Initiation and sequencing of guideline-directed medical therapy for heart failure across the ejection fraction spectrum.

Strong evidence supports the importance of rapid sequence or simultaneous initiation of quadruple guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) for substantially reducing risk of mortality and hospitalization. Barring absolute contraindications for each individual medication, employing the strategy of rapid sequence, simultaneous, and/or in-hospital initiation at the time of HF diagnosis best ensures patients with HFrEF have the opportunity to benefit from proven medications and achieve large absolute risk reductions for adverse clinical outcomes. However, despite guideline recommendations supporting this approach, implementation in clinical practice remains persistently low, with less than one-fifth of eligible patients being prescribed the quadruple GDMT regimen.

Anomalous Hall spin current drives self-generated spin-orbit torque in a ferromagnet.

Spin-orbit torques enable energy-efficient manipulation of magnetization by electric current and hold promise for applications ranging from non-volatile memory to neuromorphic computing. Here we report the discovery of a giant spin-orbit torque induced by anomalous Hall current in ferromagnetic conductors. This anomalous Hall torque is self-generated as it acts on the magnetization of the ferromagnet that engenders the torque.

Prognostic impact of expression of CD2, CD25, and/or CD30 in/on mast cells in systemic mastocytosis: a registry study of the European Competence Network on Mastocytosis.

Expression of CD2, CD25 and/or CD30 in extracutaneous mast cells (MC) is a minor diagnostic criterion for systemic mastocytosis (SM) in the classification of the World Health Organization and International Consensus Classification. So far, it remains unknown whether expression of these antigens on MC is of prognostic significance in SM. We performed a retrospective multi-center study of patients with SM using the data set of the registry of the European Competence Network on Mastocytosis, including 5034 patients with various MC disorders.

Dynamic PRC1-CBX8 stabilizes a porous structure of chromatin condensates.

The compaction of chromatin is a prevalent paradigm in gene repression. Chromatin compaction is commonly thought to repress transcription by restricting chromatin accessibility. However, the spatial organization and dynamics of chromatin compacted by gene-repressing factors are unknown.

Physical activity and quality of life among breast cancer survivors: Pink SWAN.

Purpose: To describe physical activity (PA) trajectories across 10 years post-breast cancer diagnosis and examine their association with quality of life (QoL).

Methods: Participants from the longitudinal Study of Women's Health Across the Nation who developed incident breast cancer completed the Quality of Life in Adult Cancer Survivors scale (QLACS) which has 12 domains. Breast cancer survivors (BCS) with at least one post-diagnosis measure of the Kaiser Physical Activity Survey (PA) were included (n = 96).

New Frontiers: Umbilical Cord Mesenchymal Stem Cells Uncover Developmental Roots and Biological Underpinnings of Obesity Susceptibility.

Purpose Of Review: To review evidence supporting human umbilical cord mesenchymal stem cells (UC-MSC) as an innovative model system advancing obesity precision medicine.

Recent Findings: Obesity prevalence is increasing rapidly and exposures during fetal development can impact individual susceptibility to obesity. UC-MSCs exhibit heterogeneous phenotypes associated with maternal exposures and predictive of child cardiometabolic outcomes.

Environmental gradients shape genetic variation in the desert moss, Syntrichia caninervis Mitt. (Pottiaceae).

The moss Syntrichia caninervis Mitt. is distributed throughout drylands globally, and often anchors ecologically significant communities known as biological soil crusts (biocrusts). The species occupies a variety of dryland habitats with varying levels of drought and temperature stress, suggesting the potential for ecological specialization within S.

Advancing pancreatic cancer research and therapeutics: the transformative role of organoid technology.

Research on pancreatic cancer has transformed with the advent of organoid technology, providing a better platform that closely mimics cancer biology in vivo. This review highlights the critical advancements facilitated by pancreatic organoid models in understanding disease progression, evaluating therapeutic responses, and identifying biomarkers. These three-dimensional cultures enable the proper recapitulation of the cellular architecture and genetic makeup of the original tumors, providing insights into the complex molecular and cellular dynamics at various stages of pancreatic ductal adenocarcinoma (PDAC).

Massively parallel characterization of transcriptional regulatory elements.

The human genome contains millions of candidate cis-regulatory elements (cCREs) with cell-type-specific activities that shape both health and many disease states. However, we lack a functional understanding of the sequence features that control the activity and cell-type-specific features of these cCREs. Here we used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test the regulatory activity of more than 680,000 sequences, representing an extensive set of annotated cCREs among three cell types (HepG2, K562 and WTC11), and found that 41.

Episodic and associative memory from spatial scaffolds in the hippocampus.

Hippocampal circuits in the brain enable two distinct cognitive functions: the construction of spatial maps for navigation, and the storage of sequential episodic memories. Although there have been advances in modelling spatial representations in the hippocampus, we lack good models of its role in episodic memory. Here we present a neocortical-entorhinal-hippocampal network model that implements a high-capacity general associative memory, spatial memory and episodic memory.

Cationic peptides cause memory loss through endophilin-mediated endocytosis.

The zeta inhibitory peptide (ZIP) interferes with memory maintenance and long-term potentiation (LTP) when administered to mice. However, mice lacking its putative target, protein kinase PKMζ, exhibit normal learning and memory as well as LTP, making the mechanism of ZIP unclear. Here we show that ZIP disrupts LTP by removing surface AMPA receptors through its cationic charge alone.

