A double-robust test for high-dimensional gene coexpression networks conditioning on clinical information.

It has been increasingly appealing to evaluate whether expression levels of two genes in a gene coexpression network are still dependent given samples' clinical information, in which the conditional independence test plays an essential role. For enhanced robustness regarding model assumptions, we propose a class of double-robust tests for evaluating the dependence of bivariate outcomes after controlling for known clinical information. Although the proposed test relies on the marginal density functions of bivariate outcomes given clinical information, the test remains valid as long as one of the density functions is correctly specified. Because of the closed-form variance formula, the proposed test procedure enjoys computational efficiency without requiring a resampling procedure or tuning parameters. We acknowledge the need to infer the conditional independence network with high-dimensional gene expressions, and further develop a procedure for multiple testing by controlling the false discovery rate. Numerical results show that our method accurately controls both the type-I error and false discovery rate, and it provides certain levels of robustness regarding model misspecification. We apply the method to a gastric cancer study with gene expression data to understand the associations between genes belonging to the transforming growth factor ß signaling pathway given cancer-stage information.

Effects of core resistance training on pugilism in boxers / Efeitos do treinamento de força do centro abdominal sobre o pugilismo em boxeadores / Efectos del entrenamiento de fuerza del centro abdominal sobre el pugilismo en boxeadores

ABSTRACT Introduction: Resistance training aims to improve the physical fitness of an athlete by improving their balance, movement, and agility skills. Boxers should have complementary attention to the strength of the core, a key area for boxing skills. Objective: Examine the effects of core strength training on pugilism in boxers. Methods: Ten volunteer professional boxers were selected. All undergo three months of core strength training under the described protocol. The athletes' sport quality index was studied using mathematical statistics. Results: After 3 months of core strength training, the physical test result was significantly higher (P<0.01). Although in 400-meter runs, sandbag training and interval running scores were higher than before training, the difference was insignificant (P>0.05). Conclusion: The core strength exercises improve the body mass of a boxing athlete and the level of their boxing. Supplementing athletes with core resistance training during regular exercise is indicated. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O treinamento de força visa a melhorar a aptidão física de um atleta melhorando suas habilidades de equilíbrio, movimento e agilidade. Os boxeadores devem ter uma atenção complementar na força do centro abdominal, área fundamental para as habilidades pugilistas. Objetivo: Examinar os efeitos do treinamento de força do centro abdominal sobre o pugilismo em boxeadores. Métodos: Foram selecionados dez boxeadores profissionais voluntários. Todos passam por três meses de treinamento de força do centro abdominal sob protocolo descrito. O índice de qualidade esportiva dos atletas foi estudado com a utilização de estatísticas matemáticas. Resultados: Após 3 meses de treinamento de força do centro abdominal, o resultado de teste físico foi significativamente superior (P<0,01). Embora nos 400 metros de corrida, treinamento com saco de areia e pontuação de corrida em intervalos fossem mais altos do que aqueles antes do treinamento, a diferença não foi significativa (P>0,05). Conclusão: Exercícios de força do centro abdominal melhoram a massa corporal de um atleta do boxe e o nível de seu pugilismo. É indicado aos atletas um complemento com fortalecimento do centro abdominal durante o exercício regular. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El entrenamiento de fuerza tiene como objetivo mejorar la condición física de un deportista mediante la mejora de sus habilidades de equilibrio, movimiento y agilidad. Los boxeadores deben prestar una atención complementaria a la fuerza del núcleo abdominal, una zona fundamental para las habilidades pugilísticas. Objetivo: Examinar los efectos del entrenamiento de la fuerza del núcleo abdominal en el pugilismo de los boxeadores. Métodos: Se seleccionaron diez boxeadores profesionales voluntarios. Todos se someten a tres meses de entrenamiento de fuerza en el centro abdominal según el protocolo descrito. El índice de calidad deportiva de los atletas se estudió mediante estadísticas matemáticas. Resultados: Después de 3 meses de entrenamiento de fuerza en el núcleo abdominal, el resultado de la prueba física fue significativamente mayor (P<0,01). Aunque en la carrera de 400 metros, el entrenamiento con saco de arena y la puntuación de la carrera a intervalos fueron superiores a los de antes del entrenamiento, la diferencia no fue significativa (P>0,05). Conclusión: Los ejercicios de fuerza del núcleo abdominal mejoran la masa corporal de un atleta de boxeo y el nivel de su boxeo. Para los deportistas está indicado un complemento con el entrenamiento de fuerza del núcleo abdominal durante el ejercicio regular. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Single cell T cell landscape and T cell receptor repertoire profiling of AML in context of PD-1 blockade therapy.

