Universal Wilson Loop Bound of Quantum Geometry.

We define the absolute Wilson loop winding and prove that it bounds the (integrated) quantum metric from below. This Wilson loop lower bound naturally reproduces the known Chern and Euler bounds of the integrated quantum metric and provides an explicit lower bound of the integrated quantum metric due to the time-reversal protected Z_{2} index, answering a hitherto open question. In general, the Wilson loop lower bound can be applied to any other topological invariants characterized by Wilson loop winding, such as the particle-hole Z_{2} index.

Evidence for Similar Collectivity of High Transverse-Momentum Particles in p-Pb and Pb-Pb Collisions.

Charged hadron elliptic anisotropies (v_{2}) are presented over a wide transverse momentum (p_{T}) range for proton-lead (pPb) and lead-lead (PbPb) collisions at nucleon-nucleon center-of-mass energies of 8.16 and 5.02 TeV, respectively.

The "Secret of Seven Stones": Short-Term Efficacy of an Online Intergenerational Sexual Health Education Game for Early Adolescents and Their Parents.

Intergenerational games offer a potential channel to impact parent-youth sexual health communication. The "Secret of Seven Stones" (SSS) is an 18-level online adventure game and parent website designed to engage parents and youth (11-14 years) in conversations about healthy dating relationships and sexual behavior and to provide sexual health skills training to youth. Study hypotheses were that SSS exposure would increase sexual health parent-child communication, increase youth intentions to delay sexual debut, and reduce youth exposure to situations that promote sexual activity.

The Cumulative Burden of Housing Insecurity among Children in the USA from Birth to Adolescence.

Housing insecurity is a key social determinant of a wide range of health outcomes, subject to large racial inequities, and with a likely sensitive period in childhood. Housing insecurity can manifest in multiple ways and change over time, but previous studies have primarily focused on single dimensions or a single time point. This study examines cumulative exposure to multiple forms of housing insecurity from birth to adolescence, overall, and by race in large US cities.

Antibody-bottlebrush prodrug conjugates for targeted cancer therapy.

Antibody-drug conjugates (ADCs) are effective targeted therapeutics but are limited in their ability to incorporate less-potent payloads, varied drug mechanisms of action, different drug release mechanisms and tunable drug-to-antibody ratios. Here we introduce a technology to overcome these limitations called 'antibody-bottlebrush prodrug conjugates' (ABCs). An ABC consists of an IgG1 monoclonal antibody covalently conjugated to the terminus of a compact bivalent bottlebrush prodrug that has payloads bound through cleavable linkers and polyethylene glycol branches.

Direct mortality due to humans threatens migratory shorebirds.

The decline of migratory shorebirds in the East Asian-Australasian Flyway has attracted global attention. Conservation efforts thus far have targeted habitat loss and degradation in the Yellow Sea region, with little attention having been given to direct mortality by humans. Here we studied the impacts of direct mortality of shorebirds along China's coast during migration from hunting, fishery bycatch and, at aquaculture sites, bird deterrence measures.

Racial stereotypes bias the neural representation of objects towards perceived weapons.

Racial stereotypes have been shown to bias the identification of innocuous objects, making objects like wallets or tools more likely to be identified as weapons when encountered in the presence of Black individuals. One mechanism that may contribute to these biased identifications is a transient perceptual distortion driven by racial stereotypes. Here we provide neuroimaging evidence that a bias in visual representation due to automatically activated racial stereotypes may be a mechanism underlying this phenomenon.

Structural Basis for HIV-1 Maturation Inhibition by PF-46396 Determined by MAS NMR.

Among the different types of HIV-1 maturation inhibitors, those that stabilize the junction between the capsid protein C-terminal domain (CA) and the spacer peptide 1 (SP1) within the immature Gag lattice are promising candidates for antiretroviral therapies. Here, we report the atomic-resolution structure of CA-SP1 assemblies with the small-molecule maturation inhibitor PF-46396 and the assembly cofactor inositol hexakisphosphate (IP6), determined by magic angle spinning (MAS) NMR spectroscopy. Our results reveal that although the two PF-46396 enantiomers exhibit distinct binding modes, they both possess similar anti-HIV potency.

