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Este artigo se inscreve no domínio da Análise de Discurso (AD) materialista, filiada a Michel Pêcheux, e propõe analisar os processos discursivos que produzem sentidos no discurso da/sobre a educação no Plano Nacional de Educação – PNE (2014-2024). Põe-se em debate o sentido dos postulados que sustentam a política nacional da educação brasileira: a propositura da “universalidade” em que se propaga o sentido de “educação para todos”, e o preceito da “qualidade” em que se propõe uma formação profissional corroborativa com o desenvolvimento mercadológico. Tais postulados aparecem como um “sistema axiomático” da política educacional brasileira para superar/eliminar o problema da “desigualdade social” no país. O resultado a que se chegou revela os limites de tais pressupostos, dada a natureza da realidade na qual se assenta o objeto investigado: a sociedade capitalista.

Collagen plays a critical role in regulating breast cancer progression and therapeutic resistance. An improved understanding of both the features and drivers of tumor-permissive and -restrictive collagen matrices are critical to improve prognostication and develop more effective therapeutic strategies. In this study, using a combination of in vitro, in vivo and in silico experiments, we show that type III collagen (Col3) plays a tumor-restrictive role in human breast cancer. We demonstrate that Col3-deficient, human fibroblasts produce tumor-permissive collagen matrices that drive cell proliferation and suppress apoptosis in noninvasive and invasive breast cancer cell lines. In human TNBC biopsy samples, we demonstrate elevated deposition of Col3 relative to type I collagen (Col1) in noninvasive compared to invasive regions. Similarly, in silico analyses of over 1000 breast cancer patient biopsies from The Cancer Genome Atlas BRCA cohort revealed that patients with higher Col3:Col1 bulk tumor expression had improved overall, disease-free and progression-free survival relative to those with higher Col1:Col3 expression. Using an established 3D culture model, we show that Col3 increases spheroid formation and induces formation of lumen-like structures that resemble non-neoplastic mammary acini. Finally, our in vivo study shows co-injection of murine breast cancer cells (4T1) with rhCol3-supplemented hydrogels limits tumor growth and decreases pulmonary metastatic burden compared to controls. Taken together, these data collectively support a tumor-suppressive role for Col3 in human breast cancer and suggest that strategies that increase Col3 may provide a safe and effective modality to limit recurrence in breast cancer patients.

Background: The clinical implications of the androgen receptor (AR), particularly in the context of aromatase inhibitor (AI) refractory metastatic breast cancer (MBC), are unclear. While AR is associated with more indolent primary tumors, in the absence of low estradiol/blocked ER, AR can exert a pro-survival signal. Thus, in a phase II trial of Fulvestrant (Fulv) plus Enzalutamide (Enza) in ER+/Her2- MBC (NCT02953860) we analyzed serial biopsies pre- and post-treatment. Methods: Eligible patients were women with ECOG 0-2, ER+/Her2- MBC. Fulv at 500 mg IM days 1, 15, 29 and every 4 weeks thereafter and Enzaat 160 mg po daily on a continual basis were administered. Biopsies were required at study entry and at ~4 weeks on therapy. The clinical benefit rate at 24 weeks (CBR24) was the primary endpoint for efficacy. We performed mutational analysis using a modified Archer VariantPlex Solid Tumor Assay to detect mutations in ESR1 exon 8 and 67 other gene hotspots. We examined estrogen, progesterone, androgen and glucocorticoid receptor protein by IHC and multiplex for immune cells and PD-L1. Frozen cores were utilized to perform reverse phase protein array (RPPA) based protein pathway activation analysis of over 150 proteins from LCM-enriched tumor in baseline and post-treatment metastatic biopsies. Comparisons of Responders (progression free survival (PFS) equal to or longer than 24 weeks) and Non-Responders were performed using moderated t-tests on log2 transformed data. Results: 32 patients were eligible, median age was 61 years (46-87), and 90.6% had visceral disease with an average of 4 prior non-hormonal therapies and 3 prior hormonal agents (including 37.5% with prior Fulv). PFS >24 weeks was observed in ~22% of patients treated with Fulv plus Enza, including 42% of those who had prior Fulv. When stratified by both AR and ER protein levels, median time to progression was 59 days (95% CI: 55 to Inf) when both targets were high (greater than or equal to 10%), but only 14 days (95% CI: 13 to Inf) when both were less than 10%. Metastases with ESR1 mutations in the ligand binding domain had significantly higher levels of ER and PR protein than those with wild type ESR1 (p24 weeks was observed in 22% of patients treated with Fulv plus Enza, including 42% who had prior Fulv treatment, suggesting contribution of the anti-androgen. Response was significantly better when metastases were >10% for ER and AR. Poor response to Fulv plus Enza was significantly associated with mTOR pathway activation and patients with PIK3CA and or PTEN mutated metastases had a significantly shorter PFS. Mutation status also affected hormone receptor expression and immune infiltrates. The increase in PD-L1 protein following treatment with Fulv plus Enza warrants further pre-clinical investigation into whether the addition of anti-androgen can enhance efficacy of checkpoint inhibitor therapy in ER+ metastatic disease resistant to standard endocrine therapy approaches. Citation Format: Jennifer Richer, Nicole Spoelstra, Alyse Winchester, Julia Wulfkuhlue, Rosa Gallagher, Sharon Sams, Gregory Vidal, Peter Kabos, Jennifer Diamond, Elena Shagisultanova, Anosheh Afghahi, Jose Mayordomo, Tessa McSpadded, Gloria Crawford, Virginia Borges, Dexiang Gao, Emanuel Petricoin, Anthony Elias. Response of persistent metastatic ER+/Her2- breast cancer treated with fulvestrant plus enzalutamide [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-17-01.