In contrast to the curative effect of allogenic stem cell transplantation in acute myeloid leukemia via T cell activity, only modest responses are achieved with checkpoint-blockade therapy, which might be explained by T cell phenotypes and T cell receptor (TCR) repertoires. Here, we show by paired single-cell RNA analysis and TCR repertoire profiling of bone marrow cells in relapsed/refractory acute myeloid leukemia patients pre/post azacytidine+nivolumab treatment that the disease-related T cell subsets are highly heterogeneous, and their abundance changes following PD-1 blockade-based treatment. TCR repertoires expand and primarily emerge from CD8+ cells in patients responding to treatment or having a stable disease, while TCR repertoires contract in therapy-resistant patients. Trajectory analysis reveals a continuum of CD8+ T cell phenotypes, characterized by differential expression of granzyme B and a bone marrow-residing memory CD8+ T cell subset, in which a population with stem-like properties expressing granzyme K is enriched in responders. Chromosome 7/7q loss, on the other hand, is a cancer-intrinsic genomic marker of PD-1 blockade resistance in AML. In summary, our study reveals that adaptive T cell plasticity and genomic alterations determine responses to PD-1 blockade in acute myeloid leukemia.

Evaluation of competing risks prediction models using polytomous discrimination index.

For competing risks data, it is often important to predict a patient's outcome status at a clinically meaningful time point after incorporating the informative censoring due to competing risks. This can be done by adopting a regression model that relates the cumulative incidence probabilities to a set of covariates. To assess the performance of the resulting prediction tool, we propose an estimator of the polytomous discrimination index applicable to competing risks data, which can quantify a prognostic model's ability to discriminate among subjects from different outcome groups. The proposed estimator allows the prediction model to be subject to model misspecification and enjoys desirable asymptotic properties. We also develop an efficient computation algorithm that features a computational complexity of O(n log n). A perturbation resampling scheme is developed to achieve consistent variance estimation. Numerical results suggest that the estimator performs well under realistic sample sizes. We apply the proposed methods to a study of monoclonal gammopathy of undetermined significance.

Lorsque des données comportent des risques concurrents, il est souvent important de prédire l'issue pour un patient à un temps significatif d'un point de vue clinique après avoir incorporé la censure informative due aux risques concurrents, ce qui peut être fait en adaptant un modèle de régression qui lie les probabilités cumulatives d'incidence à un ensemble de covariables. Pour évaluer la performance des outils de prévision qui en découlent, les auteurs proposent un estimateur de l'indice de discrimination polytomique applicable aux données avec des risques concurrents, et qui permet de quantifier l'habileté d'un modèle de pronostic à discriminer entre les sujets de différents groupes de dénouement. L'estimateur proposé permet au modèle de prévision un certain nombre de mauvaises classifications et exhibe des propriétés asymptotiques souhaitables. Les auteurs développent un algorithme efficace dont la complexité de calcul est d'ordre O(n log n). Ils proposent un schéma de rééchantillonnage pour obtenir une estimation convergente de la variance et présentent des résultats numériques qui suggèrent que leur estimateur offre de bonnes performances avec des tailles d'échantillons réalistes. Ils appliquent finalement leur méthode à une étude de gammopathie monoclonale dont la significativité n'est pas établie.