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How AI helps scientists design the next generation of medicines

Ultimately, Sapra says, the end-state vision for AI in biologic drug discovery is what the field calls “de novo” design. For this, the goal is for AI to generate entirely new protein sequences that precisely fit the desired drug properties. This includes designing the structure, predicting safety, how it will behave in the body and how to make it manufacturable.

“The field is making great progress toward a completely AI-generated biologic, designed from scratch all the way to a clinical candidate,” Sapra says. “As we continue to leverage frontier models and fine-tune them with the right datasets, we bring ourselves closer to this reality. I believe it will come. It’s a matter of time.”

Several key elements are needed to reach this point, however. First is richer and more standardized training data across the industry. Second, robust evaluation benchmarks for AI-generated candidates. And third, teams that know how to work at the intersection of machine learning and biology. Of all the prerequisites, however, safety prediction may be the most consequential, and perhaps the least discussed, Sapra says.

Addition of HighDose Vitamin D3 to Standard Treatment for Metastatic Colorectal Cancer

This randomized clinical trial assesses whether high-dose vitamin D3, compared with standard-dose vitamin D3, added to standard chemotherapy improves progression-free survival in patients in the US National Clinical Trials Network with previously untreated metastatic colorectal cancer.

New research shows the Golgi complex is involved in DNA repair control

Cells must constantly repair damage to their DNA that, if left unfixed, can lead to cell death, cancer, or accelerated ageing. EMBL researchers and their collaborators show that the Golgi complex, an organelle best known as the cell’s sorting and shipping centre, stores DNA-repair proteins and dispatches them to the nucleus when damage occurs. When DNA is damaged, the cell recruits the relevant repair proteins from the Golgi to the nucleus, matched to the type of damage, and clears the proteins it doesn’t need out of the nucleus, sequestering them back at the Golgi. This work reveals a new layer of regulation of DNA repair pathways from outside the nucleus, opening up new opportunities to modulate these pathways and to target related diseases such as cancer.

AI helps Stanford scientists discover “natural Ozempic” without the usual side effects

Stanford Medicine researchers have identified a naturally occurring molecule that may suppress appetite and reduce body weight in a way that resembles semaglutide, the active ingredient in Ozempic. In animal studies, the molecule also appeared to avoid several problems associated with the drug, including nausea, constipation and substantial muscle loss.

The molecule, known as BRP, works through a different but related metabolic pathway and activates a separate group of neurons in the brain. That distinction could make it a more precise tool for controlling appetite and body weight.

A simple supplement could help the immune system fight cancer and viruses

Low arginine levels may allow cancer cells and viruses to slip past the immune system by reducing production of a crucial cellular warning protein. In mice, arginine-rich diets led to fewer colon tumors and milder viral infections, suggesting a simple supplement could have powerful therapeutic potential.

Automated Speech Analysis to Identify Clinical, Anatomical, and Pathological Variants of Primary Progressive Aphasia

This cross-sectional study investigates if automated analysis of connected speech can distinguish primary progressive aphasia variants and reflect neuroanatomical and neuropathologic substrates.

Texture Analysis of 68GaDOTATOC PET/CT Images for the Prediction of Outcome in Patients with Neuroendocrine Tumors

Objectives: The aim of our study is to evaluate whether texture analysis of 68Ga-DOTATOC PET/CT images can predict clinical outcome in patients with neuroendocrine tumors (NET). Methods: Forty-seven NET patients who had undergone 68Ga-DOTATOC PET/CT were studied. Primary tumors were localized in the gastroenteropancreatic (n = 35), bronchopulmonary (n = 8), and other (n = 4) districts. NET lesions were segmented using an automated contouring program and subjected to texture analysis, thus obtaining the conventional parameters SUVmax and SUVmean, volumetric parameters of the primary lesion, such as Receptor-Expressing Tumor Volume (RETV) and Total Lesion Receptor Expression (TLRE), volumetric parameters of the lesions in the whole-body, such as wbRETV and wbTLRE, and texture features such as Coefficient of Variation (CoV), HISTO Skewness, HISTO Kurtosis, HISTO Entropy-log10, GLCM Entropy-log10, GLCM Dissimilarity, and NGLDM Coarseness. Patients were subjected to a mean follow-up period of 17 months, and survival analysis was performed using the Kaplan–Meier method and log-rank tests. Results: Forty-seven primary lesions were analyzed. Survival analysis was performed, including clinical variables along with conventional, volumetric, and texture imaging features. At univariate analysis, overall survival (OS) was predicted by age (p = 0.0079), grading (p = 0.0130), SUVmax (p = 0.0017), SUVmean (p = 0.0011), CoV (p = 0.0037), HISTO Entropy-log10 (p = 0.0039), GLCM Entropy-log10 (p = 0.0044), and GLCM Dissimilarity (p = 0.0063). At multivariate analysis, only GLCM Entropy-log10 was retained in the model (χ2 = 7.7120, p = 0.0055). Kaplan–Meier curves showed that patients with GLCM Entropy-log10 >1.28 had a significantly better OS than patients with GLCM Entropy-log10 ≤1.28 (χ2 = 10.6063, p = 0.0011). Conclusions: Texture analysis of 68Ga-DOTATOC PET/CT images, by revealing the heterogeneity of somatostatin receptor expression, can predict the clinical outcome of NET patients.

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