Background: ER+, HER2- metastatic breast cancer (MBC) patients will receive sequential, endocrine based therapy, either as monotherapy or in combination with a targeted agent until endocrine resistance develops. OP-1250 is a small molecule Complete Estrogen Receptor Antagonist (CERAN) that completely inactivates ER by blocking the 2 activation functions of ER transcription (AF-1 & AF-2). While complete antagonism is believed to be the most critical mechanism of action, OP-1250 is also a strong degrader of the ER. OP-1250 demonstrates anti-cancer activity in preclinical models, including activity against brain metastases and in tumors with activating mutations in ESR1. OP-1250 is orally bioavailable with favorable pharmacokinetics (PK) yielding high and steady drug levels in multiple species. The characteristics of OP-1250 including PK, ability to cross the blood brain barrier, and complete antagonism of the ER suggest that OP-1250 may have superior efficacy over standard of care and experimental agents, both as a monotherapy and in combination with other targeted therapies. Methods: OP-1250-001 is a phase I/II first-in-human study to determine the Dose Limiting Toxicity (DLT), Maximum Tolerated Dose (MTD) and/or Recommended Phase II Dose (RP2D) and to characterize the safety, PK profile and preliminary efficacy in subjects with ER+, HER2- MBC. Eligible patients received prior endocrine therapy. OP-1250 was given orally, once a day continuously in 28-day cycles. Using a rolling 6 design, cohorts of 3 - 6 subjects were sequentially enrolled and monitored for DLTs. The study allows for expansion of 1 or 2 doses for further evaluation of safety and PK to best inform selection of the RP2D. The phase II portion will evaluate the preliminary activity of OP-1250 in 3 cohorts: 1) measurable disease; and 2 exploratory cohorts: 2) evaluable & non-measurable; and 3) central nervous system metastasis. Plasma is being collected for ctDNA sequencing to evaluate ESR1 and other relevant mutations. Results: Between August 5, 2020 and June 4, 2021, 28 subjects with a median age of 63 (range 37-82) have been enrolled. Of the 27 subjects for whom detailed data on prior therapy was reported, all subjects received > 1 prior endocrine therapy for MBC (74% received > 2 and 37% received > 3; range 1-6). All of the 27 subjects received a CDK4/6 inhibitor and 23 of 27 (85%) had received fulvestrant. 20 subjects of 28 (71%) subjects had visceral disease affecting the liver, lung, peritoneum, and/or pleura. OP-1250 was escalated through 5 dose cohorts (range 30 - 300 mg qd). 26 patients were evaluable for a DLT. As of the data cut-off date, no DLTs occurred. Most of the TEAE were grade 1 or 2. OP-1250 is orally bioavailable and extensively distributed with an effective half-life of approximately 2-3 days. Cmax and AUC show dose proportional increase. By cycle 2, exposure levels are at steady state with limited fluctuations and at all doses significantly higher than those seen with fulvestrant. Importantly, OP-1250 has now demonstrated clinical activity at doses that were well tolerated and within the predicted exposure windows where maximum efficacy was observed in preclinical models. Detailed response and safety data will be presented. Conclusion: OP-1250 is continuing evaluation in a phase I/II study. The population enrolled reflects the evolving standard of care in that all pts received prior CDK4/6 inhibitors and the majority also received fulvestrant. OP-1250 is well tolerated with a favorable PK across dose levels ensuring target coverage throughout the dosing interval. No MTD has been identified and selection of the RP2D will be based on consideration of long-term tolerability, efficacy, and the ability to combine with targeted agents. (NCT04505826) Citation Format: Manish Patel, Carlos Alemany, Zahi Mitri, Della Makower, Virginia Borges, Joseph Sparano, Trinh Le, Pamela Klein, Julia Lawrence, Peter Kushner, Demiana Faltaos, Cyrus Harmon, David Myles, JoAnne Zujewski, Erika Hamilton. Preliminary data from a phase I/II, multicenter, dose escalation study of OP-1250, an oral CERAN/SERD, in subjects with advanced and/or metastatic estrogen receptor (ER)-positive, HER2-negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-17-12.

ImportanceIt is estimated that up to 50% of patients with ERBB2 (HER2)-positive metastatic breast cancer (MBC) will develop brain metastases (BMs), which is associated with poor prognosis. Previous reports of the HER2CLIMB trial have demonstrated that tucatinib in combination with trastuzumab and capecitabine provides survival and intracranial benefits for patients with ERBB2-positive MBC and BMs.ObjectiveTo describe overall survival (OS) and intracranial outcomes from tucatinib in combination with trastuzumab and capecitabine in patients with ERBB2-positive MBC and BMs with an additional 15.6 months of follow-up.Design, Setting, and ParticipantsHER2CLIMB is an international, multicenter, randomized, double-blind, placebo-controlled clinical trial evaluating tucatinib in combination with trastuzumab and capecitabine. The 612 patients, including those with active or stable BMs, had ERBB2-positive MBC previously treated with trastuzumab, pertuzumab, and trastuzumab emtansine. The study was conducted from February 23, 2016, to May 3, 2019. Data from February 23, 2016, to February 8, 2021, were analyzed.InterventionsPatients were randomized 2:1 to receive tucatinib (300 mg orally twice daily) or placebo (orally twice daily), both in combination with trastuzumab (6 mg/kg intravenously or subcutaneously every 3 weeks with an initial loading dose of 8 mg/kg) and capecitabine (1000 mg/m2 orally twice daily on days 1-14 of each 3-week cycle).Main Outcomes and MeasuresEvaluations in this exploratory subgroup analysis included OS and intracranial progression-free survival (CNS-PFS) in patients with BMs, confirmed intracranial objective response rate (ORR-IC) and duration of intracranial response (DOR-IC) in patients with measurable intracranial disease at baseline, and new brain lesion–free survival in all patients. Only OS was prespecified before the primary database lock.ResultsAt baseline, 291 of 612 patients (47.5%) had BMs. Median age was 52 years (range, 22-75 years), and 289 (99.3%) were women. At median follow-up of 29.6 months (range, 0.1-52.9 months), median OS was 9.1 months longer in the tucatinib-combination group (21.6 months; 95% CI, 18.1-28.5) vs the placebo-combination group (12.5 months; 95% CI, 11.2-16.9). The tucatinib-combination group showed greater clinical benefit in CNS-PFS and ORR-IC compared with the placebo-combination group. The DOR-IC was 8.6 months (95% CI, 5.5-10.3 months) in the tucatinib-combination group and 3.0 months (95% CI, 3.0-10.3 months) in the placebo-combination group. Risk of developing new brain lesions as the site of first progression or death was reduced by 45.1% in the tucatinib-combination group vs the placebo-combination group (hazard ratio, 0.55 [95% CI, 0.36-0.85]).Conclusions and RelevanceThis subgroup analysis found that tucatinib in combination with trastuzumab and capecitabine improved OS while reducing the risk of developing new brain lesions, further supporting the importance of this treatment option for patients with ERBB2-positive MBC, including those with BMs.Trial RegistrationClinicalTrials.gov Identifier: NCT02614794

