Eplontersen for Transthyretin Amyloid Cardiomyopathy.

August 28, 2026| Source: The New England journal of medicine

Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a progressive, life-threatening disease caused by deposition of misfolded transthyretin (TTR). Eplontersen, an antisense oligonucleotide, reduces the production of hepatic TTR. The effect of eplontersen on ATTR-CM is unclear. In this phase 3, international, double-blind trial, we randomly assigned, in a 1:1 ratio, patients with ATTR-CM to receive subcutaneous eplontersen (45 mg) or placebo every 4 weeks for 140 weeks, in addition to standard treatment. The primary end point was a cumulative composite of death from cardiovascular causes and recurrent cardiovascular clinical events up to week 140. The effect of death from noncardiovascular causes on the primary analysis was assessed with a cumulative composite of death from any cause and cardiovascular events up to week 140. A total of 1432 patients underwent randomization and received at least one dose of the assigned intervention (715 patients in the eplontersen group and 717 in the placebo group). The mean age of the patients was 76.4 years, and 90.6% were men. A total of 381 primary end-point events occurred in 210 patients (29.4%) receiving eplontersen, and 392 events occurred in 231 patients (32.2%) receiving placebo (rate ratio, 0.89; 95% confidence interval [CI], 0.73 to 1.09; P = 0.28). Death from cardiovascular causes, as a component of the primary end point, occurred in 74 patients in the eplontersen group and in 70 in the placebo group; there were 307 cardiovascular clinical events in the eplontersen group and 322 in the placebo group. The rate ratio for the composite of death from any cause and cardiovascular events was 0.86 (95% CI, 0.71 to 1.04). Serious adverse events occurred in 413 patients (57.8%) in the eplontersen group and in 426 (59.4%) in the placebo group. Among patients with ATTR-CM, eplontersen therapy did not lead to a lower risk of a composite of death from cardiovascular causes and recurrent cardiovascular events than placebo up to 140 weeks. (Funded by Ionis Pharmaceuticals and AstraZeneca; CARDIO-TTRansform ClinicalTrials.gov number, NCT04136171.).

Read the original source →

Indirect reciprocity with dual private assessment.

People often cooperate out of concern for their reputation. The corresponding theory of indirect reciprocity predicts that such cooperation can only evolve if people's opinions of each other are sufficiently correlated. This correlation, however, can be difficult to achieve when individuals form their opinions independently from one another, as in private assessment models. In that case, errors can generate disagreements that propagate throughout a population. Here, we identify a simple mechanis

Physical/TechSeptember 26, 2026

A genetic program for rapid initiation of axillary meristems at the onset of flowering.

Shoot branching patterns and their diversity arise from variable activities of axillary meristems (AMs). A common feature of flowering plants is delayed AM initiation and growth during the vegetative phase, followed by a sudden and rapid acceleration of apical AM initiation during the reproductive phase. The mechanisms underlying this pronounced developmental shift are poorly understood. During tomato floral transition, the primary shoot meristem (PSM) terminates in a flower after producing two

Physical/TechSeptember 26, 2026

David Botstein: A pioneering geneticist and educator 1942-2026.

David Botstein, who died on February 27, 2026, was a towering figure in the field of modern molecular genetics. His research career was largely focused on the development of methods to better understand biological systems, beginning with his early work on Salmonella phage P22 and yeast, where he exploited the use of conditional lethal mutations as suppressors to identify genes with common functions and to order them in a pathway. He is best remembered for developing restriction fragment length p

Physical/TechSeptember 26, 2026

Ultra-narrowband organic room-temperature phosphorescence achieved by boosting low-frequency vibronic coupling.

We pioneered a strategy based on low-frequency vibronic coupling to design narrowband room-temperature phosphorescent (RTP) materials. Here we select coronene derivative (CoDe) system and report that attaching aroyl group to the coronene core disrupts its intrinsic symmetry and introduces abundant low-frequency vibrational modes, thereby affording efficient room-temperature phosphorescence with a full width at half maximum (FWHM) of approximately 25 nm or narrower. In CoDe systems functionalized

Physical/TechSeptember 25, 2026

Multidomain interaction governs the filamentous assembly of the dominant-negative DNMT3A R882H mutant.

DNA methyltransferase DNMT3A-mediated de novo DNA methylation is important for proper regulation of gene expression and genomic stability in development. The DNMT3A R882H (DNMT3A R882H ) mutation, a hot-spot mutation in acute myeloid leukemia and developmental disorders, exerts a dominant-negative effect in DNMT3A-mediated DNA methylation through promoting high-order protein assembly. However, due to the lack of structural knowledge on DNMT3A homo-oligomers, the mechanism behind wild-type DNMT3A