Biochemical and Computational Characterization of Haloalkane Dehalogenase Variants Designed by Generative AI: Accelerating the S2 Step.

Generative artificial intelligence (AI) models trained on natural protein sequences have been used to design functional enzymes. However, their ability to predict individual reaction steps in enzyme catalysis remains unclear, limiting the potential use of sequence information for enzyme engineering. In this study, we demonstrated that sequence information can predict the rate of the S2 step of a haloalkane dehalogenase using a generative maximum-entropy (MaxEnt) model.

Semi-Supervised Learning Allows for Improved Segmentation With Reduced Annotations of Brain Metastases Using Multicenter MRI Data.

Background: Deep learning-based segmentation of brain metastases relies on large amounts of fully annotated data by domain experts. Semi-supervised learning offers potential efficient methods to improve model performance without excessive annotation burden.

Purpose: This work tests the viability of semi-supervision for brain metastases segmentation.

Predictors of Participation in Prenatal Substance Use Assessment, Counseling, and Treatment Among Pregnant Individuals in Prenatal Settings Who Use Cannabis.

Objectives: Assessment and counseling are recommended for individuals with prenatal cannabis use. We examined characteristics that predict prenatal substance use assessment and counseling among individuals who screened positive for prenatal cannabis use in prenatal settings.

Methods: Electronic health record data from Kaiser Permanente Northern California's Early Start perinatal substance use screening, assessment, and counseling program was used to identify individuals with ≥1 pregnancies positive for prenatal cannabis use.

A regulatory network involving calmodulin controls phytosulfokine peptide processing during drought-induced flower abscission.

Drought stress substantially decreases crop yields by causing flowers and fruits to detach prematurely. However, the molecular mechanisms modulating organ abscission under drought stress remain unclear. Here, we show that expression of CALMODULIN2 (CaM2) is specifically and sharply increased in the pedicel abscission zone (AZ) in response to drought and plays a positive role in drought-induced flower drop in tomato (Solanum lycopersicum).

Hidradenitis Suppurativa: Radical Surgical Excisions with Staged Reconstructions: A Single-Surgeon Retrospective Review of 71 Patients.

Background: Hidradenitis suppurativa is a chronic, inflammatory disease involving the pilosebaceous unit of apocrine gland-bearing skin. Wide surgical excision, wherein margins extend beyond active lesions, is considered curative.

Objective: To evaluate the safety and efficacy of wide surgical excision in the treatment of hidradenitis suppurativa.

Previous short-term disuse dictates muscle gene expression and physiological adaptations to subsequent resistance exercise.

Short-term unloading experienced following injury or hospitalisation induces muscle atrophy and weakness. The effects of exercise following unloading have been scarcely investigated. We investigated the functional and molecular adaptations to a resistance training (RT) programme following short-term unloading.

Amplicon Sequencing Reveals Diversity in Spatially Separated Microbial Communities in the Icelandic Mars Analog Environment Mælifellssandur.

Exploration missions to Mars rely on landers or rovers to perform multiple analyses over geographically small sampling regions, while landing site selection is done using large-scale but low-resolution remote-sensing data. Utilizing Earth analog environments to estimate small-scale spatial and temporal variation in key geochemical signatures and biosignatures will help mission designers ensure future sampling strategies meet mission science goals. Icelandic lava fields can serve as Mars analog sites due to conditions that include low nutrient availability, temperature extremes, desiccation, and isolation from anthropogenic contamination.

Long-Term Safety and Efficacy with Roflumilast Cream 0.15% in Patients Aged ≥6 Years with Atopic Dermatitis: A Phase 3 Open-Label Extension Trial.

Safety and efficacy of roflumilast cream 0.15% for atopic dermatitis (AD) were demonstrated in two 4-week phase 3 trials. Evaluate long-term safety, tolerability, and efficacy of roflumilast cream 0.

Surprising features of nuclear receptor interaction networks revealed by live-cell single-molecule imaging.

Type II nuclear receptors (T2NRs) require heterodimerization with a common partner, the retinoid X receptor (RXR), to bind cognate DNA recognition sites in chromatin. Based on previous biochemical and overexpression studies, binding of T2NRs to chromatin is proposed to be regulated by competition for a limiting pool of the core RXR subunit. However, this mechanism has not yet been tested for endogenous proteins in live cells.

Use of and Steering to Pharmacies Owned by Insurers and Pharmacy Benefit Managers in Medicare.

Importance: The prevalence of pharmacies owned by integrated insurers and pharmacy benefit managers (PBMs), or insurer-PBMs, is of growing regulatory concern. However, little is known about the role of these pharmacies in Medicare, in which pharmacy network protections may influence market dynamics.

Objective: To evaluate the prevalence of insurer-PBM-owned pharmacies and the extent to which insurer-PBMs steer patients to pharmacies they own in Medicare.

Medicaid Unwinding Experiences in Dual-Eligible Older Adults.

Importance: Dual-eligible older adults rely on Medicaid to pay for Medicare premiums and cost sharing in addition to supplemental services including dental and long-term care. However, the unique experiences of dual-eligible older adults with Medicaid unwinding remain unknown.

