Beyond the Abstract

Thousands of patients in the US die every year waiting for an organ transplant, often because there are not enough human organ donors. Xenotransplantation — transplantation from another species to humans — could solve this problem, but has remained the realm of science fiction given many technical obstacles. Now, with advances in gene editing, this pipe dream is becoming reality. In today's episode of Beyond the Abstract, Dan and Derek explore xenotransplantation, tell the stories of the few humans who have received pig organs, and explain why this may herald a new era in transplant medicine.Articles discussedGriffith et al. Genetically modified porcine-to-human cardiac xenotransplantation. New England Journal of Medicine. 2022. (https://www.nejm.org/doi/full/10.1056/NEJMoa2201422)Anand et al. Design and testing of a humanized porcine donor for xenotransplantation. Nature. 2023. (https://www.nature.com/articles/s41586-023-06594-4)The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

While almost all women experience nausea and vomiting during pregnancy, few are debilitated by severe symptoms: a condition known as hyperemesis gravidarum (HG). HG has been stigmatized and neglected by the biomedical community, with limited research funding for developing effective treatments. In this episode of Beyond the Abstract, Derek and Dan tell the remarkable story of one scientist who experienced HG herself, and her decades-long journey to find a cure. Articles discussedHer Doctor Said Her Illness Was All in Her Head. This Scientist Was Determined to Find the Truth. Alice Callahan. New York Times, 2023. (https://www.nytimes.com/2023/03/14/well/marlena-fejzo-hyperemesis-gravidarum.html)GDF15 linked to maternal risk of nausea and vomiting during pregnancy. Fejzo et al. 2023. Nature. (https://www.nature.com/articles/s41586-023-06921-9).Placenta and appetite genes GDF15 and IGFBP7 are associated with hyperemesis gravidarum. Fejzo et al. 2018. Nature Communications. (https://www.nature.com/articles/s41467-018-03258-0)The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

A new class of medicines has transformed the treatment of obesity -- Wegovy and Ozempic have become household names. While we discussed these GLP-1 medicines on an episode of Beyond the Abstract less than a year ago, the field has progressed so quickly we thought it was already time to review many of these recent developments. In today's episode, Derek and Dan first discuss improved versions of these medicines on the horizon for the treatment of obesity. Derek and Dan then talk about how these medicines are being studied to treat a wide range of diseases outside of obesity, ranging from cardiovascular disease to substance use disorder. Articles discussedJastreboff et al 2023 NEJM, Triple-Hormone Receptor Agonist Retatrutide for Obesity -- A Phase 2 Trial (https://www.nejm.org/doi/full/10.1056/NEJMoa2301972)Wharton et al 2023 NEJM, Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity (https://www.nejm.org/doi/full/10.1056/NEJMoa2302392)Lincoff et al 2023 NEJM, Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (https://www.nejm.org/doi/full/10.1056/NEJMoa2307563)Kosiborod et al 2023 NEJM, Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity (https://www.nejm.org/doi/full/10.1056/NEJMoa2306963)The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

Debates around artificial intelligence are everywhere: will ChatGPT usher in a new era of productivity and creativity? Or will advanced AI replace millions of workers? Doctors have similar questions about how AI may influence medicine. In today's episode of Beyond the Abstract, Dan and Derek take a deep dive into all things AI and health. They discuss the current role of AI in medicine and the promises and perils of potential new applications made possible because of ChatGPT and other emerging AI technologies. Moor et al., Foundational models for generalist medical artificial intelligence, Nature, 2023 (https://www.nature.com/articles/s41586-023-05881-4).He et al., Blinded, randomized trial of sonographer versus AI cardiac function assessment, Nature, 2023 (https://www.nature.com/articles/s41586-023-05947-3).The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

It's well known that emotions can affect the heart - we've all had an anxiety-producing thought that leads to the feeling of our heart pounding out of our chest. But what about the opposite: can the heart control our emotions? In today's episode of Beyond the Abstract, Derek and Dan discuss a fascinating new study looking at whether making the heart beat fast can cause anxiety-related behaviors.  Hsueh et al., Cardiogenic control of affective behavioral state, Nature, March 2023 (https://www.nature.com/articles/s41586-023-05748-8)The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

The effect of inappropriate blood clotting can be devastating, including heart attack and stroke. While there are many medications to reduce the risk of clotting, our understanding of why blood clots and when remains incomplete. In today’s episode of Beyond the Abstract, Derek and Dan share the remarkable story of how a team of researchers discovered new clotting biology, in a story that begins with a surprising observation about hibernating bears and ends with the characterization of a potential new drug target for humans.Thienel et al. Immobility-associated thromboprotection is conserved across mammalian species from bear to human. Science, 2023.The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

