Tag: Medication

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High-Fat Diet Works with Gut Microbes to Benefit Cancer Treatment

A high-fat diet can result in better outcomes from cancer immunotherapy by improving the balance of microbes in the gut, early research shows.

The findings reveal how diet shapes immune states and how altering it could improve cancer treatment outcomes.

The study, reported in Nature, revealed that an obesogenic diet improved response to immune checkpoint inhibitors, with this occurring outside its impact on bodyweight or metabolism.

Instead, the benefits were linked with the creation of a favorable microbial ecosystem, which worked synergistically with the diet.

The results offer a potential explanation for the obesity paradox in cancer treatment, in which high body mass index is associated with improved immunotherapy responses to several types of cancer.

“Prolonged obesogenic diets are associated with well-established health risks and are not proposed as long-term interventions for patients with cancer,” caution researcher Lysanne Desharnais, PhD, from McGill University in Montreal, Canada, and colleagues.

“Rather, our work highlights the therapeutic potential of short-term dietary modulation, and of specific bacteria or microbial-derived metabolites, to create an optimal host ecosystem for immunotherapy responses.”

Previous research has indicated that the gut microbiota regulates immunotherapy responses, with diet shaping both the microbial and metabolic states that influence immune function.

Gut dysbiosis is a hallmark feature of obesity that links diet, the microbiome and health risk factors. Yet paradoxically, studies have shown that high BMI is associated with improved ICI responses for several types of cancer.

To investigate further, Desharnais and colleagues examined the impact of 12 mouse diets to designed to reflect variation in the human diet and also studied the impact of fecal microbiota transplants (FMTs).

In addition to traditional low fat, high fat, and Western diets, they used diverse ingredients as sources of protein, carbohydrates, fat and fiber to mimic Mediterranean, Japanese, vegan, American and ketogenic diets.

The team found that the efficacy of immune checkpoint inhibitors was dependent on the diet-gut axis rather than metabolic dysfunction, creating a favorable host ecosystem for therapy.

Lactobacillus johnsonii was as one of several key gut species associated with response against programmed cell death protein (PD-1), a protein found on T immune cells that helps keep immune responses in check.

Nonetheless, the researchers reported, “FMT, monocolonization, and diet switch experiments demonstrated that diet was more influential than microbiota composition alone, with maximal benefits observed when favorable bacteria were paired with favorable diets, due to synergistic metabolic remodeling.”

Obesogenic diets were not uniformly beneficial.

For example, the Mediterranean diet—high in fat from olive oil—retained a microbiota resembling lean, metabolically healthy mice, including low Lactobacillus, and remained insensitive to immune checkpoint inhibitors.

Conversely, a diet high in the soluble plant fiber inulin was lean and responsive to immune checkpoint inhibitors, yet had a distinct microbial composition characterized by low Lactobacillus and high Bifidobacteria.

Aromatic amino acid metabolites mediated the efficacy of immune checkpoint inhibitors. Tyrosine-derived phenylpropionate metabolism was a key pathway leading to production of desaminotyrosine and related metabolites, which enhanced T cell effector function.

There were also beneficial rises in indole-containing tryptophan metabolites, including indole-3-lactic acid, although this was not specifically dependent on Lactobacillus.

The researchers concluded: “Together, our findings identify diet–microbiome synergy as a mechanistic basis for the obesity paradox in cancer immunotherapy and a tractable target for improving therapeutic responses across diverse patient populations.”

The post High-Fat Diet Works with Gut Microbes to Benefit Cancer Treatment appeared first on Inside Precision Medicine.

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Non-Invasive Brush Biopsy Test Detects Cancer Within an Hour

In the largest of its kind, involving over 1000 samples from 545 patients, a non-invasive, brush biopsy test detected oral cancer within one hour in a validation test. It is hoped the test will greatly advance oral cancer detection and prevent perhaps over 90% of unnecessary harmful scalpel biopsy procedures, which can be difficult to carry out and may damage underlying tooth and bone structure. 

“We were genuinely astonished by the fact that the brush swab test performance is comparable to a microbiopsy,” said lead author Muy-Teck Teh, PhD. “It suggests that the biological signal captured by these four genes is sufficiently strong and consistent that it can be detected even from the superficial exfoliated cells collected by a brush biopsy.”

