Podcasts about Mek

Dnes jsme si pozvlai moderátora pořadu Extrémní proměny a trenéra Martina Košťála. Probrali jsme jak se vůbec dostal k moderování tohohle pořadu, jak až v průběhu natáčení připravoval na Damu, jestli si zvykl na okamžitou popularitu, jakou má pořad sledovanost, problémy s dětskou obezitou, jak si vybírají lidi do Extrémních proměn, kolik času tráví s účinkujícími, kdo ho nejvíc překvapil, kdo naopak nejvíce selhal, jak účinkující zhubli tolik, že je nepoznala ani vlastní doktorka, jestli je zdravé hubnout tak rychle tolik kilo, jestli museli během natáčení někomu volat sanitku, jak se jim nastavují jídelníčky, o Stejkově hubnutí, o půstech, kolik kalorií má meníčko v Mekáči, kolik účinkujících má jojo efekt, jak vydržet u cvičení a hubnutí, jaký jsou největší mýty ohledně hubnutí.

Ekin Yayınları, Süleyman Ceran dostumuzun editörlüğünde Gazze'de yaşananların çok boyutlu biçimde ele alındığı ve birçok yazarın farklı bakış açılarıyla katkıda bulunduğu üç kitaplık bir ‘külliyat' yayınladı. Üç kitabın ortak ismi: ‘Kızıl Kapı'… Bu isim Mısırlı şair Ahmet Şevki'nin “Hürriyetin kızıl bir kapısı vardır ki/ Onu ancak kana bulanan eller açar” dizelerinden mülhem… Kitapların üst başlığı ise ‘Gazze'nin Hafızası'. Gerçekten çok derinlikli bir hafıza oluşturma çalışması bu. Farklı kalemler Gazze'yi farklı noktalardan bakarak görüyor, yorumluyor ve tarihe çok zengin notlar düşülüyor. Üç kitabın ‘Sembol', ‘İnsan' ve ‘Mekân' şeklinde üç farklı bağlamı var.

Po žebrech u Kapitána a drincích od George Cocktail Boye jsem si ještě před půlnocí vzal mikrofon a nahrál souhrn, postřehy, téma, virály a inspekce minulého týdne. Ano, i pro Velkou žranici můžete hlasovat v Podcastu roku, na ten můžete 16.6. i dorazit. Hlavní téma bylo jasné, nestal jsem se opravdu za ty roky už víc obhájce hospodskejch, než advokát hostů. Blíží se premiéra nových pořadů na herohero.co/gastromapalukasehejlika . A i inspekcí bylo dost, dokonce proběhl Doublecheese od Mekáče. A taky docela fail, kdy jsem padnul do natáčení, za kterým stal docela kontroverzní partner. A koprovka v KRO by se mohla jmenovat KROpovka. A narazili jsme Double Trouble od Budvaru a Obory. Ať vás to baví, díky za vaše ohlasy.

JCO PO author Dr. Dean A. Regier at the Academy of Translational Medicine, University of British Columbia (UBC), and the School of Population and Public Health, BC Cancer Research Institute shares insights into his JCO PO article, “Clinical Effectiveness and Cost-Effectiveness of Multigene Panel Sequencing in Advanced Melanoma: A Population-Level Real-World Target Trial Emulation.” Host Dr. Rafeh Naqash and Dr. Regier discuss the real-world clinical effectiveness and cost-effectiveness of multigene panels compared with single-gene BRAF testing to guide therapeutic decisions in advanced melanoma. Transcript Dr. Rafeh Naqash:Hello and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I'm your host, Dr. Rafeh Naqash, Podcast Editor for JCO Precision Oncology and Assistant Professor at the OU Health Stephenson Cancer Center in the University of Oklahoma. Today, we are excited to be joined by Dr. Dean A. Regier, Director at the Academy of Translational Medicine, Associate Professor at the School of Population and Public Health, UBC Senior Scientist at the British Columbia Cancer Research Institute, and also the senior author of the JCO Precision Oncology article entitled "Clinical Effectiveness and Cost-Effectiveness of Multigene Panel Sequencing in Advanced Melanoma: A Population-Level Real-World Target Trial Emulation." At the time of this recording, our guest's disclosures will be linked in the transcript. Dean, welcome to our podcast and thank you for joining us today. Dr. Dean Regier:Thank you. I'm delighted to be here. Dr. Rafeh Naqash:So, obviously, you are from Canada, and medicine, or approvals of drugs to some extent, and in fact approvals of gene testing to some extent is slightly different, which we'll come to learn about more today, compared to what we do in the US—and in fact, similarly, Europe versus North America to a large extent as well. Most of the time, we end up talking about gene testing in lung cancer. There is a lot of data, a lot of papers around single-gene panel testing in non-small cell lung cancer versus multigene testing. In fact, a couple of those papers have been published in JCO PO, and it has shown significant cost-effectiveness and benefit and outcomes benefit in terms of multigene testing. So this is slightly, you know, on a similar approach, but in a different tumor type. So, could you tell us first why you wanted to investigate this question? What was the background to investigating this question? And given your expertise in health economics and policy, what are some of the aspects that one tends or should tend to understand in terms of cost-effectiveness before we go into the results for this very interesting manuscript? Dr. Dean Regier:Yeah, of course, delighted to. So, one of the reasons why we're deeply interested in looking at comparative outcomes with respect to single- versus multigene testing— whether that's in a public payer system like Canada or an insurer system, a private system in the United States— is that the question around does multigene versus single-gene testing work, has not typically tested in randomized controlled trials. You don't have people randomized to multigene versus single-gene testing. And what that does, it makes the resulting evidence base, whether it's efficacy, safety, or comparative cost-effectiveness, highly uncertain. So, the consequence of that has been uneven uptake around the world of next-generation sequencing panels. And so if we believe that next-gen sequencing panels are indeed effective for our patients, we really need to generate that comparative evidence around effectiveness and cost-effectiveness. So we can go to payers, whether it be single payer or a private insurer, to say, "Here are the comparative outcomes." And when I say that uptake has been uneven, uptake there's been actually plenty, as you know, publications around that uneven uptake, whether it be in Europe, in the United States, in Canada. And so we're really interested in trying to produce that evidence to create the type of deliberations that are needed to have these types of technologies accessible to patients. And part of those deliberations, of course, is the clinical, but also in some contexts, cost-effectiveness. And so, we really start from the perspective of, can we use our healthcare system data, our learning healthcare system, to generate that evidence in a way that emulates a randomized controlled trial? We won't be able to do these randomized controlled trials for various, like really important and and reasons that make sense, quite frankly. So how can we mimic or emulate randomized controlled trials in a way that allows us to make inference around those outcomes? And for my research lab, we usually think through how do we do causal inference to address some of those biases that are inherent in observational data. So in terms of advanced melanoma, we were really interested in this question because first of all, there have been no randomized controlled trials around next-gen sequencing versus single-gene testing. And secondly, these products, these ICIs, immune checkpoint inhibitors, and BRAF and MEK inhibitors, they are quite expensive. And so the question really becomes: are they effective? And if so, to what extent are they cost-effective? Do they provide a good reason to have information around value for money? Dr. Rafeh Naqash:So now going to the biology of melanoma, so we know that BRAF is one of the tumor-agnostic therapies, it has approvals for melanoma as well as several other tumor types. And in fact, I do trials with different RAF-RAS kinase inhibitors. Now, one of the things that I do know is, and I'm sure some of the listeners know, is the DREAMseq trial, which was a melanoma study that was an NCI Cooperative Group trial that was led by Dr. Mike Atkins from Georgetown a couple of years back, that did show survival benefit of first-line immunotherapy sequencing. It was a sequencing study of whether to do first-line BRAF in BRAF-mutant melanoma followed by checkpoint inhibitors, or vice versa. And the immune checkpoint inhibitors followed by BRAF was actually the one that showed benefit, and the trial had to stop early, was stopped early because of the significant benefit seen. So in that context, before we approach the question of single-gene versus multigene testing in melanoma, one would imagine that it's already established that upfront nivolumab plus ipilimumab, for that matter, doublet checkpoint inhibitor therapy is better for BRAF-mutant melanoma. And then there's no significant other approvals for melanoma for NRAS or KIT, you know, mucosal melanomas tend to have KIT mutations, for example, or uveal melanomas, for that matter, have GNAQ, and there's no targeted therapies. So, what is the actual need of doing a broader testing versus just testing for BRAF? So just trying to understand when you started looking into this question, I'm sure you kind of thought about some of these concepts before you delved into that. Dr. Dean Regier:I think that is an excellent question, and it is a question that we asked ourselves: did we really expect any differences in outcomes between the testing strategies? And what did the real-world implementation, physician-guided, physician-led implementation look like? And so, that was kind of one of the other reasons that we really were interested is, why would we go to expanded multigene panel sequencing at all? We didn't really expect or I didn't expect an overall survival a priori. But what we saw in our healthcare system, what happened in our healthcare system was the implementation in 2016 of this multigene panel. And this panel covered advanced melanoma, and this panel cost quite a bit more than what they were doing in terms of the single-gene BRAF testing. And so when you're a healthcare system, you have to ask yourself those questions of what is the additional value associated with that? And indeed, I think in a healthcare system, we have to be really aware that we do not actually follow to the ideal extent randomized controlled trials or trial settings. And so that's the other thing that we have to keep in mind is when these, whether it's an ICI or a BRAF MEK inhibitor, when these are implemented, they do not look like randomized controlled trials. And so, we really wanted to emulate not just a randomized controlled trial, but a pragmatic randomized controlled trial to really answer those real-world questions around implementation that are so important to decision making. Dr. Rafeh Naqash:Sure. And just to understand this a little better: for us in the United States, when we talk about multigene testing, we generally refer to, these days, whole-exome sequencing with whole-transcriptome sequencing, which is like the nuclear option of of the testings, which is not necessarily cheap. So, when you talk about multigene testing in your healthcare system, what does that look like? Is it a 16-gene panel? Is it a 52-gene panel? What is the actual makeup of that platform? Dr. Dean Regier:Excellent question. Yeah, so at the time that this study is looking at, it was 2016, when we, as BC Cancer—so British Columbia is a population right now of 5.7 million people, and we have data on all those individuals. We are one healthcare system providing health care to 5.7 million people. In 2016, we had what I call our "home-brew" multigene panel, which was a 53-gene panel that was reimbursed as standard of care across advanced cancers, one of them being advanced melanoma. We have evolved since then. I believe in 2022, we are using one of the Illumina panels, the Focus panel. And so things have changed; it's an evolving landscape. But we're specifically focused on the 53-gene panel. It was called OncoPanel. And that was produced in British Columbia through the Genome Sciences Centre, and it was validated in a single-arm trial mostly around validity, etc. Dr. Rafeh Naqash:Thank you for explaining that. So now, onto the actual meat and the science of this project. So, what are some of the metrics from a health economy standpoint that you did look at? And then, methodology-wise, I understand, in the United States, we have a fragmented healthcare system. I have data only from my institution, for that matter. So we have to reach out to outside collaborators and email them to get the data. And that is different for you where you have access to all the data under one umbrella. So could you speak to that a little bit and how that's an advantage for this kind of research especially? Dr. Dean Regier:Yeah. In health economics, we look at the comparative incremental costs against the incremental effectiveness. And when we think about incremental costs, we think not just about systemic therapy or whether you see a physician, but also about hospitalizations, about all the healthcare interactions related to oncology or not that a patient might experience during their time or interactions with the healthcare system. You can imagine with oncology, there are multiple interactions over a prolonged time period depending on survival. And so what we try to do is we try to—and the benefit of the single-payer healthcare system is what we do is we link all those resource utilization patterns that each patient encounters, and we know the price of that encounter. And we compare those incremental costs of, in this case, it's the multigene panel versus the single-gene panel. So it's not just the cost of the panel, not just the cost of systemic therapy, but hospitalizations, physician encounters, etc. And then similarly, we look at, in this case, we looked at overall survival - we can also look at progression-free survival - and ask the simple question, you know, what is the incremental cost per life-year gained? And in that way, we get a metric or an understanding of value for money. And how we evaluate that within a deliberative priority setting context is we look at safety and efficacy first. So a regulatory package that you might get from, in our case, Health Canada or the FDA, so we look at that package, and we deliberate on, okay, is it safe and is it effective? How many patients are affected, etc. And then separately, what is the cost-effectiveness? And at what price, if it's not cost-effective, at what price would it be cost-effective? Okay, so for example, we have this metric called the incremental cost-effectiveness ratio, which is incremental cost in the numerator, and in this case, life-years gained in the denominator. And if it is around $50,000 or $100,000 per life-year gained—so if it's in that range, this ratio—then we might say it's cost-effective. If it's above this range, which is common in oncology, especially when we talk about ICIs, etc., then you might want to negotiate a price. And indeed, when we negotiate that price, we use the economic evaluation, that incremental cost-effectiveness ratio, as a way to understand at what price should we negotiate to in order to get value for money for the healthcare system. Dr. Rafeh Naqash:Thank you for explaining those very interesting terminologies. Now, one question I have in the context of what you just mentioned is, you know, like the drug development space, you talked about efficacy and safety, but then on the safety side, we talk about all-grade adverse events or treatment-related adverse events—two different terminologies. From a healthcare utilization perspective, how do you untangle if a patient on a BRAF therapy got admitted for a hypoxic respiratory failure due to COPD, resulting in a hospitalization from the cost, overall cost utilization, or does it not matter? Dr. Dean Regier:We try to do as much digging into those questions as possible. And so, this is real-world data, right? Real-world data is not exactly as clean as you'd get from a well-conducted clinical trial. And so what we do is we look at potential adverse event, whether it's hospitalization, and the types of therapies around that hospitalization to try- and then engage with clinicians to try to understand or tease out the different grades of the adverse event. Whether it's successful or not, I think that is a real question that we grapple with in terms of are we accurate in delineating different levels of adverse events? But we try to take the data around the event to try to understand the context in which it happens. Dr. Rafeh Naqash:Thank you for explaining that, Dean. So, again to the results of this manuscript, could you go into the methodology briefly? Believe you had 147 patients, 147 patients in one arm, 147 in the other. How did you split that cohort, and what were some of the characteristics of this cohort? Dr. Dean Regier:So, the idea, of course, is that we have selection criteria, study inclusion criteria, which included in our case 364 patients. And these were patients who had advanced melanoma within our study time period. So that was 2016 to 2018. And we had one additional year follow. So we had three total years. And what we did is that we linked our data, our healthcare system data. During this time, because the policy change was in 2016, we had patients both go on the multigene panel and on the single-gene BRAF testing. So, the idea was to emulate a pragmatic randomized controlled trial where we looked at contemporaneous patients who had multigene panel testing versus single-gene BRAF testing. And then we did a matching procedure—we call it genetic matching. And that is a type of matching that allows us to balance covariates across the patient groups, across the multigene versus BRAF testing cohorts. The idea again is, as you get in a randomized controlled trial, you have these baseline characteristics that look the same. And then the hope is that you address any source selection or confounding biases that prohibit you to have a clean answer to the question: Is it effective or cost-effective? So you address all those biases that may prohibit you to find a signal if indeed a signal is there. And so, what we did is we created—we did this genetic matching to balance covariates across the two cohorts, and we matched them one-to-one. And so what we were able to do is we were able to find, of those 364 patients in our pool, 147 in the multigene versus 147 in the single-gene BRAF testing that were very, very similar. In fact, we created what's called a directed acyclic graph or a DAG, together with clinicians to say, “Hey, what biases would you expect to have in these two cohorts that might limit our ability to find a signal of effectiveness?” And so we worked with clinicians, with health economists, with epidemiologists to really understand those different biases at play. And the genetic matching was able to match the cohorts on the covariates of interest. Dr. Rafeh Naqash:And then could you speak on some of the highlights from the results? I know you did survival analysis, cost-effectiveness, could you explain that in terms of what you found? Dr. Dean Regier:We did two analyses. The intention-to-treat analysis is meant to emulate the pragmatic randomized controlled trial. And what that does is it answers the question, for all those eligible for multigene or single-gene testing: What is the cost-effectiveness in terms of incremental life-years gained and incremental cost per life-years gained? And the second one was around a protocol analysis, which really answered the question of: For those patients who were actually treated, what was the incremental effectiveness and cost-effectiveness? Now, they're different in two very important ways. For the intention-to-treat, it's around population questions. If we gave single-gene or multigene to the entire population of advanced melanoma patients, what is the cost-effectiveness? The per-protocol is really around that clinical question of those who actually received treatment, what was the incremental cost and effectiveness? So very different questions in terms of population versus clinical cost and effectiveness. So, for the intention-to-treat, what we found is that in terms of life-years gained is around 0.22, which is around 2.5 months of additional life that is afforded to patients who went through the multigene panel testing versus the single-gene testing. That was non-statistically significant from zero at the 5% level. But on average, you would expect this additional 2.5 months of life. The incremental costs were again non-statistically significant, but they're around $20,000. And so when we look at incremental cost-effectiveness, we can also look at the uncertainty around that question, meaning what percentage of incremental cost-effectiveness estimates are likely to be cost-effective at different willingness-to-pay thresholds? Okay? So if you are willing to pay $100,000 to get one gain of life-years, around 52.8% of our estimates, in terms of when we looked at the entire uncertainty, would be cost-effective. So actually that meets the threshold of implementation in our healthcare system. So it's quite uncertain, just over 50%. But what we see is that decision-makers actually have a high tolerance for uncertainty around cost-effectiveness. And so, while it is uncertain, we would say that, well, the cost-effectiveness is finely balanced. Now, when we looked at the population, the per-protocol population, those folks who just got treatment, we actually have a different story. We have all of a sudden around 4.5 or just under 5 months of life gained that is statistically significantly different from zero, meaning that this is a strong signal of benefit in terms of life-years gained. In terms of the changes in costs or the incremental costs, they are larger again, but statistically insignificant. So the question now is, to what extent is it cost-effective? What is the probability of it being cost-effective? And at the $100,000 per life-year gained willingness-to-pay, there was a 73% chance that multigene panel testing versus single-gene testing is cost-effective. Dr. Rafeh Naqash:So one of the questions I have here, this is a clarification both for myself and maybe the listeners also. So protocol treatment is basically if you had gene testing and you have a BRAF in the multigene panel, then the patient went on a BRAF treatment. Is that correct? Dr. Dean Regier:It's still physician choice. And I think that's important to say that. So typically what we saw in both in our pre- and post-matching data is that we saw around 50% of patients, irrespective of BRAF status, get an ICI, which is appropriate, right? And so the idea here is that you get physician-guided care, but if the patient no longer performs on the ICI, then it gives them a little bit more information on what to do next. Even during that time when we thought it wasn't going to be common to do an ICI, but it was actually quite common. Dr. Rafeh Naqash:Now, did you have any patients in this study who had the multigene testing done and had an NRAS or a KIT mutation and then went on to those therapies, which were not captured obviously in the single-gene testing, which would have just tried to look at BRAF? Dr. Dean Regier:So I did look at the data this morning because I thought that might come up in terms of my own questions that I had. I couldn't find it, but what we did see is that some patients went on to clinical trials. So, meaning that this multigene panel testing allowed, as you would hope in a learning healthcare system, patients to move on to clinical trials to have a better chance at more appropriate care if a target therapy was available. Dr. Rafeh Naqash:And the other question in that context, which is not necessarily related to the gene platform, but more on the variant allele frequency, so if you had a multigene panel that captured something that was present at a high VAF, with suspicion that this could be germline, did you have any of those patients? I'm guessing if you did, probably very low number, but I'm just thinking from a cost-effective standpoint, if you identify somebody with germline, their, you know, first-degree relative gets tested, that ends up, you know, prevention, etc. rather than somebody actually developing cancer subsequently. That's a lot of financial gains to the system if you capture something early. So did you look at that or maybe you're planning to look at that? Dr. Dean Regier:We did not look at that, but that is a really important question that typically goes unanswered in economic evaluations. And so, the short answer is yes, that result, if there was a germline finding, would be returned to the patient, and then the family would be able to be eligible for screening in the appropriate context. What we have found in economic evaluations, and we've recently published this research, is that that scope of analysis is rarely incorporated into the economic evaluation. So those downstream costs and those downstream benefits are ignored. And when you- especially also when you think about things like secondary or incidental findings, right? So it could be a germline finding for cancer, but what about all those other findings that we might have if you go with an exome or if you go with a genome, which by the way, we do have in British Columbia—we do whole-genome and transcriptome sequencing through something called the Personalized OncoGenomics program. That scope of evaluation, because it's very hard to get the right types of data, because it requires a decision model over the lifetime of both the patients and potentially their family, it becomes very complicated or complex to model over patients' and families' lifetime. That doesn't mean that we should not do it, however. Dr. Rafeh Naqash:So, in summary Dean, could you summarize some of the known and unknowns of what you learned and what you're planning in subsequent steps to this project? Dr. Dean Regier:Our North Star, if you will, is to really understand the entire system effect of next-generation sequencing panels, exome sequencing, whole genomes, or whole genomes and transcriptome analysis, which we think should be the future of precision oncology. The next steps in our research is to provide a nice base around multigene panels in terms of multigene versus single-gene testing, whether that be colorectal cancer, lung cancer, melanoma, etc., and to map out the entire system implications of implementing next-generation sequencing panels. And then we want to answer the questions around, “Well, what if we do exomes for all patients? What if we do whole genomes and transcriptomes for all patients? What are the comparative outcomes for a true tumor-agnostic precision oncology approach, accounting for, as you say, things like return of results with respect to hereditary cancers?” I think the challenge that's going to be encountered is really around the persistent high costs of something like a whole-genome and transcriptome sequencing approach. Although we do see the technology prices going down—the "$1,000 genome" or “$6,000 genome" on whatever Illumina machine you might have—that bioinformatics is continuing to be expensive. And so, there are pipelines that are automated, of course, and you can create a targeted gene report really rapidly within a reasonable turnaround time. But of course, for secondary or what I call level two analysis, that bioinformatics is going to continue to be expensive. And so, we're just continually asking that question is: In our healthcare system and in other healthcare systems, if you want to take a precision oncology approach, how do you create the pipelines? And what types of technologies really lend themselves to benefits over and above next-generation sequencing or multigene panels, allowing for access to off-label therapies? What does that look like? Does that actually improve patients? I think some of the challenges, of course, is because of heterogeneity, small benefiting populations, finding a signal if a signal is indeed there is really challenging. And so, what we are thinking through is, with respect to real-world evidence methods and emulating randomized controlled trials, what types of evidence methods actually allow us to find those signals if indeed those signals are there in the context of small benefiting populations? Dr. Rafeh Naqash:Thank you so much, Dean. Sounds like a very exciting field, especially in the current day and age where cost-effectiveness, financial toxicity is an important aspect of how we improve upon what is existing in oncology. And then lots more to be explored, as you mentioned. The last minute and a half I want to ask about you as an individual, as a researcher. There's very few people who have expertise in oncology, biomarkers, and health economics. So could you tell us for the sake of our trainees and early career physicians who might be listening, what was your trajectory briefly? How did you end up doing what you're doing? And maybe some advice for people who are interested in the cost of care, the cost of oncology drugs - what would your advice be for them very briefly? Dr. Dean Regier:Sure. So I'm an economist by training, and indeed I knew very little about the healthcare system and how it works. But I was recruited at one point to BC Cancer, to British Columbia, to really try to understand some of those questions around costs, and then I learned also around cost-effectiveness. And so, I did training in Scotland to understand patient preferences and patient values around quality of care, not just quantity of life, but also their quality of life and how that care was provided to them. And then after that, I was at Oxford University at the Nuffield Department of Population Health to understand how that can be incorporated into randomized control trials in children. And so, I did a little bit of learning about RCTs. Of course, during the way I picked up some epidemiology with deep understanding of what I call econometrics, what others might call biostatistics or just statistics. And from there, it was about working with clinicians, working with epidemiologists, working with clinical trialists, working with economists to understand the different approaches or ways of thinking of how to estimate efficacy, effectiveness, safety, and cost-effectiveness. I think this is really important to think through is that we have clinical trialists, we have people with deep understanding of biostatistics, we have genome scientists, we have clinicians, and then you add economists into the mix. What I've really benefited from is that interdisciplinary experience, meaning that when I talk to some of the world's leading genome scientists, I understand where they're coming from, what their hope and vision is. And they start to understand where I'm coming from and some of the tools that I use to understand comparative effectiveness and cost-effectiveness. And then we work together to actually change our methods in order to answer those questions that we're passionate about and curious about better for the benefit of patients. So, the short answer is it's been actually quite a trajectory between Canada, the UK. I spent some time at the University of Washington looking at the Fred Hutch Cancer Research Center, looking at precision oncology. And along the way, it's been an experience about interdisciplinary research approaches to evaluating comparative outcomes. And also really thinking through not just at one point in time on-off decisions—is this effective? Is it safe? Is it cost-effective?—not those on-off decisions, but those decisions across the lifecycle of a health product. What do those look like at each point in time? Because we gain new evidence, new information at each point in time as patients have more and more experience around it. And so what really is kind of driving our research is really thinking about interdisciplinary approaches to lifecycle evaluation of promising new drugs with the goal of having these promising technologies to patients sooner in a way that is sustainable for the healthcare system. Dr. Rafeh Naqash:Awesome. Thank you so much for those insights and also giving us a sneak peek of your very successful career. Thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review, and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcast. Thank you. 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.      

