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This work compares three different approaches to automatically segment the femoral artery from 2D ultrasound images. Two of the architectures follow a sequential structure, where each ultrasound image is considered a slice of the whole vessel volume, and its previous segmentation result will be part of the input, thus leading to a spatial prior. The Dice score on test data show a better performance on the baseline U-Net (0.819) compared to the sequential U-Net approaches (0.633, 0.725) for the femoral artery segmentation. This could be attributed to the misalignment of the slices being used in those networks. A possible improvement could be assumed in the implementation of a spatially calibrated and tracked ultrasound probe. Overall, these results indicate promising approaches for an automatic segmentation of the femoral artery using 2D ultrasound data.

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.

Optical Mie resonators based on silicon nanostructures allow tuning of light-matter-interaction with advanced design concepts based on CMOS compatible nanofabrication. Optically active materials such as transition-metal dichalcogenide (TMD) monolayers can be placed in the near-field region of such Mie resonators. Here, we experimentally demonstrate and verify by numerical simulations coupling between a MoSe2 monolayer and the near-field of dielectric nanoresonators. Through a comparison of dark-field (DF) scattering spectroscopy and photoluminescence excitation experiments (PLE), we show that the MoSe2 absorption can be enhanced via the near-field of a nanoresonator. We demonstrate spectral tuning of the absorption via the geometry of individual Mie resonators. We show that we indeed access the optical near-field of the nanoresonators, by measuring a spectral shift between the typical near-field resonances in PLE compared to the far-field resonances in DF scattering. Our results prove that using MoSe2 as an active probe allows accessing the optical near-field above photonic nanostructures, without the requirement of highly complex near-field microscopy equipment., Main paper and supplement

Cardiovascular diseases (CVD´s) continue as the primary cause of death worldwide. During the past couple of years, and with the surge of the COVID-19 pandemic, deaths linked to CVD´s were -slightly overshadowed by those deaths related to COVID-19, albeit during the highest peaks of the pandemic. The present study derived form understanding the correlation between both diseases, from the standpoint of patients already diagnosed with CVD´s (n = 41883) and what comorbidities had the highest influence on overall patient death (n = 3637). Obesity, hypertension, and diabetes are all linked to worsening the outcome of COVID-19 positive patients, hence they were considered when looking at the overview of all CVD positive patients. Our finding showed that 1697 deaths were related to diabetes (p < 0.001), 987 deaths were related to obesity (p < 0.001), and lastly 2499 deaths were attributed to hypertension (p < 0.001) individually. Using logistic regression modeling, we found diabetes (OR: 1.744, p < 0.001) and hypertension (OR: 2.179, p < 0.001) had a high impact on patient deaths. Hence, having a CVD diagnosis, with hypertension and/or diabetes seems to increase the likely-hood of complication leading to death in COVID-19 positive patients.

Funding Information: The Jena group received financial support of the Deutsche Forschungsgemeinschaft (DFG) through a research infrastructure grant INST 275/257‐1 FUGG (313713174), CRC 1375 NOA (Project B2, 398816777) and SPP2244 (Project TU149/13‐1, 443361515). This project has also received funding from the joint European Union's Horizon 2020 and DFG research and innovation programme FLAG‐ERA under grant TU149/9‐1 (397373225). Ulm and Jena acknowledge financial support of the joint DFG project within grant 464283495. The authors from Toulouse received funding from the Institute for Quantum Technologies Occitanie, ANR IXTASE and the Institut Universitaire de France. Growth of hexagonal boron nitride crystals was supported by the Elemental Strategy Initiative conducted by the MEXT, Japan, Grant Number JPMXP0112101001, JSPS KAKENHI Grant Number JP20H00354, and the CREST (JPMJCR15F3), JST. A.V.K. further thanks DFG for the support through Project KR 4866/8‐1 and the Collaborative Research Center “Chemistry of Synthetic 2D Materials” SFB‐1415‐417590517. The authors also thank the HZDR Computing Center, HLRS, Stuttgart, Germany, and TU Dresden Cluster “Taurus” for generous grants of CPU time. The authors thank Stephanie Höppener and Ulrich S. Schubert for enabling the Raman spectroscopy and microscopy studies at the Jena Center for Soft Matter (JCSM). Publisher Copyright: © 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH. One-pot chemical vapor deposition (CVD) growth of large-area Janus SeMoS monolayers is reported, with the asymmetric top (Se) and bottom (S) chalcogen atomic planes with respect to the central transition metal (Mo) atoms. The formation of these 2D semiconductor monolayers takes place upon the thermodynamic-equilibrium-driven exchange of the bottom Se atoms of the initially grown MoSe2 single crystals on gold foils with S atoms. The growth process is characterized by complementary experimental techniques including Raman and X-ray photoelectron spectroscopy, transmission electron microscopy, and the growth mechanisms are rationalized by first principle calculations. The remarkably high optical quality of the synthesized Janus monolayers is demonstrated by optical and magneto-optical measurements which reveal the strong exciton–phonon coupling and enable an exciton g-factor of −3.3.