The work was published in the Nature journal Biomarker Research by a cross-University team led by Queen Mary University of London researchers. Teh is a professor of molecular oral oncology at Queen Mary of The Centre for Oral Immunobiology & Regenerative Medicine, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London.

Oral cancer is a growing global killer. According to Global Burden of Disease data, lip and oral cancer is among the world’s most rapidly increasing causes of early death. Over ten thousand people in the U.K. were diagnosed with oral cancer last year, according to the charity Mouth Cancer, and 3637 people lost their lives. Almost 650,000 people in America are estimated to get the disease each year and more than 13,000 die from it. Worldwide, it affects 650,000 a year. Risk factors include tobacco use/smoking, alcohol, infection with the HPV virus, and sun damage. Unfortunately, more than half (53%) of all mouth cancers are diagnosed in stage IV, where the cancer is at its most advanced.

Cases Human of Papillomavirus (HPV)—specifically HPV type 16 is thought to cause a large proportion of this disease. While the HPV vaccine is having tremendous effect protecting young girls and women from HPV-related cervical cancer, there has been less pick-up of the vaccine among boys.

Oral squamous cell carcinoma (OSCCs) are usually diagnosed early using scalpel biopsies. Early diagnosis is critical for the greatest chance of survival, yet most oral potentially malignant disorders (OPMDs) are benign, and patients frequently undergo unnecessary invasive scalpel biopsies, creating diagnostic delays and harms. A scalpel oral biopsy can be extremely painful—especially the tongue (the most common cancer site)—essentially because part of the tongue is removed. But the overwhelming likelihood is that the growth is benign.”

These circumstances discourage both patients and clinicians from doing biopsies repeatedly and in a timely fashion. This study aimed to find out if a successful microbiopsy-based multigene assay (qMIDS-V2) could be adapted into a rapid, non-invasive brush biopsy test (qMIDS-V3) for accurate OSCC detection. This new test could potentially spare over 90% of low-risk OPMD patients from unnecessary invasive tissue biopsies. 

The prospective diagnostic case-control study validated a multigene mRNA test (qMIDSV3) for OSCC detection using 1090 oral brush biopsies from 545 patients. Each patient provided paired brush biopsies from oral lesion and contralateral non-lesion mucosa, including OSCC (n = 443), oral leukoplakia (OL; n = 63), and oral lichen planus (OLP; n = 39). qPCR quantified mRNA levels of four genes (INHBA, S100A16, YAP1, POLR2A) from each brush biopsy, and an algorithm generated a malignancy index for cancer risk stratification.

qMIDSV3 distinguished OSCC from OL and OLP with AUC 0.975, sensitivity 95.7%, specificity 95.1%, and overall accuracy 95.5%. False-positive and false-negative rates were 4.9% and 4.3%, showing the test has high specificity for detecting malignant cells rather than premalignant or inflammatory lesions.

The test could thus give clinicians a rapid, accurate, and non-invasive way to triage patients. It can also be repeatedly administered. “That means doctors can now monitor patients with persistent pre-malignant lesions regularly and systematically—and pick up cancers much earlier than we would have been able to before,” said Teh.

Overtesting is also a problem. In the U.K., a current 10 year audit reported a 450% rise in two week wait referrals alongside a 50% drop in cancer detection rate. Subsequent audits showed that 92.5–99.5% of referred patients were cancer free, with most (96–98%) remaining cancer free at 5-year follow up. This latest study builds on substantial of prior clinical validation. 

The team included researchers from Queen Mary University of London’s Centre for Oral Immunobiology & Regenerative Medicine, King George’s Medical University in India, Modern Dental College & Research Centre in India, and the All India Institute of Medical Sciences.

 

The post Non-Invasive Brush Biopsy Test Detects Cancer Within an Hour appeared first on Inside Precision Medicine.

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Predicting Cancer Immunotherapy Response Better with COMPASS AI Model

COMPASS, a novel AI model that combines transcriptomic data with tumor-immune information, predicts immunotherapy response more accurately than existing biomarkers across different cancer types, shows data published in Nature Medicine.

