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Preventing breast cancer resistance to CDK4/6 inhibitors using genomic findings

Researchers at Memorial Sloan Kettering Cancer Center (MSK) have made an important discovery about how genetic mutations in breast cancer patients can interact and drive resistance to certain drugs called CDK4/6 inhibitors. This finding, published in Nature, suggests a new strategy for predicting and preventing resistance to specific therapies based on the tumor’s genetic profile.

“This represents a major advance in understanding and predicting cancer behavior in response to treatment,” says physician-scientist Pedram Razavi, MD, Ph.D., who led the study with physician-scientist Sarat Chandarlapaty, MD, Ph.D. The study’s first author was Anton Safonov, MD, a physician-scientist in the MSK Breast Translational Program.

“To our knowledge, this is the first example showing that a complete genomic analysis of breast cancer, including both inherited and tumor-specific alterations, can predict the precise biological mechanism of resistance before therapy even begins,” Dr. Razavi adds.

CDK4/6 Inhibitor Resistance in Hormone Receptor-Positive Metastatic Breast Cancer: Translational Research, Clinical Trials, and Future Directions

The emergence of CDK4/6 inhibitors, such as palbociclib, ribociclib, and abemaciclib, has revolutionized the treatment landscape for hormone receptor-positive breast cancer.

Cryogenic Arks — Sleeping Through the Ages

From frozen habitats to millennia-long journeys, we explore the science behind cryogenic arks and deep-time interstellar travel.

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Check out Joe Scott’s Oldest & Newest: https://nebula.tv/videos/joescott-old… my exclusive video Chronoengineering: https://nebula.tv/videos/isaacarthur–… 🚀 Join this channel to get access to perks: / @isaacarthursfia 🛒 SFIA Merchandise: https://isaac-arthur-shop.fourthwall… 🌐 Visit our Website: http://www.isaacarthur.net ❤️ Support us on Patreon: / isaacarthur ⭐ Support us on Subscribestar: https://www.subscribestar.com/isaac-a… 👥 Facebook Group: / 1,583,992,725,237,264 📣 Reddit Community: / isaacarthur 🐦 Follow on Twitter / X: / isaac_a_arthur 💬 SFIA Discord Server: / discord Credits: Cryogenic Arks – Sleeping Through the Ages Written, Produced & Narrated by: Isaac Arthur Select imagery/video supplied by Getty Images Music by Epidemic Sound: http://nebula.tv/epidemic & Stellardrone Chapters 0:00 Intro 2:50 The Need for Cryogenic Arks 6:12 From Freezing Flesh to Preserving Life 12:33 The Physics and Engineering of the Cryogenic Ark 18:46 The Problem of Time and Identity 24:59 Oldest & Newest 25:59 How Long Can We Stay Frozen? 30:48 Crew Dynamics and Risk 35:18 Beyond Cryogenics – Slowing Time Itself.
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Learning makes brain cells work together, not apart

When you get better at a skill—recognizing a familiar face in a crowd, spotting a typo at a glance, or anticipating the next move in a game—sensory neurons in your brain become more coordinated, sharing information rather than acting more independently. That’s the conclusion of a new study by researchers at the University of Rochester and its Del Monte Institute for Neuroscience, published in Science, which challenges a long-held assumption in neuroscience that learning improves efficiency by minimizing repetition across neural signals.

Led by Shizhao Liu, a graduate student in the labs of Ralf Haefner and Adam Snyder, both faculty members in the Department of Brain and Cognitive Sciences, the study shows that learning instead increases shared activity among neurons. The findings could provide insights into learning disorders and inspire more flexible, human-like artificial intelligence tools.

“The dominant view in neuroscience has been that learning makes the brain more efficient by pushing neurons to act more independently, so information can be read out more cleanly,” Liu says. “Our results support a different idea, that sensory areas of the brain aren’t just passively encoding the world. They’re actively performing inference by combining what’s coming in with what the brain has learned to expect.”


A new University of Rochester study could reshape how scientists think about perception, learning disorders, and artificial intelligence.

Navigating Postacute Care Options for Patients After Hospital Discharge: A Review

Approximately 25% to 40% of hospitalized adults are discharged to receive postacute care either at home through home health or in skilled nursing facilities, inpatient rehabilitation facilities, or long-term acute care hospitals.

This Narrative Review considers postacute care settings to assist hospital-based clinicians in effectively collaborating with patients, caregivers, and interdisciplinary care teams to facilitate transitions to high-quality postacute care.


