Podcasts about OS

Actress Jessica Lowe (The Righteous Gemstones, Minx, Wrecked) joins Nicole to share the romantic saga of falling in love on a Second City cruise ship. On the ship, she met a British bassist who became her cruise ship boyfriend - whom she later realized wasn't as smart as she thought his accent sounded (he tried to dry his pants on a ceiling fan and designed a nightmare demon tattoo for himself).Jessica recalls dating a Dutch chef with a penis that was “too much!” and recounts what might be the most romantic first date ever told on the podcast. She reflects on the men who surprised her, disappointed her, and the slow work of building a relationship that actually lasted.Plus, Jessica and Nicole reminisce about the chaos of filming Curse Friends when everyone tested positive for COVID - and Nicole opens up about sobbing in a makeup chair over a man who simply wasn't worth it.Watch this episode on our YouTube channel at https://www.youtube.com/@WhyWontYouDateMePodcastSupport this podcast and get discounts by checking out our sponsors:» OneSkin: OneSkin is redefining the aging process with their proprietary OS-01 peptide. Get 15% off OneSkin with the code DATEME at https://www.oneskin.co/ #oneskinpod» SquareSpace: Head to squarespace.com/DATEME to save 10% off your first purchase of a website or domain using code DATEME.» Booking.com: Book now at Booking.com!» Smalls: Give your cat the food they deserve. For a limited time only, get 60% off your first order PLUS free shipping when you head to Smalls.com and use code DATEME.View all of our sponsors and discounts codes at wwydm.notion.site/sponsors.Follow:Tour Dates: linktr.ee/nicolebyerwastakenYouTube: @WhyWontYouDateMePodcastTikTok: @whywontyoudatemepod Instagram: @nicolebyerX: @nicolebyerNicole's book, #VERYFAT #VERYBRAVE: indiebound.org/book/9781524850746This is a Headgum podcast. Follow Headgum on Twitter, Instagram, and Tiktok. Advertise on Why Won't You Date Me? via Gumball.fm.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

« Drame au lycée Boganda à Bangui : 29 morts : Touadéra décrète trois jours de deuil », titre Afrik.com qui parle d'un « drame d'une ampleur inédite », « une violente bousculade, survenue en pleine session du baccalauréat ». « A l'origine du chaos », explique Afrik.com, « l'explosion d'un transformateur électrique de la société nationale ENERCA, qui a semé la panique, parmi les candidats et le personnel éducatif (…) les élèves ont cru à une attaque ou à un danger imminent. Pris de panique, ils se sont précipités dans les couloirs, ce qui a déclenché une bousculade incontrôlable ». Corbeau News Centrafrique ne cache pas sa colère, à l'égard de la Société nationale d'Électricité, à laquelle il s'adresse en ces termes : « combien de temps faudra-t-il pour que vous cessiez de tuer les Centrafricains ? » Corbeau News Centrafrique accuse : « ce drame survenu en plein cœur de la capitale n'est, pas une exception. Il s'inscrit dans une longue série de négligences criminelles de la part d'Enerca, une entreprise censée fournir de l'électricité, mais qui sème la mort à chaque coin de rue ». Le journal en veut pour preuve cet accident survenu le 23 mai dernier, « lorsqu'un jeune vendeur d'œufs a été électrocuté en plein centre-ville de Bangui, foudroyé par une fuite de courant dans une flaque d'eau. » Catastrophe prévisible Corbeau News Centrafrique s'en prend aussi au ministre de l'Éducation nationale, qui a publié « un communiqué qui tente de calmer les esprits, mais ne fait qu'attiser la colère », estime le journal, « car le communiqué du ministère parle de « quelques cas de pertes en vies humaines ». « Comme s'il s'agissait, estime le journal, d'une statistique banale… C'est une insulte aux familles endeuillées ». « Des élèves ont perdu la vie, piétinés, électrocutés, dans la panique causée par l'explosion d'un transformateur, installé depuis des années sans maintenant adéquate, une bombe à retardement qu'ENERCA a laissé en place, en toute connaissance de cause », accuse encore Corbeau News Centrafrique. Intégrité territoriale À lire également dans la presse africaine, les commentaires sur l'accord de paix qui doit être signé ce vendredi à Washington, entre la RDC et le Rwanda. « RDC – Rwanda : un accord de paix pour conserver l'intégrité territoriale congolaise », titre l'Agence Congolaise de Presse, qui cite Osée Yandi, présenté comme un « analyste des questions politiques extérieures », selon lequel, « cet accord doit également permettre à la RDC, de se reconstituer en tant que force pour pouvoir dissuader tout ennemi qui adviendrait sur son terrain ». Jeune Afrique de son côté, se demande : « Quel est l'intérêt des Américains ? »  alors que « la nouvelle administration américaine se montre plutôt indifférente, voire hostile à l'égard du continent africain. ». Ce qui semble le plus évident, aux yeux de Jeune Afrique, c'est que « l'activité minière » intéresse au plus haut point l'administration américaine. « En sécurisant leur approvisionnement en minerais critiques, poursuit Jeune Afrique, les États-Unis concurrenceraient leur rival chinois, déjà bien implanté en RDC. » De manière plus anecdotique, il faut noter aussi que « Donald Trump est en quête d'une victoire diplomatique » qui, nous dit le site panafricain, « consacrerait son statut de faiseur de paix ». Prix Nobel Un statut que Félix Tshisekedi serait prêt à lui accorder ! Dans une interview exclusive à la journaliste américaine Hariana Veras Victoria, le président congolais, se déclare ainsi « prêt à voter pour Donald Trump au prix Nobel de la Paix, si ce dernier parvient à en finir avec la guerre injustement imposée à son pays par le Rwanda ». C'est ce que rapportent Objectif-Info.cd et le Journal de Kinshasa, selon lequel Tshisekedi ne « cache pas son admiration pour le président américain ». 

Os dois homens considerados culpados pelo homicídio de um adolescente indígena, que ocorreu em outubro de 2022 nos subúrbios a leste de Perth, serão condenados hoje, 27 de junho. Ministros da Educação das várias regiões da Austrália reúnem esta sexta-feira, 27 de junho, em Adelaide, para discutir reformas no setor da educação pré-escolar. Estas e outras notícias em destaque, no noticiário de hoje.

Os europeus são “estúpidos” por quererem "gastar mais em vez de gastarem melhor em defesa", diz Wolfgang Münchau

Nossos sócios Luiz Eduardo Portella, Tomás Goulart e Sarah Campos debatem, no episódio de hoje, os principais acontecimentos da semana no Brasil e no mundo. No cenário internacional, a semana se iniciou com o ataque americano às instalações nucleares do Irã, que reagiu com resposta moderada. Dos dados econômicos nos EUA, chamou atenção a revisão baixista de consumo do 1º trimestre; e o PCE reforçou sinais de desaceleração no 2º trimestre, assim como inflação mais controlada. No Brasil, o IPCA-15 veio benigno e abaixo do esperado, com núcleos em desaceleração. A ata do Copom teve tom um pouco mais dovish que o comunicado, reforçando o compromisso com juros altos por período prolongado, mas sem endurecer o discurso. O Relatório de Inflação trouxe revisão para cima do hiato do produto e ligeira alta na projeção condicional de inflação a partir de 2027. Os dados de mercado de trabalho seguiram demonstrando robustez; e o primário de maio foi negativo, em linha com o esperado. No âmbito político, o Congresso derrubou o decreto do IOF imposto pelo governo, elevando a tensão entre Executivo e Legislativo. Nos EUA, os juros fecharam (vértice de 2 anos -16 bps), e as bolsas tiveram bom desempenho – S&P 500 +3,44%, Nasdaq +4,20% e Russell 2000 +3%. No Brasil, os juros também fecharam (jan/27 -12 bps), o Ibovespa caiu 0,18% e o real valorizou 0,49%. O petróleo caiu ao redor de 12%. Na próxima semana, destaque para dados de emprego e atividade nos EUA, desenvolvimentos sobre o pacote fiscal americano, falas dos dirigentes de bancos centrais no Fórum de Sintra e, por aqui, atenção ao Caged. Não deixe de conferir!

Os cuento con un pequeño juego como hacer el examen CCSE del Instituto Cervantes que realiza todo ciudadano que aspira a la nacionalidad española. ¿Aprobarás o te tendrás que ir de España?Este podcast está asociado a la red de Sospechosos Habituales donde podréis encontrar otros muchos podcast de diferentes temáticas.

Pesquisadores do Brasil, França, Estados Unidos e Japão se reuniram - presencialmente ou online - na Escola Normal Superior (ENS), em Lyon, no oeste da França, para discutir durante dois dias (24 e 25 de junho) as perspectivas históricas e estéticas do cinema realizado pela diáspora japonesa no Brasil. Patrícia Moribe, em Lyon As discussões sobre o cinema amarelo no Brasil foram permeadas por questões de preconceito, aculturamento, ancestralidade, pertencimento e construção de identidade. Presencialmente ou online, os participantes apresentaram aspectos históricos e discutiram a identidade nipo-brasileira forjada a partir de culturas e experiências geograficamente opostas. A chegada oficial do primeiro navio de imigrantes japoneses ao porto de Santos foi em 1908. A imigração nipônica foi fruto de um acordo entre os governos do Japão, que tinha em seu território uma crescente população carente, e do Brasil, que buscava alternativas de mão de obra barata após o fim da escravidão em 1888. Essa parte da história foi retratada pelo longa “Gaijin, Os Caminhos da Liberdade”, de Tizuka Yamazaki, prêmio da crítica internacional em Cannes, em 1980. A cineasta Olga Futemma, que coordenou a Cinemateca Brasileira por mais de 30 anos, também tratou dessa temática em seus curtas. O trabalho seminal das duas cineastas foi citado por vários participantes, principalmente na mesa dedicada às mulheres cineastas. Estima-se que dois milhões de japoneses e descendentes vivam no Brasil, representando a maior comunidade de chamados “nikkei” (japoneses) fora do Japão. Fenômeno dekassegui O encontro em Lyon discutiu também o retorno, a partir dos anos 1980, de parte dessa população ao Japão. Na época, o país atravessava um boom econômico e necessitava de mão de obra não qualificada. Uma das exigências do Japão era que o candidato a dekassegui tivesse antepassados japoneses. Esse fenômeno diminuiu nas últimas décadas, mas nunca foi interrompido. Hoje cerca de 200 mil brasileiros e descendentes vivem no Japão. Há imigrantes que ficam no Japão, que voltam para o Brasil, ou que fazem idas e voltas, como retrata o documentário “Bem-Vindos De Novo” (2021), de Marcos Yoshi, exibido no encontro em Lyon. "É um filme a respeito da história da minha família, do meu núcleo familiar, dos meus pais e das minhas irmãs. Meus pais decidiram ir para o Japão como dekasseguis em 1999. E por conta disso a família se separou. Os filhos ficaram no Brasil, meus pais foram para o Japão, a princípio para ficar 3 anos, e acabaram ficando uns 13 anos. E o filme é o retrato dessa experiência. Mas também é o momento em que meus pais voltam para o Brasil e a família se reencontra e a gente precisa lidar com os sentimentosos sentimentos e com as feridas que ficaram de certa forma abertas.” Alienação e solidão Marcos Yoshi, que também é pesquisador, apresentou em uma das mesas de discussão um outro lado da moeda do fenômeno dekassegui. Muitos brasileiros sofrem com a alienação e a solidão no Japão, acabando por desenvolver problemas psiquiátricos. Essa problemática é também tema do novo projeto de documentário de Yoshi, tendo a história de um tio paterno como fio condutor para falar dos dekassegui e as consequências desse retorno. Outro filme exibido no final do primeiro dia de discussões foi “Amarela”, de André Hayato Saito, selecionado pelo festival de Cannes de 2024. O curta trata da jovem Erika, fã de futebol, na época da final da Copa do Mundo de 1998, quando fica dividida entre o seu mundo carregado ainda de forte influência japonesa e a discriminação que sofre no dia a dia. O pesquisador Hugo Katsuo, da Universidade Federal Fluminense, destacou curtas realizados em Curitiba, dando uma outra perspectiva a uma produção geralmente centrada em São Paulo. O franco-japonês Tristan Chiffoleau, pesquisador no Japão, falou sobre o filme “Okinawa-Santos” (2020), que retrata um episódio pouco conhecido da expulsão de japoneses de Santos em 1943, sendo a maioria de origem okinawana, etnia marginalizada no Japão. Já Tomyo Costa Ito, da USP, falou sobre uma descoberta que realizou quando fazia parte do projeto Nitrato, da Cinemateca Brasileira, de arquivamento e preservação de filmes. “É um filme de 1950 em que os melhores nadadores da época, que eram japoneses, vieram para o Brasil e participaram de um tour visitando cidades por São Paulo com comunidades japonesas. O filme também traz esses elementos de uma certa propaganda do desenvolvimento do Estado. Na época, os governantes estavam preocupados em transmitir uma imagem de São Paulo como um o lugar de modernidade e de desenvolvimento dentro do Brasil”. Com estética dos cinejornais da época, o material está montado e narrado, mas, no entanto, não tem créditos, ou seja, ele é virtualmente anônimo. Para descobrir pistas, Ito foi atrás de fontes como jornais da época, mas relata que a pesquisa foi um grande desafio. O Brasil como utopia Alexandre Nakahara, da USP, em participação online, apresentou filmes japoneses que tratavam do Brasil como uma utopia, o sonho do Eldorado. Entre eles, “Viver no Medo” (1955), de Akira Kurosawa, sobre o dono de uma fábrica no Japão que, abalado pelo medo de um ataque nuclear, planeja se mudar com toda a família para a segurança de uma fazenda no Brasil. Os pesquisadores apresentaram também filmes que evocavam o Brasil dos dekasseguis ou o Japão dos imigrantes, realizados por japoneses, brasileiros e franceses. O colóquio do Japão ao Brasil e vice versa, perspectivas históricas e estéticas de um cinema de diáspora, foi organizado pelos doutorandos Romane Carrière, Emmanuel Dayre e Lucie Ryzdzek.

Os impostos vão descer outra vez. O Governo pretende que o Parlamento aprove uma nova descida do IRS. Que impacto vai ter nos nossos bolsos? Análise de Helena Garrido.

FreeBSD version 14.3 is available, Reliable ZFS Storage on Commodity Hardware, My website is ugly because I made it, Semi distributed filesystems with ZFS and Sanoid, April 2025 Laptop Support and Usability Project Update, UDP sockets instead of BPF in dhcpd(8), and more NOTES This episode of BSDNow is brought to you by Tarsnap (https://www.tarsnap.com/bsdnow) and the BSDNow Patreon (https://www.patreon.com/bsdnow) Headlines FreeBSD 14.3 released (https://www.freebsd.org/releases/14.3R/announce/) Reliable ZFS Storage on Commodity Hardware (https://klarasystems.com/articles/cost-efficient-storage-commodity-hardware/) News Roundup My website is ugly because I made it (https://goodinternetmagazine.com/my-website-is-ugly-because-i-made-it/) Semi distributed filesystems with ZFS and Sanoid (https://anil.recoil.org/notes/syncoid-sanoid-zfs) April 2025 Laptop Support and Usability Project Update (https://freebsdfoundation.org/blog/april-2025-laptop-support-and-usability-project-update/) dhcpd(8): use UDP sockets instead of BPF (https://undeadly.org/cgi?action=article;sid=20250613111800) Tarsnap This weeks episode of BSDNow was sponsored by our friends at Tarsnap, the only secure online backup you can trust your data to. Even paranoids need backups. Feedback/Questions No feedback this week. Send more... Send questions, comments, show ideas/topics, or stories you want mentioned on the show to feedback@bsdnow.tv (mailto:feedback@bsdnow.tv) Join us and other BSD Fans in our BSD Now Telegram channel (https://t.me/bsdnow)

O UOL revelou que, neste ano, o Ministério da Saúde está liberando um "extra" para parlamentares da base aliada, que pode chegar a R$8 bilhões.  Os ministérios têm mais controle sobre essas verbas do que tem sobre emendas parlamentares. Mas também não há publicidade sobre quem são os "padrinhos".  Neste episódio do UOL Prime, José Roberto de Toledo conversa com Natália Portinari sobre como funciona esse instrumento de negociação política. #uolprime #PodcastUOLPrime

Durante o julgamento no STF sobre a responsabilização de redes sociais, a ministra Cármen Lúcia falou, ao proferir seu voto, em “213 milhões de pequenos tiranos” para justificar censura. O placar no Supremo ficou em 8 a 3 contra as big techs. Os votos vencidos foram os de André Mendonça, Luiz Edson Fachin e Kassio Nunes Marques. Felipe Moura Brasil e Ricardo Kertzman comentam:Papo Antagonista é o programa que explica e debate os principais acontecimentos do   dia com análises críticas e aprofundadas sobre a política brasileira e seus bastidores.     Apresentado por Felipe Moura Brasil, o programa traz contexto e opinião sobre os temas mais quentes da atualidade.     Com foco em jornalismo, eleições e debate, é um espaço essencial para quem busca informação de qualidade.     Ao vivo de segunda a sexta-feira às 18h.    Apoie o jornalismo Vigilante: 10% de desconto para audiência do Papo Antagonista  https://bit.ly/papoantagonista  Siga O Antagonista no X:  https://x.com/o_antagonista   Acompanhe O Antagonista no canal do WhatsApp. Boletins diários, conteúdos exclusivos em vídeo e muito mais.  https://whatsapp.com/channel/0029Va2SurQHLHQbI5yJN344  Leia mais em www.oantagonista.com.br | www.crusoe.com.br 