In today's episode, supported by SpringWorks Therapeutics, we spoke with Christopher L. Moertel, MD, about the evolution of treatments for neurofibromatosis type 1 (NF1)–associated plexiform neurofibromas (PN). Dr Moertel is a professor and the Pediatric Neuro-Oncology Fellowship Program director in the Division of Pediatric Hematology/Oncology, a faculty member in the Department of Pediatrics, medical director of the Pediatric Neuro-Oncology and Neurofibromatosis Programs, co-medical director of the Katie Hageboeck Children's Cancer Research Fund Clinic, clinical neuro-oncology leader of the Brain Tumor Program, and the Kenneth and Betty Jayne Dahlberg Professor at the University of Minnesota School of Medicine in Minneapolis. In our exclusive interview, Dr Moertel discussed the expansion of the NF1-associated PN treatment paradigm to include the MEK inhibitors mirdametinib (Gomekli) and selumetinib (Koselugo); the benefits of offering treatment options in oral formulations; the toxicities associated with MEK inhibitors; the importance of managing these adverse effects to ensure long-term treatment adherence; and the need for continued oncology education to optimize treatment outcomes for this population.

Konuğumuz ODTÜ Mimarlık Fakültesi Mimarlık Bölümü Ar. Gör. Semih Solak ile “Henri Lefebvre Aracılığıyla Latife Tekin Romanlarında Mimarlık, Kent ve Mekân Okuması” çalışması üzerine konuşuyoruz.  

Enjoyed our podcast? Shoot us a text and let us know—because great conversations never end at the last word!This week on TezTalks Radio, Marissa Trew sits down with Michael Alexander—better known as MEK—pixel artist, developer, and one of the minds behind Sbjkt.xyz. From his design roots to building tools that empower digital artists, MEK shares how Tezos helped shape his artistic voice and his vision for the future of Web3 creativity.Our special guest is MEK, where pixel art meets purposeful tech on Tezos.

Pakrat Estukyan ile Türkiye'nin ve Ermeni toplumunun gündemini ele alıyor, Sevag Balıkçı ve babası Garbis Balıkçı'yı anıyoruz. İkinci ve üçüncü bölümde konuğumuz yazar ve araştırmacı Nesim Ovadya İzrail ile Hrant Dink Vakfı'nın geride kalan hafta boyunca düzenlediği "Anma ve Alternatif Bir Gelecek İçin 23,5 Hafıza Mekânı'nda Buluşalım" başlıklı etkinlikler dizisi içinde gerçekleştirdiği '24 Nisan'ın İzinde' temalı Pangaltı hafıza yürüyüşünü ve bu yürüyüşte hikâyelerini aktardığı Ermeni aydınları konuşuyoruz 

Pakrat Estukyan ile Türkiye'nin ve Ermeni toplumunun gündemini ele alıyor, Sevag Balıkçı ve babası Garbis Balıkçı'yı anıyoruz. İkinci ve üçüncü bölümde konuğumuz yazar ve araştırmacı Nesim Ovadya İzrail ile Hrant Dink Vakfı'nın geride kalan hafta boyunca düzenlediği "Anma ve Alternatif Bir Gelecek İçin 23,5 Hafıza Mekânı'nda Buluşalım" başlıklı etkinlikler dizisi içinde gerçekleştirdiği '24 Nisan'ın İzinde' temalı Pangaltı hafıza yürüyüşünü ve bu yürüyüşte hikâyelerini aktardığı Ermeni aydınları konuşuyoruz

Modernite insanların köylerini aldı. Sıkıntı olmadı. Mekânlarını aldı. Sıkıntı olmadı. Zamanlarını aldı. Sıkıntı olmadı. Çiçeklerini aldı. Sıkıntı olmadı. Asmalarını aldı. Sıkıntı olmadı. Ağaçlarını aldı. Sıkıntı olmadı. Kuşlarını aldı. Sıkıntı olmadı. Karizmasını aldı. Sıkıntı olmadı. Değerlerini aldı. Sıkıntı olmadı. Ahlâkını aldı. Sıkıntı olmadı.

