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Diseases and Conditions

A Breakthrough Test for Lymphoma Patients: Predicting CAR T Cell Therapy Response with Machine Learning

A new article outlines a new tool that measures blood inflammation as a marker for poor CAR T therapy outcomes.

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The article reports on a significant breakthrough in cancer research, as City of Hope and Memorial Sloan Kettering (MSK) researchers have developed a tool using machine learning to predict the response of non-Hodgkin lymphoma patients to chimeric antigen receptor (CAR) T cell therapy. This test, called InflaMix, assesses inflammation in the blood, which is a potential cause of CAR T failure, and can identify patients at high risk for treatment failure.

The study involved 149 patients with NHL, and the machine learning model was able to find an inflammatory biomarker from a series of unique blood tests not usually employed in standard clinical practice. By analyzing this inflammatory signature, researchers found it was associated with a high risk of CAR T treatment failing, including increased risk of death or disease relapse.

The InflaMix model is an unsupervised machine learning approach, meaning it was trained without any knowledge of clinical outcomes. The team’s studies demonstrate that by using machine learning and blood tests, they could develop a highly reliable tool that can help predict who will respond well to CAR T cell therapy.

The researchers used three independent cohorts comprising 688 patients with NHL who had a wide range of clinical characteristics and disease subtypes and used different CAR T products to validate their initial findings. The study’s results were published in Nature Medicine.

City of Hope and MSK plan to investigate whether blood inflammation defined by InflaMix directly influences CAR T cell function and learn more about the source of this inflammation. This research has the potential to improve patient outcomes and inform new clinical trials that can boost the effectiveness of CAR T with additional treatment strategies.

The team’s studies were funded in part by the National Institutes of Health, the National Cancer Institute, and an MSK Support Grant. The work was primarily done at MSK where Dr. Van den Brink worked for more than two decades before coming to City of Hope in 2024.

City of Hope has treated over 1,700 patients since its CAR T program started in the late 1990s and continues to have one of the most comprehensive CAR T cell clinical research programs in the world, with about 70 ongoing clinical trials using immune cell products.

Alternative Medicine

“The Sleeping Giants: How Tai Chi, Yoga, and Jogging Rival Pills for Beating Insomnia”

Yoga, Tai Chi, walking, and jogging may be some of the best natural remedies for improving sleep and tackling insomnia, according to a large analysis comparing various treatments. While cognitive behavioral therapy (CBT) remains effective, exercise-based approaches—especially Tai Chi—were shown to deliver significant improvements in total sleep time, efficiency, and reducing how long people stay awake after falling asleep. Yoga stood out for boosting overall restfulness, and jogging helped ease insomnia symptoms.

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The rewritten article:

Tai chi, yoga, and jogging may be the best forms of exercise to improve sleep quality and ease insomnia, suggest the findings of a comparative pooled data analysis published in the online journal BMJ Evidence Based Medicine.

The study, which involved 1348 participants and 13 different treatment approaches to ease insomnia, found that these three exercise-based interventions showed promising results. Yoga likely resulted in a large increase in total sleep time of nearly 2 hours and may improve sleep efficiency by nearly 15%. Walking or jogging may result in a large reduction in insomnia severity of nearly 10 points, while Tai Chi may reduce poor sleep quality scores by more than 4 points, increase total sleep time by more than 50 minutes, and reduce time spent awake after falling asleep by over half an hour.

Further in-depth analyses revealed that Tai Chi performed significantly better on all subjectively and objectively assessed outcomes than existing treatments for up to 2 years. The researchers suggest that Tai Chi’s focus on body awareness, controlled breathing, and attentional training may alter brain activity, thereby alleviating anxiety and depressive symptoms which often interfere with a good night’s sleep.

The study also found that exercise-based interventions, including yoga, Tai Chi, and walking or jogging, have the potential to serve as viable primary treatment options for insomnia. The researchers conclude that these interventions are well-suited for integration into primary care and community health programs due to their low cost, minimal side effects, and high accessibility.

Overall, the findings of this study further underscore the therapeutic potential of exercise interventions in the treatment of insomnia, suggesting that their role may extend beyond adjunctive support to serve as viable primary treatment options.

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Diseases and Conditions

Cognitive Collapse and the Nuclear Codes: When Leaders Lose Control

A shocking study reveals that many leaders of nuclear-armed nations—including US presidents and Israeli prime ministers—were afflicted by serious health problems while in office, sometimes with their conditions hidden from the public. From dementia and depression to addiction and chronic diseases, these impairments may have affected their decision-making during pivotal global crises.