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis. In the oral cavity, clinical manifestations are considered atypical lesions. The aim of this study was to report an unusual granular ulcer secondary oral TB that does not heal, chronic, had irregular appearance with deep depression of 2 cm in diameter, and was located in buccal mucosa of the premolar area–the left mandibular arch, of a 42-year-old woman. The patient was subjected to surgical excision of ulcer in its entirety and accordingly a periodontal plastic surgery in the area of the lesion was performed positioning an autograft subepithelial connective tissue. We obtained optimal results in improving oral health, function, and patient’s comfort, in postoperative controls at 15, 30, and 60 days, respectively.

The multipole expansion of a nano-photonic structure's electromagnetic response is a versatile tool to interpret optical effects in nano-optics, but it only gives access to the modes that are excited by a specific illumination. In particular the study of various illuminations requires multiple, costly numerical simulations. Here we present a formalism we call "generalized polarizabilities", in which we combine the recently developed exact multipole decomposition [Alaee et al., Opt. Comms. 407, 17-21 (2018)] with the concept of a generalized field propagator. After an initial computation step, our approach allows to instantaneously obtain the exact multipole decomposition for any illumination. Most importantly, since all possible illuminations are included in the generalized polarizabilities, our formalism allows to calculate the total density of multipole modes, regardless of a specific illumination, which is not possible with the conventional multipole expansion. Finally, our approach directly provides the optimum illumination field distributions that maximally couple to specific multipole modes. The formalism will be very useful for various applications in nano-optics like illumination-field engineering, or meta-atom design e.g. for Huygens metasurfaces. We provide a numerical open source implementation compatible with the pyGDM python package., Comment: 13 pages, 6 figures. Includes a supporting information pdf and python examples

Two cases of lagochilascariasis minor in domestic cats from Costa Rica within a period of two months are recorded for the first time in Central America. Clinical findings included purulent discharge and a tumor in the left ear in one of the cats, whereas the other cat had an ulcerated cervical lesion. Both patients underwent surgical procedures during which nematode worms were collected and analyzed. The collected nematodes were identified using a combination of morphological and molecular assays, which revealed a 99.1% similarity in the cytochrome oxidase subunit 1 with L. minor from Mexico. The lack of information on this parasitosis, as well as the enormous harm it does to animal and human hosts, highlights the need for more research and awareness in Costa Rica and Central America. Furthermore, the unexpected occurrence of these instances in the same location emphasizes the imminent zoonotic risk to humans and the active circulation of the parasite.

Arsenic contamination in drinking water is one of the major health issues worldwide. Over 140 million people from 50+ countries are exposed to drinking water containing arsenic at levels above “safe” levels of 10 μg/L. Several studies indicate that chronic arsenic exposure is associated with the development of carcinogenic changes in the lungs, bladder, liver, and skin and other potential health problems. In this project, we aim to characterize bladder cancer mutational signatures and somatic mutations in a cohort of bladder cancer patients known to have been highly exposed to arsenic in northern Chile by using whole-exome sequencing (WES). We analyzed WES data and identified somatic mutations and mutational signatures using Mutec2 and SigProfiler. Preliminary analyses from a small number of exposed patients identified two mutational signatures, previously described as having “unknown” etiology, that showed an association with arsenic exposure. We are currently validating these findings in additional samples and with functional studies. Alma Poceros-Coba Ph.D. Candidate is the recipient of the Conacyt-UC-MEXUS Doctoral Fellowship and is the recipient of the UCDCCC Travel Award. Citation Format: Alma A. Poceros-Coba, Ana Estrada-Florez, Ted Toal, Paul Lott, Macarena Garrido, Craig Steinmaus, Catterina Ferrecio R., Luis Carvajal-Carmona. Elucidating arsenic dependent carcinogenesis in humans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 229.