Alzheimer’s disease is a devastating neurodegenerative condition affecting millions of people around the world. Current therapies are only partially effective, despite decades of research aimed at understanding the causes of the disease. Alzheimer’s is largely genetic, and the best-known genetic risk factor for Alzheimer’s comes from mutations in a gene called APOE. Until recently, however, exactly how these mutations increase risk for the disease has not been well understood. In today’s episode, Dan and Derek discuss new research on how mutations in APOE leads to Alzheimer’s disease. They talk about the new biological pathways uncovered, the potential therapeutic potential of the discovery, and a related early-stage clinical trial of gene therapy in Alzheimer’s disease. Blanchard et al., APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes. Nature, November 2022. DOI: https://doi.org/10.1038/s41586-022-05439-w The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

Approximately four in 10 Americans are obese, putting millions at increased risk of developing diabetes, heart disease, liver cancer, and other chronic illnesses. For many years it’s seemed that we’re losing the battle against this modern epidemic. However, the tide may be turning with the recent approval of a revelatory new class of medications. In today’s episode, Dan and Derek dive deep into this new type of treatments. They discuss their discovery, the biology behind them, the pivotal clinical trials showing their efficacy, and the promises and perils of this powerful new tool in the fight against obesity.Wilding et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. The New England Journal of Medicine, March 2021. DOI: 10.1056/NEJMoa2032183The information presented here is not medical advice. Consult your physician for any questions regarding your personal health.

Our episode today takes us Behind The Scenes (BTS) on Beyond The Abstract (BTA). Derek and Dan answer your questions on graduate school on everything from how we chose our research topics, how we deal with imposter syndrome and stress, how it feels to have finished our PhDs, and more! We hope you enjoy this change from our usual format. If you have questions you'd like us to answer, DM us @btapod on Instagram!

This episode is sponsored by Proteintech.Exercise is good for us - it keeps off the pounds and decreases our risk for heart attack and diabetes. What may be less known about exercise is that it's actually also good for the brain. Exercise improves memory and learning, and may even improve brain function in people with Alzheimer's disease. However, it's not know how exercise might exert these beneficial effects on the brain. In today's episode, Derek and Dan discuss a paper where researchers have identified a molecule called 'clusterin' in blood that seems to improve brain function. They also talk about how Proteintech is contributing to groundbreaking research like this through high quality antibodies and reagents.De Miguel et al. Exercise plasma boosts memory and dampens brain inflammation via clusterin. Nature, December 2021. DOI: 10.1038/s41586-021-04183-xThe information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

Preeclampsia is a pregnancy disorder characterized by high blood pressure and contributes to significant fetal and maternal deaths. However, what exactly causes preeclampsia is unclear. It's thought that preeclampsia is caused by placental dysfunction - specifically, the ability of specialized fetal cells called trophoblasts to replace and remodel maternal blood vessels. In this episode of Beyond the Abstract, Derek and Dan discuss a new paper that describes how trophoblasts "mimic" blood vessels in order to establish the maternal-fetal connection in the placenta and how this process may go awry in preeclampsia.Read more about this research in this blog post.Sung et al. VE-cadherin enables trophoblast endovascular invasion and spiral artery remodeling during placental development. eLife, April 2022. DOI: 10.7554/eLife.77241The information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

CAR T cells have been engineered to treat everything from cancer to scarring in the heart. However, one major barrier to wide-spread therapy is the fact that T cells have to be removed from the patient, engineered, and then putting them back in the patient. But what if we could create a drug that makes CAR T cells inside a patient's own body? This type of one-size-fits-all approach could be much more efficient. On this episode of Beyond the Abstract, Derek and Dan discuss how scientists at the University of Pennsylvania have successfully created CAR T cells to treat scarring in the heart with the simple injection of a drug. Using state-of-the-art gene therapy, they are able to temporarily transform T cells into soldiers to fight scarring in the heart.Rurik et al. CAR T cells produced in vivo to treat cardiac injury. Science, January 2022. DOI: 10.1126/science.abm0594The information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

COVID brain fog is a well-documented, residual symptom following COVID infection. However, how COVID infects the brain and potential causes of COVID brain fog are unclear. In this episode, Dan and Derek discuss two recent studies that show that even mild cases of COVID may have important impacts on brain structure and function.Douaud et al. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature, March 2022. PMID: 35255491Fernández-Castañeda et al. Mild respiratory SARS-CoV-2 infection can cause multi-lineage cellular dysregulation and myelin loss in the brain. bioRxiv, January 2022. https://www.biorxiv.org/content/10.1101/2022.01.07.475453v1The information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