Objective: To address the importance of medicinal plants for public management, highlighting that medicinal plants are becoming increasingly a good option for public health in the face of health-related use for its effectiveness and cost. Methods: A literature review was carried out in an exploratory descriptive way with a qualitative approach. Results: There are many reports of benefits from the use of medicinal plants, being used by much of the population both in Brazil and worldwide, as well as in developing and developed countries, but some reasons end up worrying, because the product needs to be used correctly, and a major concern is the exaggerated self-medication, associated with allopathic medications, without communication to the doctor, and the lack of knowledge about the medicinal and toxic effects of plants. Final considerations: When we talk specifically about values, the medicinal plants are inserted in the low cost and accessibility, it is easy to prepare a home remedy made with some medicinal plants found in the garden or even already prepared in the form of infusions and bottles that are bought in fairs, as well as in the form of extracts and essential oils, being many times the only economical way to have medication, for not having access to other forms. Objetivo: abordar la importancia de las plantas medicinales para la gestión pública, resaltando que las plantas medicinales se convierten cada día más en una buena opción para la salud pública frente al uso relacionado con la salud por su eficacia y cuidado. Métodos: Se realizó una investigación de revisión bibliográfica de forma exploratoria descritiva con abordaje cualitativo. Resultados: Hay muchos informes sobre los beneficios del uso de las plantas medicinales, siendo utilizadas por gran parte de la población, tanto en Brasil como en el mundo, así como en los países en desarrollo y desarrollados, pero algunas razones terminan siendo preocupantes, porque el producto necesita ser utilizado correctamente, y una gran preocupación es la automedicación exagerada, asociada a los medicamentos alopáticos, sin comunicación al médico, y la falta de conocimiento sobre los efectos medicinales y tóxicos de las plantas. Consideraciones finales: Cuando hablamos específicamente de valores, las plantas medicinales se insertan en el bajo costo y la accesibilidad, es fácil preparar un remedio casero hecho con algunas plantas medicinales encontradas en el jardín o incluso ya preparadas en forma de infusiones y frascos que se compran en las ferias, así como en forma de extractos y aceites esenciales, siendo muchas veces la única forma económica de tener medicamentos, por no tener acceso a otras formas. Objetivo: abordar a importância das plantas medicinais para a gestão pública, salientando que as plantas medicinais tornam-se a cada dia mais uma boa opção para saúde pública frente ao uso relacionado à saúde por sua eficácia e custo. Métodos: Foi realizada uma pesquisa de revisão bibliográfica de forma exploratória descritiva com abordagem qualitativa. Resultados: Inúmeros relatos de benefícios do uso de plantas medicinais, sendo utilizado por grande parte da população tanto no Brasil quanto no mundo, assim como em países em desenvolvimento quanto os desenvolvidos, porém alguns motivos acabam preocupando, pois o produto precisa ser utilizado de maneira correta, e uma grande preocupação é a automedicação exagerada, associada a medicações alopáticas, sem comunicação ao médico, além da falta de conhecimento sobre os efeitos medicinais e tóxicos das plantas. Considerações finais: Quando falamos especificamente de valores, as plantas medicinais se inserem no baixo custo e na acessibilidade, é fácil preparar um remédio caseiro feito com algumas plantas medicinais que se encontrou na horta ou mesmo já preparados em forma de infusões e garrafadas que se compra em feiras, bem como na forma de extratos e óleos essenciais, sendo muitas vezes a única forma econômica de dispor da medicação, por não ter acesso as demais formas.