Resumen Introducción. El cáncer de mama es un problema mundial de salud pública; entre el 5 y el 10 % de los casos presentan agregación familiar, lo que se explicaría por la presencia de mutaciones en genes de alto riesgo como el BRCA1 y el BRCA2. El origen fundador de la deleción BRCA1 3450del4 en Colombia ya fue reportado. Objetivo. Hacer un análisis descriptivo de seis familias del del Tolima y del Huila con la deleción BRCA1 3450del4 de la asociación de la mutación germinal, con el cáncer de mama y la agregación familiar. Materiales y métodos. Se hizo un estudio descriptivo y transversal de seis casos índice con cáncer de mama positivos para BRCA1 3450del4, que cumplían tres de los criterios establecidos por Jalkh, et al. A partir de la información de las entrevistas, se realizaron los árboles genealógicos (GenoPro™, versión 2016). Se tipificó la mutación en familiares sanos y afectados que aceptaron participar. Resultados. De los 78 individuos seleccionados por conveniencia en las seis familias, 30 presentaron la mutación BRCA1 3450del4; de ellos, seis tenían cáncer de mama, uno, cáncer de ovario, uno, cáncer de mama y ovario, y otro, cáncer de próstata; 21 no presentaban neoplasias. De los 30 individuos portadores de la variante patogénica, seis eran hombres y 24 mujeres, 13 de ellas menores de 30 años. Conclusiones. En este estudio se confirmó la asociación de la deleción BRCA1 3450del4 con el cáncer de mama de agregación familiar. Abstract Introduction: Breast cancer is a worldwide public health problem; between 5% and 10% of the cases present familial aggregation explained by genes of high risk such as BRCA1 and BRCA2. The founding origin of the deletion BRCA1 3450del4 in Colombia has been previously reported. Objective: To carry out in six families from Tolima and Huila departments a descriptive analysis of the presence of the BRCA1 3450del4 mutation associated with breast cancer and familial aggregation. Materials and methods: We conducted a descriptive and cross-sectional study of six index cases with breast cancer positive for BRCA1 3450del4 that fulfilled three of the criteria established by Jalkh, et al. The genealogical trees were made using the information of the interview data (GenoPro™, version 2016). The mutation was typified in healthy and affected relatives who agreed to participate. Results: Thirty of the 78 individuals selected by convenience in the six families presented the mutation BRCA1 3450del4 six of whom developed breast cancer, one, ovarian cancer, one ovarian and breast cancer, and one prostate cancer; 21 did not present any type of neoplasm at the time of the study. Of the 30 individuals carrying the pathogenic variant, six were men, 24 were women, and 13 of these were under 30. Conclusions: In this study of families with the deletion BRCA1 3450del4 in Tolima and Huila we confirmed its association with familial aggregation of breast cancer.

A critical and often overlooked issue is the lack of measurement tools that are congruent with the systemic and developmental guiding principles of the Marital and Family Therapy field. In this current study, we test the dyadic supervision evaluation (DSE) focusing on the internal consistency, specifically the developmental trajectory of trainee and supervisor factors during a year in supervision. This study demonstrates how these factors stabilize over time. The DSE psychometrics are evaluated with a sample of 205 dyads that are tested longitudinally over four time points. We employ repeated measures ANOVA with intra-class correlation (ICC) to measure the level of consistency of the subscales over time. The results of this analysis show that the factors for trainees have an ICC average range of 0.66–0.80, and the factors for supervisors have an ICC average range of 0.69–0.84.

espanolResumen Con el objetivo de reproducir vizcaina Curimata mivartii, ejemplares de dos anos de edad (n= 54), mantenidos en estanques en tierra (0,1 pez/m2) fueron inducidos con extracto pituitario de carpa (EPC) (Argent, USA) a razon de 6 mg/Kg de peso para las hembras en dos aplicaciones (10 % y 90% con 12 horas entre aplicacion); mientras que los machos fueron inducidos con 4,8 mg/Kg EPC en dosis unica. Antes de la induccion hormonal a cada hembra le fue realizada biopsia para verificar su estado de maduracion gonadal. La muestra de ovocitos fue tratada con solucion Serra (Chemi, Colombia) y despues de tres minutos, con la ayuda de un estereoscopio de luz, (Leica, EZ4 W, Alemania) en objetivo de 4x, se determino posicion de la vesicula germinal (centrico, migrando, periferico, sin nucleo). El analisis de la biopsia ovarica mostro que las hembras se encontraban en maduracion final. Los machos inducidos se encontraron en fase de espermiacion; los cuales a ligera presion abdominal liberaron liquido seminal. Se estimo el indice de ovulacion, fecundidad (absoluta y relativa), diametro de los ovocitos y volumen seminal. El porcentaje de fertilidad fue estimado a las cuatro horas post-eclosion (hpe) y el porcentaje de eclosion fue estimado a las 10 hpe. Las hembras ovularon entre 5 y 6 horas (28±1,0°C) e inmediatamente los huevos fueron obtenidos por extrusion, asi como el semen. La fecundidad absoluta fue de 178331,6±28773,7 ovocitos/hembra y la relativa 137,7±19,6 g ovocitos/Kg de hembra. El diametro de los ovocitos recien desovados fue de 687,2±42,8 µm. La fertilidad fue de 90,7±1,4% y la eclosion de 85,3±1,5%. Los resultados permiten concluir que EPC a dosificacion de 6mg/Kg de peso es un buen inductor de la reproduccion de vizcaina, con alto indice de ovulacion y altos porcentajes de fertilidad y eclosion. EnglishAbstract With the aim of reproducing the vizcaina Curimata mivartii, two-year-old specimens (n = 54), kept in ponds on land (0,1 fish/m2) were induced with carp pituitary extract (EPC) (Argent, USA) at a doses of 6 mg/Kg of weight for females in two applications (10% and 90% with 12 hours between applications), while males were induced with 4,8 mg / Kg EPC in a single dose. Before the hormonal induction, each female underwent an ovarian biopsy to verify the oocytes maturation stage. The oocyte sample was treated with Serra solution (Chemi, Colombia) and after three minutes, with the help of a light stereoscope (Leica, EZ4 W, Germany) in 4x objective, the position of the germinal vesicle was determined (central, migrating, peripheral, breakdown). The analysis of the ovarian biopsy showed that the females were in final maturation. Induced males were found in the spermiation phase; which at light abdominal pressure released seminal fluid. The ovulation index, fecundity (absolute and relative), oocyte diameter and seminal volume were estimated. The percentage of fertility was estimated at four hours after hatching (hah); and the hatching percentage was estimated at 10 hah. The females ovulated between 5 and 6 hours (28±1,0°C) and immediately the eggs were obtained by extrusion, as well as the semen. The absolute fecundity was 178331,6±28773,7 oocytes/female and the relative 137,7±19,6 g oocytes/Kg of female. The diameter of the newly spawned oocytes was 687,2±42,8 µm. Fertility was 90,7±1,4% and hatching 85,3±1,5%. The results allow to conclude that EPC at dosage of 6mg/Kg of weight is a good inducer of the vizcaina reproduction, which high ovulation index and high rates of fertility and hatching. portuguesResumo Com o objetivo de reproduzir vizcaina Curimata mivartii, especimenes de dois anos de idade (n = 54), mantidos em tanques em terra (0,1 peixes / m2) foram induzidos com extrato de hipofise de carpa (EPC) (Argent, USA) a uma taxa de 6 mg / kg de peso para as femeas em duas aplicacoes (10% e 90% com 12 horas entre aplicacoes), enquanto os machos foram induzidos com 4,8 mg / kg de EPC em dose unica. Antes da inducao hormonal para cada femea, uma biopsia ovariana foi realizada para verificar o seu estado de maturacao gonadal. A amostra de oocitos foi tratada com solucao de Serra (Chemi, Colombia) e apos tres minutos, com auxilio de um estereoscopio de luz (Leica, EZ4 W, Alemanha) em objetivo 4x, foi determinada a posicao da vesicula germinativa (central, migrando, periferico, sem nucleo). A analise da biopsia ovariana mostrou que as femeas estavam em maturacao final. Os machos induzidos foram encontrados na fase de espermizaҫa; que na pressao abdominal leve liberou fluido seminal. O indice de ovulacao, fecundidade (absoluta e relativa), diâmetro do oocito e volume seminal foram estimados. A percentagem de fertilidade foi estimada em quatro horas pos-eclosao (hpe); enquanto a porcentagem de eclosao foi estimada em 10 hp. As femeas ovularam entre 5 e 6 horas (28±1,0°C) e imediatamente os ovos foram obtidos por extrusao, assim como o semen. A fecundidade absoluta foi 178331,6±28773,7 oocitos / femea e a relativa 137,7±19,6 g oocitos / kg de femea. O diâmetro dos oocitos recem-gerados foi 687,2±42,8 µm. A fertilidade foi de 90,7±1,4% e incubacao de 85,3±1,5%. Os resultados permitem concluir que a EPC na dosagem de 6mg/Kg de peso e um bom indutor de reproducao de vizcaina, com alto indice de ovulacao e altas taxas de fertilidade e eclosao.