Featuring an interview with Dr Christopher L Moertel, including the following topics: Overview of neurofibromatosis type 1(NF1) (0:00) Cancer in NF1 (8:38) Dermatologic manifestations of NF1 (16:57) Treatment options for NF1 (20:43) Malignant peripheral nerve sheath tumors (MPNST) (25:14) FDA-approved MEK inhibitors for NF1 plexiform neurofibromas (28:36) Specializing in NF (44:44) CME information and select publications

Featuring a slide presentation and related discussion from Dr Christopher L Moertel, including the following topics: Overview of neurofibromatosis (0:00) Common clinical manifestations of neurofibromatosis type 1 (NF1) (14:13) Role of MEK inhibitors in the management of NF1 plexiform neurofibromas (29:30) CME information and select publications

Welcome to Episode 077 of the Beyond the Diagnosis Podcast. Curious about the latest research on treating Erdheim-Chester disease (ECD)? In this episode, we're chatting with Drs. Goyal, Abeykoon, and Acosta-Medina about their study on MEK inhibitors and what it means for patients. We'll explore how our understanding of histiocytic disorders has evolved, the challenges doctors face in choosing the right treatment, and why real-world data is so important. Plus, we'll dive into how genetic mutations can affect patient responses and why ongoing research and collaboration are key to improving outcomes. Tune in for an inside look at the latest in ECD research! Let us know what you think! Leave us a review, drop us a comment or share an idea for a future podcast with us at podcast@histio.org.   Take a screenshot and tag us @histiocytosis_association on Instagram. We'd love to hear your feedback!  Be sure to subscribe so you can be notified the moment a new episode of Beyond the Diagnosis is released.  Resources mentioned in the podcast: Survivorship Study: https://histio.org/uab-survivorship-study-and-its-impact-so-far/ Email histio@uabmc.edu  To make a gift to help the Association keep doing the important work that we're doing, go to www.histio.org and click on the big green “Donate” button in the upper right. Follow the Histiocytosis Association on social media: Facebook: https://www.facebook.com/histio Twitter: @histiocytosis Instagram: histiocytosis_association YouTube: https://www.youtube.com/histiocytosisassoc  Music: “Heroes” by Noah Smith 

Molecular differences in the profiles of low grade serous ovarian cancer (LGSOC) and high-grade SOC substantiate the need to find unique, differentiated treatment options for each epithelial ovarian cancer subtype, according to Kathleen N. Moore, MD, MS. CancerNetwork® spoke with Moore, Virginia Kerley Cade Endowed Chair of Cancer Development, associate director of Clinical Research at the Stephenson Cancer Center, director of the Oklahoma TSET Phase I Program and professor in the Section of Gynecologic Oncology the University of Oklahoma Health Sciences Center, about distinguishing low grade serous ovarian cancer from other types of ovarian cancer, current treatment options and clinical trials evaluating new regimens, as well as managing treatment in younger patients with or those seeking to preserve fertility. Moore began by differentiating LGSOC from high grade SOC, stating that this disease typically occurred in younger patients and was primarily characterized by MAP kinase alterations, specifically KRAS and BRAF mutations. She then discussed the emergence of endocrine therapies in this indication owing to the presence of estrogen receptors. Additionally, first line treatment was discussed, with the standard of care defined by primary cytoreduction followed by paclitaxel and carboplatin. She then highlighted multiple clinical trials assessing alternative treatment in this indication, particularly involving the use of letrozole (Femara). Other clinical trials evaluated the use of CDK4/6 inhibition plus fulvestrant or BRAF and MEK inhibition with letrozole, with Moore emphasizing the potential for these studies to shift the treatment paradigm in the frontline setting. Furthermore, she suggested that CDK4/6 inhibition may help enhance responses in patients with recurrent LGSOC. Moore then highlighted treatment concerns for younger patients and those seeking to preserve fertility, while expressing the importance of understanding a patient's goals, which may help optimize outcomes. She concluded by reiterating the importance of designing trials and tailoring treatment considering the molecular profile of LGSOC.

In our newest sub-series, Primus Legacy, we speak with pro musicians who have a fondness for Primus, and how the music impacted their musical paths. We begin with the great Tye Zamora, who you may know from Alien Ant Farm, 'mēk, and his stints subbing in for bands such as Slightly Stoopid. Tye charts his Primus superfandom and how it influenced his development as a bassist, and handles with ease Frankie's rapid-fire questions. We should note that his a capella versions of Primus tunes are top notch. Find Tyehttps://www.instagram.com/tyemus/https://www.instagram.com/mekband/https://www.youtube.com/@mekband2341Get involvedInstagramFacebookEmailBurn your money 

#KöşedekiKitapçı'da bugün

İlk bölümde Pakrat Estukyan ile Hrant Dink'i anıyor ve Agos'un bu haftaki özel sayısından kesitler aktarıyoruz. İkinci bölümde 23,5 Hrant Dink Hafıza Mekânı'nda hafta boyunca devam eden 'Hakikat İçin Söyleşiler' dizisindeki 'Akrabamı Arıyorum' panelinin konuşmacılarından psikolog Jülide Aral, Müslümanlaş(tırıl)mış Ermeniler ile gerçekleştirdiği grup çalışmalarından anonim notlar aktarıyor ve ayrıca kadınların 1915 ve benzeri dönemlerde yaşadıkları travmaların nasıl günümüze kadar nasıl uzandığına değiniyor.   

İlk bölümde Pakrat Estukyan ile Hrant Dink'i anıyor ve Agos'un bu haftaki özel sayısından kesitler aktarıyoruz. İkinci bölümde 23,5 Hrant Dink Hafıza Mekânı'nda hafta boyunca devam eden 'Hakikat İçin Söyleşiler' dizisindeki 'Akrabamı Arıyorum' panelinin konuşmacılarından psikolog Jülide Aral, Müslümanlaş(tırıl)mış Ermeniler ile gerçekleştirdiği grup çalışmalarından anonim notlar aktarıyor ve ayrıca kadınların 1915 ve benzeri dönemlerde yaşadıkları travmaların nasıl günümüze kadar nasıl uzandığına değiniyor.  

Göç olgusu, köklü anlam değişiklikleri geçiriyor son beş asırdır... Göçebe toplumlardan yerleşik toplumlara, oradan “sanal göçebelik hayatı” yaşayan insanlara geçiş süreci çok travmatik oldu... Önceden toplumlar yer değiştiriyordu: Mekânda gerçekleşen bir yolculuk eylemiydi göç olgusu.

BUFFALO, NY- October 29, 2024 – A new #casereport was #published in Oncotarget's Volume 15 on October 11, 2024, entitled “Complete response to encorafenib plus binimetinib in a BRAF V600E-mutant metastasic malignant glomus tumor.” As highlighted in the abstract, glomus tumors (GT) are rare mesenchymal neoplasms originating in dermal arteriovenous structures involved in thermoregulation. While generally benign, some can exhibit malignant features, leading to aggressive behavior, metastasis, and limited response to standard chemotherapy. The identification of the BRAF V600E mutation in certain malignant GT cases offers a promising therapeutic target. In their paper, researchers Marta Arregui, Antonio Calles, María del Mar Galera, Ana Gutiérrez, Carlos López-Jiménez, Carolina Agra, Adriana Fernández, Natalia Gutiérrez, María de Toro and Rosa Álvarez from Gregorio Marañón University Hospital and Fundación Jiménez Díaz University Hospital in Madrid, Spain, document a remarkable clinical and metabolic response in a case of metastatic BRAF V600E-mutated glomangiosarcoma treated with the combination of encorafenib and binimetinib. They report on a 45-year-old male patient with stage IV malignant GT carrying a BRAF V600E mutation, who was treated systemically with encorafenib and binimetinib. This approach led to a swift clinical and radiological improvement. “To our knowledge, our patient represents the first reported case of a metastatic malignant GT successfully treated with BRAF and MEK inhibitors, achieving a long-lasting complete morpho-metabolic response.” DOI - https://doi.org/10.18632/oncotarget.28654 Correspondence to - Carlos López-Jiménez - clopezjimenez@atbsarc.org Video short - https://www.youtube.com/watch?v=xjbj3Iu16P4 Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28654 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, malignant glomus tumor, glomangiosarcoma, BRAF V600E, agnostic treatment, targeted therapy About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

“One of the things that's really challenging with these BRAF inhibitors, plus MEK inhibitors, is that there's a huge scope of potential toxicity, and they're not all going to happen. So I think that there's a real need to educate patients that they need to work with us so that when a toxicity develops, we can help address it. We can help think of strategies, whether it be medication strategies or whether it be other types of strategies, to make them feel better,” Rowena “Moe” Schwartz, PharmD, BCOP, FHOPA, professor of pharmacy practice at James L. Winkle College of Pharmacy at the University of Cincinnati in Ohio, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about the BRAF inhibitor drug class. Music Credit: “Fireflies and Stardust” by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0  Earn 0.5 contact hours of nursing continuing professional development (NCPD) by listening to the full recording and completing an evaluation at courses.ons.org by September 13, 2026. The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation. Learning outcome: Learners will report an increase in knowledge related to BRAF inhibitors.  Episode Notes  Complete this evaluation for free NCPD.  Oncology Nursing Podcast episodes: Pharmacology 101 series Episode 242: Oncology Pharmacology 2023: Today's Treatments and Tomorrow's Breakthroughs ONS Voice articles: First-Line Combination Immunotherapy Prolongs Survival in BRAF Advanced Melanoma Predictive and Diagnostic Biomarkers: Identifying Variants Helps Providers Tailor Cancer Surveillance Plans and Treatment Selection BRAF Mutations Guide Treatment in Metastatic Colorectal Cancer Melanoma Prevention, Screening, Treatment, and Survivorship Recommendations Nursing Considerations for Melanoma Survivorship Care ONS books: Chemotherapy and Immunotherapy Guidelines and Recommendations for Practice (second edition) Clinical Guide to Antineoplastic Therapy: A Chemotherapy Handbook (fourth edition)  Clinical Journal of Oncology Nursing article: BRAF/MEK Inhibitor Therapy: Consensus Statement From the Faculty of the Melanoma Nursing Initiative on Managing Adverse Events and Potential Drug Interactions Oncology Nursing Forum articles:  Antineoplastic Therapy Administration Safety Standards for Adult and Pediatric Oncology: ASCO-ONS Standards MAPK Pathway–Targeted Therapies: Care and Management of Unique Toxicities in Patients With Advanced Melanoma ONS Learning Library: Oral Anticancer Medication ONS Biomarker Database Oral Chemotherapy Education Sheets To discuss the information in this episode with other oncology nurses, visit the ONS Communities.  To find resources for creating an Oncology Nursing Podcast™ Club in your chapter or nursing community, visit the ONS Podcast Library. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org. Highlights From This Episode “BRAF is a gene found on chromosome 7 that encodes for protein that is also called BRAF. And this protein is really important in cell growth and signaling and promoting cell division, as well as some other functions. When you have a variant in BRAF, this causes that gene to turn on the protein and to keep it on. That means there's a continual signaling to the cell to keep dividing and there's no instruction to stop dividing.” TS 2:24 “[Side effects] are things like pyrexia, fatigue, muscle aches, those things. There is definitely rash. And as I mentioned, there are those secondary skin cancers, which are significantly less with the combination with MEK inhibitors. GI [gastrointestinal] toxicities are not uncommon. Different patients, different tolerance in terms of like nausea, taste changes. I think taste changes are one of the ones that are really challenging.” TS 10:17  “How to get rid of the agents when they're done—I love that our institution has a program where they can bring them back, and we can help them get rid of it, because people just don't know how to get rid of them when they're no longer taking them. And you really don't want them having them around the house.” TS 15:28 “Don't assume that you can modify formulation. So if there is someone who can't take oral pills and has to use a suspension, some drugs, there's clear indications how to do that. Other ones there's not. So collaborating on that is a really good thing. I hear too much where people will say, ‘Just crush the pill.' These are not the drugs that you want to do that with.” TS 23:07

Doğa Konuşmaları'nda bu hafta, doğanın acil ve yakıcı gündemine kültür - sanat çerçevesinde odaklanıyoruz. Araştırma ve Programlar Direktörü Fatma Çolakoğlu, "Bitkiler ve Bitkileri Sevenler için Sıcak Toprak Sesleri"ni, Programlar Sorumlusu Eylül Şenses ise "Havaya Dair" sergisini anlatıyor. - Bitkiler ve Bitkileri Sevenler için Sıcak Toprak Sesleri Adını elektronik müziğin öncülerinden Mort Garson'ın bitkilere ithaf ettiği Mother Earth's Plantasia (1976) albümünden alan Bitkiler ve Bitkileri Sevenler için Sıcak Toprak Sesleri, Salt Beyoğlu'ndaki Kış Bahçesi'nde art arda yer alacak bir dizi ses enstalasyonundan oluşuyor. Garson'ın, bitkilerin gelişiminde müzik ve ses dalgalarının etkisini irdeleyen The Secret Life of Plants [Bitkilerin Gizli Yaşamı] (1973) kitabından etkilenerek hazırladığı albüm, Los Angeles'taki Mother Earth isimli çiçek dükkânında “bitkilerin dinlemesi için” kaydedilir ve dükkândan çiçek alanlara hediye edilir. Sentezleyici ile elektronik sesleri yenilikçi biçimlerde kullanan bu çalışmadan esinlenen seri, Kış Bahçesi'ndeki bitkiler ile ses ve müzik üzerinden ilişki kuran üretimleri bir araya getiriyor. Bitkiler ve Bitkileri Sevenler için Sıcak Toprak Sesleri, L'Internationale‘nin Museum of the Commons [Müşterekler Müzesi] projesi kapsamında ve EK BİÇ YE İÇ desteğiyle gerçekleştirilmektedir. Mekâna özgü olarak kurgulanan enstalasyonlar, 5 Haziran 2024–6 Nisan 2025 tarihlerinde beş ayrı programda sunulacak. - Havaya Dair Milano merkezli disiplinlerarası tasarım stüdyosu 2050+ tarafından Salt Beyoğlu'ndaki Forum alanı için tasarlanan Havaya Dair, maddi, işitsel ve görsel deneyler aracılığıyla hava kirliliğinin toplumsal ve ekolojik boyutlarını odağına alıyor. Sergide, ziyaretçileri havanın maddeselliğiyle ilişki kurmaya teşvik eden bir dizi müdahale yer alıyor: Azot dioksit, ozon, karbon dioksit, partikül madde, kükürt dioksit dâhil olmak üzere havanın kimyasal bileşimini ortaya çıkaran ve her biri farklı zehirlilik derecelerine karşılık gelen bir renkle tasvir edilmiş; zehirliliğin farklı ölçeklerdeki yaygınlığını gösteren veri ve görüntülerin işlendiği perdeler, havadaki bu maddelerin etkileşiminin tetiklediği kimyasal reaksiyonlar sonucu ortaya çıkan koşulları duyumsanabilir kılan bir ses enstalasyonu ile İstanbul'un gökyüzünün, genellikle hareketsiz ve üç boyutlu nesneleri kaydetmek için kullanılan fotogrametri tekniğiyle hazırlanmış bir animasyonu. Böylece, yeryüzünü çevreleyen gaz hâlindeki görünmez maddelerin belgelenip cisimleştirilmesi amaçlanıyor. Havaya Dair, soluduğumuz havaya içkin karmaşıklıklara ilişkin anlayışımızı genişletmeye yönelik bir davet. Yalnızca havaya nüfuz eden ve hava yoluyla yayılan zehirliliği değil, bu zehirliliğin işaret ettiği karmaşık toplumsal ve politik sonuçları, yerel ve küresel izlekleri, gezegen ölçeğindeki inkâr edilemez bağıntıları da irdeliyor. Bir bölgedeki faaliyetlerin geniş çaplı etkiler yarattığı ortak bir alan olarak havayı odağına alan sergi, temiz ve solunabilir havanın müşterek ve evrensel bir hak olduğu bir dünya için kolektif eylemin gerekliliğini de gündeme getiriyor. 8 Mayıs-18 Ağustos tarihlerinde Salt Beyoğlu'ndaki Forum alanında ziyarete açık olacak sergi paralelindeki kamu programları saltonline.org ve Salt'ın sosyal medya kanallarında duyurulacak. - Meraklısı için: Bitkiler ve Bitkileri Sevenler için Sıcak Toprak Sesleri: https://saltonline.org/tr/2739/bitkiler-ve-bitkileri-sevenler-icin-sicak-toprak-sesleri?home Havaya Dair:https://saltonline.org/tr/2725/sergi-havaya-dair?home - Neden Doğa Konuşmaları? #DoğaKonuşmaları cumartesi saat 19.30'da, pazar saat 10.30'da NTVRadyo'da. Merak ettiklerimizi, bilmemiz gerekenleri uzmanlara soruyor, yanıtları bulmayı, yeni ufuklar açmayı istiyoruz. Çünkü biz sürdürülebilir gelecek için, doğayla uyumlu, sağlıklı bir yaşam istiyoruz.

