Evolution takes multiple paths to evolvability when facing environmental change.

Life at all scales is surprisingly effective at exploiting new opportunities, as demonstrated by the rapid emergence of antimicrobial resistance and novel pathogens. How populations acquire this level of evolvability and the various ways it aids survival are major open questions with direct implications for human health. Here, we use digital evolution to show that changing environments facilitate the simultaneous evolution of high mutation rates and a distribution of mutational effects skewed toward beneficial phenotypes.

The 340B Drug Pricing Program and Management of Advanced Prostate Cancer.

Introduction: Oral targeted therapies are a standard of care for men with advanced prostate cancer. However, these therapies are expensive, which may be a barrier to some, particularly the most economically disadvantaged. Through investment in programs to assist this population, savings generated from the 340B program have the potential to mitigate barriers to initiating treatment with targeted therapies in these men.

mRNA decay pre-complex assembly drives timely cell-state transitions during differentiation.

Complexes that control mRNA stability and translation promote timely cell-state transitions during differentiation by ensuring appropriate expression patterns of key developmental regulators. The Drosophila RNA-binding protein brain tumor (Brat) promotes the degradation of target transcripts during the maternal-to-zygotic transition in syncytial embryos and uncommitted intermediate neural progenitors (immature INPs). We identify ubiquitin-specific protease 5 (Usp5) as a candidate Brat interactor essential for the degradation of Brat target mRNAs.

Proton Pump Inhibitor Use and Incident Cardiovascular Disease in Older Postmenopausal Women.

Background: Epidemiological studies have been inconsistent regarding an association between proton pump inhibitor (PPI) use and risk of primary cardiovascular disease (CVD) events.

Methods: We studied 85,189 postmenopausal women (mean age 63 years at baseline) without known CVD at enrollment into the Women's Health Initiative Observational Study (1993-1998). PPI use was determined from medication inventories at baseline and Year-3.

Associations between rural hospital closures and acute and post-acute care access and outcomes.

Objective: To determine whether rural hospital closures affected hospital and post-acute care (PAC) use and outcomes.

Study Setting And Design: Using a staggered difference-in-differences design, we evaluated associations between 32 rural hospital closures and changes in county-level: (1) travel distances to and lengths of stay at hospitals; (2) functional limitations at and time from hospital discharge to start of PAC episode; (3) 30-day readmissions and mortality and hospitalizations for a fall-related injury; and (4) population-level hospitalization and death rates.

Data Sources And Analytic Sample: 100% Medicare claims and home health and skilled nursing facility clinical data to identify approximately 3 million discharges for older fee-for-service Medicare beneficiaries.

Solution-Focused Brief Therapy for Improving Couple Dyadic Relationships in Iran: A Systematic Review.

Despite the popularity of Solution-Focused Brief Therapy (SFBT) in Iran, the existing literature synthesis has limitations due to the reliance on studies published primarily in Farsi. This systematic review addresses these gaps by synthesizing and evaluating the effectiveness of SFBT on the marital outcomes of couples in Iran, incorporating both Farsi and English sources. The search for this review yielded 1523 records, from which 26 randomized controlled trials were included.

Different Classes of HIV-Preventive Behavioral Intention Among Youths Vulnerable to HIV Acquisition.

The HIV incidence rate continues to increase among youth, especially among young men who have sex with men (YMSM) and young transgender women (YTW). To date, behavioral intention has often been viewed as the likelihood of engaging in prevention behaviors and emphasized as a key antecedent for condom use, disclosure of serostatus, and PrEP use among people living with HIV. In addition, individuals with different sociodemographic factors may have varying degrees of HIV prevention intention, which is a critical knowledge needed to identify facilitators and barriers to HIV prevention intention.

Competition increases the magnitude of dishonest reporting even when controlling for reward uncertainty.

Does competition increase cheating? This question has been investigated by both psychologists and economists in the past and received conflicting answers. Notably, prior experimental work compared how people behaved under competitive and non-competitive tasks that were associated with different levels of uncertainty about the reward that people would receive. We aim to experimentally disentangle the effect of competition from the effects of uncertain rewards.

The brain selectively allocates energy to functional brain networks under cognitive control.

Network energy has been conceptualized based on structural balance theory in the physics of complex networks. We utilized this framework to assess the energy of functional brain networks under cognitive control and to understand how energy is allocated across canonical functional networks during various cognitive control tasks. We extracted network energy from functional connectivity patterns of subjects who underwent fMRI scans during cognitive tasks involving working memory, inhibitory control, and cognitive flexibility, in addition to task-free scans.

Impact of compaction process on the carbon epoxy composite under varied environmental conditions.

Fibre-reinforced polymeric composites utilized in aerospace settings, experience varying environmental conditions throughout their operational lifespan. The major factors that can have adverse effects on their long-term performance are water and temperature. The present study investigates how the determinants such as water and temperature impact the structural integrity of plain weave woven carbon/epoxy laminated composites and further categorizing them into compacted and non-compacted groups.

Automated chest CT three-dimensional quantification of body composition: adipose tissue and paravertebral muscle.

This retrospective study developed an automated algorithm for 3D segmentation of adipose tissue and paravertebral muscle on chest CT using artificial intelligence (AI) and assessed its feasibility. The study included patients from the Boston Lung Cancer Study (2000-2011). For adipose tissue quantification, 77 patients were included, while 245 were used for muscle quantification.

Functional anatomy of zinc finger antiviral protein complexes.