Objective: To assess the awareness and experiences of dual-eligible older adults with Medicaid redetermination.

Estimating Visual Acuity With Spectacle Correction From Fundus Photos Using Artificial Intelligence.

Importance: Determining spectacle-corrected visual acuity (VA) is essential when managing many ophthalmic diseases. If artificial intelligence (AI) evaluations of macular images estimated this VA from a fundus image, AI might provide spectacle-corrected VA without technician costs, reduce visit time, or facilitate home monitoring of VA from fundus images obtained outside of the clinic.

Objective: To estimate spectacle-corrected VA measured on a standard eye chart among patients with diabetic macular edema (DME) in clinical practice settings using previously validated AI algorithms evaluating best-corrected VA from fundus photographs in eyes with DME.

Dynamics of hydrogen shift reactions between peroxy radicals.

Peroxy radicals are key intermediates in many atmospheric processes. Reactions between such radicals are of particular interest as they can lead to accretion products capable of participating in new particle formation (NPF). These reactions proceed through a tetroxide intermediate, which then decomposes to a complex of two alkoxy radicals and O, with spin conservation dictating that the complex must be formed in the triplet state.

Strong adsorption of guanidinium cations to the air-water interface.

Combining Deep-UV second harmonic generation spectroscopy with molecular simulations, we confirm and quantify the specific adsorption of guanidinium cations to the air-water interface. Using a Langmuir analysis of measurements at multiple concentrations, we extract the Gibbs free energy of adsorption, finding it larger than typical thermal energies. Molecular simulations clarify the role of polarizability in tuning the thermodynamics of adsorption, and establish the preferential parallel alignment of guanidinium at the air-water interface.

The ecdysone-induced bZIP transcription factor MafB establishes a positive feedback loop to enhance vitellogenesis and reproduction in the mosquito.

Female mosquitoes require a vertebrate blood meal to activate reproduction, transmitting numerous devastating human diseases. Vitellogenesis is a central event of female reproduction that involves the massive production of vitellogenin (Vg) in the fat body and the maturation of ovaries. This process is controlled by the steroid hormone 20-hydroxyecdysone (20E); however, its molecular regulatory basis remains not completely understood.

Infectious keratitis following photorefractive keratectomy: a 13-year study at a tertiary center.

Introduction: Infectious keratitis is a rare but devastating complication following photorefractive keratectomy (PRK) that may lead to visual impairment. This study assessed the clinical features, treatment strategies, and outcomes of post-PRK infectious keratitis.

Methods: This retrospective study was conducted on patients with post-PRK infectious keratitis presenting to Khalili Hospital, Shiraz, Iran, from June 2011 to March 2024.

Extracorporeal Membrane Oxygenation in Children with Pulmonary Atresia and Intact Ventricular Septum: Mortality and Associated Outcomes.

Data on outcomes of extracorporeal membrane oxygenation (ECMO) are limited in patients with pulmonary atresia intact ventricular septum (PAIVS). The objective of this study was to describe the use of ECMO and the associated outcomes in patients with PAIVS. We retrospectively reviewed neonates with PAIVS who received ECMO between 2009 and 2019 in 19 US hospitals affiliated with the Collaborative Research for the Pediatric Cardiac Intensive Care Society (CoRe-PCICS).

Brief Report: Stated Preferences for Long-Acting Injectable ART Among Mobile Men Living With HIV in Malawi: A Qualitative Study.

Background: Long-acting injectable (LAI) antiretroviral medications are as effective as daily oral antiretroviral therapy (ART) and offer discreet, less frequent dosing. LAIs may be ideal treatment options for people who experience challenges with adherence to daily oral ART, including mobile men living with HIV (MLHIV).

Methods: We conducted a qualitative substudy within two parent trials in 24 health facilities in Malawi that enrolled MLHIV ≥15 years not on ART.

Brief Report: Genital Microbiome, Inflammation, and Tenofovir Levels in Transgender Men and Cisgender Women Taking Oral PrEP.

Background: Little is known about the efficacy of preexposure prophylaxis (PrEP) or what biologic factors may influence HIV transmission in transgender men (TGM). In this study, we sought to explore the effect of testosterone on the vaginal microbiome, cervicovaginal fluid (CVF) tenofovir concentrations, and levels of CVF inflammatory markers in TGM on PrEP.

Methods: Cervicovaginal fluid was collected from 13 TGM (7 using testosterone) and 32 cisgender women (CGW) on PrEP.

Treatment-Emergent Major Adverse Cardiovascular and Thromboembolic Events were Infrequent During Clinical Trials of Pegloticase.

Objectives: Long-term maintenance of serum urate (SU) levels <6 mg/dl reduces gout flare frequency. However, urate-lowering therapy (ULT) initiation can induce gout flare. The incidence of thromboembolic (TE) and cardiovascular (CV) events has been shown to increase in the 30 and 120 days following gout flare, respectively; therefore, the question of ULT initiation increasing patient risk for CV/TE events has been raised.