BUFFALO, NY- August 14, 2024 – A new #casereport was #published in Oncotarget's Volume 15 on July 17, 2024, entitled, “Rapid but nondurable response of a BRAF exon 15 double-mutated spindle cell sarcoma to a combination of BRAF and MEK inhibitors.” As noted in the introduction of the Abstract, the BRAF V600E substitution predicts a cancer's sensitivity to BRAF inhibitor therapy, though the mutation is rarely found in soft-tissue sarcomas. Researchers Kseniya Sinichenkova, Iliya Sidorov, Nataliya Kriventsova, Dmitriy Konovalov, Ruslan Abasov, Nataliya Usman, Alexander Karachunskiy, Galina Novichkova, Dmitriy Litvinov, and Alexander Druy from the Dmitriy Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology (Ministry of Healthcare of Russian Federation) and the Research Institute of Medical Cell Technologies in Yekaterinburg, Russia, describe a case of undifferentiated spindle cell sarcoma that exhibited primary insensitivity to standard chemotherapy and a pronounced but non-sustained response to BRAF/MEK inhibitors at recurrence. The case presentation involved a 13-year-old girl that was diagnosed with low-grade spindle cell sarcoma of pelvic localization, BRAF exon 15 double-mutated: c.1799T>A p.V600E and c.1819T>A p.S607T in cis-position. “This is the first report of spindle cell sarcoma BRAF V600E/S607T double-mutated, responding to a combination of B-Raf and MEK inhibitors.” DOI - https://doi.org/10.18632/oncotarget.28606 Correspondence to - Kseniya Sinichenkova - ksinichenkova@gmail.com Video short - https://www.youtube.com/watch?v=QWEAaaixPxE Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28606 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, undifferentiated sarcoma, BRAF V600E mutation, low grade spindle cell sarcoma, abdominal cocoon About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

In this week's episode Nick and Eric talk about a new and emerging style of Ork list which Eric piloted at the American Team Championships. We talk about Eric's relationship with 40k over the years, how to get better at the game, and hear from the champ himself about how his team won the event.In part two of the show, available to our patrons we talk about Eric's match ups, theory, and tactics, along with his teams overall strategy and composition.To support the show please check out our patreon for weekly exclusive content patreon.com/aow40kLink to War Room --> thewarroom.vhx.tvOrksKult of SpeedStrike Force (2000 Points)CHARACTERSDeffkilla Wartrike (90 Points)• 1x Boomstikks1x Killa jet1x Snagga klaw• Enhancements: WazblastaDeffkilla Wartrike (80 Points)• 1x Boomstikks1x Killa jet1x Snagga klawDeffkilla Wartrike (80 Points)• 1x Boomstikks1x Killa jet1x Snagga klawWarboss (65 Points)• Warlord• 1x Attack squig1x Kombi-weapon1x Power klaw1x Twin sluggasOTHER DATASHEETSBoomdakka Snazzwagon (80 Points)• 1x Big shoota1x Grot blasta1x Mek speshul1x Spiked wheelsDeffkoptas (200 Points)• 6x Deffkopta• 6x Kopta rokkits6x Slugga6x Spinnin' bladesDeffkoptas (200 Points)• 6x Deffkopta• 6x Kopta rokkits6x Slugga6x Spinnin' bladesDeffkoptas (200 Points)• 6x Deffkopta• 6x Kopta rokkits6x Slugga6x Spinnin' bladesGretchin (40 Points)• 10x Gretchin• 10x Close combat weapon10x Grot blasta• 1x Runtherd• 1x Runtherd tools1x SluggaGretchin (40 Points)• 10x Gretchin• 10x Close combat weapon10x Grot blasta• 1x Runtherd• 1x Runtherd tools1x SluggaKommandos (135 Points)• 1x Bomb Squig1x Distraction Grot• 9x Kommando• 1x Breacha ram8x Choppa8x Slugga• 1x Boss Nob• 1x Power klaw1x SluggaKustom Boosta-blasta (75 Points)• 1x Burna exhausts1x Grot blasta1x Rivet kannon1x Spiked ramMegatrakk Scrapjet (80 Points)• 1x Nose drill1x Rokkit kannon2x Twin big shoota1x Wing missilesNobz (210 Points)• 2x Ammo Runt• 1x Boss Nob• 1x Power klaw1x Slugga• 9x Nob• 9x Power klaw9x SluggaShokkjump Dragsta (75 Points)• 1x Kustom shokk rifle1x Rokkits1x Saw bladesWarbikers (140 Points)• 5x Warbiker• 5x Choppa5x Close combat weapon5x Twin dakkagun• 1x Boss Nob on Warbike• 1x Close combat weapon1x Power klaw1x Twin dakkagunWarbikers (140 Points)• 5x Warbiker• 5x Choppa5x Close combat weapon5x Twin dakkagun• 1x Boss Nob on Warbike• 1x Close combat weapon1x Power klaw1x Twin dakkagunWarbikers (70 Points)• 2x Warbiker• 2x Choppa2x Close combat weapon2x Twin dakkagun• 1x Boss Nob on Warbike• 1x Close combat weapon1x Power klaw1x Twin dakkagun

Chcete zjistit: Jak vyroste česká firma na 5 miliard obratu? Jak udržet náročnou firemní kulturu i pro 200 zaměstnanců? Proč si dávat pracovní schůzky v 6 hodin ráno v Mekáči? Odpovědi v novém díle Nelidských zdrojů.

TEXT JUCKRyan Day, Jack Sawyer, Denzelle Burke and MEK take absolutely own the pressure of this season. JR from the VOICE OF COLLEGE FOOTBALL joins Juck to tell us how media days was.Join us on YouTube to see the Best Damn Buckeye Studio in the land! Go Bucksemail: juckonbucks@gmail

Playlist: Tank and the Bangas, featuring Pell - Friend GoalsKay Young, featuring Ego Ella May - Woe is MeK!MMORTAL - LoveT H R O N E, featuring kllz - ChainbearersOnra - Close Your Eyes and RememberDirty Art Club - High LifeLund Quartet - Love's MadnessMonster Rally - Sister OwlsGizmo Varillas - ParaisoMenahan Street Band - Queens HighwayKhruangbin - Hold Me Up (Thank You)Jalen Ngonda - If You Don't Want My LoveThee Sacred Souls - Running AwayHajaj - Love to LastThe Regime, featuring Pro Uno - Sunny DayAladean Kheroufi - Here With MeBobby Oroza, featuring Cold Diamond & Mink - I Got LoveIndigo Rose - LUVBADBADNOTGOOD, featuring Samuel T. Herringe - Time Moves Slow

On today's episode, we talk about MeK, an Iranian opposition group operating out of Albania who's entire purpose is to overthrow the Islamic republic of Iran. Also, they're pretty much a cult, definitely a terrorist group, and has been buying up US politicians since the early 00's. Enjoy https://www.patreon.com/brohistory #306 Learn more about your ad choices. Visit megaphone.fm/adchoices