This article presents the result of a study that sought to identify conducts, techniques and good practices related to data privacy, which can be incorporated into the user-centered process, within the scope of service design and inclusive design, using the Internet of Things (IoT). It is important to identify new guidelines that can be incorporated into service design and inclusive design. This study was supported by a Systematic Bibliographic Review, covering 150 articles in a 5-year period (2017-2021), in the Web of Science databases, Scopus databases and the Periodic Journal Portal of CAPES. As a result, it brings a list of recommendations for good practices that can be adopted in design processes, especially to the Privacy by Design (PbD) framework. Este artículo presenta el resultado de un estudio que buscó identificar conductas, técnicas y buenas prácticas relacionadas con la privacidad de datos, que puedan ser incorporadas al proceso centrado en el usuario, en el ámbito del diseño de servicios y el diseño inclusivo, utilizando el Internet de las Cosas (IoT). Es importante identificar nuevas pautas que se puedan incorporar en el diseño de servicios y el diseño inclusivo. Este estudio fue apoyado por una Revisión Bibliográfica Sistemática, que abarcó 150 artículos en un período de 5 años (2017-2021), en las bases de datos Web of Science, bases de datos Scopus y el Portal de Revistas Periódicas de la CAPES. Como resultado, trae una lista de recomendaciones de buenas prácticas que se pueden adoptar en los procesos de diseño, especialmente al marco de Privacidad por Diseño (PbD). Este artigo apresenta o resultado de um estudo que buscou identificar condutas, técnicas e boas práticas relacionadas à privacidade de dados, que podem ser incorporadas ao processo de design centrado no usuário, no âmbito do design de serviços e design inclusivo, utilizando a Internet das Coisas (IoT). É importante identificar novas diretrizes que possam ser incorporadas ao design de serviços e ao design inclusivo em virtude das novas legislações. Este estudo foi apoiado por uma Revisão Bibliográfica Sistemática, abrangendo 150 artigos em um período de 5 anos (2017-2021), nas bases de dados Web of Science, Scopus e no Portal de Periódicos da CAPES. Como resultado, traz uma lista de recomendações de boas práticas que podem ser adotadas em processos de design, especialmente para o modelo de Privacidade por Definição ou Privacy by Design (PbD).

Background: Most estrogen receptor alpha positive (ER+) breast cancers (BCs) express androgen receptor (AR) protein, but its function is unclear. High AR relative to ER is associated with endocrine resistance. This randomized phase II trial of neoadjuvant fulvestrant (F) with or without the anti-androgen enzalutamide (E) was designed to determine if the addition of E to F in women with ≥T2 ER+/Her2- primary BC would increase the % patients (pts) with limited residual disease at time of surgery as measured by modified preoperative endocrine predictive index (PEPI). Methods: 4 months of therapy was given prior to surgery (F 500 mg IM weeks 1, 3, 5, 9, and 13) and pts were randomized to receive E 160 mg po daily for 16 weeks, stratified by node status and T-stage. Tumor biopsies were required at study entry and after 4 weeks on therapy (Wk5). PEPI score at time of surgery was the primary endpoint for efficacy. The minimax two-stage design had 80% power with type I error rate of 0.08. Reverse phase phosphoprotein array (RPPA), IHC for ER/PR/AR/GR/Ki67, and Polaris multiplex immunofluorescence (IF) panel for myeloid lineage immune cells were performed. Average signal levels were compared across arms, PEPI score (0, >0), PEPI by arm, and Ki67 ( Results: 69 pts consented; 59 evaluable. 95% completed surgery. PEPI=0 observed in 10 (17%). Of 33 pts on FE arm, 21 had T3/T4 tumors, 91% ER+/PR+, median AR expression 80%, Ki67 15%. Of 26 patients on F arm, 19% had T3/T4 tumors, 96% ER+/PR+, median AR expression 85%, Ki67 10%. PEPI=0 was achieved more frequently on the FE arm (8, 24%) than the F arm (2, 8%) (p=0.16). Toxicity was as expected with endocrine therapy. IHC of baseline vs Wk5 biopsies showed decreased ER, PR, and Ki67 levels by Wk5 that remained decreased at time of surgery. AR and GR were significantly decreased only in the FE arm at the time of surgery. RPPA revealed that baseline EGFR (Y1604 and Y992) was higher in tumors with PEPI=0 tumors, whereas the average baseline mTOR activation was higher among pts with PEPI>0. Significant changes detected by RPPA upon treatment included a significant decrease in AR. Myeloid-derived suppressor cells (MDSC) were significantly reduced by treatment only in the FE arm. Conclusions: The combination FE had manageable side effects. PEPI=0 was achieved more frequently on the FE arm (8/33) than the F arm (2/26). Activated EGFR was higher pretreatment in tumors achieving PEPI=0. mTOR pathway was elevated pretreatment in PEPI>0 tumors (also observed with resistance to FE in ER+/HER2- metastatic disease (SABCS 2021). When comparing pretreatment tumor to Wk5, total AR by RPPA was the most differentially decreased protein in PEPI=0 tumors. AR signaling is known to support immunosuppressive cells and we observed a marked decrease in MDSCs with treatment only on the FE arm. Citation Format: Anthony D. Elias, Alyse Staley, Monica Fornier, Gregory A. Vidal, Sharon Sams, Nicole Spoelstra, Peter Kabos, Jennifer R. Diamond, Elena Shagisultanova, Rosa I. Gallagher, Julia Wulfkuhle, Emanuel Petricoin, Kathryn Zolman, Stephanie Biller, Vida Alami, Tessa McSpadden, Virginia Borges, Lyndsey S. Crump, Dexiang Gao, Jennifer K. Richer. Randomized phase II trial of preoperative fulvestrant with or without enzalutamide for ER+/Her2- breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT144.

Our overall goal is to understand drivers of chemoresistance in triple-negative breast cancer (TNBC) and the mechanisms that contribute to metastatic spread in young women. TNBC is more frequently diagnosed in women aged Citation Format: Kelsey Kines, Sarah Tarullo, Virginia Borges, Traci Lyons. The effect of Semaphorin 7A on breast cancer metastases and chemoresistance in young women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1284.

This paper presents an exploratory and descriptive study on the use of the prospective research applied to the design management to generate innovation guided by the meaning. Innovation has been used as a key strategy for growth and maintenance of companies in the competitive market. However, in most cases, the development of innovation is either usually based on technological change, or on traditional market research. The first needs strong investment and time and the second relies only on the needs articulated by today's consumers, what limits the innovative results. In this context, as alternative approach, prospective research is considered a strong strategy, as it anticipates future consumer’s needs. Nevertheless, aiming at the designer’s work, there is a lack of information on how to manage it to foster meaning innovation by searching emerging opportunities using prospecting surveys. Therefore, this work aimed at the proposal of requirements to improve management of design in companies, by the use of prospective research to foster innovation guided by meaning. First, the research was conduct by a bibliographical review, with systematic and unsystematic phases followed by their interpretation and analysis that resulted in a preset of guidelines. From them, a Delphi method was conducted with manager’s and designers’ experts, to reinforce our review them. Confronting the previous results, the work proposes a list of requirements for the strategic, tactic and operational levels of design management. They intend to improve the use of prospective research within design management to generate innovation guided by meaning.