O deputado federal Kim Kataguiri e o deputado estadual Guto Zacarias – ambos da União Brasil – pediram ao Ministério Público Federal (MPF) uma investigação sobre uma possível prática de improbidade administrativa por parte da deputada federal Erika Hilton (PSOL-SP).A iniciativa foi motivada pelo reembolso de 24 mil reais solicitado por Erika Hilton à Câmara, referente a uma cirurgia na região do nariz. Segundo declarações públicas da parlamentar, o procedimento teve natureza funcional e estética — sendo que a parte estética teria sido custeada por ela.Os parlamentares, no entanto, questionam a realização conjunta dos procedimentos — médico e estético — em um mesmo ato cirúrgico, o que levanta dúvidas sobre o real fracionamento dos custos e o efetivo uso de dinheiro público. Felipe Moura Brasil e Ricardo Kertzman comentam:Papo Antagonista é o programa que explica e debate os principais acontecimentos do   dia com análises críticas e aprofundadas sobre a política brasileira e seus bastidores.     Apresentado por Felipe Moura Brasil, o programa traz contexto e opinião sobre os temas mais quentes da atualidade.     Com foco em jornalismo, eleições e debate, é um espaço essencial para quem busca informação de qualidade.     Ao vivo de segunda a sexta-feira às 18h.    Apoie o jornalismo Vigilante: 10% de desconto para audiência do Papo Antagonista  https://bit.ly/papoantagonista  Siga O Antagonista no X:  https://x.com/o_antagonista   Acompanhe O Antagonista no canal do WhatsApp. Boletins diários, conteúdos exclusivos em vídeo e muito mais.  https://whatsapp.com/channel/0029Va2SurQHLHQbI5yJN344  Leia mais em www.oantagonista.com.br | www.crusoe.com.br 

Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss important advances in the treatment of prostate, bladder, and kidney cancers that were presented at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News Podcast. I am Dr. Neeraj Agarwal, your guest host of the ASCO Daily News Podcast today. I am the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah Huntsman Cancer Institute and editor-in-chief of the ASCO Daily News.  I am delighted to be joined by Dr. Jeanny Aragon-Ching, a GU medical oncologist and the clinical program director of the GU Center at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing some key abstracts in GU oncology that were presented at the 2025 ASCO Annual Meeting.  Our full disclosures are available in the transcript of this episode.  Jeanny, it is great to have you on the podcast. Dr. Jeanny Aragon-Ching: Oh, thank you so much, Neeraj. Dr. Neeraj Agarwal: Jeanny, let's begin with some prostate cancer abstracts. Let's begin with Abstract 5017 titled, “Phase 1 study results of JNJ-78278343 (pasritamig) in metastatic castration-resistant prostate cancer.” Can you walk us through the design and the key findings of this first-in-human trial? Dr. Jeanny Aragon-Ching: Yeah, absolutely, Neeraj. So this study, presented by Dr. Capucine Baldini, introduces pasritamig, a first-in-class T-cell redirecting bispecific antibody that simultaneously binds KLK2 on prostate cancer cells and CD3 receptor complexes on T cells. KLK2 is also known as human kallikrein 2, which is selectively expressed in prostate tissue. And for reference, KLK3 is what we now know as the PSA, prostate-specific antigen, therefore making it an attractive and specific target for therapeutic engagement. Now, while this was an early, first-in-human, phase 1 study, it enrolled 174 heavily pretreated metastatic CRPC patients. So many were previously treated with ARPIs, taxanes, and radioligand therapy. So given the phase 1 nature of this study, the primary objective was to determine the safety and the RP2D, which is the recommended phase 2 dose. Secondary objectives included preliminary assessment of antitumor activity. So, pasritamig was generally well tolerated. There were no treatment-related deaths. Serious adverse events were rare. And in the RP2D safety cohort, where patients received the step-up dosing up to 300 mg of IV every 6 weeks, the most common treatment-related adverse events were low-grade infusion reactions. There was fatigue and grade 1 cytokine release syndrome, what we call CRS. And no cases of neurotoxicity, or what we call ICANS, the immune effector cell-associated neurotoxicity syndrome, reported. Importantly, the CRS occurred in just about 8.9% of patients. All were grade 1. No patients required tocilizumab or discontinued treatment due to adverse events. So, this suggests a favorable safety profile, allowing hopefully for outpatient administration without hospitalization, which will be very important when we're thinking about bispecifics moving forward. In terms of efficacy, pasritamig showed promising activity. About 42.4% of evaluable patients achieved a PSA50 response. Radiographic PFS was about 6.8 months. And among patients with measurable disease, the objective response rate was about 16.1% in those with lymph node or bone metastases, and about 3.7% in those with visceral disease, with a median duration of response of about 11.3 months. So, altogether, this data suggests that pasritamig may offer a well-tolerated and active new potential option for patients with metastatic CRPC.   Again, as a reminder, with the caveat that this is still an early phase 1 study. Dr. Neeraj Agarwal: Thank you, Jeanny. These are promising results for a bispecific T-cell engager, pasritamig, in prostate cancer. I agree, the safety and durability observed here stand out, and this opens the door for further development, possibly even in earlier disease settings.  So, shifting now from immunotherapy to the evolving role of genomics in prostate cancer. So let's discuss Abstract 5094, a real-world, retrospective analysis exploring the prognostic impact of homologous recombination repair gene mutations, especially BRCA1 and BRCA2 mutations, in metastatic hormone-sensitive prostate cancer. Can you tell us more about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Sure, Neeraj. So this study was presented by Dr. David Olmos, represents one of the largest real-world analyses we have evaluating the impact of homologous recombination repair, or what we would call HRR, alterations in metastatic hormone-sensitive prostate cancer. So, this cohort included 556 men who underwent paired germline and somatic testing. Now, about 30% of patients had HRR alterations, with about 12% harboring BRCA1 or BRCA2 mutations and 16% having alterations in other HRR genes. Importantly, patients were stratified via CHAARTED disease volume, and outcomes were examined across treatment approaches, including ADT alone, doublet therapy, and triplet therapy. The prevalence of BRCA and HRR alterations were about similar between the metastatic hormone-sensitive prostate cancer and the metastatic castrate-resistant prostate cancer, with no differences observed, actually, between the patients with high volume versus low volume disease.  So, the key finding was that BRCA and HRR alterations were associated with poor clinical outcomes in metastatic hormone-sensitive prostate cancer. And notably, the impact of these alterations may actually be even greater in metastatic hormone-sensitive prostate cancer than previously reported in metastatic CRPC. So, the data showed that when BRCA mutations are present, the impact of the volume of disease is actually limited. So, poor outcomes were observed across the board for both high-volume and low-volume groups. So, the analysis showed that patients with HRR alterations had significantly worse outcomes compared to patients without HRR alterations. Median radiographic progression-free survival was about 20.5 months for the HRR-altered patients versus 30.6 months for the non-HRR patients, with a hazard ratio of 1.6. Median overall survival was 39 months for HRR-altered patients compared to 55.7 months for the non-HRR patients, with a hazard ratio of 1.5. Similar significant differences were observed when BRCA-mutant patients were compared with patients harboring non-BRCA HRR mutations. Overall, poor outcomes were independent of treatment of ARPI or taxanes. Dr. Neeraj Agarwal: Thank you, Jeanny. So, these data reinforce homologous recombination repair mutations as both a predictive and prognostic biomarker, not only in the mCRPC, but also in the metastatic hormone-sensitive setting as well. It also makes a strong case for incorporating genomic testing early in the disease course and not waiting until our patients have castration-resistant disease. Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. And I think this really brings home the point and the lead up to the AMPLITUDE trial, which is LBA5006, a phase 3 trial that builds on this very concept of testing with a PARP inhibitor, niraparib, in the hormone-sensitive space. Can you tell us a little bit more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure. So, the AMPLITUDE trial, a phase 3 trial presented by Dr. Gerhardt Attard, enrolled 696 patients with metastatic hormone-sensitive prostate cancer and HRR gene alterations. 56% of these patients had BRCA1 and BRCA2 mutations. Patients were randomized to receive abiraterone with or without niraparib, a PARP inhibitor. The majority of patients, 78% of these patients, had high-volume metastatic hormone-sensitive prostate cancer, and 87% of these patients had de novo metastatic HSPC. And 16% of these patients received prior docetaxel, which was allowed in the clinical trial. So, with a median follow-up of nearly 31 months, radiographic progression-free survival was significantly prolonged with the niraparib plus abiraterone combination, and median was not reached in this arm, compared to abiraterone alone, which was 29.5 months, with a hazard ratio of 0.63, translating to a 37% reduction in risk of progression or death. This benefit was even more pronounced in the BRCA1 and BRCA2 subgroup, with a 48% reduction in risk of progression, with a hazard ratio of 0.52. Time to symptomatic progression also improved significantly across all patients, including patients with BRCA1, BRCA2, and HRR mutations. Although overall survival data remain immature, early trends favored the niraparib plus abiraterone combination. The safety profile was consistent with prior PARP inhibitor studies, with grade 3 or higher anemia and hypertension were more common but manageable. Treatment discontinuation due to adverse events remained low at 11%, suggesting that timely dose modifications when our patients experience grade 3 side effects may allow our patients to continue treatment without discontinuation. These findings support niraparib plus abiraterone as a potential new standard of care in our patients with metastatic hormone-sensitive prostate cancer with HRR alterations, and especially in those who had BRCA1 and BRCA2 mutations. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. This trial is especially exciting because it brings PARP inhibitors earlier into the treatment paradigm. Dr. Neeraj Agarwal: Exactly. And it is exciting to see the effect of PARP inhibitors in the earlier setting.  So Jeanny, now let's switch gears a bit to bladder cancer, which also saw several impactful studies. Could you tell us about Abstract 4502, an exploratory analysis from the EV-302 trial, which led to approval of enfortumab vedotin plus pembrolizumab for our patients with newly diagnosed metastatic bladder cancer? So here, the authors looked at the outcomes in patients who achieved a confirmed complete response with EV plus pembrolizumab. Dr. Jeanny Aragon-Ching: Sure, Neeraj. So, EV-302 demonstrated significant improvements in progression-free and overall survival for patients previously treated locally advanced or metastatic urothelial cancer, I'll just call it metastatic UC, as a frontline strategy, establishing EV, which is enfortumab vedotin, plus pembro, with pembrolizumab as standard of care in this setting.  So, this year at ASCO, Dr Shilpa Gupta presented this exploratory responder analysis from the phase 3 EV-302 trial. Among 886 randomized patients, about 30.4% of patients, this is about 133, in the EV+P arm, and 14.5% of the patients in the chemotherapy arm, achieved a confirmed complete response. They call it the CCR rates. So for patients who achieved this, median PFS was not reached with EV+P compared to 26.9 months with chemotherapy, with a hazard ratio of 0.36, translating to a 64% reduction in the risk of progression. Overall survival was also improved. So the median OS was not reached in either arm, but the hazard ratio favored the EV+P at 0.37, translating to a 63% reduction in the risk of death. The median duration of complete response was not reached with EV+P compared to 15.2 months with chemotherapy. And among those patients who had confirmed CRs at 24 months, 78% of patients with the EV+P arm remained progression-free, and around 95% of the patients were alive, compared to 54% of patients who were progression-free and 86% alive of the patients in the chemotherapy arm. Safety among responders were also consistent with prior reports. Grade 3 or higher treatment-related adverse events occurred in 62% of EV+P responders and 72% of chemotherapy responders. Most adverse events were managed with dose modifications, and importantly, no treatment-related deaths were reported among those who were able to achieve complete response.  So these findings further reinforce EV and pembro as the preferred first-line therapy for metastatic urothelial carcinoma, offering a higher likelihood of deep, durable responses with a fairly manageable safety profile. Dr. Neeraj Agarwal: Thank you for the great summary, Jeanny. These findings underscore the depth and durability of responses achievable with this combination and also suggest that achieving a response may be a surrogate for long-term benefit in patients with metastatic urothelial carcinoma.  So now, let's move to Abstract 4503, an exploratory ctDNA analysis from the NIAGARA trial, which evaluated perioperative durvalumab, an immune checkpoint inhibitor, in muscle-invasive bladder cancer. So what can you tell us about this abstract? Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. So, in NIAGARA, presented by Dr. Tom Powles, the addition of perioperative durvalumab to neoadjuvant chemotherapy, gem/cis, significantly improved event-free survival, overall survival, and pathologic complete response in patients with cisplatin-eligible muscle-invasive bladder cancer. Recall that this led to the U.S. FDA approval of this treatment regimen on March 28, 2025.  So, a planned exploratory analysis evaluated the ctDNA dynamics and their association with clinical outcomes, which was the one presented recently at ASCO. So, the study found that the incidence of finding ctDNA positivity in these patients was about 57%. Following neoadjuvant treatment, this dropped to about 22%, with ctDNA clearance being more common in the durvalumab arm, about 41%, compared to the chemotherapy control arm of 31%. Notably, 97% of patients who remained ctDNA positive prior to surgery failed to achieve a pathologic CR. So, this indicates a strong association between ctDNA persistence and lack of tumor eradication. So, postoperatively, only about 9% of patients were ctDNA positive. So, importantly, durvalumab conferred an event-free survival benefit regardless of ctDNA status at both baseline and post-surgery. Among patients who were ctDNA positive at baseline, durvalumab led to a hazard ratio of 0.73 for EFS. So, this translates to a 27% reduction in the risk of disease recurrence, progression, or death compared to the control arm. In the post-surgical ctDNA-positive group, the disease-free survival was also improved with a hazard ratio of 0.49, translating to a 51% reduction in the risk of recurrence.  So, these findings underscore the prognostic value of ctDNA and suggest that durvalumab provides clinical benefit irrespective of molecular residual disease status. So, the data also supports that ctDNA is a promising biomarker for future personalized strategies in the perioperative treatment of muscle-invasive bladder cancer. Dr. Neeraj Agarwal: Thank you, Jeanny. It is great to see that durvalumab is improving outcomes in these patients regardless of ctDNA status. However, based on these data, presence of ctDNA in our patients warrants a closer follow-up with imaging studies, because these patients with positive ctDNA seem to have a higher risk of recurrence. Dr. Jeanny Aragon-Ching: I agree, Neeraj.  Let's round out the bladder cancer discussion with Abstract 4518, which reported the interim results of SURE-02, which is a phase 2 study evaluating neoadjuvant sacituzumab govitecan plus pembrolizumab in cisplatin-ineligible muscle-invasive bladder cancer. Can you tell us more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure, Jeanny. So, Dr Andrea Necchi presented interim results from the SURE-02 trial. This is a phase 2 study evaluating neoadjuvant sacituzumab govitecan plus pembrolizumab, followed by a response-adapted bladder-sparing treatment and adjuvant pembrolizumab in patients with muscle-invasive bladder cancer.  So, in this interim analysis, 40 patients were treated and 31 patients were evaluable for efficacy. So, the clinical complete response rate was 38.7%. All patients achieving clinical complete response underwent bladder-sparing approach with a repeat TURBT instead of radical cystectomy. Additionally, 51.6% of patients achieved excellent pathologic response with a T stage of 1 or less after neoadjuvant therapy. The treatment was well tolerated, with only 12.9% of patients experiencing grade 3 or higher adverse events without needing dose reduction of sacituzumab. Molecular profiling, interestingly, showed that clinical complete response correlated with luminal and genomically unstable subtypes, while high stromal gene expression was associated with lack of response.  These results suggest that sacituzumab plus pembrolizumab combination has promising activity in this setting, and tolerability, and along with other factors may potentially allow a bladder preservation approach in a substantial number of patients down the line. Dr. Jeanny Aragon-Ching: Yeah, agree with you, Neeraj. And the findings are very provocative and support completing the full trial enrollment and further exploration of this strategy in muscle-invasive bladder cancer in order to improve and provide further bladder-sparing strategies. Dr. Neeraj Agarwal: Agree. So, let's now turn to the kidney cancer, starting with Abstract 4505, the final overall analysis from CheckMate-214 trial, which evaluated nivolumab plus ipilimumab, so dual checkpoint inhibition strategy, versus sunitinib in our patients with metastatic clear cell renal cell carcinoma. Dr. Jeanny Aragon-Ching: Yeah, absolutely, Neeraj. So, the final 9-year analysis of the phase 3 CheckMate-214 trial confirms the long-term superiority of nivolumab and ipilimumab over sunitinib for first-line treatment of advanced metastatic renal cell carcinoma. So, this has a median follow-up of 9 years. Overall survival remains significantly improved with the combination. So, in the ITT patient population, the intention-to-treat, the hazard ratio for overall survival was 0.71. So, this translates to a 29% reduction in the risk of death. 31% of patients were alive at this 108-month follow-up compared to 20% only in those who got sunitinib. So, similar benefits were observed in the intermediate- and poor-risk groups with a hazard ratio of 0.69, and 30% versus 19% survival at 108 months.  Importantly, a delayed benefit was also seen in those favorable-risk patients. So, the hazard ratio for overall survival improved from 1.45 in the initial report and now at 0.8 at 9 years follow-up, with 35% of patients alive at 108 months compared to 22% in those who got sunitinib. Progression-free survival also favored the nivo-ipi arm across all risk groups. At 96 months, the probability of remaining progression-free was about 23% compared to 9% in the sunitinib arm in the ITT patient population, 25% versus 9% in the intermediate- and poor-risk patients, and 13% compared to 11% in the favorable-risk patients. Importantly, at 96 months, 48% of patients in the nivo-ipi responders remained in response compared to just 19% in those who got sunitinib. And in the favorable-risk group, 36% of patients who responded remained in response, although data were not available for sunitinib in this subgroup.  So, this data reinforces the use of nivolumab and ipilimumab as a durable and effective first-line effective strategy for standard of care across all risk groups for advanced renal cell carcinoma. Dr. Neeraj Agarwal: Thank you, Jeanny. And of course, since ipi-nivo data were presented, several other novel ICI-TKI combinations have emerged. And I'm really hoping to see very similar data with TKI-ICI combinations down the line. It is really important to note that we are not seeing any new safety signals with the ICI combinations or ICI-based therapies, which is very reassuring given the extended exposure. Dr. Jeanny Aragon-Ching: Absolutely agree with you there, Neeraj.  Now, going on and moving on to Abstract 4514, which is the KEYNOTE-564 trial, and they reported on the 5-year outcomes of adjuvant pembrolizumab in clear cell RCC in patients who are at high risk for recurrence. Can you tell us a little bit more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure. So, the KEYNOTE-564 trial established pembrolizumab monotherapy as the first adjuvant regimen to significantly improve both disease-free survival and overall survival compared to placebo after surgery for patients with clear cell renal cell carcinoma. So, Dr Naomi Haas presented the 5-year update from this landmark trial.  A total of 994 patients were randomized to receive either pembrolizumab or placebo. The median follow-up at the time of this analysis was approximately 70 months. Disease-free survival remained significantly improved with pembrolizumab. The median DFS was not reached with pembrolizumab compared to 68.3 months with placebo, with a hazard ratio of 0.71, translating to a 29% reduction in risk of recurrence. At 5 years, 60.9% of patients receiving pembrolizumab remained disease-free compared to 52.2% with placebo. Overall survival also favored pembrolizumab. The hazard ratio for OS was 0.66, translating to a 34% reduction in risk of death, with an estimated 5-year overall survival rate of 87.7% with pembrolizumab compared to 82.3% for placebo. Importantly, these benefits were consistent across all key subgroups, including patients with sarcomatoid features. In addition, no new serious treatment-related adverse events have been reported in the 3 years since treatment completion.  So, these long-term data confirm pembrolizumab as a durable and effective standard adjuvant therapy for patients with resected, high-risk clear cell renal cell carcinoma. Dr. Jeanny Aragon-Ching: Thank you for that wonderful summary, Neeraj. Dr. Neeraj Agarwal: That wraps up our kidney cancer highlights. Any closing thoughts, Jeanny, before we conclude? Dr. Jeanny Aragon-Ching: It's been so wonderful reviewing these abstracts with you, Neeraj. So, the 2025 ASCO Annual Meeting showcased a lot of transformative data across GU cancers, from first-in-class bispecifics to long-term survival in RCC. And these findings are already shaping our clinical practices. Dr. Neeraj Agarwal: I agree. And we have covered a broad spectrum of innovations in GU cancers with strong clinical relevance.  So, thank you, Jeanny, for joining me today and sharing your insights.  And thank you to our listeners for joining us. You will find links to the abstracts discussed today in the transcript of this episode. If you find these conversations valuable, please take a moment to rate, review, and subscribe to the ASCO Daily News Podcast wherever you listen. Thank you so much. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers:    Dr. Neeraj Agarwal     @neerajaiims     Dr. Jeanny Aragon-Ching   Follow ASCO on social media:       @ASCO on Twitter       ASCO on Bluesky   ASCO on Facebook       ASCO on LinkedIn       Disclosures:   Dr. Neeraj Agarwal:   Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences  Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas  Dr. Jeanny Aragon-Ching:   Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc., Pfizer/EMD Serono   Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis,    Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics

