p27Kip1 V109G as a biomarker for CDK4/6 inhibitors indication in hormone receptor–positive breast cancer

Biomarker; Hormone receptor-positive; Breast cancerBiomarcador; Cáncer de mama; Receptor hormonal positivoBiomarcador; Càncer de mama; Receptor hormonal positiuCDK4/6 inhibitors benefit a minority of patients who receive them in the breast cancer adjuvant setting. p27Kip1 is a protein that inhibits CDK/Cyclin complexes. We hypothesized that single-nucleotide polymorphisms that impaired p27Kip1 function could render patients refractory to endocrine therapy but responsive to CDK4/6 inhibitors, narrowing the patient subpopulation that requires CDK4/6 inhibitors. We found that the p27Kip1 V109G single-nucleotide polymorphism is homozygous in approximately 15% of hormone-positive breast cancer patients. Polymorphic patients experience rapid failure in response to endocrine monotherapy compared with wild-type or heterozygous patients in the first-line metastatic setting (progression-free survival: 92 vs 485 days, P < .001); when CDK4/6 inhibitors are added, the differences disappear (progression-free survival: 658 vs 761 days, P = .92). As opposed to wild-type p27Kip1, p27Kip1 V109G is unable to suppress the kinase activity of CDK4 in the presence of endocrine inhibitors; however, palbociclib blocks CDK4 kinase activity regardless of the p27Kip1 status. p27Kip1 genotyping could constitute a tool for treatment selection.MM is supported by the Spanish Ministry of Science and Innovation (RTI2018-095582-B-100; PLEC2021-007892 and RED2018-102723-T), AES (DTS21/00132) and Comunidad de Madrid (B2017/BMD-3884 and Y2020/BIO-6519). MQF is a recipient of the following grants: AES—PI 19/00454 funded by the ISCIII and co-funded by the European Regional Development Fund (ERDF), and B2017/BMD3733 (Immunothercan-CM) – Call for Coordinated Research Groups from the Madrid Region—Madrid Regional Government—ERDF funds. This study was also funded by a donation from CRIS Contra El Cancer Foundation

Efecto del nivel de concentrado sobre el perfil de ácidos grasos de la leche de vacas holstein en pastoreo

El contenido de ácido linoléico conjugado (CLA c9 t11) en leche depende principalmente de la producción en el rumen de ácido vaccénico, el cual está influenciado por el aporte de los ácidos linoléico y linolénico en la dieta. El objetivo de este estudio fue evaluar el efecto del nivel de concentrado en la producción, composición y perfil de ácidos grasos de la leche de nueve vacas Holstein en praderas asociadas de gramíneas y leguminosas. El diseño experimental fue un cuadro latino 3×3 y los tratamientos fueron: 1) 8 kg concentrado y 8 h en la pradera (8c); 2) 5 kg concentrado y 12 h en la pradera (5c), y 3) 3 kg de concentrado y 12 h en la pradera (3c). Los datos se analizaron con el procedimiento MIXTO de SAS y las medias de los tratamientos se compararon con la prueba de Tukey (p £ 0.05). La producción de leche y el contenido de grasa, proteína y lactosa fueron mayores (p £ 0.05) en el tratamiento 8c. La concentración de los ácidos grasos (AG) láurico, mirís - tico y palmítico se incrementó en la leche (p £ 0.05) al aumen - tar el nivel de concentrado. El contenido de los AG de cadena larga ( ³ C18) fue mayor (p £ 0.05) con 3 kg de concentrado, excepto para C18:2 c9c12. La reducción del concentrado su - ministrado a vacas Holstein en praderas asociadas disminuye el contenido de AG saturados, pero aumenta el contenido de los insaturados, especialmente de los ácidos oleico, linoléni - co, vaccénico y CLA c9 t11