espanolResumen El zooplancton es considerado como un alimento de gran importancia para las larvas de los peces por su excelente perfil nutricional. La mayor dificultad en el cultivo del zooplancton, en especial de cladoceros, es la susceptibilidad al alimento que consumen, pues deficiencias en los nutrientes influyen significativamente en su produccion. Por tanto, el estudio de la particula alimenticia en cantidad y calidad optima es necesario para potencializar la produccion. En la Piscicola San Silvestre S.A. se evaluo el efecto del alimento sobre las variables productivas del cladocero Macrothrix spinosa con fotoperiodo 12:12 luz: oscuridad y aireacion constante en 8 unidades experimentales con volumen de 2,5 L. Los organismos, en densidad inicial de 2 org/mL, se alimentaron con la microalga Chlorella sp, previamente cultivada en dos medios de cultivo: (T1) Chlorella sp. cultivada con F/2 de Guillard y (T2) Chlorella sp. cultivada con Nutrifoliar®. Fueron determinados los parametros poblacionales: densidad maxima (Dm), tasa instantanea de crecimiento (K), tiempo de duplicacion (Td) y rendimiento (R). Diariamente se registro la temperatura (25,86±0,36 °C), pH (7,58±0,32) y OD (5,74±0,56 mg/L). La mayor Dm fue 27,38±0,08 org/mL en T1 (P>0,05). Mayor K, menor Td y mayor R se registraron en T1 (0,24±0,00, 2,84±0,04 dias y 2,50±0,01 org/mL respectivamente) (P>0,05). Los resultados sugieren que M. spinosa, alimentada con la microalga Chlorella sp. cultivada con F/2 de Guillard, alcanza mejor desempeno poblacional en cultivo. EnglishAbstract Zooplankton is considered a food of great importance for fish larvae because of its excellent nutritional profile. The greatest difficulty in the culture of zooplankton, especially cladocerans, is the susceptibility to the food they consume, since deficiencies in the nutrients significantly influence their production. Therefore, the study of the food particle in optimal quantity and quality is necessary to potentiate production. In the Piscicola San Silvestre S.A, the effect of the food on the productive variables of the cladoceran Macrothrix spinosa with photoperiod 12:12 light: dark and constant aeration in 8 experimental units with volume of 2,5 liters was evaluated. The organisms, in initial density of 2 clad / mL, were fed with the microalga Chlorella sp, previously cultivated in two culture media: (T1) Chlorella sp. cultivated with Guillard’s F/2 and (T2) Chlorella sp. grown with Nutrifoliar®. The population parameters were determined: maximum density (Dm), instantaneous growth rate (K), doubling time (Td) and yield (R). The temperature was recorded daily (25,86±0,36 °C), pH (7,58±0,32) and OD (5,74±0,56 mg/L). The highest Dm was 27,38±0,08 org/mL in T1 (P>0,05). Higher K, lower Td and higher R were recorded in T1 (0,24±0,00, 2,84±0,04 days and 2,50±0,01 org/mL respectively) (P>0,05). The results suggest that M. spinosa fed with the microalga Chlorella sp. cultivated with Guillard’s F / 2, achieves better population performance in culture. portuguesResumo O zooplâncton e considerado um alimento de grande importância para as larvas de peixes, devido ao seu excelente perfil nutricional. A maior dificultade na cultura do zooplâncton, especialmente dos cladoceros, e a suscetibilidade aos alimentos que consomem; uma vez que deficiencias nos nutrientes influenciam significativamente sua producao. Portanto, o estudo da particula alimentar em quantidade e qualidade otimas e necessario para potencializar a producao. Na Piscicola San Silvestre S.A, foi avaliado o efeito do alimento sobre as variaveis produtivas do cladoceran Macrothrix spinosa com fotoperiodo 12:12 luz: escura e aeracao constante em 8 unidades experimentais com volume de 2,5 litros. Os organismos em densidade inicial de 2 org/mL foram alimentados com a microalga Chlorella sp., previamente cultivada com dois meios de cultura: (T1) Chlorella sp. cultivada com F/2 de Guillard e (T2) Chlorella sp. cultivada com Nutrifoliar®. Os parâmetros populacionais foram determinados: densidade maxima (Dm), taxa de crescimento instantâneo (K), tempo de duplicacao (Td) e rendimento (R). A temperatura foi registrada diariamente (25,86±0,36 °C), pH (7,58±0,32) e OD (5,74±0,56 mg/L). O maior Dm foi de 27,38±0,08 org/mL em T1 (P> 0,05). Maior K, menor Td e maior R foram registrados em T1 (0,24±0,00, 2,84±0,04 dias e 2,50±0,01 org/mL, respectivamente) (P>0,05). Os resultados sugerem que M. spinosa alimentada com a microalga Chlorella sp. cultivada com F/2 de Guillard, alcanca melhor desempenho populacional em cultura.