Os aliados acordaram em aumentar as despesas com defesa para 5% do PIB. A cimeira de Haia constitui um novo marco histórico para a organização. E Portugal vai cumprir? Madalena Moreira, jornalista, é a convidada.See omnystudio.com/listener for privacy information.

¿Qué ocurre cuando un cuadro te observa desde la pared? En este episodio de DÍAS EXTRAÑOS, Xavi Villanueva nos trae 'El Cuadro', un relato de Arturo Panero González que convertirá tu dormitorio en una pesadilla. Una historia que comienza con un niño fascinado por una pintura grotesca y evoluciona hacia algo que jamás podrás imaginar. Obsesión, locura y colores que sangran... literalmente. ADVERTENCIA: Después de escucharlo, mirarás cualquier cuadro de forma muy diferente. ¿Te atreves a descubrir qué habita realmente en los lienzos? Una experiencia auditiva que se quedará grabada en tu retina. Escucha el episodio completo en la app de iVoox, o descubre todo el catálogo de iVoox Originals

No sé cómo hemos llegado a 600 programas, ni cómo hemos llegado vivos. Ha sido una temporada emocionante en la que os hemos sentido desde el principio. Os regalamos este especial con toda vuestra banda de idiotas favorita, incluyendo alguna sorpresa que os va a gustar. Nos vemos en septiembre, no. O quizás en julio.

No sé cómo hemos llegado a 600 programas, ni cómo hemos llegado vivos. Ha sido una temporada emocionante en la que os hemos sentido desde el principio. Os regalamos este especial con toda vuestra banda de idiotas favorita, incluyendo alguna sorpresa que os va a gustar. Nos vemos en septiembre, no. O quizás en julio.

Podcast Mayhem 010 - Com Carlos Brasilio Conte - Pitágoras e a Escola Pitagórica https://projetomayhem.com.br/ O vídeo desta conversa está disponível em: https://youtu.be/FFwmiuq5fkY Bate Papo Mayhem é um projeto extra desbloqueado nas Metas do Projeto Mayhem.  Todas as 3as, 5as e Sabados as 21h os coordenadores do Projeto Mayhem batem papo com algum convidado sobre Temas escolhidos pelos membros, que participam ao vivo da conversa, podendo fazer perguntas e colocações. Os vídeos ficam disponíveis para os membros e são liberados para o público em geral duas vezes por semana, às segundas e quintas feiras e os áudios são editados na forma de podcast e liberados uma vez por semana. Faça parte do projeto Mayhem: https://www.catarse.me/tdc

+ Del Evangelio según san Lucas +En aquel tiempo Jesús dijo esta parábola a los escribas y fariseos. ¿Quién de vosotros que tiene cien ovejas, si pierde una de ellas, no deja las 99 en el desierto, y va a buscar la que se perdió hasta que la encuentra? Y cuando la encuentra, la pone contento sobre sus hombros; y llegando a casa, convoca a los amigos y vecinos, y les dice: "Alegraos conmigo, porque he hallado la oveja que se me había perdido." Os digo que, de igual modo, habrá más alegría en el cielo por un solo pecador que se convierta que por noventa y nueve justos que no tengan necesidad de conversión.Palabra del Señor.

Neste episódio selvagem do Kubicast, nos embrenhamos na mata fechada dos sistemas distribuídos ao lado de Flávio Mendes, criador do Trilhainfo. De uma floresta irlandesa direto para sua timeline, o Flávio trouxe um papo afiado sobre arquitetura de sistemas, desafios reais e boas práticas para não cair nas armadilhas do overengineering.Conversamos sobre como evoluir de um monolito para microsserviços sem perder o fôlego, quais as pegadinhas comuns ao lidar com sistemas distribuídos em produção, e como manter a sanidade num ambiente crítico com SLAs apertados. Tudo com bom humor, exemplos práticos e aquele clima descontraído que você já conhece.Se você trabalha com arquitetura, cloud, engenharia ou está pensando em escalar seu sistema, esse papo é para você.Links Importantes:- Flávio Mendes- TrilhaInfo - João Brito- Assista ao FilmeTEArapiaParticipe de nosso programa de acesso antecipado e tenha um ambiente mais seguro em instantes!https://getup.io/zerocveO Kubicast é uma produção da Getup, empresa especialista em Kubernetes e projetos open source para Kubernetes. Os episódios do podcast estão nas principais plataformas de áudio digital e no YouTube.com/@getupcloud.

Luke Cook is an actor, comedian, wellness enthusiast, and creator best known for his roles in Chilling Adventures of Sabrina and the new series Good Cop/Bad Cop, as well as co-founder of the clean-label protein company Shakewell.15 Daily Steps to Lose Weight and Prevent Disease PDF: https://bit.ly/46XTn8f - Get my FREE eBook now!Subscribe to The Genius Life on YouTube! - http://youtube.com/maxlugavereWatch my new documentary Little Empty Boxes - http://littleemptyboxes.comThis episode is proudly sponsored by:AG1 is my favorite multivitamin. Enjoy a free 1 year supply of vitamin D and 5 free AG1 travel packs with your first purchase. All you have to do is visit drinkag1.com/GENIUS.Puori provides IFOS-certified, high potency fish oil to satisfy all of your omega-3 needs! Plus a ton of other high quality, rigorously tested supplements. Visit ⁠Puori.com/MAX⁠ and use promo code MAX to get 20% off site-wide.First Light Farms produces beautiful, delicious, grass-fed meats on their pristine New Zealand farm, and ships them straight to your doorstep. Visit http://firstlight.farm and use code MAX15 for 15% off.Shopify makes it easy to accept payments, manage orders, and build relationships with customers (cha-ching!). Get everything you need to sell in person and online at http://shopify.com/genius and get a one-dollar-per-month trial period!OneSkin is a skincare company for minimalists utilizing their revolutionary OS-01 peptide which can reverse signs of skin aging according to their research. Visit http://oneskin.co/max and use code MAX for 15% off.Pique makes quadruple toxin-screened, cold extracted, and uber-delicious matcha for an all-day energy boost without the jitters! Head to http://piquelife.com/genius for up to 15% off.

Tillbakablickarna och ny-reflektionernahaglar i denna andra del av vårt Jubiléum:Betyder Musiken ingenting för vissa? ”It's just a song” ?Vad har Chris lärt sig på kort tid?Är att spela på gatan en HÅRD men nyttig skola?Skäller inte Chris ut folk längre, som inte sköter sig på repet?Har vi löst frågan om hur folk diggar sin musik med huvudet,Framåt eller bakåt?OS-invigningen tar vi också hand om.Vi strävar framåt och utlovar nytt och intressant innehålloch vad vi strävar efter i säsong 6 som står för dörren.TACK alla som lyssnar, vi är helt enkelt oerhört tacksammaför denna möjlighet att sprida musikglädje till er.Mycket välkomna!Vill du ha din låt uppspelad direktmed tillhörande analys.Maila oss låtlänk + info om projektet till: Musiksnacket@iwm.seLänk till Spellista:https://open.spotify.com/playlist/25dSufz7mpKXI0vbMclpgz?si=77c7b74518db43fd#recension #analyser #musik #analys #spotify #Podcast #podd #musiksnacket #Artist #Musiker #scen #studio #AI

Os convidados do programa Pânico dessa quarta-feira (25) são Prof. Noslen Borges e ⁠Fernando De Borthole.Professor Noslen BorgesNoslen Borges é um dos maiores comunicadores da área educacional no Brasil. Criador do maior canal de ensino de língua portuguesa do mundo e do maior canal de educação do país, acumula mais de 5 milhões de inscritos e 400 milhões de visualizações no YouTube. Formado em Letras, com mais de 20 anos de atuação em sala de aula, Noslen se reinventou nas redes sociais, onde passou a ensinar de forma moderna, criativa e acessível. Hoje, leva essa mesma energia para os palcos: suas palestras e aulões combinam conteúdo, humor e inspiração, sempre com uma linguagem atual e próxima dos estudantes.Fenômeno no YouTube, o Prof. Noslen Borges lança o primeiro livro Português para não pagar mico pelo Grupo Editorial Citadel. Na obra, o autor transmite a didática leve e bem-humorada dos vídeos para as páginas, com o dinamismo da comunicação descontraída dos jovens e das redes sociais.Com QR Codes que direcionam os leitores para videoaulas exclusivas, Português para não pagar mico é destinado especialmente a estudantes, concurseiros e profissionais que desejam se comunicar com mais precisão. A comunicação objetiva, os exemplos corriqueiros e o estilo descontraído característico do Prof. Noslen Borges tornam o aprendizado mais eficaz, mesmo para quem carrega bloqueios antigos com a gramática tradicional. Mais do que ensinar regras, ele mostra a importância de enxergar a língua portuguesa como uma aliada na busca de oportunidades.Redes Sociais:Instagram: https://www.instagram.com/professornoslen/YouTube: https://www.youtube.com/@ProfessorNoslenFernando De BortholeCom uma carreira que decola há mais de duas décadas, o aviador, empreendedor e produtor audiovisual Fernando De Borthole consolidou-se como uma das principais vozes da aviação no Brasil e no mundo. Reconhecido por sua capacidade única de unir expertise técnica com uma comunicação acessível e envolvente, Fernando transformou a complexidade do setor aeronáutico em conteúdo fascinante para milhões de espectadores e seguidores.Desde a criação do aclamado programa "Aero – Por Trás da Aviação", que se tornou um fenômeno digital e multiplataformas, Borthole tem levado o público a uma jornada inédita pelos bastidores da aviação. Com mais de 20 anos de experiência como piloto, sua formação em Aviação Civil pela Universidade Anhembi Morumbi (2004) e especialização em produção audiovisual na Vancouver Film School, no Canadá, fundamentaram a base de seu trabalho inovador.Além do sucesso estrondoso de "Aero – Por Trás da Aviação", que lhe rendeu o Prêmio ABEAR de Jornalismo em 2015 e o Prêmio iBest 2024 na categoria "Influenciador Automotivo e de Transportes", Fernando De Borthole é sócio da Escola Superior do Ar (EAR), a única faculdade 100% focada em educação aeronáutica no país. Ele também é parceiro do Projeto Transplantar, iniciativa que viabiliza o uso de aeronaves privadas para o transporte urgente de órgãos para transplante, demonstrando seu compromisso com causas sociais de grande impacto. Em 2024, foi agraciado com a Medalha Santos Dumont, em reconhecimento à sua notável contribuição para a divulgação da cultura aeronáutica.Sua presença constante na mídia, incluindo participações em programas de TV como Jornal Nacional, Encontro com Patrícia Poeta, CNN Brasil, e em podcasts populares como Flow Podcast e Ticaracaticast, solidifica sua posição como um comunicador respeitado e uma autoridade incontestável no setor.Fernando De Borthole continua a expandir fronteiras, com projetos que transcendem o ambiente digital e contribuem significativamente para a educação e a conscientização sobre a aviação, sempre com o objetivo de inspirar novas gerações e fortalecer a imagem de um dos setores mais vitais da economia global.Redes Sociais:Instagram: https://www.instagram.com/programaaero/Youtube: https://www.youtube.com/@aeroportrasdaaviacao

Episodio 324. Hay una gran cantidad de teoremas divertidamente arbitrarios que dicen que mi baticinturón pila, en términos de lo que jala, me deja amarrado como un perrito a la pared con una cola USB C que me la pongo en la espalda y está bien. La odio y está ahí desde hace siempre, pero me da miedo quitarla y que se apague la luz.

Os petistas Lindbergh Farias, Gleisi Hoffmann e Fernando Haddad voltaram a defender o decretodo governo que aumenta o IOF, em meio à movimentação no Congresso contra a medida.Lindbergh e Haddad recorreram ao discurso da luta de classes, enquanto Gleisi afirmou que  a derrubada do decreto pode “prejudicar” a execução de emendas.Felipe Moura Brasil, Dennys Xavier e Ricardo Kertzman comentam:Papo Antagonista é o programa que explica e debate os principais acontecimentos do   dia com análises críticas e aprofundadas sobre a política brasileira e seus bastidores.     Apresentado por Felipe Moura Brasil, o programa traz contexto e opinião sobre os temas mais quentes da atualidade.     Com foco em jornalismo, eleições e debate, é um espaço essencial para quem busca informação de qualidade.     Ao vivo de segunda a sexta-feira às 18h.    Apoie o jornalismo Vigilante: 10% de desconto para audiência do Papo Antagonista  https://bit.ly/papoantagonista  Siga O Antagonista no X:  https://x.com/o_antagonista   Acompanhe O Antagonista no canal do WhatsApp. Boletins diários, conteúdos exclusivos em vídeo e muito mais.  https://whatsapp.com/channel/0029Va2SurQHLHQbI5yJN344  Leia mais em www.oantagonista.com.br | www.crusoe.com.br 

Os dois países cantaram vitória na guerra, mas solução definitiva ocorreu somente por intermédio dos Estados UnidosMeio-Dia em Brasília traz as principais notícias e análises da política nacional direto   de Brasília.     Com apresentação de José Inácio Pilar e Wilson Lima, o programa aborda os temas mais quentes do cenário político e econômico do Brasil.     Com um olhar atento sobre política, notícias e economia, mantém o público bem informado.   Transmissão ao vivo de segunda a sexta-feira às 12h.   Apoie o jornalismo Vigilante: 10% de desconto para audiência do Meio-Dia em Brasília   https://bit.ly/meiodiaoa   Siga O Antagonista no X:  https://x.com/o_antagonista   Acompanhe O Antagonista no canal do WhatsApp. Boletins diários, conteúdos exclusivos em vídeo e muito mais.  https://whatsapp.com/channel/0029Va2SurQHLHQbI5yJN344  Leia mais em www.oantagonista.com.br | www.crusoe.com.br 