Find me and the show on social media @DrWilmerLeon on X (Twitter), Instagram, and YouTube Facebook page is www.facebook.com/Drwilmerleonctd   FULL TRANSCRIPT Wilmer Leon (00:00:00): As I'm sure most of you know by now, according to Iran State Media, Iran's President Ibrahim Raisi, the country's foreign minister, Hussein Amir Abdulah, have died in a helicopter crash. There are a number of questions that this unfortunate turn of events presents. Was this simply an unfortunate accident as their helicopter traveled in dense fog along Iran's border with Azerbaijan, was the helicopter taken down? What's next for Iran? What's next for the region? Announcer (00:00:43): Connecting the dots with Dr. Wilmer Leon, where the analysis of politics, culture, and history converge. Wilmer Leon (00:00:51): Welcome to the Connecting the Dots podcast with Dr. Wilmer Leon. I'm Wilmer Leon. We have a tendency to view current events as though they occur in a vacuum, failing to understand the broader historical context in which most events take place. During each episode of this program, my guests and I have probing, provocative and in-depth discussions that connect the dots between the events and the broader historic context in which they occur. This enables you to better understand and analyze these events that impact the global village in which we live. For insight into these issues, let's go to Beirut Lebanon. Let my guest, he's an award-winning broadcaster and independent journalist based in Beirut Lebanon. He's a policy consultant with the Community Media Advocacy Center, and you can find him and his work at Free Palestine dot video. He's Laith Marouf Laith. As always, welcome back. Laith Marouf (00:01:53): Thank you for having me. It's always a pleasure to be with you. Wilmer Leon (00:01:56): So let me start with who was former president Ibrahim Raisi. The western media describes him in less than glowing terms as a religious hardliner. He's seen as a potential successor to Supreme leader Ayatollah Ali Hamani. He was a former judge and allegedly a member of what the West calls the death commission, which forcibly disappeared and traditionally executed in secret thousands of political dissidents. Those are the allegations who was former President Ibrahim Raisi. Laith Marouf (00:02:41): Well, definitely he was part of the first generation that lived the Islamic Revolution and were on the front lines during the massacres that Iraq and the West commissioned in Iran, the use of chemical weapons against Iranians paid for by the Germans and the us. So he has that credential of living that revolution, and he was a judge and the accusations that are keep on being repeated there of thousands of prisoners being executed, we're talking about the terrorists that are part of the Mujah, the MEK terrorist organization that was housed in Iraq and funded by the West and is now housed in Albania that was responsible for the killing of almost 70,000 people in Iran through their terror campaign. That includes the killing of ministers and the government officials at the time. So the accusation against him is that he crushed the vessels, the terrorists that work for the CIA, that's his accusation against him and otherwise he was a judge and very respected within the country because of this background. Actually, whatever accusation that the west has against him as a discrediting thing, in reality, it is a positive thing for his reputation in Iran because of how he defended Iran against the terrorist. (00:04:31): The hype that we saw over the last month or so in the media about Rasi being going to be the next ayatollah after Hamina steps down, that there is no truth to that in terms of any speaking of that in Iranian society or Iranian media. In fact, we should take it as an indicator of that he was going to be assassinated. There's something that say it has the Sid Hasan Astra, the Secretary General of Hezbollah after the assassination of General Soleimani in 2020 by Trump. So Sid Hasan Asra a speech. He spoke about how when the media in the West suddenly gives attention to a leader in the region out of the blue and start giving them very high stature, that is maybe true, but it's not. That's an indicator of an assassination coming and that he spoke to General Soleimani the day before he was assassinated while he was in Beirut about that and warned him as he was flying to Baghdad on a domestic flight that this is actually even more worrisome that he was on a domestic flight given all this attention. So now we see kind of the same thing happening here, all this hype being pumped about Raisi in the month before the assassination, specifically since the retaliation of Iran against the assassination of its diplomats in the Damascus. So I see it as actually an indicator that he was going to be assassinated and now that's what actually happened. Wilmer Leon (00:06:26): To your point that this was an assassination, there are a couple of things that as soon as I heard that the helicopter went down that came to mind. One was, was it taken down? Apparently there were three helicopters flying in formation and his helicopter was one of the three, and it seems as though it just dropped out of the sky. They keep talking about the terrain, they keep talking about the fog. I know some US military trained helicopter pilot certified helicopter pilots. The first thing I did was call them and ask them when you heard fog, when you heard terrain, when you heard the helicopter went down. I said, what's the first thing that came to your mind? They all said, oh, they took that thing out the sky and they said, first of all, they all said to me as certified pilots, we would never have crashed our helicopter. That just was not going to happen short of some catastrophic mechanical failure. They said, which by the way, we are trained to deal with. They told me the quality of pilots that they have in Iran that those pilots, they say this goes all the way back to when Iran was an ally of the United States during the Shaw's time and that the protocols that were in place then are many of the same protocols that they follow today. (00:08:03): So there was a lot of information opinion that they gave to me, which said, and then they even mentioned, you got to understand the MEK along that region, that Azerbaijan is an ally of Israel or that there are elements within Azerbaijan that are so connect some of those dots for me please. Are these just the opinions of Ill-informed individuals or they said for the fact that the thing dropped out the sky without it, even a mayday call indicates that something was wrong here? Laith Marouf (00:08:43): Yeah, I mean, you mentioned a lot of important things. So first off, obviously there was no made call as you said. So we don't have any information about some problem happening on the helicopter. The other is that there was two other helicopters with it and they continued to reach their target and destination and they reached it. That's the question also, why didn't they stop and fly back and look for the other helicopter? That's a big indicator that there's something wrong that happened there that is not just a regular crash. The other thing is that the Iranian government took a very long time to really show us what happened and tell us that Rasi and his companions were dead. In fact, the hours after the crash, the Minister of Internal Security told the whole world that they received two calls from survivors on the plane, on the helicopter, and later on all the way around 2:00 AM PA on time, again, the minister of internal claim that they received a call from one of the crew members on the helicopter all the way that late saying that they were hearing the ambulances or the sirens in the area. (00:10:13): So while all of this was happening, the minute the helicopter crash was announced and called a soft landing, and then it took so long, I mean, this is Iran that has satellites. This is Iran that has drones that can fly and reach Israel and hit their targets thousands of kilometers away. I thought in my mind that either from the first minute that Raisi and his team were assassinated and they're dead, and the Iranians were delaying the announcements so they can tidy up their house and prepare for the transition and think about what they want to do if there's an actual assassination or that the Iranians were hiding the fact that he was alive and they were just milking it for support. This is what I thought during the whole night as they were doing this search, and obviously for them to finally tell us they're dead, that's in me confirmed that there was an assassination. (00:11:21): None of the stories that came from the Iranian government to the media during the quote search made any sense. And so now we know they're killed. I believe the Iranian government knows that they were killed and how they were killed, and I think given the fact that the Israelis have a tendency of assassinating political leaders as retaliation for their failures on the battlefield, this is historic. Look at how even recently, look at how they assassinated Hamas leadership in Beirut because they were failing on the ground in Gaza and they failed in the battle with Iran after they targeted the embassy in Damascus and Iran landed a huge blow on them and they were not able to retaliate. So their only usual behavior is to assassinate political leaders, and that's what we saw. The question is because Netanyahu attempted last month when attacking the embassy to drag the United States into a war because he sees Israel losing the battle on the ground. (00:12:47): He sees that Israel cannot even fight Hezbollah if a bigger war starts with Lebanon. He needs the United States to be around on the battlefield with him. He wanted to drag Iran into that war with the attack on the embassy, and they didn't retaliate in a way that created a war. And now he did this to try to drag again Iran into this war. But this is not what Iran wants. Iran has a clear plan with the access of resistance that we're seeing unfold over the last seven months, which is to chisel away at Israel slowly and cook it like a frog, a live frog boiling where it collapses internally, where all this support from the world collapses externally, and there's no need for a war for this Zionist colony to collapse, but Netanyahu wants a war. So I think the Iranians are not going to admit that this is an assassination because if they admit this an assassination, they have no choice but to carpet bomb the hell out of the Zionist colony, and that would derail the plan and will take it to the stage that Netanyahu wants it. So I think they're going to just bite the bullet and continue on their set plan and will not be dragged into, it's very sad. I mean, it's very sad that this is going to be what's going to happen, but that's the only thing path forward I see. Otherwise, if Iran decides to retaliate, we're going to be in World War three immediately. Wilmer Leon (00:14:24): And I think it's important for people to understand that there's a much longer term vision here, that the axis of resistance, they have a different worldview. We know that if the situation were reversed and either if somebody had shot an Netanyahu's playing out the sky or if this had happened to Tony Blinken while he was traveling in the region, that the bombs would be exploding by now. But I think there are economic concerns here that those in the region are taking into account war. As I said to Godfather, war is messy business war is very expensive. And with their economies under sanctioned, with their now finding ways to move and operate without the sanctions to go into a war right now, whether it's the Russian economy, whether it's the Chinese economy, whether it's the Iranian economy, they don't want that economic stress on their economies. They also know that I think going into a World War which, or at least a regional conflict, would shut off oil transport through both the Red Sea and the Persian Gulf, which would then collapse the world economy. They don't want do that. I don't think I'm conflating their concern for world welfare. I think they're looking much, much longer. Am I connecting some dots here? Laith Marouf (00:16:04): Yes, yes, you definitely are. And although most of the access of resistance and China, Russia, and most of Africa and Latin America want to see an end to American imperialism, no one wants the whole world to burn in the process. Okay? It's no one's interest to have a World War. People want to clip the wings of the United States, bring it back to its natural size, and the same thing for Europe and balance humanity. There's no interest in these countries to see the United States burn and Europe become a wasteland. And so there's the difference. The difference is people in the south and the East just want the foot of America off their neck. They don't want to put their own foot on America's neck. And so we will see, as we are seeing right now, both in the battlefield in Ukraine, or what's happening around Taiwan or what's happening here right now in the Western Asia battlefield is the constant attempt by the access of resistance and others around the world to take things slow, to allow time to be the biggest weapon. Wilmer Leon (00:17:33): Hence the adage. You have the watches, we have the time. So with all of this, what's next for Iran? Laith Marouf (00:17:43): Yeah, I mean, we already know that they have to have an election within 50 days. That was announced yesterday, and the current vice president was appointed as temporary president until elections happen. Iran as a constitutional democracy will fill these positions as fast as possible, even though these individuals leave a huge gap behind them because of their knowledge and portfolios. abd Ian being the youngest foreign affairs minister of Iran's history, and because of his relations in Africa and Latin America and Rasi with the relationships that he built. So where should expect that this is going to happen this election. But look at one thing, the Israelis, at least what they got from this is at least now a distraction for the next three, five days in Iran and World News while they intensify the massacres in Gaza and in the West Bank last night, for instance, eight people were killed in Janine, so Palestinians. (00:19:06): So there's a lot that we can't really predict what's going to happen. The other thing is that it's very possible that Iran, although they don't announce that this was an assassination and that they don't put the finger on Israel, that they actually conduct clandestine actions that are in kind and something nasty happens to some Israeli official, and nobody can say who it is. So those are possibilities. But I think the most probable thing is that Iran will try to stay the course that the support fronts in Lebanon and Yemen will intensify rapidly to a different level. Wilmer Leon (00:19:49): That's my next question. What happens in the region? Laith Marouf (00:19:53): Yes. Yes. So we're already seeing an intensification even before this assassination. We had a change in the tactics on the Lebanese front with Hezbollah conducting multilayered complex operations that include drones, guided missiles, and achieving huge hits. Much of the air defenses that Israel has downing two huge surveillance balloons. One of them is the biggest in the world, this Zeppelin balloon, there's only two of them in the Zionist colony, one around the Una reactor, one in the north. And the Israelis had put this one in the north because of the destruction of all of their surveillance equipment on the border with Lebanon. So to see Hezbollah not only down these drones, but also film the after from, sorry, not only down these balloons, but also film with surveillance, drones after effect of the destruction and coming back with their images, 100% high HD 4K images of the, so we're already passed into a new stage now in Lebanon, and I expect it to only intensify. And similarly with Yemen, I think that in the next 24 hours, we will see Yemen starting to attack shipping in the Mediterranean, and that will add another sea under Yemeni sovereignty. It's not only going to be the Red Sea, the Arabian Sea, and the Indian Ocean, you'll have also the Mediterranean, and that will be the smartest thing that Iran can do with the access of resistance is to intensify the battle on these fronts without addressing the issue of the assassination of Raisi. Wilmer Leon (00:21:55): When we look at the recent dynamics, and what I mean by that is if we go back to October 7th, in fact not even that, I'm sorry. What I mean is China gets involved with the Saudis, the Saudis wind up talking to Iran. There's reproach mom between Iran and the Saudis haven't heard much from the Crown Prince Ben Salman. In all of these most recent developments, are there things coming out of Saudi Arabia that are not being reported in the West, particularly now as it relates to the death of former President Raisi? And is Bin Salman concerned about his longevity? Laith Marouf (00:22:54): I think everybody is right now worried about their longevity. We've seen the assassination attempt on the Czech president, so we saw the attempted coup, all of this within 24 hours in Congo. Again, American Israeli mercenaries trying to overthrow the president of La Congo. So we're right now entering a new stage in the global battle, not only in Western Asia, we're seeing the West do the maximum they can with the hybrid war. So it's not only a media war, it's not only a sanctions war, it's not only direct confrontations or military confrontations. We're seeing these assassinations and cos and so on, intensified by the United States and its vessel states. So the Saudis issued an official statement condolences to Iran on the assassination. In fact, all of the Gulf countries, Kuwait, Bahrain, Qatar, Emirate, Oman, Saudi, all of them send their condolences. There is three days of mourning in Lebanon, in Syria, in Iraq, in Pakistan, in India, and in Tajikistan and in Turkey. And this is things that are unheard of. Maybe it was expected as Syria or Iraq, but Lebanon and Pakistan and Turkey, this is so we can see that the whole region is worried about the results of this assassination. What does it also mean to, what are the rules of the game now? What is allowed to be done? Because if you are allowed to assassinate presidents now, this means there's no rules. Wilmer Leon (00:25:05): Lemme just quickly say to that point, that reminds me of a comment that President Putin made maybe a year ago as people were talking about, oh, is Russia going to assassinate the president of Ukraine? And Putin said, no. He said, no, no, no, we don't do that. So people need to understand that there's a, I hate to use it. There's a decorum, there's a protocol. There are certain things you're not supposed to do even in the rules of war, even in warfare, you don't assassinate the leader of your opposing country. So you are making that comment just made me think about the point that Laith Marouf (00:25:57): By the way, president Putin is on the way right now on the flight to the Harran, and he's flying with escorts of Soho 35 to the Harran, and he will be there tomorrow during the funeral procession led by the Illah. Wilmer Leon (00:26:19): What is that signal? In my mind that's huge because that's huge on a couple of fronts. One, his country is in the midst of a conflict with NATO slash the United States slash the West. So he must feel incredibly comfortable to leave as he did when he went to China in the midst of this conflict. I can leave my country. I'm not concerned about a being assassinated. I'm not concerned about something happening domestically. B, he's flying into a war zone. He's flying into a country whose president was just killed, many believe assassinated. So on a number of fronts, that to me speaks volumes. Laith Marouf (00:27:07): Yes. And there's the ICC arrest warrant Wilmer Leon (00:27:10): Against that too. Laith Marouf (00:27:11): It's the National Criminal Court. So we know that yesterday, the minute the announcement was made that the crash happened, the President Putin called in the ambassador of Iran to Moscow into almost a six hour meeting with all the heads, the intelligence military in foreign affairs of Russia. It was like a special kind of war council almost. And we don't know what happened in this meeting. So what information did Russia share with Iran? What are their points that were made in that meeting? And immediately we see this visit by President Putin being confirmed, and he's flying over the Caspian Sea directly into Iran from Russian territory to Iranian territory with the military escorts. We will clearly that this indicates a lot of things. And he's flying with him the top cater of the Russian military intelligence and foreign affairs to Iran. So there's something that's going to happen there. (00:28:34): We don't know what's the exchange that's going to happen in these meetings. And to go back to the issue of assassinations, the access of resistance members have never assassinated any Israeli leadership. Not because they can't. In fact, the only time that there was any assassination of an Israeli official is the Minister of settlements during the second in the Father in 2002 was conducted by the popular front for the liberation of Palestine in retaliation for the assassination of the leader of the PLFP AB mufa when the Israelis fired missile from a helicopter into his official office. So historically, the axis of resistance does not do assassinations like this. Why? Because number one, and this is true for Russia, by the way, number one, our enemies don't have any heroes. They only got lunatics, stupid leaders. And if you kill them, Wilmer Leon (00:29:42): You martyr them. Laith Marouf (00:29:43): You create the martyrs, right? The Israelis, Wilmer Leon (00:29:48): You inflate them to an artificial sense of value in power. Laith Marouf (00:29:56): Exactly. So there's no need to create martyrs for the Ukrainians or the Israelis. These are all goals. They should never be allowed to reach that status of martyrdom. The second issue, and this is true again for Ukraine, is because we're gifted as an axis of resistance. And Russia is gifted with the stupidest kind of enemy. Why would you want to kill Zelinsky if he's so dumb? Or Netanyahu is making so many stupid mistakes. If you kill them, maybe somebody smarter will come, you'll be even cursed. And in fact, if you look at the Israelis assassinating over and over, leaderships in the axis of resistance, every time they assassinated somebody, somebody even more cunning and more ready to fight them, gets into the position. Look at Hezbollah. Say Hasan came into his position as Secretary General after the assassination by Israel of Del Mu, the former First Secretary General of Hezbollah who was very moderate, soft spoken. And then you get sala and look at what so assassinations don't work on those two grounds. So it's a stupid thing that the Israelis did, this assassination of sei, and it's just going to bring somebody more in power. And now Iran has a president as a martyr on the path of liberation of Palestine. What glory does Iran have? No other nation lost a president in defense of Palestine, not even the Palestinian authority. You see, Wilmer Leon (00:31:49): You're laying out. That logic also goes back to some fundamental organizational constructs, as in organizations that are personality led versus organizations that are structurally led. So what I understand you to be saying is that this resistance is not based upon the personality in charge, that there is a structure here. There is an ideology here that, as we've said a number of times on a number of shows, you can't kill an ideology with a military. You can only defeat an ideology with a better ideology. And so you can assassinate all the leaders you want to, but there are people right behind them that are waiting to take charge. Laith Marouf (00:32:48): Yes, it is institutionalized. Obviously, we don't want to undermine the human factor, like a human factor is very important in all of these things. And people's personalities and connections make a difference. And so yes, these losses are always big, but because of this institutionalization, hopefully the, and because of the actual human factor, this new person that will fill, will bring new openings, new connections with them. Yes, the human factor is very important and institutionalization is as important. Wilmer Leon (00:33:28): Switching gears a bit, the ICC, the International Criminal Court is seeking arrest warrants for the leader of Hamas, Yaya Sanir, as well as the Israeli Prime Minister Benjamin Netanyahu on charges of war crimes, crimes against humanity. And it seems to be centered around the October 7th retaliation by Hamas on Israel. President Biden has denounced as outrageous the request for these warrants. Biden has said, let me be clear. Whatever this prosecutor might imply, there is no evidence none between Israel and Hamas. Biden said that this is a false equivocation. A couple of things. One, people need to understand that the ICC, the prosecutor is seeking arrest warrants. No warrants have been issued yet. I also find it interesting that they are tying all of this back to the October 7th response by the resistance as though October 7th is actually the beginning of something as opposed to the continuation of something. And then I'd like to get your take on, as I understand international law, the actions taken by Hamas on October 7th do not violate international law because Hamas is, Hamas represents the occupied, Israel is the occupier. And in international law, the occupied can do anything in its power to resist occupation. There is no right to defend oneself when you are the occupier. Laith. Maro your thoughts on that analysis? Laith Marouf (00:35:35): Yeah, I mean, I agree with everything that you said, and I would add to it, can you imagine if during the Vietnam War, Vietnam was, and the Vietnamese resistance were taken to the international criminal court and their leadership were declared terrorists for defending themself against French and American occupation, or the Algerian resistance being called terrorists at the ICC for defending themself against the massacres of the French or the French resistance against the Nazis Wilmer Leon (00:36:13): Or the A NC in South Africa Laith Marouf (00:36:15): Or the A NC? So I personally think the collaboration is Palestinian Authority on purpose launched this case at the ICC because they wanted the leadership of the resistance in Hamas to be charged with war crimes. Okay, Wilmer Leon (00:36:43): Wait a minute. Start that again because man, I never saw that one coming. Start that one again, please. Laith Marouf (00:36:52): Yes, yes. I know it's sometimes hard for people to make these connections, but you see there's never been, that's why Wilmer Leon (00:36:58): You're wrong. Connecting the dots. Laith Marouf (00:37:00): Yes. There's never been in history international criminal court case of the occupied taking their occupier into court and the occupied being charged with crimes against their occupier. And it was the Palestinian authority that pursued this case. Okay? And I think it was done on purpose by Abbas Wilmer Leon (00:37:29): Mah. Abba did this Laith Marouf (00:37:31): Mahmud, Abba and his collaborationist goons to dirty the reputation of the resistance to make their resistance equal to the crimes of the occupier. Okay? And I add to it even more the these arrest warrants against Netanyahu and Ganz, who's going to actually enforce them? No Western country will stop Netanyahu from flying over its airspace or landing on its territory, that's for sure, 100%. But you know who's going to be a target? It's a smile Nia, who's sitting in Qatar, right? SSIR and Aldi are in Gaza. The Israelis can't even kill them or assassinate them. They can't reach them, let alone try to arrest them for ICC charges. But smile, Nia, the head of Hamas in foreign political borough is now the number one target. He's probably right now running to find a place that he can hide than Qatar, because Qatar is a vessel state, and they will hand them over to the Americans at any moment. Okay? So in reality, this is one of the worst things that ever happened to the Palestinians. This ICC case, there's nothing to celebrate about it. And if you notice the limitations of this case that it only, as you said, starts October 7th, Wilmer Leon (00:39:03): They don't mention genocide, Laith Marouf (00:39:05): Okay? And not only that, the case is only for crimes inside Ga Gaza, none of the historical Palestine, west Bank, east Jerusalem, any of that will be included in this. And this is not only to protect Israel from accusations of apartheid and the settlement building that is one of the biggest war crimes possible, but also to hide the fact that all these internment camps that have been built since October 7th, were thousands of Palestinians from the Gaza Strip were abducted and sent into these Guantanamo and being tortured, raped, and killed on mass, disappeared completely, because nobody even knows that they're in this. And the fact that VE turned all the Israeli prisons into that same model, 12,000 Palestinian prisoners since October 7th, have been living in these internment camps, tortured, raped, and killed with hundreds, hundreds of testimonies of rape and torture by men, women, and children coming out of these dungeons. And if you notice the docket of these requests for arrest warrants, this house, slave Han, who is a puppet of the United States and Israel, who came as a replacement to the ICC chief prosecutor before him, who got humiliated and death threats and banned from entering the United States and so on, because she even dare thought about charges Wilmer Leon (00:40:56): Even his family was under. Yes, Laith Marouf (00:40:58): Yes. So now, what does this guy do? If you look at the charges when he's talking about Hamas crimes, he speaks of them as if they're facts that rapes happen. We have no, Wilmer Leon (00:41:17): No evidence Laith Marouf (00:41:18): Any rape that babies were killed. No evidence, no evidence killed. But when he talks about the crimes of the Zionist, Wilmer Leon (00:41:27): He uses a minute, just to that point, going back to President Putin, I remember him saying, if you have evidence of these crimes, please show the world. He was very emphatic on that point. You have made these allegations. If you have evidence, please show the world. And no matter how many times Joe Biden, no matter how many times Tony Blinken wants to talk about these atrocities, they've never even pierce Morgan. I know you saw the interview with Dr. Morandi and Pi Morgan, where Morandi just cut him a new one. He said, Pierce, where's the evidence? And Pi Morgan just kept chatting, just kept chirping. Go ahead, I'm sorry. Laith Marouf (00:42:30): Yes, yes. I mean, the evidence is like you have to take the word of the chosen people for fact. What are you antisemitic, Wilmer. You don't believe every word that comes out of a chosen person mouth. I mean, that's it. That's all evidence you need. So Wilmer Leon (00:42:48): If I was antisemitic, I wouldn't be talking to you. Laith Marouf (00:42:50): Exactly. Exactly. But we're joking about it. But truly, this guy, this sock puppet had, he went down to Israel after October 7th and sat down with the families and unquote survivors, and visited the colonies that were attacked, but refused to enter Gaza Amass, opened the door for him, invited him to come and see Joe evidence, the war crimes. He refused to go to Gaza, okay? And then now he's coming and he's writing in his docket that these crimes happened by Hamas. But when he's talking about the crimes accusations against Israel, he says reasonable grounds before every accusation he is already, you could see how tainted this case is and what is its ultimate goal. I mean, yesterday, the spokesperson for the American government, I can't remember his name, the thin white guy. He was being interviewed, sorry, asked in the question period about this issue, and the guy claimed that the Palestinians have no right to go to the ICC and that their only courts that have jurisdiction are Israeli or American courts. He wants the Palestinians to come and beg at American courts, which even shows you how Israel is a colony, a vessel of the United States. But yes, this is where Wilmer Leon (00:44:32): Matthew Miller, Laith Marouf (00:44:35): Yes, Matthew Pillar, and people call him Matthew Killer. Yes, Wilmer Leon (00:44:38): Right. Matthew Miller. Laith Marouf (00:44:39): Yeah, yeah, yeah. Wilmer Leon (00:44:42): So I'm sorry, I interrupted you. You're saying he was saying that they need to come to American courts? Laith Marouf (00:44:47): Yes. That they have no right to go to the ICC, and the only place that has jurisdiction is the US or Israel over crimes in Gaza, Wilmer Leon (00:45:00): Which is also very telling in that the United States is not as signatory to the ICC, but seems to want to either use it when it's convenient or condemn it when it's convenient. But in fact, excuse me, there's a standing American law, and people can look this up, that if an American is brought before the Hague, the United States reserves the right to invade it. I might even be called the Hague Invasion Act. I'm drawing a blank on the name, but people, folks, you need to look this up. The United States has a standing American law saying, we will invade the Hague if an American is arrested and held accountable for crime. Laith Marouf (00:45:59): Yes, it's ally known as the Hague Invasion Act. And in fact, if you look at the ICC record, 42 out of the 42 people that were convicted of crimes at the ICC were African African leaders, and then add to it that the charges against President Putin. So this ICC is the most captured, un affiliated organism captured by the West, along with the International Atomic Energy Organization and the Chemical and Weapons Organization. These are the least trusted three organs of the un. And we're seeing, I believe these indictments, or if there is an arrest warrant issued, I mean, I don't see anything good coming to the Palestinians from this. Wilmer Leon (00:47:08): Wow. That's a perspective and a level of analysis that I did not see coming. But what you're saying makes sense. Bring us up to date, please on what's happening in Rafa. According to the new Arab, there are by 1.4 million Palestinians there. And that around the 7th of May, they were told that they had to leave. And the number I see is about 80,000 people have fled, but there's, I guess a slow boiling Israeli incursion into the area. What's going on in Rafa now? Laith Marouf (00:48:02): Yeah, I mean, the Israelis are doing what they call belts, fire belts. It's like bombardment from the land, from the sea, from the air on straight lines, and then going next straight line and so on. This is what they've been doing since last week. They haven't yet attempted invading Rafa. They have been stuck in Jabal since last week in the longest and fiercest battle on the ground of Gaza since the beginning of the war. The Israelis lost, according to their own media, at least 10 officers there. That includes a field general, the highest ranking military officer on the field of any army, and along with all his commanders. So we've seen the videos come out from this Jabali battle every day, two or three videos coming out from Hamas, Islamic Jihad and others that showed us tens of Israeli tanks destroyed APCs and bulldozers. So they're receiving a beating, a whipping in the battlefield of Jabal. (00:49:21): So I don't think they're going to invade RA anytime soon. They'll continue bombing from the air. But this has also happened at the same time as yesterday or the day before the Americans finished building the pier, right? Right. And we already now have images of this spear with American air defenses, radars and tanks and ABCs waiting in the landing ships. So clearly the sphere is not about delivering any aid, and it's definitely not about the mass expulsion of Palestinians. This is an invasion, beachfront landing zone in the case of total collapse of the Israeli military on the battlefield. And that's what we are seeing right now happening. Wilmer Leon (00:50:11): And is it a coincidence or should we connect dots that the pier was completed right around the same time that it was announced that, what was it, 1.2 billion more of weaponry has been approved. And so is that a coincidence or am I wrong to connect these dots? Laith Marouf (00:50:34): No, it's not a coincidence. It's also not a coincidence that it was finished the day they assassinated rasi. You see, all of these are time things. It's same thing. It's not a coincidence that the sock puppet Han announced the ICC arrest warrants at the same day of the assassination. So all of this is clearly timed together, and we now saw in the last 48 hours, the cards of the West put on the table, have opened. Now their hand, they just opened their hand with these three moves. The Wilmer Leon (00:51:15): But wait a minute, president Biden is calling for a ceasefire. How can this be true? Laith Maro, when President Biden, when he was at Morehouse giving his commencement address, he's calling for a cease fire. Help me understand this, because obviously you didn't hear him. And so now that you understand, Joe Biden wants to cease fire, how can everything that you've just said be true? Laith Marouf (00:51:44): Isn't it one of the most disgusting things that Biden could do is to lie to the black students and the administration of the university say that he will not use their black faces in his promotional materials for his election? That was one of the conditions to allow him to speak to the students who were going to demonstrate. But because their administration found a middle ground and told them, okay, you can demonstrate without, Wilmer Leon (00:52:15): Don't make any noise, shut Laith Marouf (00:52:16): Down, don't make any noise, and so on. And this guy is not going to use your faces for his election. And now he goes around and immediately, immediately releases a promotional video of using these students to try to get sympathy from the black communities in America. This is, and obviously anybody that believes American leaders should go and ask the indigenous people about all the treaties and their promises. I mean, there's 400 years of record of broken promises and broken treaties. There's not one treaty I think the United States ever abided by with anyone. Have Wilmer Leon (00:53:04): You seen this Washington Post article from last week? The Washington Post reported about a WhatsApp chat stream where New York mayor Eric Adams was chatting with a number of American multimillion and billionaires, such as the former founder of Starbucks and the CEO of Dell and a number of other financiers where they were demanding that Eric Adams send the NYPD into Columbia University. They offered campaign contributions, they offered to fund private investigators to look into the students. And he is now, of course, denying that this took place. But the Washington Post has the transcript of the WhatsApp communications, and they named these individuals by name. And it seems as though their whole concern or motivation behind this is they're losing control of the narrative. Your thoughts, lath maus. Laith Marouf (00:54:21): Yeah. I mean, it's 100% a fact that this happened. No matter what the mayor says, who was another sock puppet? And if me and you have enough money, we can buy American politicians if we want to. They're very cheap. They'll sell you their mamas if you have enough money. Okay? So it's not a surprise. It's actually great that it got leaked, and I'm sure the Washington Post only published it because it was going to be all around the internet anyways, and they needed to have a scoop to stay on top of the story. But this is the truth. The political class and the economic elite are abusing the police in the United States, abusing the power they have over the police, forcing the police to become political police, to suppress the students and the communities that are demonstrating for the liberation of Palestine. I mean, I watched these images over the weekend. The beatings that the NYPD was giving to these youth was, I mean, very similar to who Wilmer Leon (00:55:36): Were peacefully protesting, Laith Marouf (00:55:37): Peacefully protesting, being jumped and taken to the ground and punching women in the face while having your legs on their necks. I mean, it is very similar to how they treat on a daily basis, the black community, specifically black men. But now we're seeing it on a daily scale of people not being accused of any crime or just speaking out or demonstrating. And that's what was happening to the black community in the sixties and the seventies and or the Black Lives Matter movement during the Obama years. Now we are gearing up to this summer of discontent all across the west as these youth finished their exams in the universities and pour into the streets. And we should expect maximum suppression from the political class, and they will be abusing the police to do so because they can't use the courts. Look, in Canada, there's been now two court cases where Zionist students went to court to try to force the police to remove a student encampment from McGill University in Montreal. (00:57:01): McGill University is the Ivy League University in Canada, and they lost. The judge said, no, the students have a right. And then the university administration itself appealed and went to the court to also asked the court to tell the police to remove the students. And again, the court said no. And therefore, this is what's happening. The Zionists in Canada were stupid enough to think that they can win this in court. They thought like, oh, we have all the media, we have all the politicians. We can rip apart the Bill of Rights in Canada. But the Zionists in the United States are a little bit smarter. They know that if they go to court First Amendment, they cannot remove these students. Therefore, they skipped all the legal process and went immediately into abusing their access to power by moving the police, setting them like dogs on the students. Wilmer Leon (00:58:03): Laith Maro, my brother. As always, I got to thank you for joining me today. And let me reiterate to folks that they need to go to Free Palestine video. Go to Free Palestine video. You can see if you could quickly just explain to the audience what you're doing there on the ground, real time in Beirut with free Palestine video. Laith Marouf (00:58:33): So yeah, as a volunteer community television, we're teaching youth and students to produce content in English. We're also doing everyday almost reporting from the south of Lebanon, from the Warfront exclusive coverage of what's happening there, interviews of people on the ground. And we're doing weekly episode of a special show called Wartime Cafe with the biggest intellectual and political leaders in Lebanon in English. Last time, the last episode of wartime Cafe was with Ibrahim Al Mu, who is a member of Parliament, but also the former spokesperson for Hezbollah. He hasn't spoken in English media for a long time. So this is the kind of content that you will get. Please support us donations. We need membership. If there's possible, so people subscribe for monthly donation, that will be amazing. And you can add on our website, free pass. Send the video. You have the links to all our socials, so Twitter, telegram, Instagram, YouTube, brumble. Please watch the content and help us through donations. Wilmer Leon (00:59:49): My brother, my dear brother, lathe Maru, thank you so much for joining me today. Laith Marouf (00:59:54): Thank you for having me. Wilmer Leon (00:59:56): Look forward to having you back. Folks. Thank you all so much for listening to the Connecting the Dots podcast with me, Dr. Wimer Leon. Stay tuned for new episodes every week. Also, please follow and subscribe. Please leave a review, share the show, and you can follow us on social media. You'll find all the links below to the show description, contribute to this effort if you can. Nothing is too small and we know nothing is too large. We greatly, greatly appreciate the contributions that are helping to keep this program on the air. Remember, this is where the analysis of politics, culture, and history converge because talk without analysis is just chatter, and we don't chatter here on connecting the dots. See you again next time. Until then, I'm Dr. Wilmer Leon. Have a great one. Peace. I'm out Announcer (01:00:59): Connecting the dots with Dr. Wilmer Leon, where the analysis of politics, culture, and history converge.