The model also offers insight into why a patient may or may not respond to treatment, giving clinicians a better understanding of why responses might not be as expected.

To date, predicting response to immune checkpoint inhibitors (ICIs) has largely relied on tumor mutational burden (TMB) and PD-L1 immunohistochemistry. In addition, researchers have developed transcriptomic signatures that capture T cell dysfunction or score immune checkpoint activity, while network based and machine learning approaches have tried to incorporate gene interaction data, but each of these approaches has limitations because people undergoing ICI treatment often respond in unexpected ways.

“In our benchmarking against 22 of these methods, previous approaches showed inconsistent performance once tested across different cancer types and treatments, which is the core problem COMPASS addresses,” said study senior author Marinka Zitnik, PhD, associate professor of biomedical informatics in the Blavatnik Institute at Harvard Medical School.

She told Inside Precision Medicine that “most AI models for predicting immunotherapy response are validated within a single cancer type or a single drug class, which limits how much they generalize once you move to a new tumor type, a new therapy, or a different hospital’s data. This is significant because it means we can have a model that predicts response in one population of cancer patients, but fails when applied to a different population, a different tumor type, or a different treatment regimen, which is exactly the kind of gap that keeps promising biomarkers from ever reaching routine clinical use.”

Zitnik explained that “COMPASS is different because it is pretrained on transcriptomic data from over 10,000 tumors spanning 33 cancer types before it ever sees a clinical outcome, so it learns broad, biologically grounded patterns of tumor immune biology.”

The model uses a “concept bottleneck architecture” which means that rather than going straight from gene expression data to a prediction, it forces the information through an intermediate layer, or bottleneck, before making the final prediction. In this case, the bottleneck is biologically defined immune concepts, like T cell exhaustion, macrophage activity, or transforming growth factor (TGF)-β signaling. This means clinicians and researchers can see which biological programs are driving a given patient’s predicted response or resistance.

Zitnik and team tested the performance of COMPASS in 1133 patients from 16 clinical cohorts spanning seven cancers and six ICI regimens. The found that, compared with the second-best performing biomarkers of the 22 tested (these varied by cohort), COMPASS improved accuracy by 8.5 percentage points and area under the precision-recall curve by 15.7 percentage points, on average.

“In a setting where response rates to immunotherapy are already low, a meaningful jump in prediction accuracy translates directly into better patient selection,” said Zitnik. “The improvements we saw mean fewer patients would be steered toward a treatment unlikely to help them, and more responders would be correctly identified for therapies that could extend their lives. This is important in cancer where checkpoint inhibitors carry toxicity risks and cost, so gains in identifying who is likely to benefit can meaningfully change treatment decisions and clinical trial design at scale.”

In survival analyses, the team found that individuals with a COMPASS response probability (PR) of 0.5 or higher had a 1-year overall survival rate of 86% compared with 40% for those with a PR below 0.5, yielding a hazard ratio for survival of 4.7.

Performance varied by cancer type and cohort size, but the researchers note that COMPASS was still able to accurately predict response for cancer types it had never seen.

“When we excluded lung adenocarcinoma entirely from training and tested only on that held out cohort, COMPASS still achieved 76.5% accuracy,” said Zitnik. “We saw similarly strong cross cancer generalization for urothelial carcinoma, melanoma, and other tumor types.”

Furthermore, COMPASS achieved 85.3% accuracy for predicting a response to combination therapies (ipilimumab plus pembrolizumab) when trained only on monotherapy cohorts.

In addition to predicting treatment response, the tool also generates a personalized response map for each patient that traces exactly which genes and immune programs are shaping their prediction.

“This explainable AI feature means a clinician is not just given a predicted ‘yes’ or ‘no’, they can see whether a patient’s tumor looks inflamed but is failing due to TGF-β driven suppression or whether it looks immune desert but still shows residual cytotoxic activity that could respond to treatment,” said Zitnik.

“This kind of mechanistic insight could help with patient stratification in clinical trials, indication selection when a drug is being tested in a new cancer type and generating hypotheses about resistance mechanisms that could point toward combination therapies.”