The purpose of this study is to describe a large Chilean family having a Hereditary Diffuse Gastric Cancer and a possible causative mutation of cancer in this family. Gastric cancer is the leading cause of cancer-related death in Chile. Worldwide, only ten percent of gastric cancer have a familial aggregation and in Hereditary Diffuse Gastric Cancer (HDGC), E-Cadherine 1 gene (CDH1) is the most commonly mutated gene (30%). To our knowledge, only one HDGC Chilean family with a pathogenic CDH1 mutation has been reported, suggesting a low frequency of CDH1 mutations in this population. CTNNA1 mutations (alpha-1 catenin gene), also have been found in HDGC cases. E-cadherine 1 and alpha-1 catenin are part of adherens junction complex. In this family, there are eleven members affected with gastric cancer and two with breast cancer, in two following generations. The index patient was diagnosed with a diffuse gastric tumor at 51 years of age and one affected relative (a deceased brother of the index case) at 38 years of age. The index patient´s gastric tumor histology type is diffuse, but the tumor of the affected sister is papillary. Cancer gene panel sequencing was performed in index patient DNA and cascade genotyping in family members was performed using Kompetitive allele-specific PCR. A germline variant c.293G>A (p.R98Q, rs746832629) in the CTNNA1 gene was found in the index patient. This variant has been reported two times in ClinVar and is classified as an uncertain significance variant. In TCGA, CTNNA1 c.293G>A variant has been reported four times in gastric, colon, and uterine tumor samples. This variant maps to the beta-catenin binding domain of the protein, and the mutated residue is conserved from fish to primates. The variant population frequency in the Genome Aggregation Database is in Latinos is 0.0049 and worldwide is 0.000076. We searched the variant in other members of the family and carried out a co-segregation analysis, that indicates an incomplete penetrance of the variant because two non-affected brothers do have it. Based on our data, we think that this variant could be pathogenic and causative of the HDGC observed in this family, but showing an incomplete penetrance. Additionally, the variant was not found in sixty-two other early-onset Chilean cancer gastric patients, thus we are going to search the variant in a sample of the general population of the family´s region. Also, we will do a whole-exome sequence in the samples of all available affected relatives looking for other variants to explain the incomplete penetrance, search for the second hit in an index patient´s tumor sample and perform a functional analysis of the variant during this semester. Beca Chile Postdoctorado 74190063, CONICYT-FONDAP 15130011-2 (NIH). Citation Format: Graciela Molina, Ana Estrada, Alma Poceros, Carol Parra, Osvaldo Torres, Natalia Landeros, Andrés Rodríguez, Alejandro Corvalán, Luis Carvajal-Carmona. A germline CTNNA1 variant in a large Chilean family with hereditary diffuse gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 800.