Dr. Vamsi Velcheti and Dr. Nate Pennell discuss novel treatment approaches in small cell and non-small cell lung cancer that were featured at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Vamsi Velcheti: Hello, I'm Dr. Vamsi Velcheti, your guest host of the ASCO Daily News Podcast. I'm a professor of medicine and chief of hematology and oncology at the Mayo Clinic in Jacksonville, Florida. The 2025 ASCO Annual Meeting featured some exciting advancements in small cell lung cancer, targeted therapies for non-small cell lung cancer, and other novel [treatment] approaches. Today, I'm delighted to be joined by Dr. Nate Pennell to discuss some of the key abstracts that are advancing the lung cancer field. Dr. Pennell is the co-director of the Cleveland Clinic Lung Cancer Program and also the vice chair of clinical research at the Taussig Cancer Institute. Our full disclosures are available in the transcript of this episode. Nate, it's great to have you back on the podcast. Thanks so much for being here. Dr. Nate Pennell: Thanks, Vamsi. Always a pleasure. Dr. Vamsi Velcheti: Let's get started, and I think the first abstract that really caught my attention was Abstract 8516, “The Randomized Trial of Relevance of Time of Day of Immunotherapy for Progression-Free and Overall Survival in Patients With Non-Small Cell Lung Cancer.” What are your thoughts about this, Nate? Dr. Nate Pennell: I agree. I thought this was one of the most discussed abstracts, certainly in the lung cancer session, but I think even outside of lung cancer, it got some discussion. So, just to put this in perspective, there have been a number of publications that have all been remarkably consistent, and not just in lung cancer but across multiple cancer types, that immunotherapy, immune checkpoint inhibitors, are commonly used. And all of them have suggested, when looking at retrospective cohorts, that patients who receive immune checkpoint inhibitors earlier in the day – so in the morning or before the early afternoon – for whatever reason, appear to have better outcomes than those who get it later in the day, and this has been repeated. And I think many people just sort of assumed that this was some sort of strange association and that there was something fundamentally different from a prognostic standpoint in people who came in in the morning to get their treatment versus those who came later in the afternoon, and that was probably the explanation. The authors of this randomized trial actually decided to test this concept. And so, about 210 patients with previously untreated advanced non-small cell lung cancer were randomly assigned to get chemo and immune checkpoint inhibitor – either pembrolizumab or sintilimab – and half of them were randomly assigned to get the treatment before 3 PM in the afternoon, and half of them were assigned to get it after 3 PM in the afternoon. And it almost completely recapitulated what was seen in the retrospective cohorts. So, the median progression-free survival in those who got earlier treatment was 13.2 months versus only 6.5 months in those who got it later in the day. So, really enormous difference with a hazard ratio of 0.43, which was statistically significant. And perhaps even more striking, the median overall survival was not reached in the early group versus 17.8 months in the late group with a hazard ratio of 0.43, also highly statistically significant. Even the response rate was 20% higher in the early patients; 75% response rate compared to 56% in the late-time-of-day patients. So very consistent across all measures of efficacy with pretty good matched characteristics across the different groups. And so, I have to tell you, I don't know what to make of this. I certainly was a skeptic about the retrospective series, but now we have a prospective randomized trial that shows essentially the same thing. So, maybe there is a difference between getting treated in the morning, although I have yet to hear someone give a very good mechanistic explanation as to why this would be. What were your thoughts on this? Dr. Vamsi Velcheti: It's indeed fascinating, Nate, and I actually think this was a very interesting abstract. Really, I was caught off guard looking at the data. I mean, if it were a drug, we would be so excited, right? I mean, with those kind of survival benefits. I don't know. I think circadian rhythm probably has something to do with it, like different cytokine profiles at the time of administration. I mean, who knows? But I think it's a randomized trial, and I think I would expect to see a mad rush for treatment appointments early in the morning given this, and at least I want my patients to come in first thing in the morning. It'll be interesting to see. Dr. Nate Pennell: It's important to point out that in this study, everyone got chemo and immunotherapy. And, at least in our cancer center, most patients who are getting platinum-doublet chemotherapy and immunotherapy actually do get treated earlier in the day already, just because of the length of the infusion appointment that's needed. So it really is oftentimes people getting single-agent immunotherapy who are often getting the later, shorter visits. But if you have a choice, I think it would be very reasonable to have people treated earlier in the day. And I do think most of the impressions that I got from people about this is that they would like to see it reproduced but certainly well worth further investigation. And I personally would like to see more investigation into what the rationale would be for this because I still can't quite figure out, yes, if you got it at, say, you know, 5 PM, that's later in the day and I can understand that maybe your immune system is somewhat less receptive at that point than it would be in the morning. But because these checkpoint inhibitors have such long half-lives, it's still in your system the next morning when your immune system is supposedly more receptive. So I don't quite understand why that would be the case. Well, let's move on to the next study. I would like to hear your thoughts on Abstract 8515, “Plasma-Guided, Adaptive First-Line Chemoimmunotherapy for Non-Small Cell Lung Cancer.” Dr. Vamsi Velcheti: Yeah, this was another abstract that seems to be really interesting in my opinion. I think there's kind of a lot of emphasis lately on ctDNA and MRD-based assays to monitor disease. In the lung cancer space, we haven't had a lot of clinical trials looking at this prospectively, and this was one of those pilot studies where they looked at circulating free DNA (cfDNA)-based response-adaptive strategy for frontline patients who are PD-L1 positive. So, patients started with pembrolizumab monotherapy, and based on plasma molecular response after 2 cycles, those patients without response received early treatment intensification with a platinum doublet. So the approach essentially was to reduce the chemotherapy exposure in patients who respond to immunotherapy. And only about 17.5% of the patients on the trial received chemotherapy based on lack of molecular response. So, in this trial, what they found was patients with the cfDNA response had a markedly improved PFS of 16.4 months versus 4.8 months. So essentially, like, this is a really nice study to set a foundation on which we have to do larger studies to incorporate molecular markers trying to look at cfDNA response to inform treatment strategy, either escalation or de-escalation strategies. So, I thought it was a very interesting study. Dr. Nate Pennell: Yeah. I mean, we always have this question for patients, “Should they get immunotherapy alone or combined with chemo?” and I think this certainly is intriguing, suggesting that there may be ways you can monitor people and perhaps rescue those that aren't going to respond to single agent. I'd like to see a randomized trial against, you know, this strategy, perhaps against everyone getting, say, chemoimmunotherapy or make sure that you're not potentially harming people by doing this strategy. But I agree, it's time to move beyond just observing that cell-free DNA is prognostic and important and start using it to actually guide treatment. Dr. Vamsi Velcheti: Yeah, and I would just caution though, like, you know, I think we need more data, but, however, it's certainly a very interesting piece of data to kind of help inform future trials. So, there was another abstract that caught my attention, and I think this would be a very interesting abstract in the EGFR space. Abstract 8506, "Patritumab Deruxtecan (HER3-DXd) in Resistant EGFR-Mutant Advanced Non-Small Cell Lung Cancer Patients After Third-Generation EGFR TKI," it's the HERTHENA-Lung02 study. What do you think about the results of this study? Dr. Nate Pennell: Yeah, this was, I would say, very widely anticipated and ultimately a little disappointing, despite being a positive trial. So, these are patients with EGFR-mutant non-small cell lung cancer who have progressed after a third-generation EGFR TKI like osimertinib. This is really an area of major unmet need. We do have drugs like amivantamab in this space, but still definitely an area where essentially patients move from having a highly effective oral therapy to being in the realm of chemotherapy as their best option. So, this HER3 antibody-drug conjugate, patritumab deruxtecan, had some good single-arm data for this. And we're sort of hoping this would become an available option for patients. This trial was designed against platinum-doublet chemotherapy in this setting and with a primary endpoint of progression-free survival. And it actually was positive for improved progression-free survival compared to chemo with a hazard ratio of 0.77. But when you look at the medians, you can see that the median PFS was only 5.8 versus 5.4 months. It was really a modest difference between the two arms. And on the interim analysis, it appeared that there will not be a difference in overall survival between the two arms. In fact, the hazard ratio at the interim analysis was 0.98 for the two arms. So based on this, unfortunately, the company that developed the HER3-DXd has withdrawn their application to the FDA for approval of the drug, anticipating that they probably wouldn't get past approval without that overall survival endpoint. So, unfortunately, probably not, at least for the near future, going to be a new option for these patients. Dr. Vamsi Velcheti: Yeah, I think this is a space that's clearly an unmet need, and this was a big disappointment, I should say. I think all of us were going into the meeting anticipating some change in the standard of care here. Dr. Nate Pennell: Yeah, I agree. It was something that I was telling patients, honestly, that I was expecting this to be coming, and so now, definitely a bit of a disappointment. But it happens and, hopefully, it will still find perhaps a role or other drugs with a similar target. Certainly an active area. Well, let's leave the EGFR-mutant space and move into small cell. There were a couple of very impactful studies. And one of them was Abstract 8006, “Lurbinectedin Plus Atezolizumab as First-Line Maintenance Treatment in Patients With Extensive-Stage Small Cell Lung Cancer, Primary Results from the Phase III IMforte Trial.” So, what was your impression of this? Dr. Vamsi Velcheti: Yeah, I think this is definitely an interesting study, and small cell, I remember those days when we had barely any studies of small cell at ASCO, and now we have a lot of exciting developments in the small cell space. It's really good to see. The IMforte trial is essentially like a maintenance lurbinectedin trial with atezolizumab maintenance. And the study was a positive trial. The primary endpoint was a PFS, and the study showed improvement in both PFS and OS with the addition of lurbinectedin to atezolizumab maintenance. And definitely, it's a positive trial, met its primary endpoint, but I always am a little skeptical of adding maintenance cytotoxic therapies here in this setting. In my practice, and I'd like to hear your opinion, Nate, most patients with small cell after 4 cycles of a platinum doublet, they're kind of really beaten up. Adding more cytotoxic therapy in the maintenance space is going to be tough, I think, for a lot of patients. But also, most importantly, I think this rapidly evolving landscape for patients with small cell lung cancer with multiple new, exciting agents, actually like some FDA-approved like tarlatamab, also like a lot of these emerging therapeutics like I-DXd and other ADCs in this space. You kind of wonder, is it really optimal strategy to bring on like another cytotoxic agent right after induction chemotherapy, or do you kind of delay that? Or maybe have like a different strategy in terms of maintenance. I know that the tarlatamab maintenance trial is probably going to read out at some point too. I think it's a little challenging. The hazard ratio is also 0.73. As I said, it's a positive trial, but it's just incremental benefit of adding lurbi. And also on the trial, we need to also pay attention to the post-progression second-line treatments, number of patients who received tarlatamab or any other investigational agents.  So I think it's a lot of questions still. I'm not quite sure I'd be able to embrace this completely. I think a vast majority of my patients might not be eligible anyway for cytotoxic chemotherapy maintenance right away, but yeah, it's tough. Dr. Nate Pennell: Yeah. I would call this a single and not a home run. It definitely is real. It was a real overall survival benefit. Certainly not surprising that a maintenance therapy would improve progression-free survival. We've known that for a long time in small cell, but first to really show an overall survival benefit. But I completely agree with you. I mean, many people are not going to want to continue further cytotoxics after 4 cycles of platinum-doublet chemo. So I would say, for those that are young and healthy and fly through chemo without a lot of toxicity, I think certainly something worth mentioning. The problem with small cell, of course, is that so many people get sick so quickly while on that observation period after first-line chemo that they don't make it to second-line treatment. And so, giving everyone maintenance therapy essentially ensures everyone gets that second-line treatment. But they also lose that potentially precious few months where they feel good and normal and are able to be off of treatment. So, I would say this is something where we're really going to have to kind of sit and have that shared decision-making visit with patients and decide what's meaningful to them. Dr. Vamsi Velcheti: Yeah, I agree. The next abstract that was a Late-Breaking Abstract, 8000, “Overall Survival of Neoadjuvant Nivolumab Plus Chemotherapy in Patients With Resectable Non-Small Cell Lung Cancer in CheckMate-816.” This was a highly anticipated read-out of the OS data from 816. What did you make of this abstract? Dr. Nate Pennell: Yeah, I thought this was great. Of course, CheckMate-816 changed practice a number of years ago when it first reported out. So, this was the first of the neoadjuvant or perioperative chemoimmunotherapy studies in resectable non-small cell lung cancer. So, just to review, this was a phase 3 study for patients with what we would now consider stage II or stage IIIA resectable non-small cell lung cancer. And they received three cycles of either chemotherapy or chemotherapy plus nivolumab, and that was it. That was the whole treatment. No adjuvant treatment was given afterwards. They went to resection. And patients who received the chemoimmunotherapy had a much higher pathologic complete response rate and a much better event-free survival. And based on this, this regimen was approved and, I think, at least in the United States, widely adopted.  Now, since the first presentation of CheckMate 816, there have been a number of perioperative studies that have included an adjuvant component of immunotherapy – KEYNOTE-671, the AEGEAN study – and these also have shown improved outcomes. The KEYNOTE study with pembrolizumab also with an overall survival benefit. And I think people forgot a little bit about CheckMate-816. So, this was the 5-year overall survival final analysis. And it did show a statistically and, I think, clinically meaningful difference in overall survival with the 3 cycles of neoadjuvant chemo-nivo compared to chemo with a hazard ratio of 0.72. The 5-year overall survival of 65% in the chemo-IO group versus 55% with the chemo alone. So a meaningful improvement. And interestingly, that hazard ratio of 0.72 is very similar to what was seen in the peri-operative pembro study that included the adjuvant component. So, very much still relevant for people who think that perhaps the value of those neoadjuvant treatments might be really where most of the impact comes from this type of approach. They also gave us an update on those with pathologic complete response, showing really astronomically good outcomes. If you have a pathologic complete response, which was more than a quarter of patients, the long-term survival was just phenomenal. I mean, 95% alive at 5 years if they were in that group and suggesting that in those patients at least, the adjuvant treatment may not be all that important.  So, I think this was an exciting update and still leaves very much the open question about the importance of continuing immunotherapy after surgery after the neoadjuvant component. Dr. Vamsi Velcheti: Yeah, I completely agree, Nate. I think the million-dollar question is: “Is there like a population of patients who don't have complete response but like maybe close to complete response?” So, would you like still consider stopping adjuvant IO? I probably would not be comfortable, but I think sometimes, you know, we all have patients who are like very apprehensive of continuing treatments. So, I think that we really need more studies, especially for those patients who don't achieve a complete CR. I think trying to find strategies for like de-escalation based on MRD or other risk factors. But we need more trials in that space to inform not just de-escalation, but there are some patients who don't respond at all to a neoadjuvant IO. So, there may be an opportunity for escalating adjuvant therapies. So, it is an interesting space to watch out for. Dr. Nate Pennell: No, absolutely. Moving to KRAS-mutant space, so our very common situation in patients with non-small cell lung cancer, we had the results of Abstract 8500, “First-Line Adagrasib With Pembrolizumab in Patients With Advanced or Metastatic KRASG12C-Mutated Non-Small Cell Lung Cancer” from the phase 2 portion of the KRYSTAL-7 study. Why was this an interesting and important study? Dr. Vamsi Velcheti: First of all, there were attempts to kind of combine KRASG12C inhibitors in the past with immune checkpoint inhibitors, notably sotorasib with pembrolizumab. Unfortunately, those trials have led to like a lot of toxicity, with increased especially liver toxicity, which was a major issue. This is a phase 2 study of adagrasib in combination with pembrolizumab, and this is a study in the frontline setting in patients with the G12C-mutant metastatic non-small cell lung cancer. And across all the PD-L1 groups, the ORR was 44%, and the median PFS was 11 months, comparable to the previous data that we have seen with adagrasib in this setting. So it's not like a major improvement in clinical efficacy. However, I think the toxicity profile that we were seeing was slightly better than the previous trials in combination with sotorasib, but you still have a fair amount of transaminitis even in the study. At this point, this is not ready for clinical primetime. I don't think we should be using sotorasib or adagrasib in the frontline or even in the second line in combination with checkpoint inhibitors. Combining these drugs with checkpoint inhibitors in the clinical practice might lead to adverse outcomes. So, we need to wait for more data like newer-generation G12C inhibitors which are also being studied in combination, so we'll have to kind of wait for more data to emerge in this space. Dr. Nate Pennell: I agree, this is not immediately practice changing. This is really an attempt to try to combine targeted treatment with immune checkpoint inhibitor. And I agree with you that, you know, it does appear to be perhaps a little bit better tolerated than some of the prior combinations that have tried in this space. The outcomes overall were not that impressive, although in the PD-L1 greater than 50%, it did have a better response rate perhaps than you would expect with either drug alone. And I do think that the company is focusing on that population for a future randomized trial, which certainly would inform this question better. But in the meantime, I agree with you, there's a lot of newer drugs that are coming along that potentially may be more active and better tolerated. And so, I'd say for now, interesting but we'll wait and see. Dr. Vamsi Velcheti: Yeah, so now moving back again to small cell. So, there was a Late-Breaking Abstract, 8008. This is a study of tarlatamab versus chemotherapy as second-line treatment for small cell lung cancer. They presented the primary analysis of the phase III DeLLphi-304 study. What do you think about this? Dr. Nate Pennell: Yeah, I thought this was really exciting. This was, I would say, perhaps the most important lung study that was presented. Tarlatamab is, of course, the anti-DLL3 bispecific T-cell engager compound, which is already FDA approved based on a prior single-arm phase II study, which showed a very nice response rate as a single agent in previously treated small cell lung cancer and relatively manageable side effects, although somewhat unique to solid tumor docs in the use of these bispecific drugs in things like cytokine release syndrome and ICANS, the neurologic toxicities. So, this trial was important because tarlatamab was approved, but there were also other chemotherapy drugs approved in the previously treated space. And so, this was a head-to-head second-line competition comparison between tarlatamab and either topotecan, lurbinectedin, or amrubicin in previously treated small cell patients with a primary endpoint of overall survival. So, a very well-designed trial. And it did show, I think, a very impressive improvement in overall survival with a median overall survival in the tarlatamab group of 13.6 months compared to 8.3 months with chemotherapy, hazard ratio of 0.6. And progression-free survival was also longer at 4.2 months versus 3.2 months, hazard ratio of 0.72. In addition to showing improvements in cancer-related symptoms that were improved in tarlatamab compared to chemotherapy, there was actually also significantly lower rates of serious treatment-related adverse events with tarlatamab compared to chemotherapy. So, you do still see the cytokine release syndrome, which is seen in most people but is manageable because these patients are admitted to the hospital for the first two cycles, as well as a significant number of patients with neurologic side effects, the so-called ICANS, which also can be treated with steroids. And so, I think based upon the very significant improvement in outcomes, I would expect that this should become our kind of standard second-line treatment since it seems to be much better than chemo. However, tarlatamab is definitely a new drug that a lot of places are not used to using, and I think a lot of cancer centers, especially ones that aren't tied to a hospital, may have questions about how to deal with the CRS. So, I'm curious your thoughts on that. Dr. Vamsi Velcheti: Yeah, thank you, Nate. And I completely agree. I think the data looked really promising, and I've already been using tarlatamab in the second-line space. The durability of response and overall, having used tarlatamab quite a bit - like, I participated in some of the early trials and also used it as standard of care - tarlatamab has unique challenges in terms of like need for hospitalization for monitoring for the first few treatments and make sure, you know, we monitor those patients for CRS and ICANS. But once you get past that initial administration and monitoring of CRS, these patients have a much better quality of life, they're off chemotherapy, and I think it's really about the logistics of actually administering tarlatamab and coordination with the hospital and administration in the outpatient setting. It's definitely challenging, but I think it definitely can be done and should be done given what we are seeing in terms of clinical efficacy here. Dr. Nate Pennell: I agree. I think hospital systems now are just going to have to find a way to be able to get this on formulary and use it because it clearly seems to be more effective and generally better tolerated by patients. So, should move forward, I think. Finally, there's an abstract I wanted to ask you about, Abstract 8001, which is the “Neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone in resectable epidermal growth factor receptor-mutated non-small cell lung cancer: The NeoADAURA Study”. And this is one that I think was also fairly highly anticipated. So, what are your thoughts? Dr. Vamsi Velcheti: You know, I wasn't probably surprised with the results, and I believe we were all expecting a positive trial, and we certainly were handed a positive trial here. It's a phase III trial of osimertinib and chemotherapy or osimertinib in the neoadjuvant space followed by surgery, followed by osimertinib. It's a global phase 3 trial and very well conducted, and patients with stage II to stage IIIB were enrolled in the study. And in the trial, patients who had a neoadjuvant osimertinib with or without chemotherapy showed a significant improvement in major pathologic response rates over chemotherapy alone. And the EFS was also positive for osimertinib and chemotherapy, osimertinib monotherapy as well compared to chemotherapy alone. So overall, the study met its primary endpoint, and I think it sheds light on how we manage our patients with early-stage lung cancer. I think osimertinib, we know that osimertinib is already FDA approved in the adjuvant space, but what we didn't really know is how was osimertinib going to work in the neoadjuvant space. And there are always situations, especially for stage III patients, where we are on the fence about, are these patients already close to being metastatic? They have, like, almost all these patients have micrometastatic disease, even if they have stage III. As we saw in the LAURA data, when you look at the control arm, it was like a very short PFS. Chemoradiation does nothing for those patients, and I think these patients have systemic mets, either gross or micrometastatic disease at onset. So, it's really important to incorporate osimertinib early in the treatment course. And I think, especially for the locally advanced patients, I think it's even more important to kind of incorporate osimertinib in the neoadjuvant space and get effective local control with surgery and treat them with adjuvant. I'm curious to hear your thoughts, Nate. Dr. Nate Pennell: I am a believer and have long been a believer in targeted adjuvant treatments, and, you know, it has always bothered me somewhat that we're using our far and away most effective systemic therapy; we wait until after they go through all their pre-op treatments, they go through surgery, then they go through chemotherapy, and then finally months later, they get their osimertinib, and it still clearly improves survival in the adjuvant setting. Why not just start the osimertinib as soon as you know that the patient has EGFR-mutant non-small cell lung cancer, and then you can move on to surgery and adjuvant treatment afterwards? And I think what was remarkable about this study is that all of these patients almost - 90% in each arm - went to surgery. So, you weren't harming them with the neoadjuvant treatment. And clearly better major pathologic response, nodal downstaging, event-free survival was better. But I don't know that this trial is ever going to show an overall survival difference between neoadjuvant versus just surgery and adjuvant treatment, given how effective the drug is in the adjuvant setting. Nonetheless, I think the data is compelling enough to consider this, certainly for our N2-positive, stage IIIA patients or a IIIB who might be otherwise surgical candidates. I think based on this, I would certainly consider that. Dr. Vamsi Velcheti: Yeah, and especially for EGFR, like even for stage IIIB patients, in the light of the LAURA study, those patients who do not do too well with chemoradiation. So you're kind of delaying effective systemic therapy, as you said, waiting for the chemoradiation to finish. So I think probably time to revisit how we kind of manage these locally advanced EGFR patients. Dr. Nate Pennell: Yep, I agree. Dr. Vamsi Velcheti: Nate, thank you so much for sharing your fantastic insights today on the ASCO Daily News Podcast. It's been an exciting ASCO again. You know, we've seen a lot of positive trials impacting our care of non-small cell lung cancer and small cell lung cancer patients. Dr. Nate Pennell: Thanks for inviting me, Vamsi. Always a pleasure to discuss these with you. Dr. Vamsi Velcheti: And thanks to our listeners for your time today. You will find links to all of the abstracts discussed today in the transcript of the episode. Finally, if you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate, review, subscribe wherever you get your podcast. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. More on today's speakers:    Dr. Vamsi Velcheti   @VamsiVelcheti    Dr. Nathan Pennell   @n8pennell   Follow ASCO on social media:     @ASCO on Twitter     ASCO on Facebook     ASCO on LinkedIn   ASCO on BlueSky   Disclosures:   Dr. Vamsi Velcheti:   Honoraria: ITeos Therapeutics   Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus   Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline   Dr. Nathan Pennell:     Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron    Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi 