The investigators are now planning to move from using bulk RNA sequencing data for training to single cell and spatial transcriptomic data. They are also exploring how to connect COMPASS with AI agent systems, to help translate the mechanistic insights into more autonomous research workflows.

The post Predicting Cancer Immunotherapy Response Better with COMPASS AI Model appeared first on Inside Precision Medicine.

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Integrated multi-omics and deep learning analysis reveals neurotransmitter metabolism regulatory mechanisms of Tianwang Buxin Dan

BackgroundTianwang Buxin Dan is a classical Traditional Chinese Medicine formula with documented clinical use in treating neuropsychiatric disorders, yet its molecular mechanisms remain incompletely understood.MethodsWe developed an integrated analytical framework combining transcriptomic and metabolomic profiling with deep learning to investigate the neurotransmitter metabolism regulatory mechanisms of Tianwang Buxin Dan. Data were collected from a para-chlorophenylalanine (PCPA)- induced insomnia rat model following formula intervention. A multi-omics feature fusion strategy incorporating autoencoder-based dimensionality reduction and cross-modal attention mechanisms was implemented to address data heterogeneity.ResultsA total of 1,847 differentially expressed genes and 286 differential metabolites were identified. The constructed deep neural network achieved 91.2% classification accuracy with an AUC of 0.956 in five-fold cross-validation, and permutation testing confirmed that performance was significantly above chance (p < 0.001). Ablation experiments demonstrated that integrated multiomics outperformed single-omics models. Tryptophan hydroxylase 2 (TPH2) upregulation and monoamine oxidase A (MAO-A) suppression were identified as key features and partially validated by qPCR and Western blot.DiscussionTianwang Buxin Dan may modulate neurotransmitter metabolism through coordinated regulation of biosynthetic and catabolic pathways. A component-target-pathway regulatory network identified 47 key molecular targets interconnected through 156 functional associations. This work provides a computational framework applicable to mechanism studies of other compound TCM formulations.
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Power without limits: exploring emotional regulation, moral authority, and psychiatric overreach through the Wizarding World of Harry Potter

BackgroundPsychiatry has never had more tools to relieve psychological suffering. Psychopharmacology, neuromodulation, early intervention, digital monitoring, and preventive approaches have expanded what clinicians can do. Yet this growing technical capacity also raises an uneasy question: when does care become control? Cultural narratives can offer spaces for examining such tensions, particularly when they dramatize power, vulnerability, suffering, and moral authority.AimThis narrative review uses the Wizarding World of Harry Potter as a conceptual lens to examine emotional regulation, moral authority, and psychiatric overreach, focusing on two contrasting figures: Lord Voldemort and Isidora Morganach.MethodsA theory-informed narrative review was conducted using a concept-focused analytic framework and structured conceptual synthesis. Literature was identified through focused searches in PubMed, PsycINFO, Scopus, and Google Scholar from database inception to June 2026, complemented by backward reference tracking. Sources covered Harry Potter scholarship, emotional regulation, psychological flexibility, narcissism and Dark Triad traits, medicalization, overdiagnosis, clinical ethics, and narrative medicine. To improve transparency, the synthesis distinguished direct literature on the Wizarding World from indirect psychiatric, psychological, ethical, and medical humanities scholarship used for conceptual interpretation.ResultsTwo pathways to psychiatric overreach and an intermediate zone of proportionate care were identified. The first, represented by Voldemort, involves destructive domination, emotional suppression, denial of vulnerability, instrumental use of others, and coercive authority. The second, represented by Isidora Morganach, involves hyper-compassionate control, intolerance of suffering, elimination of negative affect, moral certainty, and paternalistic intervention. Between these extremes, the intermediate zone emphasizes emotional integration, psychological flexibility, shared decision-making, contextual judgment, ethical proportionality, and clinical humility. Although one pathway is cruel and the other compassionate, both illustrate power exercised without sufficient emotional integration or ethical restraint.ConclusionBy exploring psychiatric questions through the Wizarding World, this review highlights how narrative frameworks can clarify the ethical boundaries of intervention. The central lesson is not that intervention is dangerous, but that intervention must remain proportionate, reflective, and ethically bounded. Psychiatry’s task is not to abolish all distress, but to relieve suffering while preserving autonomy, meaning, and human vulnerability.
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Another big premium hike on the horizon 

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Good morning from your shriveled-up Fourth of July leftovers. On this day in 1776, the Declaration of Independence was read in public for the first time, in Philly’s Independence Square. It was subsequently published in newspapers throughout the no-longer-colonies, though not always on the front page (!).