This study addresses the need for empirically validated tools to support the training, supervision, and the discovery of best practices in Marital and Family Therapy (MFT). This project represents a first step in developing the Dyadic Supervision Evaluation (DSE), an assessment tool that is grounded in developmental and systemic theory and is psychometrically strong. An Exploratory Factor Analysis (EFA) approach was applied to data from 88 trainee-supervisor dyads across four time periods during the first year of clinical training, resulting in 20 factors, including 9 factors for trainees and 11 factors for supervisors with internal reliabilities ranging from α’s = .82–.98. Discussion addresses the utility of the DSE in documenting the developmental and dyadic progression of supervision during the first year of MFT training.

Context: A recent study reported the nonsynonymous G534E (rs7080536, allele A) variant in the HABP2 gene as causal in familial nonmedullary thyroid cancer (NMTC). Objective: The objective of this study was to evaluate the causality of HABP2 G534E in the TCUKIN study, a multicenter population-based study of NMTC cases from the British Isles. Design and Setting: A case-control analysis of rs7080536 genotypes was performed using 2105 TCUKIN cases and 5172 UK controls. Participants: Cases comprised 2105 NMTC cases. Patient subgroups with papillary (n = 1056), follicular (n = 691), and Hürthle cell (n = 86) thyroid cancer cases were studied separately. Controls comprised 5172 individuals from the 1958 Birth Cohort and the National Blood Donor Service study. The controls had previously been genotyped using genome-wide single nucleotide polymorphism arrays by the Wellcome Trust Case Control Consortium study. Outcome Measures: Association between HABP2 G534E (rs7080536A) and NMTC risk was evaluated using logistic regression. Results: The frequency of the HABP2 G534E was 4.2% in cases and 4.6% in controls. We did not detect an association between this variant and NMTC risk (odds ratio [OR] = 0.896; 95% confidence interval, 0.746–1.071; P = .233). We also failed to detect an association between the HABP2 G534E and cases with papillary (1056 cases; G534E frequency = 3.5%; OR = 0.74; P = .017), follicular (691 cases; G534E frequency = 4.7%; OR = 1.00; P = 1.000), or Hürthle cell (86 cases; G534E frequency = 6.3%; OR = 1.40; P = .279) histology. Conclusions: We found that HABP2 G534E is a low-to-moderate frequency variant in the British Isles and failed to detect an association with NMTC risk, independent of histological type. Hence, our study does not implicate HABP2 G534E or a correlated polymorphism in familial NMTC, and additional data are required before using this variant in NMTC risk assessment.

Gastric cancer is a leading cause of cancer mortality in Latinos, who are two times more likely to die of gastric cancer when compared to non-Latino Whites. Gastric cancer outcomes in this minority are poor as most tumors are detected in the metastatic setting, where five-year survival is less than 5%. Despite such a high mortality burden in Latinos and other minority populations, there are only three molecularly-guided therapies approved by the Food and Drug Administration to treat gastric cancer. To advance precision medicine in minority groups, the NCI Center to Reduce Cancer Health Disparities funded our University of California Minority Patient-Derived Xenograft (PDX) Development and Trial Center (UCaMP), which is currently creating and characterizing PDXs and patient-derived organoids from minority patients including those with gastric cancer. In this presentation, we will present an overview of recent advances in gastric cancer precision modeling using patient-derived organoids and xenografts from Latino patients. We will summarize the most promising druggable genes and pathways in gastric tumors and will present initial findings on the development of promising combinations using PIK3CA inhibitors. Citation Format: Hongyong Zhang, Nicole Coggins, Paul Lott, Ana Estrada, Guadalupe Polanco, Alexa Morales, Sienna Rocha, Amanda Kirane, Shiro Urayama, Javier Torres, Mabel Bohorquez, Magdalena Echeverry, UCaMP Consortium, Luis G. Carvajal-Carmona. Advancing gastric cancer precision medicine through minority patient derived modeling [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA13.

