Predicting Brain Age at Slice Level : Convolutional Neural Networks and Consequences for Interpretability

Funding Information: NE was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior— Brasil (CAPES)—Finance Code 001. MM was financed in part by the Conselho Nacional de Pesquisa—Brasil (CNPq). Funding Information: Conflict of Interest: BF had a research grant from Pfizer outside of this study.Peer reviewedPublisher PD

Anti-tumor efficiency of Perillylalcohol/β-Cyclodextrin inclusion complexes in a sarcoma S180-induced mice model

The low solubility and high volatility of perillyl alcohol (POH) compromise its bioavailability and potential use as chemotherapeutic drug. In this work, we have evaluated the anticancer activity of POH complexed with -cyclodextrin (-CD) using three complexation approaches. Molecular docking suggests the hydrogen-bond between POH and -cyclodextrin in molar proportion was 1:1. Thermal analysis and Fourier-transform infrared spectroscopy (FTIR) confirmed that the POH was enclosed in the -CD cavity. Also, there was a significant reduction of particle size thereof, indicating a modification of the -cyclodextrin crystals. The complexes were tested against human L929 fibroblasts after 24 h of incubation showing no signs of cytotoxicity. Concerning the histopathological results, the treatment with POH/-CD at a dose of 50 mg/kg promoted approximately 60% inhibition of tumor growth in a sarcoma S180-induced mice model and the reduction of nuclear immunoexpression of the Ki67 antigen compared to the control group. Obtained data suggest a significant reduction of cycling cells and tumor proliferation. Our results confirm that complexation of POH/-CD not only solves the problem related to the volatility of the monoterpene but also increases its efficiency as an antitumor agent.This work was supported by the Banco do Nordeste (grant FUNDECI/2016.0015), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe (Fapitec) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Eliana B. Souto would like to acknowledge the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) for the project UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Proton and Pion Production Relative to the Reaction Plane in Au + Au Collisions at AGS Energies

Results are presented of an analysis of proton and charged pion azimuthal distributions measured with respect to the reaction plane in Au + Au collisions at a beam momentum of about 11 AGeV/c. The azimuthal anisotropy is studied as a function of particle rapidity and transverse momentum for different centralities of the collisions. The triple differential (in rapidity, transverse momentum, and azimuthal angle) distributions are reconstructed. A comparison of the results with a previous analysis of charged particle and transverse energy flow as well as with model predictions is presented.Comment: 23 pages (LaTeX), 12 figure

β-cyclodextrin/isopentyl caffeate inclusion complex: synthesis, characterization and antileishmanial activity

Isopentyl caffeate (ICaf) is a bioactive ester widely distributed in nature. Our patented work has shown promising results of this molecule against Leishmania. However, ICaf shows poor solubility, which limits its usage in clinical settings. In this work, we have proposed the development of an inclusion complex of ICaf in -cyclodextrin (-CD), with the aim to improve the drug solubility, and thus, its bioavailability. The inclusion complex (ICaf:-CD) was developed applying three distinct methods, i.e., physical mixture (PM), kneading (KN) or co-evaporation (CO) in different molar proportions (0.25:1, 1:1 and 2:1). Characterization of the complexes was carried out by thermal analysis, Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and molecular docking. The ICaf:-CD complex in a molar ratio of 1:1 obtained by CO showed the best complexation and, therefore, was selected for further analysis. Solubility assay showed a marked improvement in the ICaf:-CD (CO, 1:1) solubility profile when compared to the pure ICaf compound. Cell proliferation assay using ICaf:-CD complex showed an IC50 of 3.8 and 2.7 µg/mL against L. amazonesis and L. chagasi promastigotes, respectively. These results demonstrate the great potential of the inclusion complex to improve the treatment options for visceral and cutaneous leishmaniases.This research was funded by Banco do Nordeste (grant FUNDECI/2016.0015), Coordenação Aperfeiçoamento de Pessoal de Nivel Superior (CAPES) and Fundação de Ámparo à Pesquisa do Estado de Sergipe (FAPITEC) (PROCESSO: 88887.159533/2017-00 extração, encapsulação e caracterização de bioativos para o interesse biotecnologico). Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 301964/2019-0 Chamada 06/2019, and Chamada CNPq nº 01/2019) and from the Portuguese Science and Technology Foundation (FCT) project UIDB/04469/2020 (strategic fund).info:eu-repo/semantics/publishedVersio