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As we navigate the complexities of global politics, it’s essential to consider the health and decision-making abilities of our leaders. A recent study from the University of Otago, New Zealand, has raised concerns about cognitive collapse among former leaders of nuclear-armed nations. The research analyzed the health information of 51 deceased leaders and found that many had multiple serious health issues while in office.

The study’s lead researcher, Professor Nick Wilson, noted that 15 of these leaders likely had their performance impaired by health conditions, including dementia, personality disorders, depression, and drug and alcohol abuse. This is a stark reminder that even the most powerful leaders can be vulnerable to cognitive decline.

One notable example is Ariel Sharon, who became comatose after suffering a stroke in office, and Menachem Begin, whose severe depression kept him isolated for his final year as leader. Even Richard Nixon’s heavy drinking raised concerns during a nuclear crisis involving the Middle East.

The study also highlighted instances where health information about leaders was kept secret at the time, including the cases of US presidents Dwight D Eisenhower, John F Kennedy, and Ronald Reagan. In some cases, this secrecy led to impaired decision-making, as seen in Kennedy’s poor performance during his first two years in office.

This latest research follows previous studies on the health of former New Zealand Prime Ministers, which found that at least four leaders’ performances were impaired by poor health or heavy drinking. Professor Wilson emphasizes the importance of strong leadership and governance, particularly for nuclear-armed nations like the United States.

To mitigate global security risks from leaders whose judgment is in question, Professor Wilson proposes various measures, such as removing nuclear weapons from high alert status, adopting no-first-use policies, ensuring multi-person authorization for weapon launches, and progressing nuclear disarmament treaties. He also suggests introducing term limits, recall systems, medical and psychological assessments before taking office, and maintaining a strong media with investigative journalists to expose impairment in leaders.

Ultimately, finding ways to reduce stress on politicians and better address their mental health needs can be crucial in reducing global security risks. As we move forward, it’s essential to prioritize the well-being of our leaders to ensure they make informed decisions that protect us all.

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Behavioral Science

“Decoding Human Tissue: Scientists Discover Five Universal Rules That Govern Organ Structure”

Scientists have uncovered a surprisingly simple “tissue code”: five rules that choreograph when, where, and how cells divide, move, and die, allowing organs like the colon to remain flawlessly organized even as they renew every few days. Mathematical models showed that manipulating just these parameters faithfully recreates real tissue architecture, hinting that the same code may govern skin, brain, and more. The discovery offers a fresh way to understand healing, birth defects, and cancer, and could supercharge initiatives such as the Human Cell Atlas by turning static cell maps into dynamic predictions.

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The human body is an intricate machine, constantly replacing billions of cells every day while maintaining perfect tissue organization. Researchers at ChristianaCare’s Helen F. Graham Cancer Center & Research Institute and the University of Delaware have cracked the “tissue code” – a set of five basic rules that explain how tissues like those in the colon stay organized even as their cells are constantly dying and being replaced.

After 15 years of collaboration between mathematicians and cancer biologists, the team identified these five core biological rules that govern cell behavior and tissue structure:

1. Cell migration: Cells move towards areas with specific signals.
2. Cell division: Cells divide in a controlled manner to maintain tissue density.
3. Apoptosis regulation: Cells self-destruct in a programmed way to prevent overgrowth.
4. Adhesion and detachment: Cells adhere to their neighbors and detach at the right time to maintain tissue integrity.
5. Signaling pathways: Cells communicate with each other through specific signaling pathways.

These rules work together like choreography, controlling where cells go, when they divide, and how long they stick around – keeping tissues looking and working as they should. The researchers believe these rules may apply not just to the colon but to many different tissues throughout the body, including skin, liver, brain, and beyond.

This discovery has significant implications for understanding tissue healing after injury, birth defects, and diseases like cancer that develop when this code gets disrupted. By identifying simple, universal rules that govern cell behavior and tissue structure, the findings could help guide future efforts to not only describe cells but predict how they behave in health and disease.

The team’s work also reflects a broader shift in how scientists approach complex problems – collaboration between biology and math. This kind of research aligns with national priorities, such as the National Science Foundation’s “Rules of Life” initiative, which challenges researchers to uncover fundamental principles that govern living systems.

Next steps for the team include testing the model’s predictions experimentally, refining it with additional data, and exploring its relevance to cancer biology – especially how disruptions to the tissue code may lead to tumor growth or metastasis. This is just the beginning of a promising new area of research that could lead to better understanding and treatment of diseases, as well as improved human health and longevity.

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