Gastric cancer (GC) is the 2nd leading cause of cancer-related death worldwide, with a five-year survival rate lower than 30%. GC is diagnosed in 25,000 Americans each year, with Latinos twice as likely to succumb compared to non-Hispanic whites. Treatment is currently limited to only two molecularly guided therapies. The Cancer Genome Atlas (TCGA) data show that 70% of GC patients have a mutation in a gene targetable with existing drugs. Significant spatial mutational intratumoral heterogeneity (ITH) has been identified in a variety of tumor types to date, although a GC ITH study has yet to be investigated. ITH is an important consideration for personalized therapy. Driver gene mutations are frequently found to be nonclonal, a crucial factor when assessing effective druggability. The goal of the present study was to examine GC ITH in Latino GC patients using targeted multiregional sequencing (MSEQ). Two to five biopsies from different tumor regions and adjacent normal tissue were obtained from 34 GC patients; DNA was extracted from the tumor and the normal tissues and the coding regions of 783 cancer genes were sequenced using Agilent enrichment and Illumina sequencing. Somatic mutations were called in each tumor sample, using joint analysis of all samples for each patient. Tumor cell fractions were estimated for each mutation in each sample, and phylogenetic trees were made for visualize each patient's somatic mutational patterns. We found a high degree of ITH, both intratumoral and interpatient, with the fraction of functional somatic mutations that are clonal ranging from 0 to 52%, the fraction private to one tumor sample ranging from 48% to 94%, and the fraction shared between multiple but not all samples ranging from 0 to 21%. There was at least one known drug interaction with a gene containing a clonal functional mutation for 11 of the 16 samples, and in 6 samples there were two or more known drug interactions. Our study is the first one to assess ITH in GC, and our results are important to understand the clonal architecture of these GCs and to improve molecular diagnostics. Citation Format: Ted Toal, Guadalupe M. Polanco-Echevery, Ruta Sahasrabudhe, Ana Estrada, Mabel Bohorquez, Magdalena Echeverry, Javier Torres, Luis G. Carvajal-Carmona. Gastric tumors from Latino patients show extensive intratumor heterogeneity [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C030.

En este trabajo indagamos sobre el valor de distintos corpus del español en la red para el estudio de la variación lingüística. Para ello, comparamos los resultados del estudio de cinco fenómenos lingüísticos en dos corpus de comunicación mediada por ordenador (esTenTen, constituido por distintos tipos de textos en línea, y el corpus de tuits del proyecto Proyectando la variación lingüística de Internet). Los fenómenos lingüísticos estudiados son la elisión de la /d/ intervocálica, las formas de tratamiento en plural, el uso no referencial de ello, la pluralización de haber existencial y el uso coloquial del sufijo superlativo –érrimo. El análisis muestra que los macrocorpus compilados de forma automática sin distinguir al menos los géneros de la comunicación digital documentada pueden presentar elevadas cantidades de ruido estadístico y que, por favorecer los contextos monológicos, pueden ser problemáticos para la documentación de determinados fenómenos muy marcados (ya sea diatópica, diafásica o diastráticamente). Su mayor ventaja es la elevada cantidad de datos que ofrecen. Por el contrario, los corpus más controlados y que privilegian contextos más prominentemente dialógicos son preferibles para el estudio de las variables lingüísticas propias de la inmediatez comunicativa, a pesar de que resultan más difíciles de compilar y consultar.

The G allele of the rs6983267 single-nucleotide polymorphism, located on chromosome 8q24, has been associated with increased risk of several cancer types. The association between rs6983267G and thyroid cancer (TC) has been tested in different populations, mostly of European ancestry, and has led to inconclusive results. While significant associations have been reported in the British and Polish populations, no association has been detected in populations from Spain, Italy and the USA. To further investigate the role of rs6983267G in TC susceptibility, we evaluated rs6983267 genotypes in three populations of different continental ancestry (British Isles, Colombia and Japan), providing a total of 3067 cases and 8575 controls. We detected significant associations between rs6983267G and TC in the British Isles (odds ratio (OR)=1.19, 95% CI: 1.11–1.27, P=4.03×10−7), Japan (OR=1.20, 95% CI: 1.03–1.41, P=0.022) and a borderline significant association of similar effect direction and size in Colombia (OR=1.19, 95% CI: 0.99–1.44, P=0.069). A meta-analysis of our multi-ethnic study and previously published non-overlapping datasets, which included a total of 5484 cases and 12 594 controls, confirmed the association between rs6983267G and TC (P=1.23×10−7, OR=1.13, 95% CI: 1.08–1.18). Our results therefore support the notion that rs6983267G is a bona fide TC risk variant that increases the risk of disease by ∼13%.

This article contributes to research practices in marital and family therapy, specifically the dyadic and development over time in clinical supervision, and describes and applies methodological strategies to develop measurements congruent with the systemic and developmental principles of the field. This project evaluates the psychometric properties of the dyadic supervision evaluation (DSE) in terms of measurement equivalence and causality. A structural equation analysis is conducted utilizing the actor–partner interdependent model resulting in a goodness of fit. This study presents a longitudinal model for evaluating the supervisory relationship and proposes a model of clinical supervision evaluation. The relationship among latent constructs in the DSE and its limitations related to inference and application are discussed.

In 1972, a federal court reinforced the deinstitutionalization of state psychiatric hospitals when they held that people with mental illness have a constitutional right to treatment (Wyatt v. Stickney, 1972). Although many states released patients and closed hospitals in response to this decision, they neglected to provide adequate community-based treatment resulting in the unintended reinstitutionalization of this population into our state and local jails. Recently, many state and local stakeholders have come together to address this situation. This article will discuss how the criminal justice system has become a primary mental health provider and strategies being utilized to reform the current system.