Data are lacking about the association between quality of life (QOL) and psychosocial issues of partners of young women with breast cancer who co-parent dependent children.We conducted a cross-sectional analysis of partners of women with breast cancer diagnosed at age ≤ 40. Among those partners reporting at least one dependent child under 18 years old at the time of diagnosis, we used multiple linear regression to examine associations between partner QOL and sociodemographic and psychosocial factors, and the patient's cancer stage and time since diagnosis.Of the 219 parenting partners, all identified as male with a median age of 44 years; 96% (204/213) reported working full-time at the time of the survey. Fifty-four percent endorsed behaviors indicating maladaptive coping. In adjusted analyses, less than full-time employment (β = - 8.76; 95% CI = - 17.37, - 0.14), younger age (β = - 0.35; 95% CI = - 0.069, - 0.02), greater parenting concerns (β = 0.56; 95% CI = 0.36, 0.75), clinically relevant anxiety symptoms (β = 13.79; 95% CI = 10.24, 17.35), lower post-traumatic growth score (β = - 0.33; 95% CI = - 0.51, - 0.16), lower social support (β = - 0.21; 95% CI = - 0.29, - 0.12), lower sexual satisfaction (β = - 0.40; 95% CI = - 0.62, - 0.19), and breast cancer stages 3 (β = 7.61; 95% CI = 0.19, 15.02) and 4 (β = 12.63; 95% CI = 1.91, 23.34), when compared to stage 0, were associated with lower partner QOL.Parenting partners of young women with breast cancer have substantial unmet psychosocial needs. Interventions are needed to enhance QOL and promote adaptive coping for this population.

Objetivo: abordar a importância das plantas medicinais para a gestão pública, salientando que as plantas medicinais tornam-se a cada dia mais uma boa opção para saúde pública frente ao uso relacionado à saúde por sua eficácia e custo. Métodos: Foi realizada uma pesquisa de revisão bibliográfica de forma exploratória descritiva com abordagem qualitativa. Resultados: Inúmeros relatos de benefícios do uso de plantas medicinais, sendo utilizado por grande parte da população tanto no Brasil quanto no mundo, assim como em países em desenvolvimento quanto os desenvolvidos, porém alguns motivos acabam preocupando, pois o produto precisa ser utilizado de maneira correta, e uma grande preocupação é a automedicação exagerada, associada a medicações alopáticas, sem comunicação ao médico, além da falta de conhecimento sobre os efeitos medicinais e tóxicos das plantas. Considerações finais: Quando falamos especificamente de valores, as plantas medicinais se inserem no baixo custo e na acessibilidade, é fácil preparar um remédio caseiro feito com algumas plantas medicinais que se encontrou na horta ou mesmo já preparados em forma de infusões e garrafadas que se compra em feiras, bem como na forma de extratos e óleos essenciais, sendo muitas vezes a única forma econômica de dispor da medicação, por não ter acesso as demais formas.

The purpose of this study was to search for Lutzomyia longipalpis and Lutzomyia cruzi in the urban area of the Água Clara Municipality, Mato Grosso do Sul State, Brazil. Two CDC traps were placed in the intradomicile and the peridomicile areas in four residences once a month, for three consecutive nights during 24 months. Were collected 11 species of sand flies totaling 3,418 specimens, 2,762 males and 656 females. Lu. longipalpis was the dominant species and there was no statistical difference between the peridomicile and intradomicile areas. Lu. cruzi was not found. The high capture rate for Lu. longipalpis in the urban area of Água Clara is cause for concern regarding necessary preventive measures to avoid future cases of visceral leishmaniasis. KEY WORDS: Leishmaniasis; Lutzomyia longipalpis; Phlebotominae; calazar.

