Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
7Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA.
8Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Application of guidelines to the day-to-day clinical practice of clinicians is not always straightforward. Guidelines often provide a structure to the thought process demanded during clinical decision-making, which requires the application of evidence as best suited for each individual patient. These guidelines provide recommendations and suggestions, and the weight of these recommendations relies heavily on the quality of evidence and the vote of experts in the field, when evidence is lacking or insufficient.
Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA.
2Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.
3Department of Medicine, School of Medicine, National Yang-Ming Chiao-Tung University, Taipei, Taiwan.
The contemporary university system faces an unprecedented crisis of epistemic legitimacy. While empirical and vocational disciplines (such as clinical medicine, structural engineering, and applied physics) remain constrained by real-world falsifiability and physical safety, non-rigorous, non-vocational fields—predominantly spanning theoretical humanities and speculative social sciences—have descended into self-referential group-think. This paper argues that the legacy model of peer-reviewed, paywalled academic journals in these non-empirical fields is economically extractive, intellectually calcified, and functionally obsolete in the era of artificial intelligence. Through an examination of institutional incentive structures, the performative jargon of soft disciplines, and the democratizing force of generative AI, we show how legacy publishing cartels protect ideological conformity rather than academic rigor.
Scientists have just announced the results from the first clinical trial in people with HIV-1 of a new antiretroviral drug, which suggests it could be a very useful new tool in treating the virus.
The drug is currently known as ‘VH-499’ (that’s short for VH4011499), and it works by inhibiting the virus’s capsid protein, without which HIV cannot proliferate to harmful or transmissible levels.
“Advancements in care and prevention have transformed HIV-1 into a manageable chronic condition and reduced transmission rates,” write clinical pharmacologist Rulan Griesel and team in a paper announcing the clinical trial results.
The amino acid arginine helps keep the human body humming, most notably by synthesizing proteins that carry out a range of cellular processes. It’s produced by our bodies and found in common high-protein foods. Low levels of arginine are associated with a number of diseases, including colon cancer.
Sohail Tavazoie, head of Rockefeller University’s Elizabeth and Vincent Meyer Laboratory of Systems Cancer Biology, has been investigating that connection for years. In 2023, Tavazoie’s team found that starving colon cancer cells of arginine increases the number of mutations they accumulate. Now they’ve discovered that an arginine-deficient diet also affects the immune system by stalling the production of the MHC-I protein, which alerts the immune system to dangers such as a mutating cell or an invading virus.
Intriguingly, they also found that a moderate dose of arginine—about as much as is found in a couple of over-the-counter tablets—could potentially restore expression of the genes responsible for MHC-I production. They published the results in the journal Cell.
For years, scientists have known that the heart has its own network of nerves, the intrinsic cardiac nervous system (ICNS), sometimes called its “little brain.” Exactly how it functions has remained something of a mystery, but a new paper published in the journal Cell sheds light on how these heart nerves work to keep the heart beating steadily.
The heart’s nerve cells fine-tune signals coming from the brain to control heart function, including heart rate. But because they are so few, doctors have struggled to determine exactly what they do. To solve this, researchers from Yale University School of Medicine genetically engineered adult mice so their heart nerves would glow, making them much easier to study.
After locating the nerves, the team analyzed which genes were active in them. They discovered that the nerves fell into two categories, which they called Npy neurons and Ddah1 neurons.
In a promising sign for the potential of focused sound waves to improve care for brain tumors, UVA Health researchers have determined that tumors called gliomas may be even more receptive to targeted drug delivery than normal brain tissue.
While the research is still in its early stages, the findings help allay concerns that brain tumors might have properties that would make them stubbornly resistant to the cutting-edge approach. The UVA scientists are using tiny “microbubbles” that are activated by sound waves to open the brain’s natural protective barrier, known as the “blood-brain barrier,” so that drugs can enter exactly where needed.
Inside brain tumors, cancer cells mutate the structure of the blood-brain barrier and its function becomes unpredictable. In turn, this raises questions about how effectively focused ultrasound can deliver therapies in the brain tumor environment and what sizes of drug molecules can be delivered most effectively. The new research from UVA Health’s Focused Ultrasound Cancer Immunotherapy Center provides important insights on both fronts.
Pathogenic B cell activation underlies many autoimmune diseases (AIDs), and their depletion is an attractive therapeutic approach. Chimeric antigen receptor (CAR)-expressing cells-initially developed and successfully used to treat certain cancers-are increasingly being developed to selectively deplete B cells and ‘reset’ the immune system in AIDs. In this Review, we survey this fast-developing field, providing insights on the current unmet needs in the treatment of AIDs and how CAR T cells could address these needs. In particular, we explore the concept of deep B cell depletion, discuss the currently available technologies and review the key targets (CD19 and B cell maturation antigen) relevant for the treatment of AIDs. We summarize current evidence on the efficacy, safety, risks and limitations of autologous and allogeneic CAR T cells in this setting. Finally, we discuss the future outlook-from a technological and clinical standpoint-for development of engineered CAR-expressing cell therapies for AIDs.
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