Notas sobre didáctica de la poesía y la recitación (Una propuesta metodológica para la E.G.B.)

Se intenta con esta colaboración ofrecer a los maestros y a cuantos estén interesados en el tema, unas orientaciones didácticas y un modelo práctico de actuación para la enseñanza de la poesía y la recitación en la escuela, tanto de manera individual como colectiva. Este aspecto de la lengua oral ha sido siempre la cenicienta en el proceso enseñanza-aprendizaje de la lengua materna, debido, entre otras muchas razones, al desconocimiento de los objetivos que se pueden lograr en todos los niveles del área del lenguaje, si se realiza de manera sistemática, programada y con el entusiasmo o la motivación que son necesarios. Nuestra propuesta nace de la experiencia, pasada por el crisol de muchos intentos en diversos medios escolares, y queremos exponerla para que pueda seguir dando resultados positivos en manos de maestros que se entusiasmen por la lengua y por sus valores estéticos y literarios, con el convencimiento de que esto no se puede olvidar si queremos o perseguimos una formación integral de los educandos. Es una estrategia didáctica que se irá perfeccionando cada vez que se ponga en práctica, porque cada educador le dará o añadirá un matiz distinto, que enriquecerá paulatinamente la propuesta. Después de unas consideraciones generales sobre la relación del niño con la poesía y el valor de ésta en el aula, exponemos los pasos o las fases de que consta la metodología que a nosotros nos ha sido tan válida en muchas ocasiones

Reflexiones didácticas sobre el habla andaluza

La didáctica de la lengua en Andalucía plantea unos problemas específicos, derivados de las peculiaridades y características de las hablas andaluzas, de su diversidad y de la necesaria distinción en sus producciones orales y escritas. Ante un hecho diferenciador lingüístico de tanta magnitud, como es el dialecto andaluz, el maestro o el profesor no puede permanecer ajeno, sino que se ve obligado, por su propia condición de educador, a adoptar una determinada actitud que va a tener repercusiones significativas y considerables en el. conocimiento, valoración y dominio que los niños van a poseer de su modalidad de habla. El objetivo fundamental que se debe conseguir es que los niños andaluces adquieran un uso solvente y rico de la lengua en y desde su propia variedad de uso del español, en la expresión oral, ya que el código escrito lo comparten con todos los hispanohablantes. Para ello se requiere por parte del profesor un conocimiento profundo de la lengua española y del dialecto andaluz, junto a la preparación sociolingüística y didáctica que requiere su alta misión formativa. Además, hemos de facilitar, con una metodología inductiva, el correcto aprendizaje de la escritura que, sin duda, presenta más dificultades para nuestros niños

First-in-human, open-label, phase 1/2 study of the monoclonal antibody programmed cell death protein-1 (PD-1) inhibitor cetrelimab (JNJ-63723283) in patients with advanced cancers

Melanoma; Monoclonal antibody PD-1 inhibitor efficacy; Pharmacokinetics/pharmacodynamicsMelanoma; Eficacia del inhibidor del anticuerpo monoclonal PD-1; Farmacocinética/farmacodinamiaMelanoma; Eficàcia de l'inhibidor de l'anticòs monoclonal PD-1; Farmacocinètica/farmacodinàmicaPurpose To assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of cetrelimab (JNJ-63723283), a monoclonal antibody programmed cell death protein-1 (PD-1) inhibitor, in patients with advanced/refractory solid tumors in the phase 1/2 LUC1001 study. Methods In phase 1, patients with advanced solid tumors received intravenous cetrelimab 80, 240, 460, or 800 mg every 2 weeks (Q2W) or 480 mg Q4W. In phase 2, patients with melanoma, non-small-cell lung cancer (NSCLC), and microsatellite instability–high (MSI-H)/DNA mismatch repair-deficient colorectal cancer (CRC) received cetrelimab 240 mg Q2W. Response was assessed Q8W until Week 24 and Q12W thereafter. Results In phase 1, 58 patients received cetrelimab. Two dose-limiting toxicities were reported and two recommended phase 2 doses (RP2D) were defined (240 mg Q2W or 480 mg Q4W). After a first dose, mean maximum serum concentrations (Cmax) ranged from 24.7 to 227.0 µg/mL; median time to Cmax ranged from 2.0 to 3.2 h. Pharmacodynamic effect was maintained throughout the dosing period across doses. In phase 2, 146 patients received cetrelimab 240 mg Q2W. Grade ≥ 3 adverse events (AEs) occurred in 53.9% of patients. Immune-related AEs (any grade) occurred in 35.3% of patients (grade ≥ 3 in 6.9%). Overall response rate was 18.6% across tumor types, 34.3% in NSCLC, 52.6% in programmed death ligand 1–high (≥ 50% by immunohistochemistry) NSCLC, 28.0% in melanoma, and 23.8% in centrally confirmed MSI-H CRC. Conclusions The RP2D for cetrelimab was established. Pharmacokinetic/pharmacodynamic characteristics, safety profile, and clinical activity of cetrelimab in immune-sensitive advanced cancers were consistent with known PD-1 inhibitors.This study was funded by Janssen Research & Development

