuentemente mejorar la calidad de vida de los productores.

Women of Latin American origin in the United States are more likely to be diagnosed with advanced breast cancer and have a higher risk of mortality than non-Hispanic White women. Studies in U.S. Latinas and Latin American women have reported a high incidence of HER2 positive (+) tumors; however, the factors contributing to this observation are unknown. Genome-wide genotype data for 1,312 patients from the Peruvian Genetics and Genomics of Breast Cancer Study (PEGEN-BC) were used to estimate genetic ancestry. We tested the association between HER2 status and genetic ancestry using logistic and multinomial logistic regression models. Findings were replicated in 616 samples from Mexico and Colombia. Average Indigenous American (IA) ancestry differed by subtype. In multivariate models, the odds of having an HER2+ tumor increased by a factor of 1.20 with every 10% increase in IA ancestry proportion (95% CI, 1.07–1.35; P = 0.001). The association between HER2 status and IA ancestry was independently replicated in samples from Mexico and Colombia. Results suggest that the high prevalence of HER2+ tumors in Latinas could be due in part to the presence of population-specific genetic variant(s) affecting HER2 expression in breast cancer. Significance: The positive association between Indigenous American genetic ancestry and HER2+ breast cancer suggests that the high incidence of HER2+ subtypes in Latinas might be due to population and subtype-specific genetic risk variants.

This article explores the variation in the wage distributions of two Latin American countries, Bolivia and Colombia, which have had different political and economic strategies in recent years. Using data from household surveys, a decomposition of the wage distribution in each country using functional principal component analysis is conducted. The results suggest that Bolivia, which has implemented state-centered policies, has experienced a general increase in wages, especially benefiting the least skilled workers and the informal sector. On the other hand, the wage distribution in Colombia, whose economic policy has leaned towards market-oriented principles, has become more concentrated around the median wage, mainly due to changes in formal sector wages.

Aunque la mayoría de las universidades ecuatorianas se han propuesto formar emprendedores, son muy pocas las que han construido un modelo de emprendimiento serio, aplicable y riguroso que proponga una solución a los problemas de la sociedad. Una de estas instituciones de educación superior es la Universidad Politécnica Estatal del Carchi (UPEC), la cual, a partir de la demanda social, la actividad económica y la realidad social de la frontera colombo-ecuatoriana ha logrado concebir y aplicar un ecosistema de emprendimiento que puede resultar útil para muchas otras instituciones. De eso precisamente trata este libro: de las particularidades teóricas, analíticas y estratégicas del modelo de emprendimiento construido en la UPEC.

El proceso del beneficio del café altera sensiblemente el entorno ambiental, afectando agua, suelo, biodiversidad circundante, causando la disminución de la calidad del café. El objetivo de este estudio es diseñar herramientas agroambientales que permitan reducir la contaminación que se produce en la actividad del beneficio del café, para un adecuado manejo y conservación de los recursos naturales. Mediante recorridos en cafetales se diligenció listas de componentes ecosistémicos, identificación de aspectos e impactos ambientales, generación de una matriz ambiental y el diagnóstico de residuos. Se registró variedad de flora y fauna, constante contaminación sobre el recurso hídrico debido al vertimiento directo de aguas residuales y acumulación puntual de cascarilla, producto del despulpado de café. La conectividad de fragmentos del bosque andino mediante corredores ecológicos en el paisaje cafetero, el beneficio del uso de bienes y servicios ambientales por parte de la comunidad, permitieron identificar nueve impactos negativos y tres positivos. Durante el proceso del beneficio de café, varios componentes ambientales son alterados; principalmente, el agua y suelo, por la inadecuada disposición de residuos, lo cual genera graves problemas de contaminación en los ecosistemas aledaños.