Está no ar, o Data Hackers News !! Os assuntos mais quentes da semana, com as principais notícias da área de Dados, IA e Tecnologia, que você também encontra na nossa Newsletter semanal, agora no Podcast do Data Hackers !!Aperte o play e ouça agora, o Data Hackers News dessa semana !Para saber tudo sobre o que está acontecendo na área de dados, se inscreva na Newsletter semanal:⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.datahackers.news/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Links mencionados:⁠Breaking Data Hackers - com a SnowflakeConheça nossos comentaristas do Data Hackers News:⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Monique Femme⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Paulo VasconcellosDemais canais do Data Hackers:⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Site⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Linkedin⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Instagram⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Tik Tok⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠You Tube⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠

Os franceses são rudes? Se vestem sempre bem? Estão sempre com uma baguete debaixo do braço?Neste episódio, vamos conversar sobre os estereótipos mais comuns sobre os franceses — e separar o que é mito do que realmente faz parte da cultura. Uma ótima forma de entender melhor o povo, os costumes e até mesmo como evitar gafes culturais.Se você sonha em conhecer a França ou já está aprendendo a língua, esse papo vai te ajudar a ir além do clichê e se aproximar de um olhar mais verdadeiro sobre o país.

Agradece a este podcast tantas horas de entretenimiento y disfruta de episodios exclusivos como éste. ¡Apóyale en iVoox! Hablamos del fenómeno desconocido, controvertido pero muy interesante que es el Missing Time. Os contamos casos que hemos investigado de primera mano. laruedadelmisterio2010@gmail.com ®© La Rueda del MisterioEscucha este episodio completo y accede a todo el contenido exclusivo de La Rueda del Misterio. Descubre antes que nadie los nuevos episodios, y participa en la comunidad exclusiva de oyentes en https://go.ivoox.com/sq/4754

Desde o início do atual mandato do presidente Luiz Inácio Lula da Silva, em janeiro de 2023, as estatais brasileiras criaram 273 novos cargos abertos à indicação política, segundo levantamento exclusivo do Estadão. Os postos são usados para empregar petistas, figuras ligadas aos partidos da base e familiares. O custo dessa expansão é de pelo menos R$ 206 milhões por ano, se contabilizados salários e benefícios, e abrange 16 empresas. "É muita coisa. Esses cargos são para políticos do PT, da base aliada e a familiares deles, em grandes empresas brasileiras - como DataPrev e Petrobras. Para piorar, o déficit das estatais no ano passado foi de R$ 6,7 bilhões. O Mensalão foi todo em cima de o governo Lula 'metendo a mão' para favorecer políticos e partidos aliados", diz Cantanhêde.See omnystudio.com/listener for privacy information.

Randonáutica ha vuelto y nos ha traído nuevos casos, cada cual más terrorífico que el anterior. Os recomendamos no solo escuchar el capítulo, sino verlo también en el videopodcast que tenéis en Spotify o nuestro canal de Youtube. ¿Te atreverías a utilizar esta aplicación? ¡No te olvides de hacerte mecenas para tener además UN CAPÍTULO EXTRA cada semana! https://open.spotify.com/show/0azaM9tNLAiMKrFK6ZMlS1?si=e3d6fdb722c14844 Recuerda que puedes ver el videopodcast de este capítulo en nuestro canal de Youtube  https://www.youtube.com/@Terrores_TRN Ya a la venta el libro de Terrores Nocturnos “La españa Misteriosa”, en el que recopilamos los mejores casos paranormales, crímenes y lugares embrujados de nuestro país  https://bit.ly/3EkjU2u  Síguenos en nuestras redes sociales y escríbenos a nuestro correo: Instagram: @terroresnocturnos.trn Tiktok: @terroresnocturnos.trn Youtube: Terrores_TRN Twitter: @Terrores_TRN Twitch: terrores_trn Instagram Emma Entrena: @emma.e_trn Instagram Silvia Ortiz: @sil_trn Facebook: Terrores Nocturnos Correo: terroresnocturnosradio@gmail.com Presentado por Emma Entrena y Silvia Ortiz, producido por Yes We Cast e ilustrado por The Gray (@danionlybars) Learn more about your ad choices. Visit megaphone.fm/adchoices

If your fundraising strategy still runs on 2010 logic, this is your wake-up call. In this episode, I break down the concept of NextGen Fundraising—not just for Gen Z, but for every generation of donor who now expects fast, friction-free, modern giving experiences. I share why traditional tactics are burning you out, why your board doesn't need another gala, and how to cut the clutter and focus on what actually works. Get ready for mindset shifts, strategy overhauls, and some tough love on why clinging to the past is costing you funding. If your nonprofit is still waiting on permission, outdated systems, or “someday” grants—this one's for you.Topics:What “NextGen Fundraising” really meansWhy traditional fundraising tactics are failing — and how donor habits have shifted fasterThe outdated “fundraising OS” most orgs are still usingThe myth of long cultivation cyclesWhy chasing new donors while losing your current ones is the ultimate leaky bucketWhat nonprofit leaders can learn from Shopify and AmazonHow to use Social Street Team® to expand reachWhy being grant-dependent is a risk, not a strategy — and what to do right now if you've lost a major funder's supportReal wins from real nonprofitsWhy holding out for board meetings or retreats is costing you more than you realizeFor a full list of links and resources mentioned in this episode, click here.Bloomerang is the complete donor, volunteer, and fundraising management solution that helps thousands of nonprofits deliver a better giving experience and create sustainable, thriving organizations. Combining robust, easy-to-use technology with people-powered support and training, Bloomerang empowers nonprofits to work efficiently, improve supporter relationships, and grow their donor and volunteer bases. Learn more here. What's Actually Working in 2025 - Free Registration HereResources: Purpose & Profit Club® Coaching Program [Get on the waitlist for bonuses] The SPRINT Method™: Your shortcut to 10K fundraisers [details here] Instagram, LinkedIn, website , weekly newsletter [FREE] The Brave Fundraiser's Guide: Stop getting ignored. Start raising more. May contain affiliate links

Updating developer tools is essential for developers who want to stay efficient, secure, and competitive. In this episode of Building Better Developers with AI, Rob Broadhead and Michael Meloche explore how maintaining modern toolsets helps individuals and teams deliver better software, faster. With support from AI-generated analysis and real-world experience, they outline the risks of falling behind—and how to move forward. Listen to the full episode of Building Better Developers with AI for practical insights and ideas you can start applying today. Efficiency and Profitability When Updating Developer Tools AI captured the core message well: using outdated tools slows down delivery, creates unnecessary friction, and ultimately reduces profitability. For side hustlers and teams alike, this loss of efficiency can make or break a project. Rob pointed out that many developers begin their careers using only basic tools. Without proper exposure to modern IDEs like IntelliJ, Visual Studio Code, or Eclipse, they miss out on powerful features such as debugging tools, plugin support, container integration, and real-time collaboration. Warning Signs You Should Be Updating Developer Tools How do you know it's time to update your development tools? Rob and Michael discussed key red flags: Frequent crashes or poor performance Lack of support for modern languages or frameworks Weak integration with tools like GitHub Actions or Docker Outdated or unsupported plugins Inconsistent tooling across team members Neglecting to update developer tools can lead to slow onboarding, poor collaboration, and increased bugs—especially in fast-paced or regulated environments. Tool Standardization vs. Flexibility When Updating Tools There's a balance between letting developers choose their tools and ensuring consistency across a team. While personal comfort can boost productivity, it may also cause challenges when teams debug or collaborate. Rob and Michael recommend hosting internal hackathons to explore new toolchains or standardize workflows. These events give teams a structured way to evaluate tools and share findings. The Security Risk of Not Updating Developer Tools Michael highlighted that outdated tooling doesn't just slow developers down—it creates serious security and compliance risks. Being just one or two versions behind can open vulnerabilities that violate standards like HIPPA, OWASP or SOX. Regular updates to SDKs, plugins, and IDEs are essential for staying compliant, especially in sensitive industries like finance or healthcare. How to Evaluate New Tools Before Updating Developer Toolchains Rob offered a practical framework for evaluating new tools: Does it solve a real pain point? Start with a side project or proof of concept. Check for strong community support and documentation. Balance between stable and innovative. Michael added a note of caution: avoid adopting tools with little community activity or long-term support. If a GitHub project has only a couple of contributors and poor maintenance, it's a red flag. Developer Tools to Review and Update Regularly To keep your development environment current, Rob suggested reviewing these tool categories often: IDEs and code editors Version control tools CI/CD systems and build automation Testing and QA frameworks Package managers and dependency systems Containerization and environment management platforms Using AI to convert simple apps into different frameworks can also help evaluate new tools—just make sure not to share proprietary code. Final Thoughts Modern development demands modern tooling. From cleaner code to faster deployment and stronger team collaboration, the benefits of updating developer tools are clear. Whether you're an independent developer or part of a larger organization, regularly reviewing and upgrading your toolset is a habit worth forming. Stay Connected: Join the Developreneur Community We invite you to join our community and share your coding journey with us. Whether you're a seasoned developer or just starting, there's always room to learn and grow together. Contact us at info@develpreneur.com with your questions, feedback, or suggestions for future episodes. Together, let's continue exploring the exciting world of software development. Additional Resources Navigating Communication Tools in Modern Workplaces Building a Portable Development Environment That is OS-agnostic Modern Tools For Monetizing Content Updating Developer Tools: Keeping Your Tools Sharp and Efficient Building Better Developers With AI Podcast Videos – With Bonus Content