Epstein-Barr Virus (EBV) is best known for causing mononucleiosis, or the 'kissing disease,' in teenagers. Almost all adults get EBV at some point in their lives, even if they don't get mono. New research shows that EBV infection may have longer-lasting impacts. Using data from the American military, researchers now show that EBV infection drastically increases an individual's risk for multiple sclerosis, a debilitating autoimmune disorder. In this episode, Dan and Derek discuss how these researchers figured this out and potential ways to prevent EBV infection (and potentially multiple sclerosis) altogether.Bjornevik et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science, January 2022. DOI: 10.1126/science.abj8222The information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

Hair greying is thought to be an irreversible event related to life stress, but the process has never been extensively studied. For the first time, researchers at Columbia University use novel techniques with hair imaging and a daily diary to demonstrate that hair greying is not only associated with stressful life events, but that the process is reversible and correlated with metabolic changes in mitochondria. Better understanding this process may give us more information on how our bodies biologically respond to psychological stressors and opens new roads to potentially reversing hair greying.Rosenberg et al. Quantitative mapping of human hair greying and reversal in relation to life stress. eLife, June 2021. DOI: 10.7554/eLife.67437The information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

The placenta is a transient organ of pregnancy that supports fetal growth and organ development. Placental dysfunction underlies many developmental defects, but this connection is poorly understood. Furthermore, many neuropsychiatric disorders, such as autism spectrum disorder, are linked to altered brain development and are more common in men than women for unknown reasons. In this episode, Derek and Dan talk about a new paper that explores a new role for the placenta in autism spectrum disorder and how secreted placental hormones can influence brain development and even explain certain sex differences in autism. Understanding how early developmental events can affect sex-specific development gives insight to potential therapeutic interventions for neuropsychiatric disorders.Vacher et al. Placental endocrine function shapes cerebellar development and social behavior. Nature Neuroscience, October 2021. DOI: 10.1038/s41593-021-00896-4The information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

Bone marrow stem cell transplants are some of the most important tools in treating diseases like leukemia and multiple myeloma. However, harvesting enough stem cells for transplantation is often a big issue for doctors. Finding new ways to elicit stem cell mobilization from the bone marrow to improve harvesting could go a long way in improving treatment. Today's episode of Beyond the Abstract features work by scientists who find a surprising role for pain nerves, known as nociceptive neurons, in promoting stem cell mobilization. Ellen and Derek discuss how they stumbled upon this finding and how there might be more to a chili pepper than meets the eye.Gao et al. Nociceptive nerves regulate haematopoietic stem cell mobilization. Nature, January 2021. DOI: 10.1038/s41586-020-03057-yThe information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

Multiple Sclerosis (MS) is a devastating autoimmune disease that result from the immune system attacking parts of the nervous system. For a long time, MS has been treated with broad immunosuppression using corticosteroids that puts the patient at risk for infections, but this might soon change. In today's Beyond the Abstract episode, Derek and Dan talk about a new paper that uses a novel mRNA vaccine to prevent and even treat MS, brought to you in part by BioNTech (the same company that helped develop the COVID-19 vaccine).Krienke et al. A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis. Science, January 2021. DOI: 10.1126/science.aay3638The information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

High cholesterol and clogged arteries are the main cause of heart attacks. While modern medicine has developed ways to keep cholesterol down, these medications must be taken daily in order to be effective and come with their own list of side effects. This is where CRISPR comes in. Scientists have now developed a way to safely and durably reduce cholesterol in monkeys with a single injection of CRISPR gene therapy. In this episode, Dan and Derek discuss how this new therapy actually works, some of the interesting history behind it, and why it might be coming to a clinic near you sooner than you think...Musunuru et al. In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates. Nature, May 2021. DOI: 10.1038/s41586-021-03534-yThe information presented here is not medical advice. Consult your physician on any questions regarding your personal health.

When patients have low oxygen levels, doctors use various types of breathing machines to deliver oxygen to the lungs - but it's not always effective. Now, scientists have taken inspiration from a small fish called the loach and developed a method to deliver oxygen through... the butt. This is particularly pertinent in the face of the COVID-19 pandemic, where physicians have struggled to find adequate ways to oxygenate patients in respiratory failure due to viral pneumonia. In this episode, Ellen and Derek discuss a new, rather eccentric paper that delivers oxygen anally in order to treat respiratory failure. This technology could prove to be a useful method in effectively treating hypoxia and respiratory failure.Okabe et al. Mammalian enteral ventilation ameliorates respiratory failure. Med, June 2021. DOI: 10.1016/j.medj.2021.04.004The information presented here is not medical advice. Consult your physician on any questions regarding your personal health.