Heavy quarkonium: progress, puzzles, and opportunities

A golden age for heavy quarkonium physics dawned a decade ago, initiated by the confluence of exciting advances in quantum chromodynamics (QCD) and an explosion of related experimental activity. The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress. However, the broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles could only be partially anticipated. Since the release of the YR, the BESII program concluded only to give birth to BESIII; the $B$-factories and CLEO-c flourished; quarkonium production and polarization measurements at HERA and the Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the deconfinement regime. All these experiments leave legacies of quality, precision, and unsolved mysteries for quarkonium physics, and therefore beg for continuing investigations. The plethora of newly-found quarkonium-like states unleashed a flood of theoretical investigations into new forms of matter such as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b}, and b\bar{c} bound states have been shown to validate some theoretical approaches to QCD and highlight lack of quantitative success for others. The intriguing details of quarkonium suppression in heavy-ion collisions that have emerged from RHIC have elevated the importance of separating hot- and cold-nuclear-matter effects in quark-gluon plasma studies. This review systematically addresses all these matters and concludes by prioritizing directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K. Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D. Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A. Petrov, P. Robbe, A. Vair

Actividad de acetilcolinesterasa y niveles totales de antioxidantes en perros con tumores de mama antes y después de la extirpación quirúrgica

Objective. The aim of this study was to evaluate AChE activity in total blood and the FRAP levels in samples from dogs with mammary tumors before and after surgery, as well as the relationship between these variables with immunohistochemical markers of tumor (E-caderina, ki-67, COX-2). Materials and methods. In this study, 13 dogs with mammary tumors were divided into two groups (A and B). The group A was formed by dogs with tumors smaller than 3 cm of diameter, and the group B was formed by dogs with tumor of 3 cm of diameter or larger. The AChE activity and FRAP levels were evaluated before and after surgery and the immunohistochemistry were performed at the tumors. Results. The AChE activity was significantly increased (p<0.05) in dogs with mammary cancer compared to control animals, and neither surgery or tumor size affected the AChE activity (p>0.05). FRAP levels before surgery were significantly lower (p<0.05) compared to control animals. Also, FRAP levels increased significantly after surgery in animals of the group A compared to data before surgery, a fact not observed in dogs from the group B. E-cadherin showed low significant positive correlation with FRAP levels (r=0.37, P-value=0.05); COX-2 showed a moderate significant positive correlation to FRAP (r=0.55, P-value<0.05); and COX-2 showed a low significant positive correlation to AChE (r=0.32, P-value=0.01). Conclusions. AChE and antioxidant levels are modified in dogs with mammary cancer. These variables are involved in various physiological functions, and thus, they might be related to disease pathogenesis.Objetivo. El objetivo de este estudio fue evaluar la actividad de la AChE en sangre total y los niveles de FRAP en muestras de perros con tumores mamarios antes y después de la cirugía, así como la relación entre estas variables con marcadores inmunohistoquímicos de tumores (E-caderina, ki-67 , COX - 2). Materiales y métodos. En este estudio, 13 perros con tumores mamarios se dividieron en dos grupos (A y B). El grupo A estaba formado por perros con tumores menores de 3 cm de diámetro y el grupo B estaba formado por perros con tumor de 3 cm de diámetro o más. La actividad de AChE y los niveles de FRAP se evaluaron antes y después de la cirugía y la inmunohistoquímica se realizó en los tumores. Resultados. La actividad de la AChE aumentó significativamente (p <0,05) en perros con cáncer mamario en comparación con los animales control, y ni la cirugía ni el tamaño tumoral afectaron la actividad de la AChE (p> 0,05). Los niveles de FRAP antes de la cirugía fueron significativamente más bajos (p <0,05) en comparación con los animales control. Además, los niveles de FRAP aumentaron significativamente después de la cirugía en animales del grupo A en comparación con los datos antes de la cirugía, hecho que no se observó en perros del grupo B. La E-cadherina mostró correlación positiva baja con los niveles de FRAP (r = 0,37, valor P = 0,05); COX-2 mostró una moderada correlación positiva significativa con FRAP (r = 0,55, P-valor <0,05); Y la COX-2 mostró una correlación positiva de baja significación con la AChE (r = 0.32, P-valor = 0.01). Conclusiones. AChE y los niveles de antioxidantes se modifican en perros con cáncer de mama. Estas variables están implicadas en diversas funciones fisiológicas, y por lo tanto, pueden estar relacionadas con la patogénesis de la enfermedad

Isokinetic evaluation of knee muscles in soccer players: discriminant analysis [Avaliação isocinética dos músculos do joelho em jogadores de futebol: análise discriminante]; [Evaluación isocinética de los músculos de la rodilla en jugadores de fútbol: análisis discriminante]