27. Juni 1995, 10.15 Uhr. Vor der Commerzbank-Filiale im Berliner Stadtteil Zehlendorf fährt ein weißer Lieferwagen vor. Vier maskierte Männer mit Maschinenpistolen bewaffnet springen heraus, stürmen die Bank und nehmen 16 Kunden und Angestellte als Geiseln. Sie verdunkeln die Fenster, legen die Überwachungskameras lahm und deponieren Handgranaten vor der Tür. Ihre Forderung: 17 Millionen Mark Lösegeld bis 17 Uhr, einen Hubschrauber und ein Fluchtfahrzeug. Die Polizei sperrt das Viertel ab und fordert das Spezialeinsatzkommando an. Was folgt, sind Telefonate, Verhandlungen, endloses Warten und weitere Verhandlungen, während sich draußen auf der Straße Schaulustige und Medienvertreter drängeln. Der Sender Freies Berlin (heute RBB) berichtet damals live. Die Polizei treibt 5,6 Millionen DM auf, die sie in fünf blauen Plastiksäcken vor das Gebäude bringt. Dafür erreicht sie eine Verlängerung des Ultimatums auf 3 Uhr morgens. Doch die Geiselnehmer stellen neue Forderungen. Sie verlangen, dass eine Beetumrandung aus Metall direkt vor dem Eingang der Bank verschwinden soll, damit der Fluchtwagen dort halten kann. Dieses wird gleich darauf von den Einsatzkräften weggeflext. Doch nach Mitternacht melden sich die Geißelnehmer immer seltener. Dann herrscht plötzlich Funkstille. Was passiert in den Räumen der Bank? Sind die Geiseln noch am Leben? Erster Kriminalhauptkommissar Ralf Kahlbau, ehemaliger Leiter der Ermittlungen, berichtet Rudi Cerne und Conny Neumeyer von den dramatischen Szenen, die sich während der Geiselnahme ereignet haben. So drohten die Täter, einem der Geiseln im Schaufenster ins Knie zu schießen, falls das Ultimatum ergebnislos verstreichen sollte. Was zu diesem Zeitpunkt noch niemand wusste: Die Geiseln waren nur ein großes Ablenkungsmanöver für einen ganz anderen, bis ins kleinste Detail ausgetüftelten Plan. Außerdem im Interview: Polizeidirektor Manfred Textor, ehemaliger Chef der Berliner Spezialeinheiten beim Landeskriminalamt Berlin. Als Kopf des SEK, MEK und der VG (Verhandlungsgruppe) ist er unter anderem durch den Fall Dagobert prominent geworden (Podcast-Folge mit dem Titel: Der Erpresser Dagobert). Er weiß, wie traumatisch es für Opfer werden kann, wenn so eine Spezialeinheit zum Einsatz kommt. *** Wenn ihr Kritik oder Anregungen zu Fällen habt, schreibt uns gerne eine E-Mail an xy@zdf.de. Die aktuelle Sendung und mehr findet ihr in der ZDFmediathek: aktenzeichenxy.zdf.de. *** Moderation: Rudi Cerne, Conny Neumeyer   Gäste & Experten: EKHK Ralf Kahlbau, LKA Berlin, Martin Textor, PD a.D., LKA Berlin Autorin dieser Folge: Eva Marel Jura Audioproduktion: Christina Maier Technik: Anja Rieß  Produktionsleitung Securitel: Marion Biefeld  Produktionsleitung Bumm Film: Melanie Graf, Nina Kuhn  Produktionsmanagement ZDF: Julian Best Leitung Digitale Redaktion Securitel: Nicola Haenisch-Korus   Redaktion Securitel: Corinna Prinz, Erich Grünbacher Produzent Securitel: René Carl   Produzent Bumm Film: Nico Krappweis    Redaktion ZDF: Sonja Roy, Kirsten Schönig    Regie Bumm Film: Alexa Waschkau