ZAP is an antiviral protein that binds to and depletes viral RNA, which is often distinguished from vertebrate host RNA by its elevated CpG content. Two ZAP cofactors, TRIM25 and KHNYN, have activities that are poorly understood. Here, we show that functional interactions between ZAP, TRIM25 and KHNYN involve multiple domains of each protein, and that the ability of TRIM25 to multimerize via its RING domain augments ZAP activity and specificity.

Grain engineering for efficient near-infrared perovskite light-emitting diodes.

Metal halide perovskites show promise for next-generation light-emitting diodes, particularly in the near-infrared range, where they outperform organic and quantum-dot counterparts. However, they still fall short of costly III-V semiconductor devices, which achieve external quantum efficiencies above 30% with high brightness. Among several factors, controlling grain growth and nanoscale morphology is crucial for further enhancing device performance.

Immune checkpoint inhibitor-induced severe epidermal necrolysis mediated by macrophage-derived CXCL10 and abated by TNF blockade.

Immune checkpoint inhibitors (ICI) represent new anticancer agents and have been used worldwide. However, ICI can potentially induce life-threatening severe cutaneous adverse reaction (SCAR), such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hindering continuous ICI therapy. We examine 6 cohorts including 25 ICI-induced SJS/TEN patients and conduct single-cell RNA sequencing (scRNA-seq) analysis, which shows overexpression of macrophage-derived CXCL10 that recruits CXCR3 cytotoxic T lymphocytes (CTL) in blister cells from ICI-SJS/TEN skin lesions.

Association of structured continuum emission with dynamic aurora.

Patterns of ionospheric luminosity provide a unique window into our complex, coupled space environment. The aurora, for example, indicates plasma processes occurring thousands of km away, depositing immense amounts of energy into our polar ionospheres. Here we show observations of structured continuum emission associated with the dynamic aurora.

Magnetic Resonance Imaging of Gastric Motility in Conscious Rats.

Introduction: Gastrointestinal (GI) magnetic resonance imaging (MRI) enables simultaneous assessment of gastric peristalsis, emptying, and intestinal filling and transit. However, GI MRI in animals typically requires anesthesia, which complicates physiology and confounds interpretation and translation to humans. This study aimed to establish GI MRI in conscious rats, and for the first time, characterize GI motor functions in awake versus anesthetized conditions.

Changes in Disc Status and Condylar Regeneration After Intracapsular Condylar Fractures in Rabbits.

Background: The treatment procedure for intracapsular condylar fractures (ICF) is still being debated. The temporomandibular joint (TMJ) disc is a key factor for treating ICF. The study aims to investigate the changes in TMJ disc status and condylar cartilage regeneration following ICF in a rabbit model, to assist in planning treatment.

Large Differences in Herbivore Performance Emerge From Simple Herbivore Behaviours and Fine-Scale Spatial Heterogeneity in Phytochemistry.

Patterns of phytochemistry localisation in plant tissues are diverse within and across leaves. These spatial heterogeneities are important to the fitness of herbivores, but their effects on herbivore foraging and dietary experience remain elusive. We manipulated the spatial variance and clusteredness of a plant toxin in a synthetic diet landscape on which individual caterpillars fed.

Current and Historical Resource Nitrogen Supply Affects the Eco-Physiological Traits and the Ionome of a Diazotrophic Cyanobacterium.

Diazotrophic cyanobacteria can overcome nitrogen (N)-limitation by fixing atmospheric N; however, this increases their energetic, iron, molybdenum, and boron costs. It is unknown how current and historic N-supplies affect cyanobacterial elemental physiology beyond increasing demands for elements involved in N-fixation. Here, we examined the changes in pigment concentrations, N-storage, and the ionome (i.

The Metapopulation Bridge to Macroevolutionary Speciation Rates: A Conceptual Framework and Empirical Test.

Whether large-scale variation in lineage diversification rates can be predicted by species properties at the population level is a key unresolved question at the interface between micro- and macroevolution. All else being equal, species with biological attributes that confer metapopulation stability should persist more often at timescales relevant to speciation and so give rise to new (incipient) forms that share these biological traits. Here, we develop a framework for testing the relationship between metapopulation properties related to persistence and phylogenetic speciation rates.

Environmental Conditions Modulate Warming Effects on Plant Litter Decomposition Globally.

Empirical studies worldwide show that warming has variable effects on plant litter decomposition, leaving the overall impact of climate change on decomposition uncertain. We conducted a meta-analysis of 109 experimental warming studies across seven continents, using natural and standardised plant material, to assess the overarching effect of warming on litter decomposition and identify potential moderating factors. We determined that at least 5.

Predicting Sarcopenia and Frailty Risk in Patients Post Heart Transplantation.

Introduction: Currently, there is little evidence on the prevalence and factors associated with sarcopenia risk or frailty risk in patients post heart transplantation (HTx). The objective of this study was to analyze the influence of sociodemographic, lifestyle, physical, and psychological factors on sarcopenia and frailty risk in patients post-HTx.

Methods: 133 patients post-HTx (59.

Meta-Analysis of Solution-Focused Brief Therapy Research Conducted in Iran: Does Outcome Type, Intervention Modality, or Delivery Format Make a Difference?

This meta-analysis synthesized randomized and non-randomized controlled trials of solution-focused brief therapy (SFBT) in Iranian populations, examining the effectiveness and the applications of SFBT in all Iranian settings and evaluated if the various outcomes being studied, research intervention modality, or therapy delivery format made statistical differences in outcomes. A comprehensive search strategy across three Iranian and four US databases, one Iranian conference website, and three professional websites resulted in the inclusion of 34 included studies for meta-analytic analysis. The outcomes reported an overall large significant treatment effect size (d = 0.