Whole-Exome sequencing analysis identified TMSB10/TRABD2A locus to be associated with carfilzomib-related cardiotoxicity among patients with multiple myeloma

BackgroundProteasome inhibitor Carfilzomib (CFZ) is effective in treating patients with refractory or relapsed multiple myeloma (MM) but has been associated with cardiovascular adverse events (CVAE) such as hypertension, cardiomyopathy, and heart failure. This study aimed to investigate the contribution of germline genetic variants in protein-coding genes in CFZ-CVAE among MM patients using whole-exome sequencing (WES) analysis.MethodsExome-wide single-variant association analysis, gene-based analysis, and rare variant analyses were performed on 603,920 variants in 247 patients with MM who have been treated with CFZ and enrolled in the Oncology Research Information Exchange Network (ORIEN) at the Moffitt Cancer Center. Separate analyses were performed in European Americans and African Americans followed by a trans-ethnic meta-analysis.ResultsThe most significant variant in the exome-wide single variant analysis was a missense variant rs7148 in the thymosin beta-10/TraB Domain Containing 2A (TMSB10/TRABD2A) locus. The effect allele of rs7148 was associated with a higher risk of CVAE [odds ratio (OR) = 9.3 with a 95% confidence interval of 3.9—22.3, p = 5.42*10−7]. MM patients with rs7148 AG or AA genotype had a higher risk of CVAE (50%) than those with GG genotype (10%). rs7148 is an expression quantitative trait locus (eQTL) for TRABD2A and TMSB10. The gene-based analysis also showed TRABD2A as the most significant gene associated with CFZ-CVAE (p = 1.06*10−6).ConclusionsWe identified a missense SNP rs7148 in the TMSB10/TRABD2A as associated with CFZ-CVAE in MM patients. More investigation is needed to understand the underlying mechanisms of these associations

Improved annotation of the insect vector of citrus greening disease: Biocuration by a diverse genomics community

The Asian citrus psyllid (Diaphorina citri Kuwayama) is the insect vector of the bacterium Candidatus Liberibacter asiaticus (CLas), the pathogen associated with citrus Huanglongbing (HLB, citrus greening). HLB threatens citrus production worldwide. Suppression or reduction of the insect vector using chemical insecticides has been the primary method to inhibit the spread of citrus greening disease. Accurate structural and functional annotation of the Asian citrus psyllid genome, as well as a clear understanding of the interactions between the insect and CLas, are required for development of new molecular-based HLB control methods. A draft assembly of the D. citri genome has been generated and annotated with automated pipelines. However, knowledge transfer from well-curated reference genomes such as that of Drosophila melanogaster to newly sequenced ones is challenging due to the complexity and diversity of insect genomes. To identify and improve gene models as potential targets for pest control, we manually curated several gene families with a focus on genes that have key functional roles in D. citri biology and CLas interactions. This community effort produced 530 manually curated gene models across developmental, physiological, RNAi regulatory and immunity-related pathways. As previously shown in the pea aphid, RNAi machinery genes putatively involved in the microRNA pathway have been specifically duplicated. A comprehensive transcriptome enabled us to identify a number of gene families that are either missing or misassembled in the draft genome. In order to develop biocuration as a training experience, we included undergraduate and graduate students from multiple institutions, as well as experienced annotators from the insect genomics research community. The resulting gene set (OGS v1.0) combines both automatically predicted and manually curated gene models.Peer reviewedBiochemistry and Molecular BiologyEntomology and Plant Patholog

Hiperplasia endometrial asociada al uso del tamoxifeno en pacientes con cáncer de mama en Barranquilla, Colombia, 2012-2017

La incidencia de cáncer de mama ha aumentado considerablemente en los últimos años, ubicándose dentro de los diez canceres más frecuentes y entre los cinco con mayor mortalidad según la OMS. El tamoxifeno ha sido una de las más útiles herramientas para combatir el cáncer de mama con receptores hormonales positivos, pero debido a su naturaleza de modulador selectivo de los receptores de estrógenos (SERM), puede llegar a tener efectos sobre otros tejidos con dichos receptores, tal es el caso del útero, donde el estímulo estrogénico podría ocasionar distintas alteraciones que podrían culminar incluso en un cáncer de endometrio. El objetivo de esta investigación se centró específicamente en el desarrollo de hiperplasia endometrial asociándola al uso de tamoxifeno. Para determinar esta relación se realizó un estudio de casos y controles retrospectivo utilizando pacientes de la Organización Clínica Bonnadona Prevenir de Barranquilla, Colombia. Se tomaron pacientes mayores de 18 años diagnosticadas con cáncer de mama y tratadas en la clínica entre los años 2012-2017, tomando una muestra de 68 casos con hiperplasia endometrial tras ser diagnosticadas y tratadas y 134 controles, se analizaron distintas variables con el fin de realizar una caracterización sociodemogr‡fica de esta población y establecer una asociación de riesgo. Se encontró una asociación estad’stica significativa entre la presencia de hiperplasia endometrial y el uso del tamoxifeno con un OR de 3.902, determinándolo como factor de riesgo y logrando caracterizar a esta población en la costa caribe donde existen pocos estudios al respecto a pesar del amplio uso del medicamento.PregradoMedic

Transcultural adaptation of the children's anxiety questionnaire in Brazil

Abstract Aim To describe the transcultural adaptation process of the Children's Anxiety Questionnaire (CAQ) for the Brazilian culture. Design This is a methodological study of cross‐cultural adaptation. Methods Study conducted in Brazil and Sweden involved the following steps: preparation, translation, synthesis of translations, back‐translation and review, and harmonization of the translations by a committee of 13 healthcare professionals using the content validity index (CVI). Cognitive debriefing, using children between 4–10 years old, was completed by 15 children to determine if the images corresponded with their meanings and 17 children to determine if they could understand the Global CAQ after listening. Results Convergences and discrepancies between the original instrument in Swedish, the English version and the Brazilian translation were compared. The process of culturally adapting the CAQ to Brazilian Portuguese was validated, as demonstrated by a satisfactory S‐CVI (0.94) among professionals and an agreement of 95% and above by children

Hiperplasia endometrial asociada al uso del tamoxifeno en pacientes con cáncer de mama en Barranquilla

Introducción: el tamoxifeno ha sido el medicamento de primera línea para el tratamiento del cáncer de mama; sin embargo, se han evidenciado serios eventos adversos con su uso. El objetivo de este trabajo fue determinar la hiperplasia endometrial asociada al uso de tamoxifeno en mujeres con cáncer de mama, en una institución oncológica de la ciudad de Barranquilla- Colombia. Metodología: estudio de casos y controles retrospectivo. Se incluyeron 202 pacientes con cáncer de mamá tratadas entre 2012 y 2017. Fueron evaluadas variables antropométricas, sociodemográficas, personales, clínicas y patológicas. Se estimaron los Odds ratios (OR) crudos y ajustados. Resultados: 68 participantes fueron diagnosticadas con hiperplasia endometrial secundaria al tratamiento antineoplásico. De éstas, 59 (86,7 %) usaron tamoxifeno, la mayoría (37,2 %) por un lapso de 6-11 meses. El análisis bivariado mostró asociación entre la hiperplasia endometrial y uso del tamoxifeno con un OR de 3,9 (IC95 %: 1,8-8,5) y 2,9 (IC95 %: 1,18-7,5) en los análisis crudos y ajustados, respectivamente. Conclusión: el uso de tamoxifeno se asocia con la presencia de hiperplasia endometrial