Biorefinery of brewery spent grain by solid-state fermentation and ionic liquids

Novel environmentally friendly pretreatments have been developed in recent years to improve biomass fractionation. Solid-state fermentation (SSF) and treatment with ionic liquids show low environmental impact and can be used in biorefinery of biomass. In this work, these processes were assessed with brewery spent grain (BSG). First, BSG was used as a substrate to produce cellulases and xylanases by SSF with the fungi Aspergillus brasiliensis CECT 2700 and Trichoderma reesei CECT 2414. Then, BSG was pretreated with the ionic liquid [N1112OH][Gly] and hydrolyzed with the crude enzymatic extracts. Results showed that SSF of BSG with A. brasiliensis achieved the highest enzyme production; meanwhile, the pretreatment with ionic liquids allowed glucan and xylan fractions to increase and reduce the lignin content. In addition, a mixture of the extracts from both fungi in a ratio of 2.5:0.5 Aspergillus/Trichoderma (v/v) efficiently hydrolyzed the BSG previously treated with the ionic liquid [N1112OH][Gly], reaching saccharification percentages of 80.68%, 54.29%, and 19.58% for glucan, xylan, and arabinan, respectively. In conclusion, the results demonstrated that the BSG biorefinery process developed in this work is an effective way to obtain fermentable sugar-containing solutions, which can be used to produce value-added products.São Paulo Research Foundation | Ref. 2018/25511-1São Paulo Research Foundation | Ref. 2021/15138-4National Council for Scientific and Technological Development | Ref. 408783/2021-4National Council for Scientific and Technological Development | Ref. 312923/2020-1Xunta de Galicia | Ref. GPC-ED431B 2021/23Ministerio de Ciencia e Innovación | Ref. PID2020-115879RB-I0

Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study

Breast cancer; Lurbinectedin; Response rateCáncer de mama; Lurbinectedina; Tasa de respuestaCàncer de mama; Lurbinectedina; Taxa de respostaBackground Lurbinectedin, a selective inhibitor of oncogenic transcription, has shown preclinical antitumor activity against homologous recombination repair-deficient models and preliminary clinical activity in BRCA1/2 breast cancer. Patients and methods This phase II basket multitumor trial (NCT02454972) evaluated lurbinectedin 3.2 mg/m2 1-h intravenous infusion every 3 weeks in a cohort of 21 patients with pretreated germline BRCA1/2 breast cancer. Patients with any hormone receptor and human epidermal growth factor receptor 2 status were enrolled. The primary efficacy endpoint was overall response rate (ORR) according to RECIST v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Results Confirmed partial response (PR) was observed in six patients [ORR = 28.6%; 95% confidence interval (CI) 11.3% to 52.2%] who had received a median of two prior advanced chemotherapy lines. Lurbinectedin was active in both BRCA mutations: four PRs in 11 patients (36.4%) with BRCA2 and two PRs in 10 patients (20.0%) with BRCA1. Median DoR was 8.6 months, median PFS was 4.1 months and median OS was 16.1 months. Stable disease (SD) was observed in 10 patients (47.6%), including 3 with unconfirmed response in a subsequent tumor assessment [ORR unconfirmed = 42.9% (95% CI 21.8% to 66.0%)]. Clinical benefit rate (PR + SD ≥ 4 months) was 76.2% (95% CI 52.8% to 91.8%). No objective response was observed among patients who had received prior poly (ADP-ribose) polymerase inhibitors. The most common treatment-related adverse events (AEs) were nausea (61.9%), fatigue (38.1%) and vomiting (23.8%). These AEs were mostly grade 1/2. The most common grade 3/4 toxicity was neutropenia (42.9%: grade 4, 23.8%: with no febrile neutropenia). Conclusions This phase II study met its primary endpoint and showed activity of lurbinectedin in germline BRCA1/2 breast cancer. Lurbinectedin showed a predictable and manageable safety profile. Considering the exploratory aim of this trial as well as previous results in other phase II studies, further development of lurbinectedin in this indication is warranted.This work was supported by PharmaMar S.A, including partial funding by grants from the Centro para el Desarrollo Tecnológico IndustrialCentro para el Desarrollo Tecnológico Industrial (CDTI) during the conduct of the study (grant number IDI-20150006). VS is supported by NIH [grant number R01CA242845]. MD Anderson Cancer Center Department of Investigational Cancer Therapeutics is supported by the Cancer Prevention and Research Institute of Texas [grant number RP1100584], the Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy [grant number 1U01 CA180964], NCATS [grant number UL1 TR000371] (Center for Clinical and Translational Sciences) and the MD Anderson Cancer Center Support [grant number P30 CA016672]