Introduction: Muscle activity in soccer players can be measured by isokinetic dynamometer, which is a reliable tool for assessing human performance. Objectives: To perform isokinetic analyses and to determine which variables differentiate the under-17 (U17) soccer category from the professional (PRO). Methods: Thirty four players were assessed (n=17 for each category). The isokinetic variables used for the knee extension-flexion analysis were: peak torque (Nm), total work (J), average power (W), angle of peak torque (deg.), agonist/ antagonist ratio (%), measured for three velocities (60°/s, 120°/s and 300°/s), with each series containing five repetitions. Three Wilks' Lambda discriminant analyses were performed, to identify which variables were more significant for the definition of each of the categories. Results: The discriminative variables at 60°/s in the PRO category were: extension peak torque, flexion total work, extension average power and agonist/antagonist ratio; and for the U17s were: extension total work, flexion peak torque and flexion average power. At 120°/s for the PRO category the discriminant variables were: flexion peak torque and extension average power; for the U17s they were: extension total work and flexion average power. Finally at 300°/s, the variables found in the PRO and U17 categories respectively were: extension average power and extension total work. Conclusion: Isokinetic variables for flexion and extension knee muscles were able to significantly discriminate between PRO and U17 soccer players. RESUMO Introdução: A atividade muscular em jogadores de futebol pode ser medida por meio do dinamômetro isocinético, que é um instrumento confiável para avaliação do desempenho humano. Objetivos: Conduzir análises isocinéticas e discriminar quais variáveis diferenciam a categoria sub-17 (S17) da profissional (PRO). Métodos: Trinta e quatro jogadores de futebol (n=17 para cada categoria) foram avaliados. As variáveis isocinéticas utilizadas para a análise de extensão-flexão do joelho foram: pico de torque (Nm), trabalho total (J), potência média (W), ângulo de pico de torque (graus), razão agonista/antagonista (%), testadas em três velocidades (60°/s, 120°/s e 300°/s), com cada série contendo cinco repetições. Três análises discriminantes foram feitas usando o método Wilk's Lambda para identificar quais variáveis fariam uma discriminação significativa entre as duas categorias. Resultados: As variáveis discriminantes a 60°/s na categoria PRO foram: pico de torque extensores, trabalho total flexores, potência média de extensores e razão agonista/antagonista; e para os S17 foram: trabalho total de extensores, pico de torque de flexores e potência média de flexores. A 120°/s para a categoria PRO as variáveis discriminantes foram: pico de torque de flexores e potência média de extensores; para os S17 foram: trabalho total de extensores e potência média de flexores. A 300°/s, as variáveis encontradas para as categorias PRO e S17 foram, respectivamente: potência média de extensores e trabalho total de extensores. Conclusão: As variáveis isocinéticas para os músculos do joelho flexores e extensores foram capazes de fazer uma discriminação significativa entre jogadores de futebol PRO e S17. RESUMEN Introducción: La actividad muscular en jugadores de fútbol puede ser medida por medio del dinamómetro isocinético, que es un instrumento confiable para evaluación del desempeño humano. Objetivos: Conducir análisis isocinéticos y discriminar qué variables diferencian la categoría sub-17 (S17) de la profesional (PRO). Métodos: Fueron evaluados treinta y cuatro jugadores de fútbol (n=17 para cada categoría). Las variables isocinéticas utilizadas para el análisis de extensión-flexión de la rodilla fueron: pico de torque (Nm), trabajo total (J), potencia media (W), ángulo de pico de torque (grados), razón agonista/antagonista (%), probadas en tres velocidades (60°/s, 120°/s y 300°/s), con cada serie conteniendo cinco repeticiones. Fueron realizados tres análisis discriminantes usando el método Wilk's Lambda para identificar qué variables harían una discriminación significativa entre las dos categorías. Resultados: Las variables discriminantes a 60°/s en la categoría PRO fueron: pico de torque extensores, trabajo total flexores, potencia media de extensores y razón agonista/antagonista; y para los S17 fueron: trabajo total de extensores, pico de torque de flexores y potencia media de flexores. A 120°/s para la categoría PRO las variables discriminantes fueron: pico de torque de flexores y potencia media de extensores; para los S17 fueron: trabajo total de extensores y potencia media de flexores. A 300°/s, las variables encontradas para las categorías PRO y S17 fueron, respectivamente: potencia media de extensores y trabajo total de extensores. Conclusión: Las variables isocinéticas para los músculos de la rodilla flexores y extensores fueron capaces de hacer una discriminación significativa entre jugadores de fútbol PRO y S17