Dr. Shaalan Beg and Dr. Kristen Ciombor discuss practice-changing studies in GI cancers and other novel treatment approaches that were presented at the 2025 ASCO Annual Meeting. Transcript Dr. Shaalan Beg: Hello, I'm Dr. Shaalan Beg, welcoming you to the ASCO Daily News Podcast. I'm a medical oncologist and an adjunct associate professor at UT Southwestern Medical Center in Dallas, Texas. There were some remarkable advances in gastrointestinal cancers that were presented at the 2025 ASCO Annual Meeting, and I'm delighted to be joined by Dr. Kristen Ciombor to discuss some exciting GI data. Dr. Ciombor is the Ingram Associate Professor of Cancer Research and a co-leader of Translational Research and the Interventional Oncology Research Program at the Vanderbilt Ingram Cancer Center. Our full disclosures are available in the transcript of this episode. Dr. Ciombor, it's great to have you on the podcast today. Dr. Kristen Ciombor: Thanks, Dr Beg. It's great to be here. Dr. Shaalan Beg: Alright, let's kick it off. Big year for GI cancers. We'll start off with LBA1. This was the ATOMIC study sponsored by NCI and the National Clinical Trials Network (NCTN) and the Alliance group. This is a randomized study of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for stage III mismatch repair deficient colorectal cancer. Dr. Kristen Ciombor: I think this study was really definitely practice-changing, as you can tell because it was a Plenary. But I do have some concerns in terms of how we're actually going to implement this and whether this is the final answer in this disease subtype. So, as you said, the patients were enrolled with stage III resected mismatch repair deficient colon cancer, and then they were randomized to either modified FOLFOX6 with or without atezolizumab. And that's where it starts to become interesting because not many of us give FOLFOX for 6 months like was done in this study. Obviously, the study was done over many years, so that was part of that answer, but also the patients received atezolizumab for a total of 12 months. So the question, I think, that comes from this abstract is, is this practical and is this the final answer? I do think that this is practice-changing, and I will be talking to my patients with resected mismatch repair deficient colon cancer about FOLFOX plus atezolizumab. I think the big question is, do these patients need chemotherapy? And can we do a neoadjuvant approach instead? And that's where we don't have all the answers yet. Dr. Shaalan Beg: Yeah, but it has been great to see immunotherapy make its way into the adjuvant space after having made such a big impact in the metastatic space, but still some unanswered questions in terms of the need for chemotherapy and then the duration of therapy, which I guess we'll have to stay tuned in for the next couple of years to to get a lot of those questions answered. Dr. Kristen Ciombor: Yeah, but a big congratulations to the study team, to the NCTN, the NCI. I mean, this is really a great example of federally funded research that needs to continue. So, great job by the study team. The DFS 10% difference is really very large and certainly a practice-changing study. Dr. Shaalan Beg: Yeah, and and sticking with colon cancer, and and this another federally funded study, but this time funded by a Canadian cancer clinical trials group was LBA3510. This is the CHALLENGE study. It's a randomized phase 3 trial of the impact of a structured exercise program on disease-free survival for stage III or high-risk stage II colon cancer. This study got a lot of buzz, a lot of mainstream press coverage, and a lot of discussions on what that means for us for the patients who we're going to be seeing next week in our clinic. What was your takeaway? Dr. Kristen Ciombor: Yeah, this is a really interesting study, and I was so glad to see it presented because this partially answers one of the questions that patients always have for us in clinic, right? You know, once they've completed their standard chemotherapy and surgery, what else can they do to help prevent recurrence? And so we've always known and sort of extrapolated that healthy lifestyle habits are good, but now we have data, particularly in these patients. Most of them were stage III colon cancer patients, those had high-risk stage II cancer. And basically, the goal was to increase their physical activity by at least 10 MET hours per week. So, my big question, of course, as I came into this presentation was, “Okay, what does that mean exactly? How does that translate to real life?” And really what the author presented and explained was that basically most patients could hit their target by adding a 45- to 60-minute brisk walk 3 to 4 times a week. So I think this is very approachable.  Now, in the confines of the study, this was a structured exercise program, so it wasn't just patients doing this on their own. But I do think kind of extrapolating from that, that this is very achievable for most patients. And not only did this prevent recurrence of their prior cancer, but actually the rate of new primary cancer diagnoses, was less, which is really interesting, especially in the breast and prostate cancer. So this was a really interesting, and I think practice-changing study as well, especially given that this is something that most patients can do. Dr. Shaalan Beg: Yeah, and there was a lot of discussion in the hallways after the presentation in terms of how this really changes our existing practice because most folks already recommend exercise as a way for improving outcomes in cancer patients. So we've already been doing that. Now we have some data on how much it can impact the benefit. But there was some discussion about what the actual degree of impact was. There was a drop-off rate in terms of how long folks were able to stick with this exercise regimen. But you've seen this in clinic when someone have their surgery, they have their chemotherapy, they've been so intimately involved with the oncology world, with the oncology practice, and they somehow feel that they're being let loose into this mean, angry world without any guidance and they're looking for something to do. “What more can I do in terms of my lifestyle?” And then here we have very solid data, as solid as can be for an intervention like exercise, showing that there is an impact and you can give a prescription for exercise when someone wraps up their chemotherapy for colon cancer, thanks to the study. Dr. Kristen Ciombor: Yeah. It was a great study. Dr. Shaalan Beg: Moving to gastroesophageal cancer, another late-breaking abstract. This is LBA5. The MATTERHORN trial was a phase 3 trial of durvalumab plus FLOT for resectable GE junction and gastric cancer. And again, another area where immunotherapy has made an impact, and here we're seeing it move closer for earlier-stage disease. What was your take-home for the MATTERHORN trial? Dr. Kristen Ciombor: Yeah, so this study looked at neoadjuvant perioperative durvalumab plus our current standard chemotherapy of FLOT versus placebo plus FLOT. And this was a large study, almost 1,000 patients were randomized. And the primary endpoint was event-free survival, and it was definitely met in favor of the D + FLOT arm, as Dr. Klempner discussed after Dr Janjigian's presentation. I do think there are still some unanswered questions here. Overall survival is not yet mature, so we do have to wait and see how that shakes out. But it's very interesting and kind of is reflective of what, as you said, we're looking at earlier and earlier lines of therapy, particularly with immunotherapy, in these GI cancer spaces. So it makes a lot of sense to test this and and to look at this. So the toxicity was pretty similar to what we would expect. Primary endpoint was met, but again, we'll have to wait and see what the survival data looks like. Dr. Shaalan Beg: Yeah, and in oncology, we know, especially for treatment that does add additional cost, it does add additional potential toxicity that we want to see that overall survival nudged. I did see some polls on social media asking folks whether their practices changed from this, and I think the results were favoring adding durvalumab for this group of patients but understanding that there are caveats to the addition of treatments and the eventual FDA approval in that indication as well. Dr. Kristen Ciombor: Exactly. I completely agree with that. Dr. Shaalan Beg: All right. How about we stick with gastroesophageal cancer? LBA4002 was trastuzumab deruxtecan versus ramucirumab plus paclitaxel for second-line treatment in HER2-positive unresectable or metastatic gastric cancer or GE junction cancer. This was the DESTINY-Gastric04 study. And again, antibody-drug conjugates making a big impact across different diseases. And here we have more data in the HER2-positive gastric cancer space. Your thoughts on this study? Dr. Kristen Ciombor: Yeah, so this is a really important space in gastroesophageal cancer because the HER2 positivity rate is fairly high as compared to some of our other tumor types. So, I do think one of the important things was that patients did have biopsy confirmation of HER2 status, which was very important, and then they were randomized to either T-DXd versus the kind of second-line standard of ramucirumab-paclitaxel. So this was a great practical study and really answers a question that we had for a while in terms of does anti-HER2 therapy in the second-line really impact and improve survival. So we did see a statistically significant improvement favoring T-DXd. I do think it's always important to look at toxicity, though, too. And there was about almost 14% rate of interstitial lung disease, which of course is the most feared toxicity from some of these antibody-drug conjugates, especially T-DXd. So I do think it's important to keep that in mind, but this is definitely a great addition to the armamentarium for these HER2-positive patients. Dr. Shaalan Beg: And pancreas cancer was on the stage after a very long time with a positive clinical trial. This is Abstract 4006. These were preliminary results from a phase 2 study of elraglusib in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel alone for previously untreated metastatic pancreas cancer. This is a frontline clinical trial of gemcitabine/nab-paclitaxel plus/minus the study drug. There were other cohorts in this study as well, but they reported the results of their part 3B arm. And great to see some activity in the pancreas space. And your thoughts? Dr. Kristen Ciombor: Yeah, we definitely need better treatments in pancreas cancer. This was a very welcome presentation to see. The elraglusib is an inhibitor of GSK-3beta, and it's thought that that mediates drug resistance and EMT. And so this is, I think, a perfect setting to test this drug. So patients basically were randomized. Patients with metastatic pancreas cancer were randomized 2: 1 to gemcitabine/nab-paclitaxel plus or minus this elraglusib. So, what we saw was that overall survival was better with the addition of this new drug. And overall, not only the 1-year overall survival, but also median overall survival.  The thing that was interesting, though, was that we saw that the overall survival rates were 9.3 months with the combination versus 7.2 months with just gemcitabine/nab-paclitaxel. And that's a little bit lower than we've seen in other studies. So, not sure what was going on there. Was it the patients that were a bit sicker? Was it a patient selection, you know, thing? I'm not really sure how to explain that so much. Also, the toxicity profile was much higher in terms of visual impairment, with over 60% of patients being treated with the combination versus 9% with gemcitabine/nab-paclitaxel. So these were mild, grade 1 and 2, but still something to be cautious about. Dr. Shaalan Beg: And especially with this being a phase 2 trial, making sure that in a larger study we're able to better evaluate the toxicity and see if the control arm in the larger confirmatory study performs differently will be really important before this compound makes it to the clinic in our space. But very exciting to see these kinds of results for pancreas adenocarcinoma. Dr. Kristen Ciombor: Yeah. Dr. Shaalan Beg: We've talked, it seems, a couple of times on this podcast about the BREAKWATER clinical trial. We did hear PFS and updated OS data, updated overall survival data on first-line encorafenib plus cetuximab plus modified FOLFOX6 for BRAF-mutated colorectal cancer. This was LBA3500. And eagerly anticipated results – we have all previously heard the progression-free survival results – but here we heard updated overall survival results, and very well-received study it seemed from the audience that time. So what are your takeaways on the updated results for BREAKWATER? Dr. Kristen Ciombor: In my opinion, this was one of the most practice-confirming studies. As you mentioned, we've already seen some of the preliminary data of BREAKWATER at prior meetings. But really what was particularly impactful for me was the median overall survival with the BREAKWATER regimen. So, again, patients received FOLFOX, encorafenib cetuximab in the first line if they had BRAF-mutated V600E-mutated colorectal cancer. And the median PFS was 12.8 months, which was actually really remarkable in this traditionally very aggressive, poor prognosis subtype of tumors. So, by seeing a median overall survival of 30.3 months was just incredible, in my opinion. Just a few years ago, that was considered the median overall survival for all comers for metastatic colorectal cancer. And we know the median overall survival was more in the less than 12 months range for BRAF. So this was incredibly impactful, and I think should be absolutely practice-changing for anyone who is eligible for this regimen.  I think again, where the practice meets the study is what's kind of important to think about too, how long did patients get FOLFOX, and certainly it adds toxicity to add a BRAF-targeted regimen on top of FOLFOX already. So, one of the other interesting things about the study, though, was that even though it didn't complete treatment, they actually did look at encorafenib/cetuximab alone and in the first line without chemotherapy. And those preliminary results actually looked okay, especially for patients who might not be able to tolerate chemotherapy, which we certainly see in practice. So, overall, definitely more data. And I agree that it's certainly practice-changing. Dr. Shaalan Beg: And it completely, as you mentioned, changes the outlook for a person who's diagnosed with BRAF-mutated metastatic colon cancer today versus even 7 or 8 years ago. Dr. Kristen Ciombor: And we're seeing this over and over in other subtypes too, but how you choose to treat the patient up front really matters. So really giving the right regimen up front is the key here. Dr. Shaalan Beg: And along the same lines, Abstract 3501 wanted to answer the question on whether people with MSI-high metastatic colorectal cancer need double checkpoint inhibitor therapy or is single therapy enough. So this [CheckMate-8HW] study compared nivo plus ipi with nivo alone, nivo monotherapy for MSI-high metastatic colorectal cancer. And we've known that both of these are fairly active regimens, but we also know the chance of immune-related adverse events is significantly higher with combination therapy. So this was a much-needed study for this group of patients. And what were your takeaways here? Dr. Kristen Ciombor: This, of course, has been really nivo-ipi in the first-line MSI-high metastatic colorectal cancer is now a standard of care. And not everybody is eligible for it, and there could be reasons, toxicity reasons, and other things too. But as we've been seeing for the last couple of years, immunotherapy clearly beats chemo in this space. And now looking at doublet versus single immunotherapy treatment in the first line, I think really nivo-ipi does beat out monotherapy. I will say, however, there is a caveat in that we still haven't seen the nivo-ipi versus nivo in the first line. So what has been presented thus far has been across all lines of therapy, and that does muddy the waters a little bit. So definitely looking forward and and we've asked this many times and based on the statistical plan and and what not, you know, we just haven't seen that data yet. But I do think it's becoming increasingly important to consider doublet immunotherapy for these patients as long as there are no contraindications. With the again, with the caveat that we have to have these toxicity discussions in the clinic with patients because many patients can tolerate it, you know, this regimen fairly well, but there can be very severe toxicities. So, I think an informed discussion should really be had with each patient before moving forward. Dr. Shaalan Beg: Yeah, informed decision, making them aware of the potential of real significant toxicities, immune-related toxicities with double therapy. But I am curious in your practice, how often do you see people choosing doublet therapy as frontline? Dr. Kristen Ciombor: So patients are really savvy, and a lot of times they've heard this data before or have come across it in patient advocacy groups and other things, and it's really nice to be able to have that conversation of the risk versus benefit. So I will say not all of my patients choose doublet, and many of them are still cured with immunotherapy monotherapy. So the big question there is, will we ever understand who actually needs the doublet versus who can still be cured or have very good long-term outcomes with just the single agent? And that has not been answered yet. Dr. Shaalan Beg: What a great point. So the last abstract I was hoping we could talk about is POD1UM-303 or the INTERAACT2 subgroup analysis and impact of delayed retifanlimab treatment for patients with squamous cell carcinoma of the anal canal. What were your thoughts here? Dr. Kristen Ciombor: This was a study, actually we saw at ESMO, we saw the primary data at ESMO last year, and this was an update with some exploratory analyses. But this was really an important study because once again, we're looking at immunotherapy in later lines of therapy. That's how we started looking at and investigating immunotherapy, and now we're moving it up and up in the treatment course. So this was a study of carboplatin/paclitaxel plus or minus retifanlimab. Actually it was retifanlimab versus placebo. And it was a positive study, as we heard last year. This actually led to FDA approval of this regimen last month, just before ASCO, and it has now been incorporated in the NCCN guidelines as the preferred first-line option.  So what I thought was important from the additional data presented at ASCO was looking at the different subgroups, it did not appear that patients with liver mets or not had different outcomes. So that was really good to see because sometimes in colon cancer we see that immunotherapy doesn't work as well when patients have liver mets. And interestingly, because we use immunotherapy in anal cancer without any biomarkers, unlike with colon cancer or some of the other tumor types, also the authors looked at PD-L1 status, and it did look like maybe patients did a little bit better if they had higher PD-L1 expression, but patients still could benefit even if they were PD-L1 negative. So that was important, I think, and we will continue to see further data come out from this study. I want to mention also that EA2176 just completed accrual, so that was carbo-taxol plus or minus nivolumab. And so we should be seeing that data sometime soon, which will hopefully also confirm the ongoing role for immunotherapy in the first-line setting for anal cancer. Dr. Shaalan Beg: That was a fantastic review. Thank you, Dr Ciombor. Thanks for sharing your valuable insights with us today on the ASCO Daily News Podcast. Dr. Kristen Ciombor: Thanks for having me here. Dr. Shaalan Beg: And thank you to our listeners for your time today. You will find links to the abstracts discussed today in the transcript of this episode. And if you value the insights that you hear on the podcast, please take a moment to rate, review, and subscribe, wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. More on today's speakers:   Dr. Shaalan Beg  @ShaalanBeg  Dr. Kristen Ciombor @KristenCiombor Follow ASCO on social media:    @ASCO on Twitter   @ASCO on BlueSky  ASCO on Facebook    ASCO on LinkedIn    Disclosures:   Dr. Shaalan Beg:   Consulting or Advisory Role: Ipsen, Cancer Commons, Foundation Medicine, Science37, Nant Health, Lindus Health Speakers' Bureau: Sirtex Research Funding (Inst.): Delfi Diagnostics, Universal Diagnostics, Freenome Dr. Kristen Ciombor: Consulting or Advisory Role: Pfizer, Incyte, Exelixis, Bayer, ALX Oncology, Tempus, Agenus, Taiho Oncology, Merck, BeiGene Research Funding (Inst.): Pfizer, Boston Biomedical, MedImmune, Onyx, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Novartis, Incyte, Amgen, Sanofi, Bristol-Myers Squibb, Array BioPharma, Incyte, Daiichi Sankyo, Nucana, Abbvie, Merck, Pfizer/Calthera, Genentech, Seagen, Syndax Travel, Accommodations, Expenses: Incyte, Tempus

¿Y si te dijera que el cielo siempre ha sido verde? ¿Pensarías que estoy loco... o empezarías a dudar de tu propia memoria? En este episodio explosivo de DÍAS EXTRAÑOS destapamos las cuatro técnicas de manipulación psicológica que están siendo utilizadas AHORA MISMO para moldear tu realidad. Desde los aparentemente inocentes flash mobs hasta el control sutil del lenguaje que usas, descubrirás cómo los estrategas del siglo XXI han convertido tu mente en el campo de batalla definitivo. Porque en esta guerra invisible, el objetivo no es destruir tu cuerpo... sino reprogramar tu cerebro. ¿Estás preparado para ver la Matrix? Escucha el episodio completo en la app de iVoox, o descubre todo el catálogo de iVoox Originals

Os ouvintes confessam-nos a pior disciplina que tiveram na escola, a Inês e a Joana apresentam os “Factos para os que vão a caminho da Escola da Vida” e discutimos a guerra Israel-Irão no podcast “Médio Orienta-te, Mano”

We're finally digging into “Voodoo” - D'Angelo's Grammy-winning album that changed the sound of R&B, soul, and hip-hop forever. And the album a young Adam Maness had on repeat, seriously influencing his playing as well as countless musicians since.With Questlove's “Dilla-drag” drumming, Pino Palladino's funky bass lines, Roy Hargrove's jazzy horn arrangements, and Charlie Hunter's chicken-picking guitar, Voodoo is packed with the kind of cross-genre musicality that makes jazz musicians lose their minds.Twenty-five years later, Voodoo still grooves harder, hits deeper, and sounds more human than many albums of its generation.In this episode, you'll hear:What makes D'Angelo's groove so unique (and hard to imitate)Isolated tracks, rare demos, and interviews with the artistsHow “Spanish Joint” came together in a single takeWhether “Feel Like Makin' Love” tops the Roberta Flack originalAnd whether “Voodoo” is even an R&B album at allABOUT OPEN STUDIO------------------------------------------------------------------------------------------------------------------------------------------------------------As the premier online jazz education platform, with an ever-expanding course library and 20,000+ members, Open Studio (OS) has everything you need to excel and thrive on your jazz journey.Featuring everything from beginner to advanced lessons, engaging courses from A-list instructors, step-by-step curriculum, real-time classes and a thriving and incredibly supportive community, OS is the perfect platform to level up your jazz playing, whether you're a total beginner, or an advanced pro-level improvisor.

