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Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

Strongly enhanced optical nonlinearities and an ultrafast transition from coherent to incoherent polariton excitations are demonstrated by coupling an atomically thin WS₂ layer to a plasmonic nanostructure using ultrafast multidimensional spectroscopy.

By integrating macro-scale and nano-scale experiments that reproduce the seismic cycle, this study reveals that feldspars, very common minerals, reduce the rate at which faults heal after a seismic rupture under certain hydrothermal conditions.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

In the proof-of-concept phase 2 ROME trial, comprehensive genomic profiling followed by molecular tumor board evaluation and randomization of patients with metastatic solid cancer to receive personalized therapy or standard of care led to a significantly higher objective response rate and longer progression-free survival in patients who received personalized therapy.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Correlated photons from parametric down-coversion driven by a CW laser are used for time- and frequency-resolved spectroscopy, enabling sub-second acquisition times on biological samples and single-photon excitation of photosynthetic processes.

As presented at the 2025 ASCO Annual Meeting: in a randomized platform phase II trial, high rates of pathologic complete response were seen for neoadjuvant durvalumab plus chemotherapy when combined with new agents, most notably a TROP2-targeting antibody–drug conjugate, in patients with resectable non-small-cell lung cancer.

Researchers created a periodically poled van der Waals semiconductor (3R-MoS₂) and achieved a macroscopic frequency conversion efficiency of 0.03% over a thickness of 3.4 μm. The quasi-phase-matched second harmonic signal surpasses the usual quadratic enhancement by 50% and broadband generation of photon pairs at telecom wavelength is demonstrated with a coincidence-to-accidental ratio of 638 ± 75.

This flagship study from the European Solve-Rare Diseases Consortium presents a diagnostic framework including bioinformatic analysis of clinical, pedigree and genomic data coupled with expert panel review, leading to 500 new diagnoses in a cohort of 6,000 families with suspected rare diseases.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

An analysis of 18 metagenomic datasets of individuals with colorectal cancer, adenomas and healthy controls yields improved cancer prediction accuracy based solely on gut metagenomics, as well as the identification of new species associated with the development of cancer.

Photo-excitation in strongly correlated materials is usually modelled as an increase of electronic energy that is then transferred to other degrees of freedom. Contrarily, Novelli et al.show that in a charge-transfer insulator, sub-gap excitation forms electrons that are suddenly dressed by the boson field.

Tumor-associated macrophages are pivotal in control over solid tumors. Here the authors show that these macrophages express chemosensors that detect lipid variants in the tumor microenvironment that can regulate the function of these cells.

Encapsulation of large-size DNA molecules into lipid nanoparticles (LNPs) remains challenging. Here, the authors engineer PEGylated LNPs with DNA and plasma proteins to improve the delivery of large DNA molecules, enhancing the gene therapy potential.

Frontal polymerization is a self-sustaining, energy-efficient technique for rapidly converting monomers into polymers. This Primer explores frontal polymerization mechanisms, experimental set-up, applications and future directions, offering practical guidance for researchers and highlighting its potential for the design of sustainable, high-performance materials.

Krisai et al. compare brain structure and cognitive function in elderly patients with and without atrial fibrillation using brain MRI and cognitive testing. They find that atrial fibrillation is associated with more brain lesions and lower cognitive function, but the cognitive impairment occurs primarily through direct effects of the arrhythmia rather than through brain damage.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

VEGF-C induced lymphangiogenesis combined with immunotherapy approaches can promote anti-tumor immune responses. Here the authors report that lymphaticderived oxysterols promote anti-tumor immunity and response to immunotherapy in preclinical melanoma models

The history of human populations in the islands of the central and western Mediterranean is poorly understood. Here, the authors generate ancient-DNA data from the Balearic Islands, Sicily and Sardinia, and estimate the level and timing of steppe pastoralist, Iranian and North African ancestries in these populations.

Earthquakes often originate along faults in the presence of hot and pressurized water. Experiments conducted on simulated faults reveal that the physical state of water (liquid, vapor or supercritical) controls the frictional resistance of faults.

Ultrafast quantum control of helium atoms is obtained by shaping the extreme ultraviolet pulses generated by a seeded free-electron laser.

Combined analysis of new genomic data from 116 ancient hunter-gatherer individuals together with previously published data provides insights into the genetic structure and demographic shifts of west Eurasian forager populations over a period of 30,000 years.

Salt passivation of perovskite often results in formation of 2D perovskite layers, which impaired charge transport behaviour. Here, the authors study the energy barrier of 2D perovskite formation upon passivation by different iodide salt, and provide insight how to manipulate this to maximise device performance.

Dengue and chikungunya are an increasing public health concern in Europe, and Italy is particularly affected. Here, the authors analyse travel-related cases and outbreaks in Italy from 2006 to 2023 and assess current transmission risks.

Francesco Cucca and colleagues perform a genome-wide association study for multiple sclerosis in Sardinians. The authors identify variants within CBLB that are associated with MS.

Electromechanical characterization during atrial fibrillation (AF) remains a significant gap in the understanding of AF-related atrial myopathy. Here, the authors use non-invasive atrial electromechanical assessment during AF to identify early remodeling changes associated with underlying myopathy, which in the clinic decrease the probability of acute and mid-term successful rhythm control.

Hsp chaperones stabilize the inactive conformation of androgen receptor (AR) and are released upon hormone-induced AR activation. Here, the authors locate the Hsp binding region on AR, and show that Hsp70 reduces AR aggregation and promotes AR degradation in cellular and mouse models of a neuromuscular disorder.

Excitatory pyramidal neurons preferentially target inhibitory interneurons with the same selectivity and, in turn, inhibitory interneurons preferentially target pyramidal neurons with opposite selectivity, forming an opponent inhibition motif that supports decision-making.

Double membrane vesicles (DMV) are used as replication organelles by several RNA viruses. Applying proteomics and lipidomics, Tabata and Prasad et al. find that two cellular acyltransferases (AGPAT1/2), responsible for synthesis of phosphatidic acid, play a role in the DMV-biogenesis of HCV and SARS-CoV-2, highlighting a common biogenesis mechanism for evolutionary distant positive-strand RNA viruses.

By amplifying a soliton in a multistage cascade, few-femtosecond extreme-ultraviolet free-electron laser pulses are achieved.

Spintronic devices will require long spin lifetimes, but the effect of exciton-lattice coupling on spin lifetime in metal-halide perovskites is not well understood. Here, the authors find a 100-fold increase in the lifetime of exciton spins in a 2D perovskite by exciting with excess energy, resulting from strong coupling between excitons and optically excited phonons.

Human embryonic stem cells can be differentiated in vitro into primordial germ cell-like cells (PGCLCs) that resemble early primordial germ cells (PGCs). Here the authors transplant PGCLCs generated from rhesus macaque iPSCs into mouse and rhesus macaque seminiferous tubules, which matures these into late PGCs and spermatogonia-like cells.