Patients with DCIS Seen at a Specialized High-Risk Breast Clinic Run by Surgical Advanced Practice Providers Have High Rates of Preventive Medication Uptake.

Background: Preventative medication (PM) uptake is low among patients at an elevated risk of breast cancer, largely due to fears of intolerance. This study aimed to investigate whether a new, surgical advanced practice provider (APP)-run clinic was effectively prescribing PM. We hypothesized equivalent rates of PM uptake compared to consultation with medical oncologists (MD).

The Landmark Series: The Future of Pancreatic Cancer Clinical Trials.

Pancreatic cancer has a poor prognosis despite ongoing advances in systemic and multimodal therapies. This review analyzes recent progress and future directions in pancreatic cancer clinical trials, emphasizing the evolution from traditional approaches to a more personalized and biologically-driven treatment paradigm. While improvements in overall survival have been achieved through perioperative therapies, gaps remain in our understanding of optimal treatment strategies.

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.

Spatiotemporal imaging of nonlinear optics in van der Waals waveguides.

Van der Waals (vdW) semiconductors have emerged as promising platforms for efficient nonlinear optical conversion, including harmonic and entangled photon generation. Although major efforts are devoted to integrating vdW materials in nanoscale waveguides for miniaturization, the realization of efficient, phase-matched conversion in these platforms remains challenging. Here, to address this challenge, we report a far-field ultrafast imaging method to track the propagation of both fundamental and harmonic waves within vdW waveguides with femtosecond and sub-50 nanometre spatiotemporal precision.

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.

Racial and Educational Isolation are Associated with Worse Outcomes in Congenital Heart Disease.

Sociodemographic factors influence outcomes in children with congenital heart disease (CHD). We predict an association between measures of social isolation and outcomes in infants with complex CHD. These measures, racial (RI) and educational (EI) isolation range from 0 to 1, with 0 being no isolation and 1 being fully isolated within a specific population.

Resting beat-to-beat blood pressure variability in humans: role of alpha-1 adrenergic receptors.

Purpose: Resting beat-to-beat blood pressure variability is a strong predictor of cardiovascular events and mortality. However, its underlying mechanisms remain incompletely understood. Given that the sympathetic nervous system plays a pivotal role in cardiovascular regulation, we hypothesized that alpha-1 adrenergic receptors (the main sympathetic receptor controlling peripheral vasoconstriction) may contribute to resting beat-to-beat blood pressure variability.

Cannabidiol abrogates cue-induced anxiety associated with normalization of mitochondria-specific transcripts and linoleic acid in the nucleus accumbens shell.

Anxiety disorders are one of the top contributors to psychiatric burden worldwide. Recent years have seen a dramatic rise in the potential anxiolytic properties ascribed to cannabidiol (CBD), a non-intoxicating constituent of the Cannabis Sativa plant. This has led to several clinical trials underway to examine the therapeutic potential of CBD for anxiety disorders.

Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study.

In the MAIA study (median follow-up, 56.2 months), daratumumab plus lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival (PFS) and overall survival versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). In this post hoc analysis of clinically important subgroups in MAIA (median follow-up, 64.

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.

GestaltGAN: synthetic photorealistic portraits of individuals with rare genetic disorders.

The facial gestalt (overall facial morphology) is a characteristic clinical feature in many genetic disorders that is often essential for suspecting and establishing a specific diagnosis. Therefore, publishing images of individuals affected by pathogenic variants in disease-associated genes has been an important part of scientific communication. Furthermore, medical imaging data is also crucial for teaching and training deep-learning models such as GestaltMatcher.

Lung endothelial cell senescence impairs barrier function and promotes neutrophil adhesion and migration.

Cellular senescence contributes to inflammation and organ dysfunction during aging. While this process is generally characterized by irreversible cell cycle arrest, its morphological features and functional impacts vary in different cells from various organs. In this study, we examined the expression of multiple senescent markers in the lungs of young and aged humans and mice, as well as in mouse lung endothelial cells cultured with a senescence inducer, suberoylanilide hydroxamic acid (SAHA), or doxorubicin (DOXO).

Deep learning reveals diverging effects of altitude on aging.