O Impacto da IA Generativa no Presente e Futuro dos DadosPrepare-se para uma conversa de altíssimo nível sobre como a Inteligência Artificial Generativa está transformando o mundo dos dados, das empresas e das carreiras. Neste episódio, Luan Moreno recebe Eduardo Ordax, Líder de IA Generativa na AWS, e Mateus Oliveira para discutir, sem rodeios, os impactos reais da IA no mercado.O que você vai aprender neste episódio:Como a IA Generativa está mudando a forma como construímos pipelines, produtos e soluções de dados.Os principais desafios que empresas enfrentam ao implementar GenAI — e por que tecnologia não é mais o problema, mas sim pessoas e dados.O papel da Engenharia de Dados no mundo da IA e como ela se conecta com conceitos como LLMOps, Fine-Tuning, Prompt Engineering e Data-Centric AI.Por que o domínio dos fundamentos nunca foi tão importante para quem trabalha (ou quer trabalhar) com dados e IA.Reflexões sobre o futuro das carreiras em dados e IA — será que os engenheiros de dados, cientistas de dados e desenvolvedores serão substituídos ou terão um papel ainda mais relevante?As diferenças entre usar IA para brincar no ChatGPT e levar IA para resolver problemas de negócios no mundo real, em escala e em produção.Este é um papo sobre IA. É uma imersão completa sobre os desafios, as oportunidades e a visão de futuro para quem trabalha com dados, engenharia, machine learning e inteligência artificial. Luan Moreno = https://www.linkedin.com/in/luanmoreno/

Olha só o que aconteceu aqui com estes pobres ratinhos quando os cientistas simplesmente trocaram a noite pelo dia nestes animais... Os ratos ganharam muito mais peso ao longo do tempo comendo exatamente a mesma dieta de antes e exatamente a mesma quantidade de calorias só por terem começado a comer fora de hora... Uau... será que isso também é algo que acontece em nós humanos? Será que comer mais tarde por si só pode ser algo que promove o ganho de peso mesmo que tenha uma dieta excelente? Vamos ver isso agora…   ▶ ️ Minisérie da Dieta do ATP: https://youtube.com/playlist?list=PL0ZwP-OIgrSxlLgg0wJsViiPLRWhUTvW1&si=WyLQ46doh6IYrrpt   

A gente já imaginava que isso era uma possibilidade e agora temos confirmado: Marathon foi adiado e por enquanto não tem uma nova data de lançamento. Essa não é a única notícia ruim no reino de PlayStation, que também teve demissões fortes na Sony Bend, responsáveis por Days Gone. O episódio da semana também tem o novo acordo firmado entre Xbox e AMD, e a reportagem contando os bastidores do desenvolvimento de Dragon Age: The Veilguard.Participantes:Guilherme JacobsHeitor De PaolaAssuntos abordados:03:00 - Marathon é adiado, ainda sem nova data de lançamento12:00 - Xbox reforça acordo com a AMD e fala de futuros consoles33:00 - Os bastidores do desenvolvimento de Dragon Age: The Veilguard50:00 - Sony Bend tem quase 1/3 dos funcionários mandados embora1:01:00 - Como jogos de emrpesas terceiras se saíram no lançamento do Switch 21:15:00 - Rápidas e curtasPré-venda da camiseta do OverloadrVenha fazer parte do Discord do Overloadr! Hosted on Acast. See acast.com/privacy for more information.

Dr. Allison Zibelli and Dr. Rebecca Shatsky discuss advances in breast cancer research that were presented at the 2025 ASCO Annual Meeting, including a potential new standard of care for HER2+ breast cancer, the future of ER+ breast cancer management, and innovations in triple negative breast cancer therapy. Transcript Dr. Allison Zibelli: Hello and welcome to the ASCO Daily News Podcast. I'm Dr. Allison Zibelli, your guest host of the podcast today. I'm an associate professor of medicine and a breast medical oncologist at the Sidney Kimmel Comprehensive Cancer Center at Jefferson Health. There was a substantial amount of exciting breast cancer data presented at the 2025 ASCO Annual Meeting, and I'm delighted to be joined by Dr. Rebecca Shatsky today to discuss some of these key advancements. Dr. Shatsky is an associate professor of medicine at UC San Diego and the head of breast medical oncology at the UC San Diego Health Moores Cancer Center, where she also serves as the director of the Breast Cancer Clinical Trials Program and the Inflammatory and Triple-Negative Breast Cancer Program.  Our full disclosures are available in the transcript of this episode. Dr. Shatsky, it's great to have you on the podcast today. Dr. Rebecca Shatsky: Thanks, Dr. Zibelli. It's wonderful to be here. Dr. Allison Zibelli: So, we're starting with DESTINY-Breast09, which was trastuzumab deruxtecan and pertuzumab versus our more standard regimen of taxane, trastuzumab pertuzumab for first-line treatment of metastatic HER2-positive breast cancer. Could you tell us a little bit about the study? Dr. Rebecca Shatsky: Yeah, absolutely. So, this was a long-awaited study. When T-DXd, or trastuzumab deruxtecan, really hit the market, a lot of these DESTINY-Breast trials were started around the same time. Now, this was a global, randomized, phase 3 study presented by Dr. Sara Tolaney from the Dana-Farber Cancer Institute of Harvard in Boston. It was assessing essentially T-DXd in the first-line setting for metastatic HER2-positive breast cancer in addition to pertuzumab. And that was randomized against our standard-of-care regimen, which was established over a decade ago by the CLEOPATRA trial, and we've all been using that internationally for at least the past 10 years. So, this was a large trial, and it was one-to-one-to-one of patients getting T-DXd plus pertuzumab, T-DXd alone, or THP, which mostly is used as docetaxel and trastuzumab and pertuzumab every three weeks for six cycles. And this was in over 1,000 patients; it was 1,159 patients with metastatic HER2-positive breast cancer. This was a very interesting trial. It was looking at the use of trastuzumab deruxtecan, but patients were started on this treatment for their first-line metastatic HER2-positive breast cancer with no end date to their T-DXd. So, it was, you know, you were started on T-DXd every 3 weeks until progression. Now, CLEOPATRA is a little bit different than that, though, as we know. So, CLEOPATRA has a taxane plus trastuzumab and pertuzumab. But generally, patients drop the taxane after about six to seven cycles because, as we know, you can't be really on a taxane indefinitely. You get pretty substantial neuropathy as well as cytopenias, other things that end up happening. And so, in general, that regimen has sort of a limited time course for its chemotherapy portion, and the patients maintained after the taxane is dropped on their trastuzumab and their pertuzumab, plus or minus endocrine therapy if the investigator so desires. And the primary endpoint of the trial was progression-free survival by blinded, independent central review (BICR) in the intent-to-treat population. And then it had its other endpoints as overall survival, investigator-assessed progression-free survival, objective response rates, and duration of response, and of course, safety. As far as the results of this trial, so, I think that most of us key opinion leaders in breast oncology were expecting that this was going to be a positive trial. And it surely was. I mean, this is a really, really active drug, especially in HER2-positive disease, of course. So, the DESTINY-Breast03 data really established that, that this is a very effective treatment in HER2-positive metastatic breast cancer. And this trial really, again, showed that. So, there were 383 patients that ended up on the trastuzumab plus deruxtecan plus pertuzumab arm, and 387 got THP, the CLEOPATRA regimen. What was really interesting also to note of this before I go on to the results was that 52% of patients on this trial had de novo metastatic disease. And that's pretty unusual for any kind of metastatic breast cancer trial. It kind of shows you, though, just how aggressive this disease is, that a lot of patients, they present with de novo metastatic disease. It's also reflecting the global nature of this trial where maybe the screening efforts are a little bit less than maybe in the United States, and more patients are presenting as later stage because to have a metastatic breast cancer trial in the United States with 52% de novo metastatic disease doesn't usually happen. But regardless, the disease characteristics were pretty well matched between the two groups. 54% of the patients were triple positive, or you could say hormone-positive because whether they were PR positive or ER positive and PR negative doesn't really matter in this disease. And so, the interim data cutoff was February of this year, of 2025. So, the follow-up so far has been about 29 months, so the data is still really immature, only 38% mature for progression-free survival interim analysis. But what we saw is that T-DXd plus pertuzumab, it really improved progression-free survival. It had a hazard ratio that was pretty phenomenal at 0.56 with a confidence interval that was pretty narrow of 0.44 to 0.71. So, very highly statistically significant data here. The progression-free survival was consistent across all subgroups. Overall survival, very much immature at this time, but of course, the trend is towards an overall survival benefit for the T-DXd group. The median durable response with T-DXd plus pertuzumab exceeded 3 years. Now, importantly, though, I want to stress this, is grade 3 or above treatment-emergent adverse events occurred in both subgroups pretty equally. But there were 2 deaths in the T-DXd group due to interstitial lung disease. And there was a 12.1% adjudicated drug-induced interstitial lung disease/pneumonitis event rate in the T-DXd group and only 1%, and it was grade 1-2, in the THP group. So, that's really the caveat of this therapy, is we know that a percentage of patients are going to get interstitial lung disease, and that some may have very serious adverse events from it. So, that's always something I keep in the back of my mind when I treat patients with T-DXd. And so, overall, the conclusions of the trial were pretty much a slam dunk. T-DXd plus pertuzumab, it had a highly statistically significant and clinically meaningful improvement in progression-free survival versus the CLEOPATRA regimen. And that was across all subgroups for first-line metastatic HER2-positive breast cancer here. And so, yeah, the data was pretty impressive. Just to go into the overall response rate, because that's always super important as well, you had 85.1% of patients having a confirmed overall RECIST response rate in the T-DXd plus pertuzumab group and a 78.6 in the CLEOPATRA group. The complete CR rate, complete response was 15.1% in the T-DXd group and 8.5 in the CLEOPATRA regimen. And it was really an effective regimen in this group, of course. Dr. Allison Zibelli: So, the investigators say at the end of their abstract that this is the new standard of care. Would you agree with that statement? Dr. Rebecca Shatsky: Yeah, that was a bold statement to make because I would say in the United States, not necessarily at the moment because the quality of life here, you have to think really hard about. Because one thing that's really important about the DESTINY-Breast09 data is that this was very much an international trial, and in many of the countries where patients enrolled on this, they were not able to access T-DXd off trial. And so, for them, this means T-DXd now or potentially never. And so, that is a really big difference whereas internationally, that may mean standard of care. However, in the US, patients have no issues accessing T-DXd in the second- or third-line settings. And right now, it's the standard of care in the second line in the United States, with all patients basically getting this second-line therapy except for some unique patients where they may be doing a PATINA trial regimen, which we saw at San Antonio Breast Cancer in 2024 of the triple-positive patients getting hormonal therapy plus palbociclib, which had a really great durable response. That was super impressive as well. Or there is the patient that the investigator can pick KADCYLA because the patient really wants to preserve their hair or maybe it's more indolent disease. But the quality of life on T-DXd indefinitely in the first-line setting is a big deal because, again, that CLEOPATRA regimen allows patients to drop their chemotherapy component about five to six months in. And with this, you're on a drug that feels very chemo-heavy indefinitely. And so, I think there's a lot more to investigate as far as what we're going to do with this data in the United States because it's a lot to commit a patient in the first-line metastatic setting. These de novo metastatic patients, some of them may be cured, honestly, on the HER2-targeting regimen. That's something we see these days. Dr. Allison Zibelli: So, very interesting trial. I'm sure we'll be talking about this for a long time.  So, let's move on to SERENA-6, which was, I thought, a very interesting trial. This trial took patients with ER positive, advanced breast cancer after six months on an AI (aromatase inhibitor) and a CDK4/6 inhibitor. They did ctDNA every two to three months, and when they saw an ESR1 mutation emerge, they changed half of the patients to camizestrant plus CDK4/6 and kept the other half on the AI plus CDK4/6. Can you talk about that trial a little bit, please? Dr. Rebecca Shatsky: Yeah, so this was a big trial at ASCO25. This was presented as a Plenary Session. So, this was camizestrant plus a CDK4/6 inhibitor, and it could have been any of the three, so palbo, ribo, or abemaciclib in the first-line metastatic hormone-positive population, and patients were on an AI with that. They were, interestingly, tested by ctDNA at baseline to see if they had an ESR1 mutation. So, that was an interesting feature of this trial. But patients had to have already been on their CDK4/6 inhibitor plus AI for at least 6 months to enroll. And then, as you mentioned, they got ctDNA testing every 2 to 3 months. This was also a phase 3, double-blind, international trial. And I do want to highlight again, international here, because that's important when we're considering some of this data in the U.S. because it influences some of the results. So, this was presented by Dr. Nick Turner of the Royal Marsden in the UK. So, just a little bit of background for our listeners on ESR1 mutations and why they're important. This is the most common, basically, acquired resistance mutation to patients being treated with aromatase inhibitors. We know that treatment with aromatase inhibitors can induce this. It makes a conformational change in the estrogen receptor that makes the estrogen receptor constitutively active, which allows the cell to signal despite the influence of the aromatase inhibitor to decrease the estrogen production so that the ligand binding doesn't matter as much as far as the cell signaling and transcription is concerned. And camizestrant, you know, as an oral SERD, just to explain that a little bit too; these are estrogen receptor degraders. The first-in-class of a selective estrogen receptor degrader to make it to market was fulvestrant. And that's really been our standard-of-care estrogen degrader for the past 25 years, almost 25 years. And so, a lot of us are just looking for some of these oral SERDs to replace that. But regardless, they do tend to work in the ESR1-mutated population. And we know that patients on aromatase inhibitors, the estimates of patients developing an ESR1 mutation, depending on which study you look at, somewhere between 30% to 50% overall, patients will develop this mutation with hormone-positive metastatic breast cancer. There is a small percentage of patients that have these at baseline without even treatment of an aromatase inhibitor. The estimates of that are somewhere between 0.5 and up to 5%, depending on the trial you look at and the population. But regardless, there is a chance someone on their CDK4/6 inhibitor plus AI at 6 months' time course could have had an ESR1 mutation at that time. But anyway, so they got this ctDNA every 2 to 3 months, and once they were found to develop an ESR1 mutation, the patients were then switched to the oral SERD. AstraZeneca's version of the oral SERD is camizestrant, 75 mg daily. And then their type of CDK4/6 inhibitor was maintained, so they didn't switch the brand of their CDK4/6 inhibitor, importantly. And that was looked at then for progression-free survival, but these were patients with measurable disease by RECIST version 1.1. And the data cut off here was November of 2024. This was a big trial, you know, and I think that that's influential here because this was 3,256 patients, and that's a lot of patients. So, they were all eligible. And then 315 patients ended up being randomized to switch to camizestrant upon presence of that ESR1 mutation. So, that was 157 patients. And then the other half, so they were randomized 1:1, they continued on their AI without switching to an oral SERD. That was 158 patients. They were matched pretty well. And so, their baseline characteristics, you know, the two subgroups was good. But this was highly statistically significant data. I'm not going to diminish that in any way. Your hazard ratio was 0.44. Highly statistically significant confidence intervals. And you had a median progression-free survival in those that switched to camizestrant of 16 months, and then the non-switchers was 9.2 months. So, the progression-free survival benefit there was also consistent across the subgroups. And so, you had at 12 months, the PFS rate was 60.7% for the non-treatment group and 33.4% in the treatment group. What's interesting, though, is we don't have overall survival data. This is really immature, only 12% mature as far as overall survival. And again, because this was an international trial and patients in other countries right now do not have the access to oral SERDs that the United States does, the crossover rate, they were not allowed to crossover, and so, a very few patients, when we look at progression-free survival 2 and ultimately overall survival, were able to access an oral SERD in the off-trial here and in the non-treatment group. And so, that's really important as far as we look at these results. Adverse events were pretty minimal. These are very safe drugs, camizestrant and all the other oral SERDs. They have some mild toxicities. Camizestrant is known for something weird, which is called photopsia, which is some flashing lights in the periphery of the eye, but it doesn't seem to have any serious clinical significance that we know of. It has a little bit of bradycardia, but it's otherwise really well tolerated. You know, I hate to say that because that's very subjective, right? I'm not the one taking the drug. But it doesn't have any serious adverse events that would cause discontinuation. And that's really what we saw in the trial. The discontinuation rates were really low. But overall, I mean, this was a positive trial. SERENA-6 showed that switching to camizestrant at the first sign of an ESR1 mutation on CDK4/6 inhibitor plus AI improved progression-free survival. That's all we can really say from it right now. Dr. Allison Zibelli: So, let's move on to ASCENT-04, which was a bit more straightforward. Sacituzumab govitecan plus pembrolizumab versus chemotherapy plus pembrolizumab in PD-L1-positive, triple-negative breast cancer. Could you talk about that study? Dr. Rebecca Shatsky: Yeah, so this was also presented by the lovely Sara Tolaney from Dana-Farber. And this study made me really excited. And maybe that's because I'm a triple-negative breast cancer person. I mean, not to say that I don't treat hundreds of patients with hormone- positive, but our unmet needs in triple negative are huge because this is a disease where you have got to throw your best available therapy at it as soon as you can to improve survival because survival is so poor in this disease. The average survival with metastatic triple-negative breast cancer in the United States is still 13-18 months, and that's terrible. And so, for full disclosure, I did have this trial open at my site. I was one of the site PIs. I'm not the global PI of the study, obviously. So, what this study was was for patients who had had at least a progression-free survival of 6 months after their curative intent therapy or de novo metastatic disease. They were PD-L1 positive as assessed by the Dako 22C3 assay of greater than or equal to a CPS score of 10. So, that's what the KEYNOTE-355 trial was based on as well. So, standard definition of PD-L1 positive in breast cancer here. And basically, these patients were randomized 1:1 to either their sacituzumab govitecan plus pembrolizumab, day 1 they got both therapies, and then day 8 just the saci, as is standard for sacituzumab. And then the other group got the KEYNOTE-355 regimen. So, that is pembrolizumab with – your options are carbogem there, paclitaxel or nab-paclitaxel. And it's up to investigator's decision which upon those they decided. They followed these patients for disease progression or unacceptable toxicity. It was really an impressive trial in my opinion because we know already that this didn't just improve progression-free survival, because survival is so poor in this disease, of course, we know that it improved overall survival. It's trending towards that very much, and I think that's going to be shown immediately. And then the objective response rates were better, which is key in this disease because in the first-line setting, you've got a lot of people who, especially your relapsed TNBC that don't respond to anything. And you lose a ton of patients even in the first-line setting in this disease. And so, this was 222 patients to chemotherapy and pembro and 221 to sacituzumab plus pembro. Median follow-up has only been 14 months, so it's still super early here. Hazard ratio so far of progression-free survival is 0.65, highly statistically significant, narrow confidence intervals. And so, the median duration of response here for the saci group was 16.5 months versus 9.2 months. So, you're getting a 7-month progression-free survival benefit here, which in triple negative is pretty fantastic. I mean, this reminds me of when we saw the ASCENT data originally come out for sacituzumab, and we were all just so happy that we had this tool now that doubled progression-free and overall survival and made such a difference in this really horrible disease where patients do poorly. So, OS is technically immature here, but it's really trending very heavily towards improvement in overall survival. Importantly, the treatment-related adverse events in this, I mean, we know sacituzumab causes neutropenia, people who are experienced with this drug know how to manage it at this point. There wasn't any really unexpected treatment-related adverse events. You get some people with sacituzumab who have diarrhea. It's usually pretty manageable with some Imodium. So, it was cytopenias predominantly in this disease in this population that were highlighted as far as adverse events. But I'm going to be honest, like I was surprised that this wasn't the plenary over the SERENA-6 data because this, in my mind, there we have a practice-changing trial. I will immediately be trying to use this in my PD-L1 population because, to be honest, as a triple-negative breast cancer clinical specialist, when I get a patient with metastatic triple-negative breast cancer who's PD-L1 positive, I think, "Oh, thank God," because we know that part of the disease just does better in general. But now I have something that really could give them a durable response for much longer than I ever thought possible when I started really heavily treating this disease. And so, this was immediately practice-changing for me. Dr. Allison Zibelli: I think that it's pretty clear that this is at least an option, if not the option, for this group of patients. Dr. Rebecca Shatsky: Yeah, the duration of responses here was – it's just really important because, I mean, I do think this will make people live longer. Dr. Allison Zibelli: So, moving on to the final study that we're going to discuss today, neoCARHP (LBA500), which was neoadjuvant taxane plus trastuzumab, pertuzumab, plus or minus carbo(platin) in HER2-positive early breast cancer. I think this is a study a lot of us have been waiting for. What was the design and the results of this trial? Dr. Rebecca Shatsky: I was really excited about this as well because I'm one of those people that was waiting for this. This is a Chinese trial, so that is something to take note of. It wasn't an international trial, but it was a de-escalation trial which had become really popular in HER2-positive therapy because we know that we're overtreating HER2-positive breast cancer in a lot of patients. A lot of patients we're throwing the kitchen sink at it when maybe that is not necessary, and we can really de-escalate and try to personalize therapy a little bit better because these patients tend to do well. So, the standard of care, of course, in HER2-positive curative intent breast cancer with tumors that are greater than 2 cm is to give them the TCHP regimen, which is docetaxel, carboplatin, trastuzumab, and pertuzumab. And that was sort of established by several trials in the NeoSphere trial, and now it's been repeated in a lot of different studies as well. And so, that's really the standard of care that most people in the United States use for HER2-positive curative intent breast cancer. This was a trial to de-escalate the carboplatin, which I was super excited about because many of us who treat this disease a lot think carbo is the least important part of the therapy you're giving there. We don't really know that it's necessary. We've just been doing it for a long time, and we know that it adds a significant amount of toxicity. It causes thrombocytopenia, it causes severe nausea, really bad cytopenias that can be difficult in the last few cycles of this to manage. So, this trial was created. It randomized patients one to one with stage 2 and 3 HER2-positive breast cancer to either get THP, a taxane, pertuzumab, trastuzumab, similar to the what we do in first-line metastatic HER2-positive versus the whole TCHP with a carboplatin AUC of 6, which is what's pretty standard. And it was a non-inferiority trial, so important there. It wasn't to establish superiority of this regimen, which none of us, I think, were looking for it to. And it was a modified intent-to-treat population. And so, all patients got at least one cycle of this to be assessed as a standard for an intent-to-treat trial. And so, they assumed a pCR rate of about 62.8% for both groups. And, of course, it included both HER2-positive triple positives and ER negatives, which are, you know, a bit different diseases, to be honest, but we all kind of categorize them and treat them the same. And so, this trial was powered appropriately to detect a non-inferiority difference. And so, we had about 380 patients treated on both arms, and there was an absolute difference of only 1.8% of those treated with carbo versus those without. Which was fantastic because you really realized that de-escalation here may be something we can really do. And so, the patients who got, of course, the taxane regimen had fewer adverse events. They had way fewer grade 3 and 4 adverse events than the THP group. No treatment-associated deaths occur, which is pretty standard for- this is a pretty safe regimen, but it causes a lot of hospitalizations due to diarrhea, due to cytopenias, and neutropenic fever, of course. And so, I thought that this was something that I could potentially enact, you know, and be practice-changing. It's hard to say that when it's a trial that was only done in China, so it's not necessarily the United States population always. But I think for patients moving forward, especially those with, say, a 2.5 cm tumor, you know, node negative, those, I'd feel pretty comfortable not giving them the carboplatin here. Notes that I want to make about this population is that the majority were stage 2 and not stage 3. They weren't necessarily your inflammatory HER2-positive breast cancer patients. And that the taxane that was utilized in the trial is a little different than what we use in the United States. The patients were allowed to get nab-paclitaxel, which we don't have FDA approval for in the first-line curative intent setting for HER2-positive breast cancer in the United States. So, a lot of them got abraxane, and then they also got paclitaxel. We tend to use docetaxel every 3 weeks in the United States. So, just to point out that difference. We don't really know if that's important or not, but it's just a little bit different to the population we standardly treat. Dr. Allison Zibelli: So, are there patients that you would still give TCHP to? Dr. Rebecca Shatsky: Yeah, great question. I've been asked that a lot in the past like week since ASCO. I'd say in my inflammatory breast cancer patients, that's a group I do tend to sometimes throw the kitchen sink at. Now, I don't actually use AC in those because I know that that was the concern, but I think the TRAIN-2 trial really showed us you don't need to use Adriamycin in HER2-positive disease unless it's like refractory. So, I don't know that I would throw this on my stage 3C or inflammatory breast cancer patients yet because the majority of this were not stage 3. So, in your really highly lymph node positive patients, I'm a little bit hesitant to de-escalate them from the start. This is more of a like, if there's serious toxicity concerns, dropping carbo is absolutely fine here. Dr. Allison Zibelli: All right, great.  Thank you, Dr. Shatsky, for sharing your valuable insights with us on the ASCO Daily News Podcast today. Dr. Rebecca Shatsky: Thanks so much, Dr. Zibelli and ASCO Daily News. I really want to thank you for inviting me to talk about this today. It was really fun, and I hope you find my opinions on some of this valuable. And so, I just want to thank everybody and my listeners as well. Dr. Allison Zibelli: And thank you to our listeners for joining us today. You'll find the links to all the abstracts discussed today in the transcript of this episode. Finally, if you like this podcast and you learn things from it, please take a moment to rate, review, and describe because it helps other people find us wherever you get your podcasts. Thank you again. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. More on today's speakers Dr. Allison Zibelli Dr. Rebecca Shatsky @Dr_RShatsky Follow ASCO on social media:  @ASCO on Twitter  @ASCO on Bluesky  ASCO on Facebook  ASCO on LinkedIn   Disclosures: Dr. Allison Zibelli: No relationships to disclose Dr. Rebecca Shatsky: Consulting or Advisory Role: Stemline, Astra Zeneca, Endeavor BioMedicines, Lilly, Novartis, TEMPUS, Guardant Health, Daiichi Sankyo/Astra Zeneca, Pfizer Research Funding (Inst.): OBI Pharma, Astra Zeneca, Greenwich LifeSciences, Briacell, Gilead, OnKure, QuantumLeap Health, Stemline Therapeutics, Regor Therapeutics, Greenwich LifeSciences, Alterome Therapeutics  