Loose ends: almost one in five human genes still have unresolved coding status

Seventeen years after the sequencing of the human genome, the human proteome is still under revision. One in eight of the 22 210 coding genes listed by the Ensembl/GENCODE, RefSeq and UniProtKB reference databases are annotated differently across the three sets. We have carried out an in-depth investigation on the 2764 genes classified as coding by one or more sets of manual curators and not coding by others. Data from large-scale genetic variation analyses suggests that most are not under protein-like purifying selection and so are unlikely to code for functional proteins. A further 1470 genes annotated as coding in all three reference sets have characteristics that are typical of non-coding genes or pseudogenes. These potential non-coding genes also appear to be undergoing neutral evolution and have considerably less supporting transcript and protein evidence than other coding genes. We believe that the three reference databases currently overestimate the number of human coding genes by at least 2000, complicating and adding noise to large-scale biomedical experiments. Determining which potential non-coding genes do not code for proteins is a difficult but vitally important task since the human reference proteome is a fundamental pillar of most basic research and supports almost all large-scale biomedical projects.National Institutes of Health [2 U41 HG007234 to I.J., L.M., J.M.R. and M.L.T., R01 HG004037 to I.J.]. Funding for open access charge: NIH [2 U41 HG007234].S

Anthropometric Dimensions and Bone Quality in International Male Beach Handball Players: Junior vs. Senior Comparison

Background: Beach handball is a recent team sport characterized by defensive and offensive actions on a sand surface. Scientific evidence has shown that body composition is fundamental in sports performance. The main objective of this study was to know the body composition, anthropometric characteristics, and bone mineral density of elite beach handball players. Furthermore, another purpose was to analyze the differences between categories (junior and senior) and playing position. Methods: A descriptive, cross-sectional study of 36 male players (18 juniors and 18 seniors) of the Spanish National Beach Handball Team was conducted. Full profile anthropometry and calcaneal ultrasound measurements were used. Results: Significant differences between categories (p < 0.05) were found in: height, body mass, arm span, BMI, muscle mass, fat mass, bone mass, skinfolds, and body perimeters. The somatotype changes depending on the playing position. Bone mineral density of the players was adequate. No significant differences were found by playing position. Conclusions: Senior players had a better body composition due to the presence of less fat mass than junior players. This study provides reference values of elite junior and senior beach handball players and by playing positions. This data is useful for the identification of talents and players who should be trained to improve their body composition

Effect of a calcified-seaweed extract as rumen buffer on ruminal disappearance and fermentation in steers

In the last 3 decades, steers with elevated daily weight gains have been fed diets with a relatively high concentration of grain Laving high concentration of rapidly fermentable carbohydrates that reduce rumen pH, degradation of structural carbohydrates, feed intake, and productivity (Soto-Navarro et al. 2000). The effects of ruminal buffers (salt, weak acid, oxide or hydroxide) able to neutralize acids and reduce drastic changes of rumen pH (Staples and Lough 1989) were variable, mostly due to the wide variety of conditions in which these were tested (Erdman 1988). Rumen buffers seem to improve feed efficiency of ruminants fed diets with highgrain concentration (Kennelly et al. 1999). In the last decade, new ruminal buffers have emerged such as calcified-seaweed extracts (CSE). Therefore, the objective of this study was to evaluate the effects of CSE on ruminal disappearance and fermentation of steers fed diets with 30% forage and 70% concentrate

[BOCIO FETAL OVINO: ESTUDIO DE CASO EN MÉXICO]

En un rebaño ovino de pequeña escala, localizado en el Estado de México, con ocho ovejas y un semental, de las cuales cuatro ovejas presentaron signos clínicos de bocio endémico, dos fetos abortados fueron usados para un estudio de diagnóstico. De ambos fetos, muestras de la glándula tiroides fueron usadas para la evaluación histopatológica, y muestras de hígado, corazón, riñón y músculo esquelético fueron usadas para medir el contenido de selenio. En el suero sanguíneo de las ovejas se midió el perfil de las hormonas tiroideas por la prueba de ELISA. En ambos fetos hubo un aumento de tamaño de la glándula tiroides (6-8 cm), con consistencia firme y color rojo intenso, así como escases de vellón y edema subcutáneo; también hubo hiperplasia e hipertrofia de las células foliculares de la tiroides, con aspecto cuboide, expansión difusa, contorno irregular y distensión con presencia de vacuolas y abundante coloide eosinofílico. Las concentraciones de selenio en el hígado y riñón fueron bajas (0.25 y 0.90 ppm). En las ovejas los contenidos de las hormonas tiroxina (T4) y triyodotironina (T3) fueron deficientes (0.48±0.08 y 4.14±0.29 μg dL-1), y la relación (T4:T3) fue muy amplia (1:8.6 μg dL-1). Se concluye que los corderos sufrieron de bocio coloide. Las concentraciones de hormonas tiroideas en las ovejas fueron bajas y confirmaron un metabolismo tiroideo alterado; adicionalmente, el bocio puede ser agravado por la deficiencia de selenio

