Nature Biotechnology, Published online: 14 April 2026; doi:10.1038/s41587-026-03095-3
FAMSA2 accurately aligns millions of protein sequences at high speed.
The gut microbiome as a fingerprint of antibiotic use history
Nature Medicine, Published online: 14 April 2026; doi:10.1038/s41591-026-04360-3
Antibiotic use over the past 8 years was associated with alterations in the gut microbiome composition in 14,979 individuals. These analyses integrated data from the Swedish National Prescribed Drug Register and stool metagenomic profiles. Alterations were found even after a single antibiotic course and varied markedly across different antibiotic classes.
Editorial Expression of Concern: Isolated small intestinal segments support auxiliary livers with maintenance of hepatic functions
Nature Medicine, Published online: 14 April 2026; doi:10.1038/s41591-026-04390-x
Editorial Expression of Concern: Isolated small intestinal segments support auxiliary livers with maintenance of hepatic functions
KRAS-targeting PROTAC drug passes first clinical test
Nature Medicine, Published online: 14 April 2026; doi:10.1038/d41591-026-00020-8
A phase 1 study evaluating setidegrasib shows promising safety and clinical activity, establishing targeted protein degradation as a viable new approach for treating KRAS G12D-driven solid tumors.
Antisense oligonucleotide-mediated knockdown therapy in two infants with severe KCNT1 epileptic encephalopathy
Nature Medicine, Published online: 14 April 2026; doi:10.1038/s41591-026-04314-9
Two individuals with KCNT1-related epileptic encephalopathy were treated with a KCNT1-targeting antisense oligonucleotide, leading to significant reductions in seizure frequency and intensity, but also the development of hydrocephalus.
Intravitreal photoswitch therapy in advanced retinitis pigmentosa: a phase 1 open-label trial
Nature Medicine, Published online: 14 April 2026; doi:10.1038/s41591-026-04317-6
A first-in-human phase 1 trial shows that intravitreal photoswitch therapy can be administered safely in advanced retinitis pigmentosa, with exploratory signals compatible with light responsiveness following treatment.
White matter pathways mediating dorsolateral prefrontal TMS therapy for depression
Nature Neuroscience, Published online: 14 April 2026; doi:10.1038/s41593-026-02248-6
Seguin et al. show that the efficacy of transcranial magnetic stimulation for depression depends on how stimulation spreads through the brain’s wiring. Patients with shorter communication pathways between stimulated sites and mood-related regions had better clinical outcomes.
HSV-1 strain H129 co-opts neuronal synaptic transmission machinery for its transsynaptic spread
Nature Neuroscience, Published online: 14 April 2026; doi:10.1038/s41593-026-02254-8
By assembling into ‘virion vesicles’, the H129 strain of herpes simplex virus-1 hijacks synaptic machinery for its anterograde spread, co-opting voltage-gated Ca2+ channels, Syt7 and SNAREs for presynaptic exit, then nectin-1/CME for postsynaptic entry.
Rapid temporal processing in the olfactory bulb underlies concentration-invariant odor identification and signal decorrelation
Nature Neuroscience, Published online: 14 April 2026; doi:10.1038/s41593-026-02250-y
This study shows that the brain’s smell center uses precise timing and inhibition to read out early odor signals, enabling reliable odor identity across concentrations while rapidly separating (decorrelating) similar smell patterns for better discrimination.
Prediction of Relapse Using Digital Technology in People in Recovery From Substance Use Disorders: Early Economic Evaluation With a Case Study of the Subreal App
Background: Many people relapse after achieving abstinence in substance use disorders. Health care providers may scan the horizon for new technologies to predict response that allow interventions to be targeted rather than routine. Currently, no such predictive technologies are available in the United Kingdom. The Subreal app is available for use in research contexts, but no clinical data specific to the app are yet available. Early health economic modeling can use data from the literature to explore characteristics essential for the new technology to be cost-effective. This information can guide developers in setting performance targets and pricing and estimating potential cost savings and/or cost-effectiveness for health care providers. Objective: This study was supported by a UK industry funding body to explore the potential of digital technologies such as the Subreal app to offer cost savings or cost-effectiveness for health care providers. We explored the threshold price and clinical effectiveness required to deliver cost savings and cost-effectiveness in 2 subpopulations with substance use disorders in a UK setting. Methods: Deterministic models were used to estimate costs per relapse and quality-adjusted life years over 1-, 5-, and 20-year time horizons for people who have achieved abstinence after treatment for alcohol or opioid misuse. The intervention was a digital technology predicting relapse, provided—in addition to standard care—for 1 year post achievement of abstinence. In Subreal, biomarker data are collected daily through the app, and artificial intelligence–enhanced risk assessment flags patients who require additional support. The comparator was event-driven, reactive response to relapse. Costs and quality-of-life estimates were calculated using Markov models with data from existing published sources. The base-case estimate of 15% reduction in first-year relapse rates was based on a previous study on a similar but simpler digital technology. Results: Digital technologies such as the Subreal app have the potential to be cost-saving from a UK health and social care perspective, especially when used over a longer time horizon. Assuming a reduction of 15% in first-year relapse rates, digital technologies have the potential to be cost-saving, provided that they do not cost more than £300 (US $400.09) and £460 (US $613.47) per patient per annum for alcohol and opioid use disorders, respectively. No cost was included for postalert care, as it was assumed that this could be met within existing resources. Cost savings would be achieved predominantly through a reduction in treatment requirements as fewer people relapse. Price thresholds would reduce correspondingly if a <15% reduction in relapse rates were achieved. Conclusions: Developers of digital technologies that aim to reduce relapse need to focus on the generation of evidence of clinical effectiveness and develop a commercially sustainable pricing model that allows health care providers to benefit from cost savings.
