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Category: biotech/medical – Page 8

Deep contrastive learning enables genome-wide virtual screening

Recent breakthroughs in protein structure prediction have opened new avenues for genome-wide drug discovery, yet existing virtual screening methods remain computationally prohibitive. We present DrugCLIP, a contrastive learning framework that achieves ultrafast and accurate virtual screening, up to 10 million times faster than docking, while consistently outperforming various baselines on in silico benchmarks. In wet-lab validations, DrugCLIP achieved a 15% hit rate for norepinephrine transporter, and structures of two identified inhibitors were determined in complex with the target protein. For thyroid hormone receptor interactor 12, a target that lacks holo structures and small-molecule binders, DrugCLIP achieved a 17.5% hit rate using only AlphaFold2-predicted structures.

AI Model for Imaging-Based Extranodal Extension Detection in Human HPV-Positive Oropharyngeal Cancer

An AI-powered pipeline accurately classified imaging-based extranodal extension from CT scans in HPV-positive oropharyngeal carcinoma and predicted worse oncologic outcomes, outperforming expert radiologist assessment and offering a promising prognostic tool for clinical decision-making.

Question Can an artificial intelligence (AI)−driven model predict imaging-based extranodal extension (iENE) and oncologic outcomes from pretreatment computed tomography scans of patients with human papillomavirus (HPV)−positive oropharyngeal squamous cell carcinoma (OPSCC)?

Findings In this single-center cohort study of 397 patients with HPV-positive cN+ OPSCC, an automated pipeline integrating lymph node segmentation and iENE classification achieved an area under the receiver operating characteristic curve of 0.81. AI-predicted iENE was significantly associated with worse distant failure, recurrence-free survival, and overall survival, and outperformed expert radiologist assessment.

Meaning These findings suggest that automated iENE detection using AI models may offer a powerful prognostic tool to complement clinical decision-making in HPV-positive OPSCC and extend iENE interpretation capabilities to centers that lack specialized radiologists.

NfL and Differentiation of bvFTD From Psychiatric Disorders

Neurofilament light chain levels in cerebrospinal fluid and blood are higher in patients with behavioral variant frontotemporal dementia than psychiatric disorders, suggesting its potential as a biomarker to aid in differentiating these conditions.

This systematic review aimed to determine whether elevated CSF or blood NfL can aid clinicians in differentiating bvFTD from psychiatric disorders. Across 12 studies reviewed, CSF and blood NfL levels were consistently significantly higher in patients with bvFTD than patients with psychiatric disorders at the group level. Furthermore, CSF and blood NfL demonstrated reasonable sensitivity and specificity to differentiate bvFTD from psychiatric disorders,38 though classification accuracy varied somewhat by study. While some of the AUCs for NfL differentiating bvFTD from psychiatric disorders had wide confidence intervals, these findings suggest a possible role for NfL in diagnostic clarification of patients with neuropsychiatric presentations. Misdiagnosing bvFTD as a psychiatric disorder may delay patients with bvFTD from early access to clinical trials when treatments may be more effective. Conversely, misdiagnosing a psychiatric disorder as bvFTD may worsen quality of life and delay treatment of ameliorable conditions.39-41

The existing literature has important limitations. Most studies were case control in design since they enrolled patients meeting diagnostic criteria for bvFTD or psychiatric disorders and then examined the association of NfL with these diagnoses. While these studies are essential for determining construct validity, they are not representative of the real-world clinical conditions by which NfL would be used. Also, such methods risk biased interpretations of the relationship of NfL with these conditions. Further studies are needed that prospectively recruit patients with neuropsychiatric symptoms and obtain NfL using clinically available assays to aid in real-time differential diagnosis.

An additional limitation of the reviewed studies is the selection and heterogeneity of psychiatric disorders. Several of the reviewed studies included patients with primary substance use, adjustment, or functional neurological disorder diagnoses.27, 31, 32,34, 35 Mood disorders, schizophrenia, and OCD may have the greatest symptom overlap with bvFTD.42 However, only 5 studies reported enrolling a total of 9 patients with OCD,25, 29, 31, 35, 36 a condition with an estimated OR of onset of 4.9 among individuals aged 45 to 59 years,43 suggesting a need for studies that include more patients with psychiatric disorders more likely to mimic core features of bvFTD despite absence of suspected neurodegenerative pathology. Moreover, FTD phenocopy syndromes (phFTD), clinical features that mimic FTD of mid-to late-life onset but do not progress to dementia, are understudied.44 Only 1 study in this review included a total of 2 patients with phFTD.

