Subgroup analyses within randomized controlled trials are often underpowered due to limited sample sizes. We address this challenge by leveraging trial participants outside the subgroup of interest to augment estimation within the subgroup. Specifically, we study two Targeted Maximum Likelihood Estimators (TMLEs) that borrow information from non-subgroup participants within the same trial: a TMLE with pooled regression (TMLE-PR) and an Adaptive Targeted Maximum Likelihood Estimator (A-TMLE). Both estimators enable information sharing without relying on any external real-world data, thereby capitalizing on key strengths of the trial: most importantly, the protection against bias afforded by the randomized treatment, but also harmonized data collection, and consistent treatment and outcome definitions. The general strategy proposed here directly advances the priorities of key regulatory agencies, including the FDA, by improving the precision of subgroup-specific treatment effect estimates without introducing external sources of bias, thereby facilitating rigorous inference to support equitable labeling, access, and post-market evaluation. In a case study based on analysis of data from a cardiovascular outcome trial (LEADER, NCT01179048), we estimate the risk reduction of major adverse cardiac events (MACE) under liraglutide treatment among Black and Asian subgroups -- each comprising less than 10\% of the trial population -- using the proposed estimators that borrow information from the remainder of the trial. Using A-TMLE, in particular, we find estimated absolute MACE risk reductions of 1.6, 1.5, and 1.5 percentage points among Asian participants and 2.1, 2.0, and 2.1 percentage points among Black participants at 365, 540, and 730 days, respectively, with 95\% confidence intervals excluding the null at each time point.

Single-arm trials are an important study design for evaluating drug efficacy and safety without enrolling patients into a control arm. Although they do not provide the gold-standard evidence of randomized controlled trials, they are increasingly used in clinical development as they offer an efficient, ethical, and practical alternative. A wide variety of approaches can be used to construct control comparators and estimate treatment effects, from fixed comparators informed by clinical knowledge to data-based and model-based patient-level comparators, also known as synthetic controls. Powerful and flexible machine learning models can allow outcome-model-based synthetic controls to overcome key limitations of direct data-based approaches, yield more robust estimates of treatment effects, and provide a principled way to incorporate corrections or encode additional assumptions when external data are not directly comparable. In this work, we argue that outcome-model-based synthetic control arms are an important tool for single-arm trials. We focus on digital twins, personalized predictions of disease progression generated from machine learning models trained on historical datasets, which naturally leverage these flexible approaches. We review doubly robust estimators, present power and sample size formulas, and discuss trade-offs in selecting historical data for training and analysis. We also outline practical considerations for deploying digital twins within the framework of recent FDA draft guidance on the use of artificial intelligence in drug development. Finally, we reanalyze data from trials in amyotrophic lateral sclerosis and Huntington's disease to demonstrate the proposed methods.

Post-deployment monitoring of healthcare AI requires statistically valid, label-efficient methods, but gold-standard labels from clinician chart review are expensive. Prediction-powered inference (PPI) and active statistical inference (ASI) reduce label cost by combining a small labeled sample with abundant model predictions, but both are restricted to a single predictor, a poor fit for modern clinical pipelines that have multiple predictors of differing cost and accuracy available at inference time. We propose Active Multiple-Prediction-Powered Inference (AM-PPI), which routes each instance to a cost-appropriate predictor subset, samples gold-standard labels in proportion to the chosen subset's residual uncertainty, and reweights predictions to minimize estimator variance, all under a single deployment-time budget. AM-PPI generalizes ASI to leverage multiple predictors and extends Multiple-PPI from global per-predictor allocation to per-instance adaptive routing. We derive closed-form Karush-Kuhn-Tucker (KKT) conditions for all three decisions and prove, via biconvexity and strong duality, that the resulting fixed point is a global optimum despite the joint problem being non-jointly-convex. We establish asymptotic normality with valid coverage, minimum-variance unbiasedness within the linear-prediction augmented inverse propensity weighted (AIPW) class, and a closed-form criterion identifying when multiple predictors help. On synthetic data and three healthcare monitoring tasks, AM-PPI produces 10 to 40 percent narrower confidence intervals (CIs) than single-predictor ASI in the budget regime where routing matters, and matches the better baseline elsewhere.

The United States Supreme Court has temporarily reinstated a rule allowing an abortion pill to be prescribed through telemedicine and dispensed through the mail, lifting a judicial ban that narrowed access to the medication nationwide. Justice Samuel Alito issued an interim order on Monday, pausing for one week a decision by the New Orleans-based 5th US Circuit Court of Appeals to reimpose an older federal rule requiring an in-person clinician visit to receive mifepristone. The Supreme Court's action, called an "administrative stay", gives the justices more time to review emergency requests by two manufacturers of mifepristone to ensure that the drug can be provided via telehealth and the mail while the legal challenge plays out. Alito ordered Louisiana to respond to the drugmakers' requests by Thursday and indicated that the administrative stay would expire on May 11. The court would be expected to extend the interim stay or formally decide the requests by that time.