Jaký je vztah mezi Pornem a Štěstím? Ve dnešním dílu se bavíme o systému našich chtíčů, o tom, jak porno ovlivňuje chování v intimních chvílích nebo o tom, jak vrstvení potěšení mění naše primární zdroje potěšení. Může být porno prospěšné? Jaký efekt má porovnávání porna a Seggsu? A kdy může škodit? Proč jsou muži po aktu ospalí? Jak Porno pomáhá kompenzovat nepříjemné emoce a jak s tím můžeme pracovat? Jak pracovat s kompulzivním chováním? To vše a mnohem víc ve dnešním peprném dílu! Odebírej VIP krátký formát RED PILL na našem Spotify jen za 65,- / měsíc ttps://podcasters.spotify.com/pod/show/brainweare/subscribe⁠⁠⁠⁠⁠⁠ Parťákem dnešního dílu je ⁠⁠⁠⁠⁠⁠⁠⁠GymBeam⁠⁠⁠⁠⁠⁠ ⁠⁠⁠ https://gymbeam.cz/⁠⁠⁠⁠⁠⁠ ⁠⁠⁠⁠https://gymbeam.cz/⁠⁠⁠⁠⁠⁠ zadej kód BWA5 pro 5% slevu a koukni na naše oblíbené produkty od proteinů, až po nootropika Minutáž: 01:01 Odkud plyne potěšení 02:15 Ztišování mysli & Jak funguje dopamin 03:17 Sociální sítě aneb Scrolluješ u ranního sra...? 04:36 Primární zdroje štěstí 05:57 Sociální zdroje & Seggs 08:13 Porovnáváme se při Seggsu? 12:21 Zdroje potěšení & Telefon jako externí stimulace 21:00 Škálování uspokojení Dopaminem 23:52 Co znamená Hédonická adaptace & Příklad Mekáče na Sahaře 29:31 Dopaminová trajektorie & Co když klesá dopamin? 35:40 Citát: Potěšení VS Prožívání 37:10 Experiment: Zkus si pustit P*rno... 39:42 Jsou představy lepší než P*rno? 41:00 Co je to Prostaglandin? aneb Proč nechceš 2. kolo 44:05 Ženský orgasmus & Porno u žen 45:15 Kompulzivní chování: Co to je? Kdo to má? PRAXE a TIPY 49:25 Praktické rady pro kompulzivní chování 54:15 Jedno řešení pro nával frustrace 57:35 Citát: Slast VS Důsledek slasti 57:58 Antihédonistické aktivity & Co to je? 59:37 No-go signály & Inhibiční okruhy 01:02:57 Silný nástroj aneb Já VS Ty perspektiva 01:06:11 P*rno VS Meditace aneb Extrémy stimulace 01:07:49 Citát: Nuda VS Mír 01:08:42 Scitilivování potěšení pomocí Vděčnosti 01:11:50 Shrnutí & Závěr

İlk bölümde Pakrat Estukyan ile Türkiye'nin ve Ermeni toplumunun gündemini konuşuyoruz. İkinci bölümde 23,5 Hrant Dink Hafıza Mekânı'ndan Nayat Karaköse ve Aslı Yolcu Sağlam, hafta boyunca sürecek 'Anma ve Alternatif Bir Gelecek İçin 23,5 Hafıza Mekânı'nda Buluşalım' etkinliklerini anlatıyorlar. Son bölümde ise Surp Haç Tıbrevank Lisesi  Müdürü Serkan Kıyıcı, Paris'te Sorbonne Üniversitesi'nde düzenlenen ‘SIMUN 2024' konferansına katılan Tıbrevank Lisesi ekibi ve öğrencilerinin edindikleri deneyim hakkında bilgi veriyor.

This week the whole crew is together. We discuss generalization and does changed behavior mean more than words. Jo, Syd, Mek, Mal --- Send in a voice message: https://podcasters.spotify.com/pod/show/baltimore-podcast-studio/message

LTHM 748 - Diego ValleLatest LTHM label release:Mr. Bremson - Lost & Foundhttps://music.lthmmusic.com/lost-foundTrack List:1.Alex Tolstey, Myad – Whale Lotta Love (Alex Tolstey & Earl Peal Remix 2024 Lysergic Long Version [Boshke Beats Records]2.Psyk, Orbe – Atonal [Mote Evolver]3.Tehotu – Ice Breaking [Tridimensional Recordings]4. EMKAY – Space Momentum [Instinkt Lab]5.Axel Toben, Abstract Seeds – Cosmonaut [Boshke Beats Records]6.Cosmic Xplorer – Soft Light [Hypnosis Multiplex]7.Uvall – Against Guidelines [Inguma]8.Linear System – March 229.Victor Fernandez – Keep It Real [ANAOH]10.Marcal – Steady [UNCAGE]11.Volster – Granite [Kongres]12.Uvall – Witchcraft [Inguma]13.Axel Toben, Abstract Seeds – Cosmonaut [Boshke Beats Records]14.Linear System & Yrsen – Synthetic Reverie [Edit Select]LTHM Music Releases:lthm.bandcamp.com/Shop LTHM Apparel by Happy Harry Taggs here:happyharrytaggs.com/www.instagram.com/happyharrytaggs/Follow:www.instagram.com/diegovalle_lthm/www.instagram.com/lthm_music/LTHM Label Website:www.lthmmusic.com/

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Soru: “Cennet çepeçevre mekârihle sarılmış, cehennem de şehevâtla kuşatılmıştır.” mealindeki hadis-i şerifte nazara verilen “mekârih” ne demektir? Mekârihe neler dahildir? -Mekârih, “mekruh” kelimesinin çoğuludur; nefsin hoşuna gitmeyen şeyler; dertler, sıkıntılar ve meşakkatler demektir. Şehevât ise, “şehvet” kelimesinin cem'idir; nefsin aşırı istekleri ve cismanî arzular manasına gelmektedir. (00.15) -Cennet, aklın zahirî nazarına göre nahoş ve nefse ağır gelen şeylerle kuşatılmıştır. Abdest almak, namaz kılmak, hacca gitmek, zekat vermek, mücahede etmek, Allah yolunda zorluklara katlanmak, yer yer cemiyet içinde bir parya muamelesine tâbi tutulmak, her türlü insanî haklardan mahrum bırakılmak… işte Cennet bunlarla kuşatmıştır. (02.23) -Dinin bazı emirlerinde zâhiren bir meşakkat görünse bile, onlar da aslında hakiki meşakkat değildir; hikmetleri açısından ya bizzat güzeldir ya da neticeleri itibarıyla hayırlıdır. Onlar, uzun bir yolculuğa çıkmış bulunan insanın hedefine sağ-salim varabilmesi için yol azığı mesabesindedir; ileride çıkması muhtemel tehlike ve engellere karşı birer korunma vesilesidir. (04.00) -Cihad da mekârihin bir şubesidir; İslam'da harbin bazı esasları ve hiçbir dinde olmayan kaideleri vardır. Günümüzdeki canlı bombaların İslam'ın dırahşan çehresini karartmaya matuf olduğu âşikârdır. (06.40) -Cehennem, cismanî hevesleri ve şehevî arzuları kendisine tuzak yapmış bir cadıdır. Çoğu kimseler, biraz sonra hayatına mâl olacağından habersiz, tıpkı sineklerin bala koşması gibi, o cadının elindeki zehire koşmaktadırlar. (10.24) -Rehber-i Ekmel Efendimiz (aleyhi ekmelüttehâyâ) bize ibadet ü taati tabiatın bir yanı haline getirmeyi öğrettiği gibi, şehevanî duygulardan kaçınmayı da tabiatın bir derinliği kılmayı talim buyurmuştur. (11.11) -Rasûl-ü Ekrem (sallallahu aleyhi ve sellem) Efendimiz'in, “Evlenin, çoğalın; zira ben, kıyamet gününde sizin çokluğunuzla iftihar ederim.” hadis-i şerifindeki “iftihar” ifadesi hangi manaya gelmektedir? (13.08)

In this rebroadcasted episode of the IJGC podcast, Editor-in-Chief Dr. Pedro Ramirez is joined by Drs. Rachel Grisham, David Gershenson, and Brian Slomovitz to discuss "Low Grade Ovarian Cancer: The Expert Consensus".    Highlights:   A panel of experts convened in October 2022 to discuss recent scientific and clinical progress, resulting in a consensus document that provides recommendations for diagnosis, treatment, and ongoing research to improve patient care of low-grade serous ovarian cancer.  Alterations affecting the MAPK pathway are frequent in low-grade serous ovarian cancer and provide prognostic information  Recent advances in the use of targeted therapy (in particular with novel MEK inhibitor and endocrine therapy regimens) have led to unprecedented response rates in patients with recurrent low-grade serous ovarian cancer 

Es ist der längste Erpressungsfall der deutschen Kriminalgeschichte und sie beginnt 1988 mit der Erpressung des Berliner Nobelkaufhauses KaDeWe. Der Täter fordert 500.000 DM. Nachdem er nachts einen Sprengsatz detonieren lässt, bekommt er sein Geld. Geschnappt wird der Unbekannte nicht. Weitere Erpressungsversuche bleiben zunächst aus. Vier Jahre später, 1992, geht in einem Hamburger Kaufhaus schließlich doch ein weiteres Erpresserschreiben ein. Der Täter fordert zunächst 1 Million, dann 1,4 Million DM. Die Geschäftsführung der Kaufhauskette soll die Bereitschaft zur Zahlung mit einer Zeitungsannonce signalisieren mit dem Text: „Onkel Dagobert grüßt seine Neffen.“ Es beginnt ein Katz- und Mausspiel mit der Polizei, bei dem es zu fünf Bombenanschlägen auf Filialen in mehreren Bundesländern und zahlreichen Geldübergabeversuchen kommt. Der Täter scheint der Polizei dabei immer einen Schritt voraus zu sein. Der Druck auf die Behörden steigt, so auch das Interesse der Medien. Zu Gast im Studio: Polizeidirektor Martin Textor a.D.. Der Berliner leitete das Referat 63 und damit das SEK und MEK – eine Truppe von über 400 Einsatzkräften. Im Gespräch mit Rudi Cerne und seiner Kollegin Conny Neumeyer berichtet er von aufwändigen Einsätzen mit über 3000 Mann, der Häme von Medienvertretern und schließlich dem Tag des Zugriffs, der für alle Kollegen und Kolleginnen auch ein Tag zum Feiern war. Außerdem im Interview: Dr. Claudia Paganini, Professorin für Medienethik. Sie wirft einen kritischen Blick auf die Rolle der Presse in dem Fall. *** Wenn ihr Kritik oder Anregungen zu Fällen habt, schreibt uns gerne eine E-Mail an xy@zdf.de. Die aktuelle Sendung und mehr findet ihr in der ZDFmediathek: aktenzeichenxy.zdf.de. *** Moderation: Rudi Cerne, Conny Neumeyer   Gäste & Experten: PD Martin Textor a.D., Polizeipräsidium Berlin; Prof. Dr. Claudia Paganini, Hochschule für Philosophie München Autorin dieser Folge:  Julia Heyne Audioproduktion: Anja Rieß  Technik: Anja Rieß  Produktionsleitung Securitel: Marion Biefeld  Produktionsleitung Bumm Film: Melanie Graf, Nina Kuhn  Produktionsmanagement ZDF: Carolin Klapproth, Ina Willems  Leitung Digitale Redaktion Securitel: Nicola Haenisch-Korus   Redaktion Securitel: Erich Grünbacher, Corinna Prinz   Produzent Securitel: René Carl   Produzent Bumm Film: Nico Krappweis    Redaktion ZDF: Sonja Roy, Kirsten Schönig    Regie Bumm Film: Alexa Waschkau

BUFFALO, NY- October 11, 2023 – A new research paper was published in Oncotarget's Volume 14 on October 4, 2023, entitled, “Inhibiting BRAF/EGFR/MEK suppresses cancer stemness and drug resistance of primary colorectal cancer cells.” Drug resistance is a major barrier against successful treatments of cancer patients. Gain of stemness under drug pressure is a major mechanism that renders treatments ineffective. Identifying approaches to target cancer stem cells (CSCs) is expected to improve treatment outcomes for patients. In their new study, researchers Astha Lamichhane, Gary D. Luker, Seema Agarwal, and Hossein Tavana from The University of Akron, University of Michigan and Georgetown University aimed to elucidate the role of cancer stemness in resistance of colorectal cancer cells to targeted therapies. “[...] we developed spheroid cultures of patient-derived BRAFmut and KRASmut tumor cells and studied resistance mechanisms to inhibition of MAPK pathway through phenotypic and gene and protein expression analysis.” They found that treatments enriched the expression of CSC markers CD166, ALDH1A3, CD133, and LGR5 and activated PI3K/Akt pathway in cancer cells. The team examined various combination treatments to block these activities and found that a triple combination against BRAF, EGFR, and MEK significantly reduced stemness and activities of oncogenic signaling pathways. This study demonstrates the feasibility of blocking stemness-mediated drug resistance and tumorigenic activities in colorectal cancer. “Our approach to identify mechanisms of drug resistance of patient-derived cancer cells to targeted therapies and develop effective treatments is promising toward cancer precision medicine.” DOI - https://doi.org/10.18632/oncotarget.28517 Correspondence to - Hossein Tavana - tavana@uakron.edu Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28517 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, drug resistance, cancer stem cells, patient-derived tumor model, colorectal cancer, combination treatment About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

In this episode of the IJGC podcast, Editor-in-Chief Dr. Pedro Ramirez is joined by Drs. Rachel Grisham, David Gershenson, and Brian Slomovitz to discuss "Low Grade Ovarian Cancer: The Expert Consensus".   Highlights:   A panel of experts convened in October 2022 to discuss recent scientific and clinical progress, resulting in a consensus document that provides recommendations for diagnosis, treatment, and ongoing research to improve patient care of low-grade serous ovarian cancer.  Alterations affecting the MAPK pathway are frequent in low-grade serous ovarian cancer and provide prognostic information.  Recent advances in the use of targeted therapy (in particular with novel MEK inhibitor and endocrine therapy regimens) have led to unprecedented response rates in patients with recurrent low-grade serous ovarian cancer.

On COI #445, Kyle Anzalone and Connor Freeman cover escalations against China, Iran, and Palestine. Kyle discusses Secretary of State Antony Blinken's upcoming trip to Indonesia where he will attempt to wrangle members of the Association of Southeast Asian Nations to “push back” against Beijing in the South China Sea. Connor discusses Israel's brutal invasion and bombing against the Jenin refugee camp in the northern occupied West Bank and Mike Pence's calls for regime change in Tehran during an MEK rally. Odysee Rumble  Donate LBRY Credits bTTEiLoteVdMbLS7YqDVSZyjEY1eMgW7CP Donate Bitcoin 36PP4kT28jjUZcL44dXDonFwrVVDHntsrk Donate Bitcoin Cash Qp6gznu4xm97cj7j9vqepqxcfuctq2exvvqu7aamz6 Patreon Subscribe Star YouTube Facebook  Twitter  MeWe Apple Podcast  Amazon Music Google Podcasts Spotify iHeart Radio

On COI #445, Kyle Anzalone and Connor Freeman cover escalations against China, Iran, and Palestine. Kyle discusses Secretary of State Antony Blinken's upcoming trip to Indonesia where he will attempt to wrangle members of the Association of Southeast Asian Nations to “push back” against Beijing in the South China Sea. Connor discusses Israel's brutal invasion and bombing against the Jenin refugee camp in the northern occupied West Bank and Mike Pence's calls for regime change in Tehran during an MEK rally.