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Opinion: The AI licensure debate is missing the point of licensure

A cardiologist reviews an echocardiogram flagged by an algorithm she did not choose, trained on data she has never seen, deployed by a health system that did not ask for her input. The algorithm recommends a diagnosis. She disagrees. She overrides it. The patient does well.

No one will remember this moment. But if she had acquiesced and the patient suffered harm, she would be the one in the deposition, with her license on the line. Not the engineer who built the algorithm. Not the vendor who sold it. Not the health system that deployed it.

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Drug Candidate Shows Early Promise for Treating Alzheimer’s Damage

A drug candidate developed at King’s College London boosts DNA repair and reduces neuronal damage, as well as lowering neuroinflammation and could become a new treatment option for people with early stage Alzheimer’s disease in the future.

Writing in the journal FEBS Open Bio, lead author Jonathan Corcoran, PhD, a professor at King’s College London, and colleagues report results of a study carried out in a mouse model of Alzheimer’s disease that tested KCL-286, a retinoic acid receptor-beta agonist, and showed it had beneficial effects in the animals.

As Alzheimer’s disease develops, amyloid-beta accumulates and suppresses the brain’s natural retinoic acid signaling. This, as well as other factors, leaves neurons increasingly unable to repair DNA damage. The unrepaired damage then triggers microglial and astrocyte overactivation, which contributes to further neuronal injury in a self-reinforcing loop.

Mice treated with KCL-286 had significantly fewer DNA double-strand breaks in neurons than untreated mice, something seen in Alzheimer’s patients. They also had increased neuronal expression of BRCA1 protein, a DNA repair and tumor suppressor protein, suggesting KCL-286 partly works by ramping up the brain’s own repair machinery. In certain cancers, a BRCA1 mutation results in reduced or absent functional protein, which increases cancer risk over time.

KCL-286 also seemed to reduce inflammation in the brain of treated mice. Microglia and astrocytes were both abnormally enlarged and activated in the animals before treatment. However, after treatment the size and shape of these cells went back towards normal, in other words, calming dangerous inflammation without getting rid of the cells.

“We think of the drug as repairing potholes in a road—once the damage is fixed, normal traffic can flow again and the system settles down. By repairing the underlying damage, we can allow the system to reset,” said Corcoran in a press statement.

This is an early stage study and still needs to be tested in humans, but KCL-286 has already completed a Phase I trial in healthy human volunteers with no drug-related adverse events and is known to cross the blood-brain barrier efficiently. This is because the drug candidate is also being tested for treatment of spinal cord injury, hence the earlier Phase I study.

Both acute spinal cord injury and chronic neurodegeneration in Alzheimer’s involve accumulation of DNA double-strand breaks in neurons. In the former this is caused by the mechanical trauma and subsequent inflammation, whereas in the latter it builds up gradually over years.

The lack of side effects seen in the Phase I study is also important for KCL-286’s development as a possible Alzheimer’s treatment, as two earlier, non-selective retinoid drugs tested for treatment of Alzheimer’s caused side effects because they hit multiple off target receptor subtypes. KCL-286’s selectivity for the retinoic acid receptor-beta is designed to avoid this.

“Together with its favorable human safety profile, the data support further investigation of selective retinoic acid receptor-beta agonism as a therapeutic strategy for modifying pathogenic processes associated with Alzheimer’s disease,” conclude the authors.

The researchers think that if KCL-286 reaches the clinic early treatment is likely to be key to success. They also note there is potential for this type of therapy to be used in combination with approved Alzheimer’s treatments like lecanemab, which act to reduce harmful amyloid beta in the brain.

The post Drug Candidate Shows Early Promise for Treating Alzheimer’s Damage appeared first on Inside Precision Medicine.