Background: Metastatic triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype lacking hormone receptor expression and HER2 over-expression. Metastatic TNBC has been difficult to treat due to a general lack of targeted therapies, however, immunotherapy has shown substantial activity in a subset of patients. In metastatic TNBC patients with PD-L1-positive (combined positive score (CPS) ≥ 10) disease, KEYNOTE-355 demonstrated that addition of pembrolizumab (PD-1 inhibitor) to chemotherapy (nab-paclitaxel, paclitaxel, or carboplatin/gemcitabine) prolonged median progression free survival (PFS) compared to chemotherapy alone (9.7 months vs 5.6 months). Median 1-year PFS was also increased from 12.0% to 39.1% in these patients treated with pembrolizumab. These data led to the FDA approval of pembrolizumab with chemotherapy in PD-L1-positive metastatic TNBC patients. Despite these encouraging results, the majority of patients do not have long-term disease control. Radiotherapy (RT) in combination with immunotherapy and chemotherapy represents a promising avenue to prolong long-term response. RT can stimulate cellular damage and cause the release of tumor antigens, promoting a local T cell response. In addition, localized RT can result in the shrinkage of distant sites of metastasis via the abscopal effect when used with immunotherapy. The purpose of this study is to investigate the benefit of combining RT with pembrolizumab and chemotherapy in patients with metastatic PD-L1-positive TNBC. Methods: This two-stage, single-arm phase II study will assess the efficacy of RT in combination with nab-paclitaxel/paclitaxel plus pembrolizumab in PD-L1-positive unresectable or metastatic TNBC patients aged ≥18 years. To be included, patients must have only received < 1 prior line of systemic therapy in the metastatic setting or adjuvant/neoadjuvant setting if metastatic recurrence was within 12 months of treatment. The primary endpoint of the study is the 1-year PFS rate and a total of 29 subjects will be enrolled. Patients will be treated first with RT followed by the initiation of systemic therapy within seven days. Ablative RT will be directed at 1-4 sites of metastatic disease in 3 fractions of 8 Gy each. Nab-paclitaxel or paclitaxel will be given weekly day 1, day 8 every 3 weeks and pembrolizumab will be given every 3 weeks. Imaging will be repeated every 9 weeks to assess response based on RECIST 1.1. Systemic treatment will be continued until disease progression or intolerable toxicity. Treatment beyond progression will be allowed in certain patients who had initial response followed by progression. In these patients, repeat RT to new sites of disease can be administered with continuation of pembrolizumab to investigate the potential of re-sensitizing patients to immunotherapy. Blood will be collected before and after treatment for immune profiling. The sample size was determined using a null hypothesis for the 1-year PFS rate of 39% and an alternate hypothesis of 60%. The sample size of 29 yields a power of 80% to detect this difference with an alpha of 0.1 (1-sided). An interim analysis will be performed after enrollment of seventeen subjects in stage one. Citation Format: Anna R. Schreiber, Jodi Kagihara, Andrew Nicklawsky, Dexiang Gao, Anosheh Afghahi, Anthony Elias, Peter Kabos, Elena Shagisultanova, Todd Pitts, Julie Lang, Sana Karam, Virginia Borges, Christine Fisher, Jennifer R. Diamond. Phase II study of radiotherapy in combination with chemotherapy and immunotherapy in patients with PD-L1-positive metastatic triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT120.

Background: Tucatinib is an oral tyrosine kinase inhibitor highly specific for HER2 that is approved for use in combination with trastuzumab and capecitabine in adults with advanced or metastatic HER2+ breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. In the HER2CLIMB trial, the tucatinib regimen significantly prolonged progression-free survival (PFS) and overall survival (OS) in patients with HER2+ metastatic breast cancer (Murthy, NEJM 2020), including in patients with untreated, treated stable, and treated progressing brain metastases (Lin, J Clin Oncol, 2020). With an additional 15.6 months of follow-up, addition of tucatinib continued to show clinically meaningful prolongation of PFS and OS in the total study population (Curigliano, ASCO Meeting, 2021). We report updated results of exploratory efficacy analyses in patients with brain metastases. Methods: All patients in HER2CLIMB had a baseline brain MRI. Patients with brain metastases were eligible and classified as untreated, treated stable, or treated progressing. Patients were randomized 2:1 to receive tucatinib 300 mg twice daily or placebo, in combination with trastuzumab and capecitabine. Following the primary analysis, the protocol was amended to unblind sites to treatment assignment and allowed crossover from the placebo regimen to the tucatinib regimen. Efficacy analyses in patients with brain metastases at baseline were performed at approximately 2 years from the last patient randomized by applying RECIST 1.1 to the brain based on investigator evaluation. OS and CNS-PFS (progression in the brain or death) were evaluated in all patients with brain metastases. Patients without CNS-PFS events were censored at the last brain MRI. Confirmed intracranial (IC) objective response rate (ORR-IC) was evaluated in patients with measurable IC disease. Results: At a median follow-up of 29.6 months, median OS was 21.6 months vs 12.5 months in all patients with brain metastases (HR: 0.60; 95% CI: 0.44, 0.81), 21.4 months vs 11.8 months in patients with untreated/treated progressing brain metastases (HR: 0.52; 95% CI: 0.36, 0.77), and 21.6 months vs 16.4 months in patients with treated stable brain metastases (HR: 0.70; 95% CI: 0.42, 1.16). Median CNS-PFS was 9.9 months vs 4.2 months in all patients with brain metastases (HR: 0.39; 95% CI: 0.27, 0.56), 9.6 months vs 4.0 months in patients with untreated/treated progressing brain metastases (HR: 0.34; 95% CI: 0.22, 0.54), and 13.9 months vs 5.6 months in patients with treated stable brain metastases (HR: 0.41; 95% CI: 0.19, 0.85). ORR-IC was higher in the tucatinib arm (47.3%; 95% CI: 33.7, 61.2) vs the placebo arm (20.0%; 95% CI: 5.7, 43.7) for patients with brain metastases, and median duration of response (DOR) was 8.6 months (95% CI: 5.5, 10.3) vs 3.0 months (95% CI: 3.0, 10.3). Conclusions: With 15.6 months of additional follow-up, the tucatinib-trastuzumab-capecitabine regimen resulted in a robust and durable prolongation of OS for all patients with HER2+ metastatic breast cancer and brain metastases. Additionally, this benefit was maintained in patients with untreated/treated progressing and treated stable brain metastases. Treatment with tucatinib continued to show clinically meaningful benefit in CNS-PFS consistent with the primary analysis. Citation Format: Nancy U Lin, Rashmi K Murthy, Vandana Abramson, Carey Anders, Thomas Bachelot, Philippe Bedard, Virginia Borges, David Cameron, David Cameron, Lisa Carey, A Jo Chien, Giuseppe Curigliano, Michael DiGiovanna, Karen Gelmon, Gabriel Hortobagyi, Sara Hurvitz, Ian Krop, Sherene Loi, Sibylle Loibl, Volkmar Mueller, Mafalda Oliveira, Elisavet Paplomata, Mark Pegram, Dennis Slamon, Amelia Zelnak, Jorge Ramos, Wentao Feng, Eric Winer. Updated results of tucatinib vs placebo added to trastuzumab and capecitabine for patients with previously treated HER2-positive metastatic breast cancer with brain metastases (HER2CLIMB) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD4-04.