Diagnostic Approach and Management of Iliac Artery Endofibrosis in Athletes: A Scoping Review.

Iliac artery endofibrosis (IAE) is a rare vascular condition with an estimated global prevalence of 0.01%. It primarily affects endurance athletes, especially cyclists, and often presents with exercise-induced leg discomfort or reduced performance.

Receptor transporter protein 4 (RTP4)-mediated repression of hepatitis C virus replication in mouse cells.

Hepatitis C virus (HCV) exhibits a narrow species tropism, causing robust infections only in humans and experimentally inoculated chimpanzees. While many host factors and restriction factors are known, many more likely remain unknown, which has limited the development of mouse or other small animal models for HCV. One putative restriction factor, the black flying fox orthologue of receptor transporter protein 4 (RTP4), was previously shown to potently inhibit viral genome replication of several ER-replicating RNA viruses.

Design of Two Randomized, Placebo-Controlled, Phase 3 Trials of Deucravacitinib, an Oral, Selective, Allosteric TYK2 Inhibitor, in Systemic Lupus Erythematosus.

Background And Objectives: Deucravacitinib, a first-in-class, oral, selective, allosteric tyrosine kinase 2 inhibitor, demonstrated efficacy across the primary endpoint and all key secondary endpoints in the phase 2 PAISLEY SLE trial in patients with active systemic lupus erythematosus (SLE). Here, we describe 2 phase 3 trials [POETYK SLE-1 (NCT05617677), POETYK SLE-2 (NCT05620407)] which will assess the efficacy and safety of deucravacitinib in patients with active SLE. These phase 3 trials have been designed to replicate the successful elements of the phase 2 trial, including its glucocorticoid-tapering strategy and disease activity adjudication.

Route to chaos in multi-species ecosystems.

We investigate species-rich mathematical models of ecosystems. While much of the existing literature focuses on the properties of equilibrium fixed-points, persistent dynamics (e.g.

Control simulations of many-body quantum systems by a synergism of discrete real-time learning and optimal control theory.

We present a self-consistent algorithm for optimal control simulations of many-body quantum systems. The algorithm features a two-step synergism that combines discrete real-time machine learning (DRTL) with Quantum Optimal Control Theory (QOCT) using the time-dependent Schrödinger equation. Specifically, in step (1), DRTL is employed to identify a compact working space (i.

Integrating the thermal dependence of sex ratio into distribution models to predict suitable habitats for the invasive freshwater pond slider turtle, .

Unlabelled: Biological invasions represent one of the main anthropogenic drivers of global change with a substantial impact on biodiversity. Traditional studies predict invasion risk based on the correlation between species' distribution and environmental factors, with little attention to the potential contribution of physiological factors. In this study, we incorporated temperature-dependent sex determination (TSD) and sex-ratio data into species distribution models (SDMs) to assess the current and future suitable habitats for the world's worst invasive reptile species, the pond slider turtle ().

Consortium profile: the methylation, imaging and NeuroDevelopment (MIND) consortium.

Epigenetic processes, such as DNA methylation, show potential as biological markers and mechanisms underlying gene-environment interplay in the prediction of mental health and other brain-based phenotypes. However, little is known about how peripheral epigenetic patterns relate to individual differences in the brain itself. An increasingly popular approach to address this is by combining epigenetic and neuroimaging data; yet, research in this area is almost entirely comprised of cross-sectional studies in adults.

Patient-reported efficacy of adjunctive brexpiprazole in major depressive disorder in a phase 4, open-label, interventional study.

Objectives: In ENGAGE, patients with major depressive disorder (MDD) demonstrated improvements in patient-reported depression and life engagement while taking adjunctive brexpiprazole. This analysis aimed to further characterize patient perspectives on the effects of adjunctive brexpiprazole, using patient diary data from ENGAGE, and describe development of a 'word of the day' activity.

Methods: Prior to ENGAGE, word lists describing a 'good,' 'average,' and 'bad' day with depression were generated from semi-structured interviews with patients with MDD.

When is Not Enough: Evaluating Simple Metrics for Predicting Phase Separation of Intrinsically Disordered Proteins.