Aging is influenced by a complex interplay of multifarious factors, including an individual's genetics, environment, and lifestyle. Notably, high altitude may impact aging and age-related diseases through exposures such as hypoxia and ultraviolet (UV) radiation. To investigate this, we mined risk exposure data (summary exposure value), disease burden data (disability-adjusted life years (DALYs)), and death rates and life expectancy from the Global Health Data Exchange (GHDx) and National Data Management Center for Health of Ethiopia for each subnational region of Ethiopia, a country with considerable differences in the living altitude.

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).

Proteolysis-targeting influenza vaccine strains induce broad-spectrum immunity and in vivo protection.

Generating effective live vaccines from intact viruses remains challenging owing to considerations of safety and immunogenicity. Approaches that can be applied in a systematic manner are needed. Here we created a library of live attenuated influenza vaccines by using diverse cellular E3 ubiquitin ligases to generate proteolysis-targeting (PROTAR) influenza A viruses.

A novel human fetal lung-derived alveolar organoid model reveals mechanisms of surfactant protein C maturation relevant to interstitial lung disease.

Alveolar type 2 (AT2) cells maintain lung health by acting as stem cells and producing pulmonary surfactant. AT2 dysfunction underlies many lung diseases, including interstitial lung disease (ILD), in which some inherited forms result from the mislocalization of surfactant protein C (SFTPC) variants. Lung disease modeling and dissection of the underlying mechanisms remain challenging due to complexities in deriving and maintaining human AT2 cells ex vivo.

The microcephaly-associated transcriptional regulator AUTS2 cooperates with Polycomb complex PRC2 to produce upper-layer neurons in mice.

AUTS2 syndrome is characterized by intellectual disability and microcephaly, and is often associated with autism spectrum disorder, but the underlying mechanisms, particularly concerning microcephaly, remain incompletely understood. Here, we analyze mice mutated for the transcriptional regulator AUTS2, which recapitulate microcephaly. Their brains exhibit reduced division of intermediate progenitor cells (IPCs), leading to fewer neurons and decreased thickness in the upper-layer cortex.

Tests for segregation distortion in tetraploid F1 populations.

In tetraploid F1 populations, traditional segregation distortion tests often inaccurately flag SNPs due to ignoring polyploid meiosis processes and genotype uncertainty. We develop tests that account for these factors. Genotype data from tetraploid F1 populations are often collected in breeding programs for mapping and genomic selection purposes.

Aromatic side-chain crosslinking in RiPP biosynthesis.

Peptide cyclization is a defining feature of many bioactive molecules, particularly in the ribosomally synthesized and post-translationally modified peptide (RiPP) family of natural products. Although enzymes responsible for N- to C-terminal macrocyclization, lanthipeptide formation or heterocycle installation have been well documented, a diverse array of cyclases have been discovered that perform crosslinking of aromatic side chains. These enzymes form either biaryl linkages between two aromatic amino acids or a crosslink between one aliphatic amino acid and one aromatic amino acid.

PROTAR Vaccine 2.0 generates influenza vaccines by degrading multiple viral proteins.

Manipulating viral protein stability using the cellular ubiquitin-proteasome system (UPS) represents a promising approach for developing live-attenuated vaccines. The first-generation proteolysis-targeting (PROTAR) vaccine had limitations, as it incorporates proteasome-targeting degrons (PTDs) at only the terminal ends of viral proteins, potentially restricting its broad application. Here we developed the next-generation PROTAR vaccine approach, referred to as PROTAR 2.

Orthogonalized human protease control of secreted signals.

Synthetic circuits that regulate protein secretion in human cells could support cell-based therapies by enabling control over local environments. Although protein-level circuits enable such potential clinical applications, featuring orthogonality and compactness, their non-human origin poses a potential immunogenic risk. In this study, we developed Humanized Drug Induced Regulation of Engineered CyTokines (hDIRECT) as a platform to control cytokine activity exclusively using human-derived proteins.

Practical approach to extracardiac findings in CT and MR for the non-radiologist.

Cross-sectional cardiac imaging plays an essential role in the evaluation of pediatric patients with congenital and acquired heart disease. While the focus of cardiac imaging is primarily on evaluating cardiac structures, it also provides valuable insights into extracardiac structures and associated abnormalities. The radiologists and cardiologists interpreting these exams play a critical role in recognizing these findings and providing recommendations for follow-up testing when indicated.