Background: Endocrine therapy administered sequentially as monotherapy or in combination with targeted therapy is the primary treatment for HR+, and HER2- metastatic breast cancer (MBC). Most patients with HR+, HER2- MBC will develop resistance to available therapies. More effective therapies are needed for HR+, HER2- MBC and for the treatment of endocrine therapy-resistant disease. OP-1250 is a small molecule Complete Estrogen Receptor ANtagonist (CERAN) that completely inactivates ER, blocking the activity of both the AF1 and AF2 transcriptional activation functions, inhibits ER-driven breast cancer cell growth, and induces ER degradation. OP-1250 demonstrates anti-cancer activity in vitro and in vivo, including activity against mouse models of metastases in the brain and tumors with activating mutations in ESR1. OP-1250 is orally bioavailable with a favorable pharmacokinetic (PK) profile enabling once-daily dosing. OP-1250’s complete ER antagonism is hypothesized to result in superior efficacy compared to agents that only partially antagonize and/or degrade but do not completely antagonize ER. Trial design: Goals of this phase 1/2 are to determine the Dose Limiting Toxicity (DLT), Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D), to characterize the safety and PK profile, and to determine the preliminary activity of OP-1250 in subjects with HR+, HER2- MBC. Ph 1 (Dose Escalation) will evaluate escalating doses of orally administered OP-1250 to determine the safety, pharmacology, MTD (if any) and/or the RP2D. Cohorts of 3 to 6 subjects will be sequentially enrolled and monitored for DLTs during cycle 1. Eligibility criteria include males, and both pre- and post-menopausal females, age 18 or older, with ER+, HER2- advanced or MBC (pre-menopausal women must be on an LHRH antagonist); prior CDK4/6 and SERD and fulvestrant are permitted; ECOG of 0 or 1. The objectives of the phase 1 are: identification of the DLT, MTD and/or RP2D and assessment of the safety and tolerability and PK of OP-1250. Objectives of the phase 2 are to assess the objective response rate (ORR) of OP-1250 in 1) subjects with HR+, HER2- MBC who have progressed on endocrine therapy and have no evidence of central nervous system (CNS) metastases, 2) in patients with non-measurable disease, and 3) in patients with CNS disease. Correlative analyses include ER, PR, Ki67 in tumor biopsies and ctDNA pre- and post-therapy for activating mutations in ESR1. Summary: OP-1250, a complete estrogen receptor antagonist (CERAN), is currently being evaluated in a phase 1/2 study in ER+, HER2- MBC. For more information, please contact clinical@olema.com (NCT04505826) Citation Format: Carlos Alemany, Manish Patel, Zahi Mitri, Joseph Sparano, Virginia Borges, Della Makower, Pam Klein, Julia Lawrence, Trinh Le, Jo Anne Zujewski, Erika Harmilton. A phase 1/2 dose escalation and expansion study of OP-1250 in adults with advanced and/or metastatic hormone receptor-positive (HR+), HER2-negative (HER2−) breast cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P037.

Este artigo trata-se de um ensaio teorico que contempla os temas “Inovacao Tradicional” e a “Inovacao Guiada pelo Design” – Design Driven Innovation, com base em Verganti e Rampino. Os estudos no campo da gestao de design com foco na inovacao vem apresentando avancos no modelo de inovacao orientada pelo design, o qual apresenta particularidades diferentes dos modelos tradicionais de inovacao. Assim, este artigo tem como objetivo identificar pontos comuns e diferentes entre essas duas modalidades teoricas de conceituacao da inovacao. Os resultados alcancados demonstram que existem semelhancas entre as teorias, contudo, a Inovacao Guiada pelo Design caracteriza o design enquanto elemento independente no processo inovativo.

Este artigo apresenta um estudo sobre a gestao de design face a transferencia de tecnologia, por meio da adaptacao de plataformas de produtos existente para novos mercados A importacao de produtos do mercado externo, nem sempre tem obtido o sucesso esperado. O uso de plataformas tem sido entao adotado, com vistas a melhorar a participacao das empresas no mercado, buscando a inovacao. Assim, este estudo buscou identificar como se deu o processo em uma empresa nacional, em que a gestao de design buscou o desenvolvimento de produtos inovadores. Com esse objetivo, a metodologia, inicialmente se apoiou em uma pesquisa bibliografica, seguida de um estudo de caso, em uma empresa que adota essa abordagem, relatando o desenvolvimento de uma linha de micro-ondas no Brasil. A principal contribuicao desta pesquisa foi a verificacao de como a inovacao incremental e a gestao do design estao associadas ao desenvolvimento de produto. Ela aponta para a inovacao incremental quanto ao uso de plataformas de produtos pre-existentes, sendo gerida de forma tatica e operacional pelo design de forma nao planejada, nao atingindo o nivel estrategico.

This work presents a systematic review of the Design Management research in the whole country of Brazil. Focusing on existent research groups, it sought to characterize a current design management research scenario. To do so, a systematic review was done considering the design management groups registered at National Council of Scientific Development – CNPq. As result, it was found 53 research groups located in thirteen Brazilian Federal States working with nine different research themes. The results made possible to discuss the group’s geographical distribution, the progress of the studies, the growth of the groups over time. It also suggests, towards the advancement in the area, the creation of a research network.