Understanding and predicting the phase behavior of intrinsically disordered proteins (IDPs) is of significant interest due to their role in many biological processes. However, effectively characterizing phase behavior and its complex dependence on protein primary sequence remains challenging. In this study, we evaluate the efficacy of several simple computational metrics to quantify the propensity of single-component IDP solutions to phase separate; specific metrics considered include the single-chain radius of gyration, the second virial coefficient, and a newly proposed quantity termed the expenditure density.

PAX3-FOXO1 Drives Targetable Cell State-Dependent Metabolic Vulnerabilities in Rhabdomyosarcoma.

PAX3-FOXO1, an oncogenic transcription factor, drives a particularly aggressive subtype of rhabdomyosarcoma (RMS) by enforcing gene expression programs that support malignant cell states. Here, we showed that PAX3-FOXO1+ RMS cells exhibit altered pyrimidine metabolism and increased dependence on enzymes involved in de novo pyrimidine synthesis, including dihydrofolate reductase (DHFR). Consequently, PAX3-FOXO1+ cells displayed increased sensitivity to inhibition of DHFR by the chemotherapeutic drug methotrexate, and this dependence was rescued by provision of pyrimidine nucleotides.

Origami frustration and its influence on energy landscapes of origami assemblies.

Harnessing instabilities of multicomponent multistable structural assemblies can potentially lead to scalable and reversible functionalities, which can be enhanced by exploring frustration. For instance, standard Kresling origami cells exhibit nontunable intrinsic energy landscapes determined by their geometry and material properties, limiting their adaptability after fabrication. To overcome this limitation, we introduce frustration to enable fine-tuning of the energy landscape and resulting deformation states.

Impact of Monomer Sequence and Interaction Parameter on Polymer Glass Transition Temperature.

Control of the glass transition temperature () is a major goal in polymer engineering as is a key determinant of mechanical behavior, barrier properties, and material processability. In copolymers of nonpolar monomers, the Fox equation can provide an approximate description of the dependence of on copolymer composition (monomer ratio), based on a harmonic weighted average of values for the individual homopolymers. However, the Fox equation does not consider the influence of intermonomer interactions, nor does it account for self-concentration effects.

Tutorial on computing nonadiabatic proton-coupled electron transfer rate constants.

Proton-coupled electron transfer (PCET) is pervasive throughout chemistry, biology, and physics. Over the last few decades, we have developed a general theoretical formulation for PCET that includes the quantum mechanical effects of the electrons and transferring protons, including hydrogen tunneling, as well as the reorganization of the environment and the donor-acceptor fluctuations. Analytical rate constants have been derived in various well-defined regimes.

The people behind the papers - Maria Avdeeva, Madeline Chalifoux and Eszter Posfai.

During pre-implantation development of the mouse embryo, cells must undergo their first fate decision. While key regulators of this process are known, the variability in lineage trajectories within and between embryos during this stage of development remain poorly understood. In a new study, Avdeeva and colleagues used Bayesian modelling to understand the dynamics of key regulators YAP, SOX2 and CDX2 in this cell fate decision and characterise the variability in this system.

Comprehensive review of avobenzone (butyl methoxydibenzoylmethane) toxicology data and human exposure assessment for personal care products.

A comprehensive review of existing toxicity and human exposure data for the ultraviolet filter avobenzone (butyl methoxydibenzoylmethane) was conducted to assess its safety as currently used in over-the-counter sunscreen formulations. Avobenzone has a suitable safety profile without any clear markers of toxicity or endpoints of concern. There are sufficient clinical studies and and toxicity studies in animal models to assess avobenzone's pharmacokinetics, pharmacodynamics, and potential toxicological properties, supportive of its long history of safe use.

Streamlined CRISPR-based assays for detection and subtyping of avian influenza.

Avian influenza viruses (AIVs) are zoonotic pathogens that pose an increasing global threat due to their potential for significant economic losses in agriculture, spillover into humans, and the risk of a pandemic should human-to-human transmission occur. These concerns underscore the need for rapid, sensitive and specific tools to detect and differentiate circulating AIV subtypes and clades. Current AIV diagnostic methods rely on specialized equipment and trained personnel, limiting their use in the field and in low-resource settings.