Clinicians often care for patients who cannot return to their previous level of support in the community due to new functional impairments or complex posthospital care needs. After hospital discharge, these patients may require postacute care (PAC)—broadly defined as medical and rehabilitative services intended to help individuals recuperate and rehabilitate. PAC can be provided at home through home health (HH) or in skilled nursing facilities (SNFs), inpatient rehabilitation facilities (IRFs), and long-term acute care hospitals (LTACHs). A key criterion for PAC eligibility is the need for skilled nursing and/or rehabilitative services as determined by the treating physician.1-3 Payers require that these health services be reasonable and necessary for the treatment of a specific illness or injury, and that given their complexity (eg, wound care, intravenous infusion), they be provided only by a health professional. Yet, clinicians often play a passive role in PAC planning; many report a lack of knowledge around PAC capabilities, quality, and constraints.4-6

The epidemiology of PAC in the US is best understood for Traditional Medicare (or fee-for-service). Among hospitalized Medicare beneficiaries, approximately 40% were discharged to PAC in 2023: 18% to HH, 17% to SNF, 5% to IRFs, and 1% to LTACHs,7 accounting for approximately $60 billion of Medicare spending annually.7 Up to three-quarters of regional differences in Medicare spending are attributable to PAC, suggesting that discharge decisions are often driven by local practice norms rather than patient need. This underscores the need to improve and standardize PAC best practices.8,9

Hospital-based physicians, nurse practitioners, and physician assistants play an important role in PAC discharge planning due to their in-depth understanding of a patient’s complex medical needs. A better understanding of the qualifications and services provided can help clinicians engage in a more helpful role in the PAC discharge planning process. This Narrative Review provides an overview of PAC settings with the goal of helping clinicians collaborate most effectively with patients, caregivers, and interdisciplinary care teams to promote transition to high-quality PAC. We present a general summary of the most common types of PAC, followed by a comparison of the supporting evidence for each PAC setting. Descriptions of elements of PAC are based on the benefits covered by Traditional Medicare, which generally inform other payers’ coverage policies. Lastly, we review best practices for clinicians to actively discuss PAC options with patients, helping to orchestrate transitions of care to PAC for eligible individuals.

Why the “Immortal” Jellyfish Can Age Backwards — And What That Means for Human Aging

A tiny jellyfish found in the ocean possesses an extraordinary ability to reverse its life cycle. This creature can transform from an adult back to a polyp, essentially resetting its biological clock. Scientists are studying its DNA to understand this process. This discovery offers new insights into aging and regeneration, potentially impacting future medical research.

The role of liver sinusoidal endothelial cells in liver diseases: Key players in health and pathology

Liver sinusoidal endothelial cells (LSECs) are specialised endothelial cells that orchestrate hepatic homeostasis within the liver sinusoid. Besides their key role in regulating intrahepatic vascular tone, trafficking and cellular crosstalk, their scavenging and immune-regulatory role makes them central to the development of liver disease. LSEC dysfunction includes loss of fenestrae, inflammatory activation and the gain of vasoconstrictive and prothrombotic functions. Robust evidence has demonstrated how preserving LSECs is crucial in a pathological context, placing LSECs at the centre of novel therapeutic and diagnostic strategies.

Pharmacologic reversal of advanced Alzheimer’s disease in mice and identification of potential therapeutic nodes in human brain

Here, we show that pharmacologic restoration of NAD+ homeostasis via P7C3-A20, a neuroprotective compound that restores NAD+ homeostasis without producing supraphysiologic NAD+ levels,51,52,53,54,55,56 reverses cognitive deficits and neuropathology in advanced Aβ- and tau-driven AD models. We identify conserved molecular signatures between human and mouse AD and show that the magnitude of NAD+ homeostasis disruption correlates with pathology and symptom severity in mouse and human AD. We also demonstrate that NDAN brains display transcriptional profiles compatible with preserved NAD+ homeostasis and that P7C3-A230 restores NAD+ homeostasis and prevents oxidative damage and mitochondrial dysfunction in oxidatively stressed human brain microvascular endothelial cells (HBMVECs), a key component of the BBB. We additionally identify 46 conserved protein alterations in human and mouse AD brain that are corrected by AD reversal, together with overlapping transcriptomic changes in human AD. This highlights potential mechanisms and therapeutic targets for preserving and restoring brain resilience to AD.

These findings of cognitive recovery and pathological reversal in diverse models of advanced AD support disease progression as modifiable and driven by diminished brain resilience, with early cognitive impairment resulting from processes that promote neurodegeneration rather than solely from fixed neuronal loss. We propose that therapies to restore brain resilience, such as normalization of NAD+ homeostasis, merit clinical evaluation for prevention and reversal of AD and related dementias.

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