O ato de pensar e criar estratégias para marcas origina inúmeras discussões sobre a sociedade de consumo. Neste artigo, que tem como objeto de estudo o discurso publicitário, procuramos refletir sobre as questões éticas e legais da publicidade que incita o medo e a superstição. Mais especificamente, procuramos desvelar os efeitos de sentido do discurso da marca Hyundai, por meio dos pressupostos teórico-metodológicos da Análise de Discurso, de linha francesa, fundada no final da década de 1960, por Michel Pêcheux. Dedicamo-nos a uma análise materialista das práticas de linguagem ao trabalhar, na materialidade da língua, articulando o materialismo, a psicanálise, a linguagem e o sujeito. O estudo reflete sobre as estratégias discursivas da marca na relação entre desejo e consumo na sociedade capitalista, para então pensar sobre a publicidade que é ensinada e praticada atualmente. The act of thinking and creating strategies for brands leads to countless discussions about consumer society. In this article, which aims to study the advertising discourse, we try to reflect on the ethical and legal issues of advertising that incites fear and superstition. More specifically, we sought to unveil the Hyundai brand's meaningful sense effects through the theoretical-methodological assumptions of the French Line Discourse Analysis, founded in the late 1960s by Michel Pêcheux. We are dedicated to a materialistic analysis of language practices in working in the materiality of language, articulating materialism, psychoanalysis, language and subject. The study reflects on the discursive strategies of the brand in the relation between desire and consumption in capitalist society, to then think about the publicity that is taught and practiced today. El acto de pensar y crear estrategias para marcas origina innumerables discusiones sobre la sociedad de consumo. En este artículo, que tiene como objeto de estudio el discurso publicitario, tratamos de reflexionar sobre las cuestiones éticas y legales de la publicidad que incita el miedo y la superstición. Más específicamente, buscamos desvelar los efectos de sentido del discurso de la marca Hyundai, por medio de los presupuestos teórico-metodológicos del Análisis de Discurso, de línea francesa, fundada a finales de la década de 1960, por Michel Pêcheux. Dedicamos a un análisis materialista de las prácticas de lenguaje al trabajar, en la materialidad de la lengua, articulando el materialismo, el psicoanálisis, el lenguaje y el sujeto. El estudio refleja sobre las estrategias discursivas de la marca en la relación entre deseo y consumo en la sociedad capitalista, para entonces pensar sobre la publicidad que se enseña y se practica actualmente.

Este artigo apresenta uma revisão teórico-conceitual que visa discutir a integração dos temas: gestão de design e retorno sobre investimento (ROI). O estudo é motivado pela constatação de que, apesar dos resultados positivos do impacto que as atividades de design geram para as empresas, gestores alegam existir ainda um déficit na comunicação entre designers (qualificadores) e executivos (quantificadores). Dessa forma, pesquisadores e designers buscam meios para validar o valor do design nos negócios. O método adotado apoia-se em uma revisão bibliográfica integrativa (revisão bibliográfica sistemática com uma revisão bibliográfica narrativa), apresentando como resultado um quadro teórico qual visa fomentar o objetivo deste estudo. Finalmente, a mensuração do impacto da gestão de design no ROI se mostra complexa. Lacunas são apontadas sobre o valor multifacetado do design.

This article resulted from a study conducted in the course of Postgraduate Sensu Lato Media in Education from the Federal University of Mato Grosso do Sul in 2012. He was elected as an object of study: teacher formation in educational technology through the National Formation Program Continuing Educational Technology (Integrated PROINFO) in the city of Corumbá, State of Mato Grosso do Sul (MS), from 2008 to 2011, but for the purposes of this communication upgraded from the present data. It was defined as problematic the question: how the theoretical and didactic and technological knowledge present in the core courses of the Integrated PROINFO were appropriated and incorporated by the teachers of public schools of basic education of Corumbá- MS? In an attempt to answer that question, it was defined as a general objective: to analyze the process of theoretical and technological appropriation for basic education teachers in achieving the basic courses of the Integrated PROINFO in Corumbá-MS. The research was documentary and theoretical. Search procedures consisted of analytical reading of primary sources that had as empirical basis the edited documents and legislation about the studied object. Secondary sources were based specifically on the analysis of the annual reports prepared by the Educational Technology Center (NTE) and the theoretical dialogue with the authors who study the subject teacher education and information and communication technologies. It was concluded that teachers to use ICT in teaching and methodological activities need to be have the technological fluency and appropriate pedagogical concepts, teaching methods and techniques with ICT.

This paper presents a theoretical-conceptual review that aims to discuss the integration of two themes: design management and return on investment (ROI). The study is motivated by the realization that, despite the positive impact of the design activities for the companies, managers claim there is still a communication deficit between designers (qualifiers) and executives (quantifiers). In this sense, researchers and designers have struggled to reinforce the value of design in business. The method adopted is a combination of systematic and narrative bibliographical reviews, resulting in a theoretical framework that aims to support the objective of this study. Finally, measuring the impact of design management on ROI is complex. Gaps are pointed at the multifaceted value of the design process. Este artigo apresenta uma revisão teórico-conceitual que visa discutir a integração dos temas: gestão de design e retorno sobre investimento (ROI). O estudo é motivado pela constatação de que, apesar dos resultados positivos do impacto que as atividades de design geram para as empresas, gestores alegam existir ainda um déficit na comunicação entre designers (qualificadores) e executivos (quantificadores). Dessa forma, pesquisadores e designers buscam meios para validar o valor do design nos negócios. O método adotado apoia-se em uma revisão bibliográfica integrativa (revisão bibliográfica sistemática com uma revisão bibliográfica narrativa), apresentando como resultado um quadro teórico qual visa fomentar o objetivo deste estudo. Finalmente, a mensuração do impacto da gestão de design no ROI se mostra complexa. Lacunas são apontadas sobre o valor multifacetado do design.

This article contributes to the discussion about autonomous vehicles and impaired people. It presents a bibliographic survey, followed by the exploratory study with interviews with two blinded people and with an expert from automobile industry. It argues that to contain these emphases and gaps it is necessary to map the process of dislocation of blind people guided by a computational system, considering all type of obstacle encountered and to promote studies in the scope of Design, Engineering and Assistive Technology (AT).