In theory, Motif Neurotech's berry-sized device would work like a continuous glucose monitor. More information Adding us as a Preferred Source in Google by using this link indicates that you would like to see more of our content in Google News results. Patients receiving the experimental new implant would not need to undergo a complicated surgery. Breakthroughs, discoveries, and DIY tips sent six days a week. Earlier this week, the United States Food and Drug Administration (FDA) approved a human trial for a blueberry-sized brain implant intended to target treatment-resistant depression.

Aleksandra Mendoza, aka Alorah Ziva, alleges that the 20-year-old influencer injected her with drugs on a livestream and had nonconsensual sex with her while she was underage. An 18-year-old woman who promotes herself as the "#1 female looksmaxxer" is suing the highly controversial streamer Braden Eric Peters, aka Clavicular, for fraud, battery, and alleged sexual assault. In the suit, which was filed in Miami-Dade County court and obtained by WIRED, Aleksandra Mendoza, who goes by the name @zahloria, or Alorah Ziva, on Instagram, alleges that she first encountered Peters in May 2025, when she was just 16 years old. According to the complaint, Peters promised Mendoza he could make her "the female face of looksmaxxing," the online trend of using surgery or drugs to enhance one's facial features. Eager to grow her social media following, Mendoza agreed to make four looksmaxxing videos for Peters in exchange for a $1,000 payment, court documents say.

We introduce AbDiffuser, an equivariant and physics-informed diffusion model for the joint generation of antibody 3D structures and sequences. AbDiffuser is built on top of a new representation of protein structure, relies on a novel architecture for aligned proteins, and utilizes strong diffusion priors to improve the denoising process. Our approach improves protein diffusion by taking advantage of domain knowledge and physics-based constraints; handles sequence-length changes; and reduces memory complexity by an order of magnitude, enabling backbone and side chain generation.

Nicotine pouches are revered among tech workers, who tout them as the perfect brain-boosting, productivity-jacking stimulants. Entrepreneur Garrett Campbell has a 6-mg "cool mint" Zyn tucked under his lip at all times during his mammoth 15-hour workdays, aside from when he is eating. "I was always very against nicotine," says the software company founder. The 26-year-old saw his peers using nicotine pouches at college, when they first emerged as a potential productivity-boosting hack, and considered it a "degenerate thing to do." But then all of his fellow founders started fueling themselves with nicotine pouches, of which the Philip Morris International-owned Zyn is the market leader.

Drug-induced toxicity is one of the leading reasons new drugs fail clinical trials. Machine learning models that predict drug toxicity from molecular structure could help researchers prioritize less toxic drug candidates. However, current toxicity datasets are typically small and limited to a single organ system (e.g., cardio, renal, or liver). Creating these datasets often involved time-intensive expert curation by parsing drug labelling documents that can exceed 100 pages per drug. Here, we introduce UniTox, a unified dataset of 2,418 FDA-approved drugs with drug-induced toxicity summaries and ratings created by using GPT-4o to process FDA drug labels.

ROTC students at Old Dominion subdued and killed ISIS-linked gunman who left one dead, two wounded after shouting'Allahu Akbar' and opened fire Horrifying next twist in the Alexander brothers case: MAUREEN CALLAHAN exposes an unthinkable perversion that's been hiding in plain sight Kentucky mother and daughter turn down $26.5MILLION to sell their farms to secretive tech giant that wants to build data center there Hollywood icon who starred in Psycho after Hitchcock dubbed her'my new Grace Kelly' looks incredible at 95 Kylie Jenner's total humiliation in Hollywood: Derogatory rumor leaves her boyfriend's peers'laughing at her' behind her back Tucker Carlson erupts at Trump adviser as she hurls'SLANDER' claim linking him to synagogue shooting Ben Affleck'scores $600m deal' with Netflix to sell his AI film start-up Long hair over 45 is ageing and try-hard. I've finally cut mine off. Alexander brothers' alleged HIGH SCHOOL rape video: Classmates speak out on sickening footage... as creepy unseen photos are exposed Heartbreaking video shows very elderly DoorDash driver shuffle down customer's driveway with coffee order because he is too poor to retire Amber Valletta, 52, was a '90s Vogue model who made movies with Sandra Bullock and Kate Hudson, see her now Model Cindy Crawford, 60, mocked for her'out of touch' morning routine: 'Nothing about this is normal' READ MORE: 38,000 gallons of bottled water recalled because of'foreign substance' More than 650,000 plastic water bottles have been recalled after they were produced'under insanitary conditions.' The FDA issued an alert for Valley Springs 100% Natural Bottled Water, noting the recall was voluntarily initiated by the Wisconsin-based Valley Springs Artesian Gold. While details are limited, insanitary conditions mean products were prepared, packed, or held under conditions that could allow them to become contaminated with filth or rendered injurious to health.