Stochastic unit commitment in microgrids based on model predictive control

This article deals with the problem of Stochastic Unit Commitment (SUC), considering the stochastic nature of demand and meteorological phenomena. This paper shows the optimal operation of a hybrid microgrid composed of the following generation units: wind turbine (WT), photovoltaic solar panel (PV), diesel engine generator (DE), micro-turbine (MT), as well as storage devices such as Battery Energy Storage (BES), considering its constraints and the requirements of the reserve generation. For this purpose, a Model-based Predictive Control (MPC), which uses dynamic models of prediction of renewable power and demand in real time, is developed, allowing feedback at each step of time, which corrects the uncertainty of the models. A comparison with a classic UC formulation has been made. The results reach a lower cost solution

Velocidad media de infiltración en un vertisol bajo distintos sistemas de labranza

Soil compaction is regarded as the most serious environmental problem caused by conventional agriculture. Few studies are concerned with the assessment of soil compaction using infiltration speed, specifically in the Vertisol soil characteristic of the main maize producing area of the Toluca-Atlacomulco Valley in central Mexico. The aim of this research was to examine the effect on infiltration speed and penetration resistance of a Vertisol soil when compacted by wheeled agricultural traffic in three different types of tillage systems: zero, minimal and conventional. Penetration resistance was measured on the wheel track with a portable digital penetrometer, and the mean infiltration speed was determined according to the double cylinder infiltrometer method. The pressure exerted by the number of wheeled traffic passes increased Vertisol soil compaction at 30 cm depth. Even though the benefits of zero tillage were similar to those showed by mínimum tillage during the experimental period, minimum tillage reported the highest infiltration spee

Computer assisted enhanced volumetric segmentation magnetic imaging data using a mixture of artificial neural networks

An accurate computer-assisted method able to perform regional segmentation on 3D single modality images and measure its volume is designed using a mixture of unsupervised and supervised artificial neural networks. Firstly, an unsupervised artificial neural network is used to estimate representative textures that appear in the images. The region of interest of the resultant images is selected by means of a multi-layer perceptron after a training using a single sample slice, which contains a central portion of the 3D region of interest. The method was applied to magnetic resonance imaging data collected from an experimental acute inflammatory model (T(2) weighted) and from a clinical study of human Alzheimer's disease (T(1) weighted) to evaluate the proposed method. In the first case, a high correlation and parallelism was registered between the volumetric measurements, of the injured and healthy tissue, by the proposed method with respect to the manual measurements (r = 0.82 and p < 0.05) and to the histopathological studies (r = 0.87 and p < 0.05). The method was also applied to the clinical studies, and similar results were derived of the manual and semi-automatic volumetric measurement of both hippocampus and the corpus callosum (0.95 and 0.88

Tuberculine reaction measured by infrared thermography

Setting: The infection with Mycobacterium tuberculosis gives a delayed immune response, measured by the tuberculine skin test. We present a new technique for evaluation based on automatic detection and measurement of skin temperature due to infrared emission.; Design: 34 subjects (46.8+/-16.9 years) (12/22, M/F) with suspected tuberculosis disease were examined with an IR thermal camera, 48h after tuberculin skin injection.; Results: In 20 subjects, IR analysis was positive for tuberculine test. Mean temperature of injection area was higher, around 1 degrees C, for the positive group (36.2+/-1.1 degrees C positive group; 35.1+/-1.6 degrees C negative group, p < 0.02 T test for unpaired groups).; Conclusion: IR image analysis achieves similar estimation of tuberculin reaction as the visual evaluation, based on higher temperature due to increased heat radiation from the skin lesion.Peer ReviewedPostprint (author's final draft