Ensemble reactivations during brief rest drive fast learning of sequences.

During motor learning, breaks in practice are known to facilitate behavioural optimizations. Although this process has traditionally been studied over long breaks that last hours to days, recent studies in humans have demonstrated that rapid performance gains during early motor sequence learning are most pronounced after very brief breaks lasting seconds to minutes. However, the precise causal neural mechanisms that facilitate performance gains after brief breaks remain poorly understood.

Draft genome sequence of Kei apple, an underutilized African tree crop.

To address food and nutrition security in the face of burgeoning global populations and erratic climatic conditions there is a need to include nutrient dense, climatic resilient but neglected indigenous fruit trees in agrifood systems. Here we present the draft genome sequence of Kei Apple, Dovyalis afra, a neglected indigenous African fruit tree with untapped potential to contribute to nutrient security and improved livelihoods. Our long-read-based genome assembly comprises 440 Mbp sequence across 1190 contigs with a N50 and L50 of 13.

Selected microwave irradiation effectively inactivates airborne avian influenza A(H5N1) virus.

The highly pathogenic avian influenza A(H5N1) virus threatens animal and human health globally. Innovative strategies are crucial for mitigating risks associated with airborne transmission and preventing outbreaks. In this study, we sought to investigate the efficacy of microwave inactivation against aerosolized A(H5N1) virus by identifying the optimal frequency band for a 10-min exposure and evaluating the impact of varying exposure times on virus inactivation.

The Octocoral Trait Database: a global database of trait information for octocoral species.

Trait-based approaches are revolutionizing our understanding of high-diversity ecosystems by providing insights into the principles underlying key ecological processes, such as community assembly, species distribution, resilience, and the relationship between biodiversity and ecosystem functioning. In 2016, the Coral Trait Database advanced coral reef science by centralizing trait information for stony corals (i.e.

The Toxoplasma rhoptry protein ROP55 is a major virulence factor that prevents lytic host cell death.

Programmed-cell death is an antimicrobial defense mechanism that promotes clearance of intracellular pathogens. Toxoplasma counteracts host immune defenses by secreting effector proteins into host cells; however, how the parasite evades lytic cell death and the effectors involved remain poorly characterized. We identified ROP55, a rhoptry protein that promotes parasite survival by preventing lytic cell death in absence of IFN-γ stimulation.

Dynamically reconfigurable acoustofluidic metasurface for subwavelength particle manipulation and assembly.

Particle manipulation plays a pivotal role in scientific and technological domains such as materials science, physics, and the life sciences. Here, we present a dynamically reconfigurable acoustofluidic metasurface that enables precise trapping and positioning of microscale particles in fluidic environments. By harnessing acoustic-structure interaction in a passive membrane resonator array, we generate localized standing acoustic waves that can be reconfigured in real-time.

Herpesviruses mimic zygotic genome activation to promote viral replication.

Zygotic genome activation (ZGA) is crucial for maternal to zygotic transition at the 2-8-cell stage in order to overcome silencing of genes and enable transcription from the zygotic genome. In humans, ZGA is induced by DUX4, a pioneer factor that drives expression of downstream germline-specific genes and retroelements. Here we show that herpesviruses from all subfamilies, papillomaviruses and Merkel cell polyomavirus actively induce DUX4 expression to promote viral transcription and replication.

Long-term exposure to ambient air pollution and epigenetic age acceleration in children.

Long-term exposure to ambient air pollution has been associated with epigenetic age acceleration (EAA) in adults, but its impact on children remains less understood. This study analyzed data from 457 children (mean age: 7.9 years) in the Project Viva cohort (2007-2010, eastern Massachusetts, USA).

Ribosome profiling reveals hidden world of small proteins.

The development of ribosome profiling (Ribo-seq) by Ingolia et al. introduced a powerful new method for monitoring translation genome-wide. Application of Ribo-seq across multiple organisms has since revealed thousands of unannotated translated small open reading frames (ORFs) and enhanced efforts to study their encoded proteins, called microproteins.

Novel Neurocognitive Testing Tool for Early Neurotoxicity Detection Following Anti-CD19 and Anti-BCMA Chimeric Antigen Receptor (CAR) T-cell Therapy: A Pilot Study.

Background: Immune effector cell-associated neurotoxicity syndrome (ICANS) can be a severe, life-threatening toxicity following CAR T-cell therapy. While currently evaluated by the immune effector cell-associated encephalopathy (ICE) score, not all patients have changes in their ICE score and not all signs and symptoms of neurotoxicity are captured.

Methods: We conducted a prospective, single center cohort pilot study to evaluate a novel, rapid neurocognitive assessment tool (CART-NS) in detecting early, subtle neurotoxicity prior to the onset of ICANS and any deterioration in the ICE score.

Bridging the gap: pathway programs for inclusion and persistence in microbiology.

Microbiology plays an important role in most sectors. Future progress in critical areas requires diverse workforce development. We outline a pathway program that aims to provide equitable exposure to high-impact research experiences and course-based instruction to provide crucial training in growing areas of microbiology (phage discovery, synthetic biology and data science/AI).