On this week's show Patrick Gray and Adam Boileau discuss the week's security news. They cover: Albanian authorities raid MEK over Iran hacks Microsoft admits “Anonymous Sudan” took down its services US Government puts $10m bounty on CL0P A deeper look at the Barracuda hack campaign Much, much more This week's show is brought to you by Material Security. We'll be hearing from one of Material's friends – Courtney Healey, senior manager of insider threat at Coinbase – in this week's sponsor interview. Links to everything that we discussed are below and you can follow Patrick or Adam on Mastodon if that's your thing. Show notes Police raid Iranian opposition camp in Albania, seize computers | AP News Risky Biz News: Microsoft embarrassingly admits it got DDoSed into the ground by Anonymous Sudan Anonymous Sudan and Killnet strike again, target EIB Pro-Russian hackers remain active amid Ukraine counteroffensive | CyberScoop Hackers infect Russian-speaking gamers with fake WannaCry ransomware US puts $10M bounty on Clop as federal agencies confirm data compromises | Cybersecurity Dive (1) Catherine Herridge on Twitter: "Tonight, sources tell @cbsnews senior government officials are racing to limit impact - of what one cyber expert calls - potentially the largest theft + extortion event in recent history. USG official says no evidence to date US MIL or INTEL compromised. https://t.co/R4f6naFqFx" / Twitter U.S. government says several agencies hacked as part of broader cyberattack Clop names a dozen MOVEit victims, but holds back details | Cybersecurity Dive Another MOVEit vulnerability found, as state and federal agencies reveal breaches | Cybersecurity Dive Barracuda ESG Zero-Day Vulnerability (CVE-2023-2868) Exploited Globally by Aggressive and Skilled Actor, Suspected Links to China | Mandiant New DOJ unit will focus on prosecuting nation-state cybercrime EU states told to restrict Huawei and ZTE from 5G networks ‘without delay' The US Navy, NATO, and NASA Are Using a Shady Chinese Company's Encryption Chips | WIRED Widow of slain Saudi journalist Jamal Khashoggi files suit against Pegasus spyware maker Jamal Khashoggi's wife to sue NSO Group over Pegasus spyware | Jamal Khashoggi | The Guardian Bipartisan bill would protect Americans' data from export abroad District of Nebraska | Massachusetts Man Sentenced for Computer Intrusion | United States Department of Justice I Was Sentenced to 18 Months in Prison for Hacking Back - My Story | HackerNoon CID-FLYER-TEMPLATE New FCC privacy task force takes aim at data breaches, SIM-swaps | CyberScoop Bloodied Macbooks and Stacks of Cash: Inside the Increasingly Violent Discord Servers Where Kids Flaunt Their Crimes Russian National Arrested and Charged with Conspiring to Commit LockBit Ransomware Attacks Against U.S. and Foreign Businesses | OPA | Department of Justice BrianKrebs: "Haha love it when a data ranso…" - Infosec Exchange

On this week's show Patrick Gray and Adam Boileau discuss the week's security news. They cover: Albanian authorities raid MEK over Iran hacks Microsoft admits “Anonymous Sudan” took down its services US Government puts $10m bounty on CL0P A deeper look at the Barracuda hack campaign Much, much more This week's show is brought to you by Nucleus Security. We'll be hearing from one of Material's friends – Courtney Healey, senior manager of insider threat at Coinbase – in this week's sponsor interview. Links to everything that we discussed are below and you can follow Patrick or Adam on Mastodon if that's your thing. Show notes Police raid Iranian opposition camp in Albania, seize computers | AP News Risky Biz News: Microsoft embarrassingly admits it got DDoSed into the ground by Anonymous Sudan Anonymous Sudan and Killnet strike again, target EIB Pro-Russian hackers remain active amid Ukraine counteroffensive | CyberScoop Hackers infect Russian-speaking gamers with fake WannaCry ransomware US puts $10M bounty on Clop as federal agencies confirm data compromises | Cybersecurity Dive (1) Catherine Herridge on Twitter: "Tonight, sources tell @cbsnews senior government officials are racing to limit impact - of what one cyber expert calls - potentially the largest theft + extortion event in recent history. USG official says no evidence to date US MIL or INTEL compromised. https://t.co/R4f6naFqFx" / Twitter U.S. government says several agencies hacked as part of broader cyberattack Clop names a dozen MOVEit victims, but holds back details | Cybersecurity Dive Another MOVEit vulnerability found, as state and federal agencies reveal breaches | Cybersecurity Dive Barracuda ESG Zero-Day Vulnerability (CVE-2023-2868) Exploited Globally by Aggressive and Skilled Actor, Suspected Links to China | Mandiant New DOJ unit will focus on prosecuting nation-state cybercrime EU states told to restrict Huawei and ZTE from 5G networks ‘without delay' The US Navy, NATO, and NASA Are Using a Shady Chinese Company's Encryption Chips | WIRED Widow of slain Saudi journalist Jamal Khashoggi files suit against Pegasus spyware maker Jamal Khashoggi's wife to sue NSO Group over Pegasus spyware | Jamal Khashoggi | The Guardian Bipartisan bill would protect Americans' data from export abroad District of Nebraska | Massachusetts Man Sentenced for Computer Intrusion | United States Department of Justice I Was Sentenced to 18 Months in Prison for Hacking Back - My Story | HackerNoon CID-FLYER-TEMPLATE New FCC privacy task force takes aim at data breaches, SIM-swaps | CyberScoop Bloodied Macbooks and Stacks of Cash: Inside the Increasingly Violent Discord Servers Where Kids Flaunt Their Crimes Russian National Arrested and Charged with Conspiring to Commit LockBit Ransomware Attacks Against U.S. and Foreign Businesses | OPA | Department of Justice BrianKrebs: "Haha love it when a data ranso…" - Infosec Exchange

On this week's show Patrick Gray and Adam Boileau discuss the week's security news. They cover: China's lolbin-powered intrusions into critical infrastructure Trend Micro backs BlackBerry's Cuba call Anonymous Sudan shakes down Scandanavian Airlines Iranian opposition party MEK publishes gargantuan leak Much, much more This week's show is brought to you by Kubernetes security company KSOC. Jimmy Mesta is this week's sponsor guest and he joins us to talk about the big security challenges in Kubernetes. Links to everything that we discussed are below and you can follow Patrick or Adam on Mastodon if that's your thing. Show notes Volt Typhoon targets US critical infrastructure with living-off-the-land techniques | Microsoft Security Blog (1) New Messages! U.S. warns China could hack infrastructure, including pipelines, rail systems | Reuters Factbox: What is Volt Typhoon, the alleged China-backed hacking group? | Reuters Chinese Malware Hits Systems on Guam. Is Taiwan the Real Target? - The New York Times COSMICENERGY: New OT Malware Possibly Related To Russian Emergency Response Exercises | Mandiant Void Rabisu's Use of RomCom Backdoor Shows a Growing Shift in Threat Actors' Goals Hacker group Anonymous Sudan demands $3 million from Scandinavian Airlines Iranian dissidents take over high-security servers of regime presidency | Iran-linked hackers Agrius deploying new ransomware against Israeli orgs Exclusive: Chinese hackers attacked Kenyan government as debt strains grew | Reuters Risky Biz News: PyPI to enforce 2FA, reduce stored IP addresses NSO spyware used in Armenia-Azerbaijan conflict, report finds Mercenary mayhem: A technical analysis of Intellexa's PREDATOR spyware SMS pumping fraud: take care how you configure MFA - TechHQ Full Disclosure: Printerlogic multiple vulnerabilities Barracuda Networks issue added to CISA vulnerability list Barracuda patches actively exploited zero-day vulnerability in email gateways | Cybersecurity Dive Developing: RaidForums users db leaked Phishing Domains Tanked After Meta Sued Freenom – Krebs on Security Broad coalition of advocacy groups urges Slack to protect users' messages from eavesdropping | CyberScoop

On this week's show Patrick Gray and Adam Boileau discuss the week's security news. They cover: China's lolbin-powered intrusions into critical infrastructure Trend Micro backs BlackBerry's Cuba call Anonymous Sudan shakes down Scandanavian Airlines Iranian opposition party MEK publishes gargantuan leak Much, much more This week's show is brought to you by Kubernetes security company KSOC. Jimmy Mesta is this week's sponsor guest and he joins us to talk about the big security challenges in Kubernetes. Links to everything that we discussed are below and you can follow Patrick or Adam on Mastodon if that's your thing. Show notes Volt Typhoon targets US critical infrastructure with living-off-the-land techniques | Microsoft Security Blog (1) New Messages! U.S. warns China could hack infrastructure, including pipelines, rail systems | Reuters Factbox: What is Volt Typhoon, the alleged China-backed hacking group? | Reuters Chinese Malware Hits Systems on Guam. Is Taiwan the Real Target? - The New York Times COSMICENERGY: New OT Malware Possibly Related To Russian Emergency Response Exercises | Mandiant Void Rabisu's Use of RomCom Backdoor Shows a Growing Shift in Threat Actors' Goals Hacker group Anonymous Sudan demands $3 million from Scandinavian Airlines Iranian dissidents take over high-security servers of regime presidency | Iran-linked hackers Agrius deploying new ransomware against Israeli orgs Exclusive: Chinese hackers attacked Kenyan government as debt strains grew | Reuters Risky Biz News: PyPI to enforce 2FA, reduce stored IP addresses NSO spyware used in Armenia-Azerbaijan conflict, report finds Mercenary mayhem: A technical analysis of Intellexa's PREDATOR spyware SMS pumping fraud: take care how you configure MFA - TechHQ Full Disclosure: Printerlogic multiple vulnerabilities Barracuda Networks issue added to CISA vulnerability list Barracuda patches actively exploited zero-day vulnerability in email gateways | Cybersecurity Dive Developing: RaidForums users db leaked Phishing Domains Tanked After Meta Sued Freenom – Krebs on Security Broad coalition of advocacy groups urges Slack to protect users' messages from eavesdropping | CyberScoop

From the writer of The Book of Eli and co-writer of Rogue One: A Star Wars Story comes an all-new sci-fi epic starring Shannon Woodward (Westworld) and Troy Baker (The Last of Us).In the near future, Earth has been conquered by a race of brutal alien machines known as the Mek. When a young woman stumbles across a mysterious map that may hold the secret to humanity's liberation, she embarks on a dangerous odyssey that leads her to an amazing discovery — a long-lost prototype war machine known as a Gundog. Now she must confront a legacy she never knew she had to face down an overwhelmingly superior enemy in the hope of sparking a new flame of human resistance.You can listen to all nine episodes of Gundog wherever you get your podcasts. Or use these links:Apple Podcasts: apple.co/gundogRealm: https://www.realm.fm/shows/gundog Get Build Mama a Coffin, Black Mouthed Dog and other exclusive content on Patreon!Support this show http://supporter.acast.com/old-gods-of-appalachia. Hosted on Acast. See acast.com/privacy for more information.

From the writer of The Book of Eli and co-writer of Rogue One: A Star Wars Story comes an all-new sci-fi epic performed by Shannon Woodward (Westworld, The Last of Us Part II). In the near future, Earth has been conquered by a race of brutal alien machines known as the Mek. When a young woman stumbles across a mysterious map that may hold the secret to humanity's liberation, she embarks on a dangerous odyssey that leads her to an amazing discovery — a long-lost prototype war machine known as a Gundog. Now she must confront a legacy she never knew she had to face down an overwhelmingly superior enemy in the hope of sparking a new flame of human resistance... Learn more about your ad choices. Visit megaphone.fm/adchoices

The panel is ill-prepared for these questions, but unites once more to cover The Game Awards 2022, cool ladies, and the greatest game of all time no one is talking about yet. Brandon Sheffield reviews the first four episodes of Bleach and One Piece. Hosted by Alex Jaffe, with Frank Cifaldi, Tim Rogers and Brandon Sheffield. Edited by Esper Quinn, original music by Kurt Feldman. Questions this week: Do we want to talk about the FTC suing to block Microsoft from buying Activision Blizzard? (06:37) From Ash Parrish: if you could lock Geoff Keighley in a room and make him reveal the video game industry's biggest secret, what would you ask him? (09:13) Let's try to have a sincere discussion about The Game Awards (11:43) Let's predict The Game Awards (20:48) How have video games influenced our vocabulary? (37:24) Does a video game protagonist have to be likable? (42:47) Insert Credit Anime Review: Bleach vs. One Piece (48:32) Mek asks: has there ever been a good boss fight in a first person shooter? (54:54) Which fighting game has the coolest lady? (01:00:37) What is the Jeanne Dielman, 23 quai du Commerce, 1080 Bruxelles of video games? (01:05:24) LIGHTNING ROUND: Improv Zone - Introducing the Nominees (01:16:20) Recommendations and Outro (01:22:02) A SMALL SELECTION OF THINGS REFERENCED: Michigan J. Frog - “Hello My Baby” Paper Mario: The Thousand-Year Door Osu! Tatakae! Ouendan / Elite Beat Agents series Dragon Quest series The Sopranos Dororo Parasite Eve Gungrave series FTC Seeks to Block Microsoft Corp.'s Acquisition of Activision Blizzard Monopoly The Game of Life Itadaki Street series Disney's Bonkers Bonk series Geoff Keighley The Game Awards 2022 what me suit should look like? FINAL FANTASY XVI REVENGE trailer Tetsuya Nomura Independent Games Festival IndieCade D.I.C.E. Awards Dredd (2012) Call of Duty: Warzone Sayonara Wild Hearts Disco Elysium Stray Xenoblade Chronicles 3 A Plague Tale: Requiem Elden Ring Horizon II: Forbidden West God of War: Ragnarök Sekiro: Shadows Die Twice Fortnite: Battle Royale Final Fantasy XIV Online: A Realm Reborn Genshin Impact Apex Legends Destiny 2 Final Fantasy VII: The First Soldier Marvel Snap The Legend of Zelda: Tears of the Kingdom Starfield Resident Evil 4 Mass Effect series Skyrim series League of Legends Dota 2 Counter-Strike series Valorant Rocket League Splatoon 3 Teenage Mutant Ninja Turtles: Shredder's Revenge Overwatch series MultiVersus Baskin-Robbins Sonic the Hedgehog 2 (2022) Uncharted (2022) The Cuphead Show! Cyberpunk: Edgerunners Arcane Sonic the Hedgehog 2 Nintendo Switch Sports Kirby and the Forgotten Land LEGO Star Wars: The Skywalker Saga Mario + Rabbids: Sparks of Hope Immortality Grammy Awards Academy Awards Triangle Strategy Live A Live Pokémon Legends: Arceus Ashly Burch Gran Turismo 7 Sifu Neon White Tunic Cult of the Lamb Vampire Survivors Evo Los Angeles Thieves GamePro Casino (1995) Pacific Pinball Museum Tim's Elden Ring guy Chuck Rock series Joe & Mac: Caveman Ninja Joe & Mac Returns Toki Clockwork Knight Bug! series Bleach One Piece Hunter × Hunter Turok: Dinosaur Hunter Wolfenstein II: The New Colossus Descent series Halo series Titanfall series Metroid Prime series Left 4 Dead series DOOM series Street Fighter series Sonya Blade Makoto Elena King of Fighters series Angel Yuri Sakazaki Asuka 120% series May Jam Kuradoberi King Tekken series King Marvel vs. Capcom series Iron Fist Akira Skullomania Superman Terry Bogard Super Smash Brothers series Mai Shiranui Kyo Kusanagi Ryu Ken Masters Bayonetta Bayonetta series Jeanne Dielman, 23 quai du Commerce, 1080 Bruxelles (1975) ‘Jeanne Dielman' Tops Sight & Sound's 2022 Poll of the Best Films of All Time Citizen Kane (1941) Vertigo (1958) Tokyo Story (1953) Bicycle Thieves (1948) Bomberman: Act:Zero Fallout: New Vegas BioShock Journey Linda³ Oreshika: Tainted Bloodlines Gears of War series Frank's photo of Ed Semrad Recommendations: Frank: The Prototypes in Ed Semrad's Basement Brandon: Watch a few episodes of Hunter X Hunter, wishlist Hyper Gunsport on Steam Support on Patreon Subscribe: RSS, Apple Podcasts, Google Podcasts, Spotify, and more!

From the writer of The Book of Eli and co-writer of Rogue One: A Star Wars Story comes an all-new sci-fi epic performed by Shannon Woodward (Westworld, The Last of Us Part II). In the near future, Earth has been conquered by a race of brutal alien machines known as the Mek. When a young woman stumbles across a mysterious map that may hold the secret to humanity's liberation, she embarks on a dangerous odyssey that leads her to an amazing discovery — a long-lost prototype war machine known as a Gundog. Now she must confront a legacy she never knew she had to face down an overwhelmingly superior enemy in the hope of sparking a new flame of human resistance... Learn more about your ad choices. Visit megaphone.fm/adchoices