Gastric cancer (GC) is the third common cause of cancer related deaths worldwide and its risk is partially mediated by inherited factors. However, the majority of GC heritability remains to be discovered. The goal of this study was to identify novel GC genes. To identify novel GC genes, we undertook a multi-staged approach of whole exome sequencing (WES), followed by targeted sequencing and genotyping in germline DNA samples from hereditary diffuse GC (HDGC) and isolated GC cases recruited in Europe and Latin America. We also performed WES in 4 available tumor samples to analyze loss of heterozygosity and somatic mutation signature. Our study identified eleven cases with mutations in homologous recombination repair (HR) genes, including seven with PALB2 mutations, three with BRCA1 mutations and one with a RAD51C mutation. Out of 361 total unrelated GC cases analyzed, 6.45% of the HDGC cases (2 out of 31) and 2.7% (9 out of 330) of isolated/non-HDGC cases had mutations in PALB2, BRCA1 or RAD51C. Most of these mutations are known as pathogenic in other cancer types and three were shared by multiple Hispanic and European cases. None of these mutations were present in 1,170 population-matched controls (P=5.75x10-7). Tumor samples from four mutation carriers exhibited mutational signature indicative of defects in HR pathway. Our results suggest that mutations in HR genes are likely involved in GC susceptibility. Our findings have potential clinical implications as these cases and their families could benefit from risk reducing surveillance and possibly benefit from platinum or PARP inhibitor based therapies. Citation Format: Ruta Sahasrabudhe, Paul Lott, Mabel Bohorquez, Ted Toal, Ana Estrada, John Suarez, Alejandro Brea-Fernández, Jose Cameselle-Teijeiro, Carla Pinto, Irma Ramos, Alejandra Mantilla, Rodrigo Prieto, Alejandro Corvalan, Enrique Norero, Carolina Alvarez, Teresa Tapia, Pilar Carvallo, Luz Gonzalez, Alicia Cock-Rada, Angela Solano, Florencia Neffa, Adriana Della Valle, Chris Yau, Gabriela Soares, Alexander Borowsky, Xiao-You Han, Li-JI He, Phillip Taylor, Alisa Goldstein, Nan Hu, Javier Torres, Magdalena Echeverry, Clara Ruiz-Ponte, Manuel Teixeira, Luis G. Carvajal-Carmona. Germline mutations in PALB2, BRCA1 and RAD51C observed in gastric cancer cases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-158. doi:10.1158/1538-7445.AM2017-LB-158

Breast cancer (BC) is the most commonly diagnosed cancer among women, with 1 in every 7 women in the U.S. developing BC in their lifetime. While BC may not be the leading cause of cancer incidence in many minority populations, such as Hispanics, it is the leading cause of cancer death, highlighting a cancer disparity. Moreover, the contribution of mutations in BC susceptibility genes remains poorly investigated in Hispanic populations. To begin to address these voids, we screened Colombian BC patients for common BRCA1 and BRCA2 mutations using the KASP genotyping system. Strikingly, 27 of 722 unselected cases (4%) harbored the same BRCA1 3450del4 mutation. Clinical data and family history indicate that these individuals originate from a distinct geographic region in Colombia, Neiva. Significantly, 10% of the unselected BC cases in Neiva and the surrounding region harbor the 3450del4 mutation, potentially representing one of the most profound founder effects reported in human populations. Interesting, this BRCA1 mutation has also been reported in other countries, including Portugal, Spain, and Chile. To determine whether this mutation stems from a single origin, mutation carriers from each of these countries (n = 26), along with mutation carriers from Colombia (n = 27), were subjected to the Affymetrix Axiom Human UK Biobank Array (>800 thousand markers). Haplotypes in which the BRCA1 mutation resides were estimated by SHAPEIT, and pairwise segmental sharing was determined using GERMLINE. Our data suggest that the mutation carriers, although from different countries and continents, share a core haplotype, likely to have originated from Spain. Additionally, the mutation seems to be fairly new to Colombia, with individuals sharing up to a 40Mb haplotype comprising the mutation. We are currently estimating the age of the mutation using the bioinformatic software DMLE+, which exploits the rate of linkage disequilibrium decay due to recombination. By understanding the prevalence of mutations in known breast cancer risk genes in minority populations, cancer disparities can be better addressed and breast cancer screening can be improved. Furthermore, these findings have direct implications in robust and cost-effective targeted screening in regions where there is a high prevalence of the BRCA1 3450del4 mutation. Citation Format: Anna Marie De Asis Tuazon, Carolina Ramirez, Mabel Bohorquez, Rodrigo Prieto, Paul Lott, Angel Criollo, Ana Estrada, Gillbert Mateus, Alejandro Velez, Justo Ramirez, COLUMBUS Consortium, Manuel Teixeira, Ana Vega, Conxi Lazaro, Eva Tornero, Cristina Martinez, Mar Infante, Miguel De La Hoya, Orland Diez, Pilar Carvallo, Magdalena Echeverry, Luis Carvajal-Carmona. Transcontinental characterization of the Hispanic BRCA1 3450del4 breast cancer founder mutation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2739. doi:10.1158/1538-7445.AM2015-2739