A PJ tem finalmente acesso ao conteúdo do telemóvel de José Valbom (Tiago Teotónio Pereira). Entre vídeos e fotos comprometedoras, o inspetor João Durães (Paulo Calatré) descobre várias trocas de mensagens suspeitas. O pai de Zé, o poderoso engenheiro Vicente Valbom (José Raposo) pressiona a investigação e ameaça Durães. E uma nova pista relacionada com a universidade surge na investigação. O “Zé faz 25” é um podcast de ficção para ouvir em oito episódios. Uma coprodução do Observador com a Coyote Vadio, que conta ainda no elenco com Sara Matos, Madalena Almeida, Cristovão Campos, Vicente Wallenstein, José Raposo e Carla Maciel. Pode ouvir semanalmente os episódios de “O Zé faz 25” na playlist própria do podcast na Apple Podcasts, Spotify, Youtube ou outras plataformas de podcast. Os assinantes standard e premium do Observador terão acesso antecipado a todos os episódios no site do Observador.See omnystudio.com/listener for privacy information.

Bate-Papo Mayhem 468 - Alan Chapman - Magia Avançada para Iniciantes https://projetomayhem.com.br/ O vídeo desta conversa está disponível em: https://youtu.be/l4B0BQV2eug Bate Papo Mayhem é um projeto extra desbloqueado nas Metas do Projeto Mayhem.  Todas as 3as, 5as e Sabados as 21h os coordenadores do Projeto Mayhem batem papo com algum convidado sobre Temas escolhidos pelos membros, que participam ao vivo da conversa, podendo fazer perguntas e colocações. Os vídeos ficam disponíveis para os membros e são liberados para o público em geral duas vezes por semana, às segundas e quintas feiras e os áudios são editados na forma de podcast e liberados uma vez por semana. Faça parte do projeto Mayhem: https://www.catarse.me/tdc

In "Mobile Views 567," Todd Ogasawara and Jon Westfall discuss various tech topics, starting with Ogasawara's review of a new 4K webcam with stereo speakers and AI-powered digital zoom and voice tracking, which he is very pleased with.  They then delve into a "rant" about the ongoing debate regarding tablets, specifically the sentiment that iPads should be more like Macs.  Both speakers express their disagreement with this idea, with Westfall highlighting that many people, including himself, have valid use cases for tablets that differ from laptops or phones.  They liken this to past skepticism surrounding smartwatches and the need for a monthly calendar view in older versions of Windows Mobile, suggesting a fundamental misunderstanding of diverse user needs by some tech enthusiasts and developers.  The conversation also covers Ogasawara's experience with Adobe Project Indigo, a free photography app for iPhone that shoots in raw format, and the release of Android 16.  Todd cautions against purchasing unbranded budget Android tablets due to a lack of OS and security updates.  Finally, they brainstorm ideas for future "bionic devices" and "smart jewelry," expressing a desire for more innovative wearables beyond current fitness trackers.  These concepts include a Vision Pro with an integrated battery, AR smart glasses with built-in vision correction and recording, and advanced bone-conducting headphones.

🎭 Lo que vas a escuchar cambiará tu forma de ver la realidad para siempre. Charles Dickens esquivaba a sus personajes por Londres. Virginia Woolf predijo una muerte mientras escribía. Un niño de 4 años fue atacado por el pato Donald en su habitación. Y Alan Moore... Alan Moore se encontró cara a cara con John Constantine en una cafetería. En este episodio escalofriante de DÍAS EXTRAÑOS, descendemos por la madriguera más profunda del fenómeno paranormal: las incursiones ficticias, esos momentos imposibles donde personajes de libros, películas y cómics cruzan la delgada línea entre ficción y realidad. Basado en la investigación de Joshua Cutchin, exploramos casos documentados que la ciencia no puede explicar: desde escritores amenazados por sus propias creaciones hasta OVNIs con forma de naves de Star Wars. Advertencia: Después de escuchar esto, puede que empieces a mirar con otros ojos a ese extraño del metro que se parece sospechosamente a tu personaje favorito. Con casos reales, testimonios estremecedores y una revelación final que te hará cuestionar si tú mismo no eres un personaje en la historia de alguien más. Y además: Cuentos Fantásticos, El Cuadro, de Arturo Panero. Ciencia Extraordinario, con Pablo Fuente. Escucha el episodio completo en la app de iVoox, o descubre todo el catálogo de iVoox Originals

A bíblia fala sobre oração o tempo inteiro. Os patriarcas, o Rei Davi, Jó, Daniel, e tantos outros oravam a Deus. Pra. Pamela Cruz nos ensina sobre oração como uma disciplina espiritual essencial para nossa fé e relacionamento com Deus.

TV writer Lauren Ashley Smith (A Black Lady Sketch Show, Smith Sisters Live) joins Nicole to talk about how she met her wife the old-fashioned way - through Time Out New York's Singles issue.Lauren reveals the strange public response to being a “bachelor” in a magazine, how her wife was one of the only white women working at BET, and the complications that came with planning an interracial lesbian wedding.She also recalls a bizarre school Valentine's Day test that matched students based on compatibility, and she and Nicole discuss who gets to keep the friends after a breakup. Plus, Nicole gets a magical hot massage and somehow walks away being fluent in Greek.And Lauren shares one big piece of dating advice: why straight people should try dating more like lesbians -letting go of the gender roles getting in the way.Watch this episode on our YouTube channel at https://www.youtube.com/@WhyWontYouDateMePodcastSupport this podcast and get discounts by checking out our sponsors:» OneSkin: OneSkin is redefining the aging process with their proprietary OS-01 peptide. Get 15% off OneSkin with the code DATEME at https://www.oneskin.co/ #oneskinpod» EarnIn: Make Any Day Payday! When you download the EarnIn app, type in Why Won't You Date Me under PODCAST when you sign up – it'll really help the show. » Booking.com: Book now at Booking.com!» Wayfair: Wayfair. Every Style, Every Home.View all of our sponsors and discounts codes at wwydm.notion.site/sponsors.Follow:Tour Dates: linktr.ee/nicolebyerwastakenYouTube: @WhyWontYouDateMePodcastTikTok: @whywontyoudatemepod Instagram: @nicolebyerX: @nicolebyerNicole's book, #VERYFAT #VERYBRAVE: indiebound.org/book/9781524850746This is a Headgum podcast. Follow Headgum on Twitter, Instagram, and Tiktok. Advertise on Why Won't You Date Me? via Gumball.fm.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Did you know that 50% of your hair disappears before you even notice it's thinning – AND – it might not just be because of hormones? Groundbreaking research reveals the real culprit: "zombie cells" accumulating in your scalp that literally sabotage your hair follicles from within. In this eye-opening conversation, Natalie sits down with Carolina, co-founder of OneSkin, to uncover the cellular science behind why traditional hair loss treatments often fall short—and why a revolutionary patented  OS-01 peptide targets aging cells at the molecular level to rejuvenate both skin and scalp. You'll discover why your scalp ages just like your skin, what creates the perfect storm for hair loss, and the surprising truth about why natural solutions can actually outperform chemical treatments when they target the right mechanisms. Carolina shares the fascinating story behind their breakthrough discovery of the OS-01 peptide, which took years to develop after testing over 900 different compounds. Whether you're already noticing thinning or want to prevent it, this conversation will completely transform how you think about hair health and aging. Plus, Natalie shares her own 3-month experiment results that surprised even her—including why she almost gave up at 8 weeks and what changed her mind.   Interested in trying OS-01 HAIR? Visit https://oneskin.co/NATALIEJILL and use code NATALIEJILL for 15% off.   Note: The bottle shown in this episode is OneSkin's OS-01 HAIR refill bottle, which is meant to refill the primary bottle that customers receive when purchasing the product. For instructions on how to properly apply OS-01 HAIR, please visit oneskin.co/nataliejill   Catch the full episode on YOUTUBE HERE: https://bit.ly/MidlifeConversationsYouTube    Learn More About OneSkin:   https://www.instagram.com/oneskin.co  http://oneskin.co/NATALIEJILL   Free Gifts for being a listener of Midlife Conversations! Mastering the Midlife Midsection Guide: https://theflatbellyguide.com/ Age Optimizing and Supplement Guide: https://ageoptimizer.com   Thank you to our show sponsors! BIOPTIMIZERS: Get the digestive enzymes I take with every meal here https://www.bioptimizers.com/nataliejill Connect with me on social media! Instagram: www.Instagram.com/Nataliejllfit Facebook: www.Facebook.com/Nataliejillfit   For advertising inquiries: https://www.category3.ca/  Disclaimer: Information provided in the Midlife Conversations podcast is for informational purposes only. This information is NOT intended as a substitute for the advice provided by your physician or other healthcare professional. Do not use the information provided in this podcast for diagnosing or treating a health problem or disease, or prescribing medication or other treatment. Always speak with your physician or other healthcare professional before making any changes to your current regimen.  Information provided in this podcast and the use of any products or services related to this podcast does not create a client-patient relationship between you and the host of Midlife Conversations or you and any doctor or provider interviewed and featured on this show. Information and statements may have not been evaluated by the Food and Drug Administration and are not intended to diagnose, treat, cure, or prevent ANY disease. Advertising Disclosure: Some episodes of Midlife Conversations may be sponsored by products or services discussed during the show. The host may receive compensation for such advertisements or if you purchase products through affiliate links. Opinions expressed about products or services are those of the host and/or guests and do not necessarily reflect the views of any sponsor. Sponsorship does not imply endorsement of any product or service by healthcare professionals featured on this podcast.