New toothpaste stops periodontal pathogens

Periodontitis is widespread and can have serious consequences for overall health. Researchers at Fraunhofer have identified a substance that selectively inhibits only those bacteria that cause periodontitis, thereby preserving the natural balance of the oral microbiome. This technology has been further developed and commercialized as a range of oral care products by the spin-off company PerioTrap.

The oral microbiome is home to more than 700 different bacterial species, of which only a few can cause periodontitis. These adhere to dental plaque, particularly along the gum line, where they trigger inflammation (gingivitis). This can potentially lead to chronic periodontitis, which does more than just cause receding gums and loose teeth. If these bacteria enter the bloodstream, they can also contribute to the development of diabetes, rheumatic disease, arthritis, cardiovascular disease, chronic inflammatory bowel disease and even Alzheimer’s disease.

Pathogenic bacteria are killed by conventional oral care products such as alcohol-based mouthwashes and products containing the antiseptic chlorhexidine, but these also eliminate beneficial microorganisms. When the oral microbiome re-establishes itself after treatment, pathogenic bacteria such as Porphyromonas gingivalis gain an early advantage because they proliferate particularly well in inflamed gum tissue. Beneficial bacteria grow more slowly, and the oral microbiome quickly shifts back from its natural balance into dysbiosis, allowing the disease to recur.

Stem cell engineering breakthrough paves way for next-generation living drugs

For the first time, researchers at UBC have demonstrated how to reliably produce an important type of human immune cell — known as helper T cells — from stem cells in a controlled laboratory setting. The findings, published today in Cell Stem Cell, overcome a major hurdle that has limited the development, affordability and large-scale manufacturing of cell therapies. The discovery could pave the way for more accessible and effective off-the-shelf treatments for a wide range of conditions like cancer, infectious diseases, autoimmune disorders and more.

“This is a major step forward in our ability to develop scalable and affordable immune cell therapies.”

Dr. Peter Zandstra

Ranked among the world’s top medical schools with the fifth-largest MD enrollment in North America, the UBC Faculty of Medicine is a leader in both the science and the practice of medicine. Across British Columbia, more than 12,000 faculty and staff are training the next generation of doctors and health care professionals, making remarkable discoveries, and helping to create the pathways to better health for our communities at home and around the world.

Radiotracers could improve choice of bladder cancer therapies

A research team at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) has developed a radiopharmaceutical molecule marker that can visualize tumors that carry the cell surface protein Nectin-4. This primarily occurs in the body in cases of urothelial carcinoma, a common form of bladder cancer.

In pre-clinical trials, the drug candidate, NECT-224, proved stable and was successfully used in humans for the first time. As the team has now reported in the Journal of Medicinal Chemistry, in the future, it could be used to better identify patients who would benefit from Nectin-4-targeted therapies.

Many modern cancer drugs only work when the target structure to which they are supposed to bind is also present on the tumor cells. In the case of urothelial carcinoma, the cell surface protein Nectin-4 lends itself to this purpose. It serves as a “door sign” for antibody-coupled agents that are able to eliminate tumor cells in a targeted fashion. But not every tumor produces the same amount of Nectin-4.

How does glass ‘shake’ and why does it start flowing when pushed hard enough?

Glassy materials are everywhere, with applications far exceeding windowpanes and drinking glasses. They range from bioactive glasses for bone repair and amorphous pharmaceuticals that boost drug solubility to ultra-pure silica optics used in gravitational-wave detectors. In principle, any substance can become glass if its hot liquid is cooled fast enough to avoid forming an ordered crystal.

A distinguishing feature of glass is that its atoms freeze into an irregular, disordered arrangement. This stands in contrast to crystals, where atoms sit in a regular pattern. This disorder gives glass many of its unique and useful properties, but scientists still struggle to understand how atomic-scale disorder produces the properties observed in everyday glasses.

‘Motivation brake’ may explain why it’s so hard to get started on an unpleasant task

Most of us know the feeling: maybe it is making a difficult phone call, starting a report you fear will be criticized, or preparing a presentation that’s stressful just to think about. You understand what needs to be done, yet taking that very first step feels surprisingly hard.

When this difficulty becomes severe, it is known medically as avolition. People with avolition are not lazy or unaware: they know what they need to do, but their brain seems unable to push the “go” button.

Avolition is commonly seen in conditions such as depression, schizophrenia, and Parkinson’s disease, and it seriously disrupts a person’s ability to manage daily life and maintain social functions.

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