Structural analysis of human ADAR2-RNA complexes by X-ray crystallography.

Adenosine deaminases acting on RNAs (ADARs) are a class of RNA editing enzymes found in metazoa that catalyze the hydrolytic deamination of adenosine to inosine in duplexed RNA. Inosine is a nucleotide that can base pair with cytidine, therefore, inosine is interpreted by cellular processes as guanosine. ADARs are functionally important in RNA recoding events, RNA structure modulation, innate immunity, and can be harnessed for therapeutically-driven base editing to treat genetic disorders.

Multiple roles for retinoid signaling in craniofacial development.

Retinoic acid (RA) signaling plays multiple essential roles in development of the head and face. Animal models with mutations in genes involved in RA signaling have enabled understanding of craniofacial morphogenic processes that are regulated by the retinoid pathway. During craniofacial morphogenesis RA signaling is active in spatially restricted domains defined by the expression of genes involved in RA production and RA breakdown.

Vitamin A supply in the eye and establishment of the visual cycle.

Animals perceiving light through visual pigments have evolved pathways for absorbing, transporting, and metabolizing the precursors essential for synthesis of their retinylidene chromophores. Over the past decades, our understanding of this metabolism has grown significantly. Through genetic manipulation, researchers gained insights into the metabolic complexity of the pathways mediating the flow of chromophore precursors throughout the body, and their enrichment within the eyes.

Retinoid signaling in pancreas development, islet function, and disease.

All-trans retinoic acid (ATRA) signaling is essential in numerous different biological contexts. This review highlights the diverse roles of ATRA during development, function, and diseases of the pancreas. ATRA is essential to specify pancreatic progenitors from gut tube endoderm, endocrine and exocrine differentiation, and adult islet function.

Psychometric Properties of a Questionnaire for Assessing the Extent and Severity of the Concerns of People With an Implanted Cardioverter-Defibrillator.

Considering the numerous concerns patients express about having implantable cardioverter-defibrillators (ICDs) and the potential clinical implications of these concerns, it is essential to develop a valid and reliable measure of ICD-related concerns. The implantable cardioverter-defibrillator concerns (ICDC) questionnaire was initially designed for ICD recipients in England to assess and address these concerns. However, it remains uncertain whether this questionnaire possesses similar measurement properties and is suitable for ICD recipients in the United States.

A Community Initiative to Increase Colorectal Cancer Knowledge, Awareness, and Intent to Screen in an Underserved Region.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths in the United States despite the availability of effective preventive screening. This project was designed as a community awareness initiative to increase CRC awareness, knowledge, and intent to discuss and complete CRC screening. This quasi-experimental study had a QI focus and used a convenience sample in a public setting assessing CRC awareness, knowledge, and intent to discuss and complete screening after participating in an inflatable colon tour.

A year in review: new treatments and expanded indications in dermatology in 2024.

Methods: A literature search was conducted on Drugs@FDA: FDA-Approved Drugs for the year 2024 to identify new dermatologic treatments.

Results: In 2024, the FDA approved seven new dermatologic therapies and expanded the indications for seven current therapies. These therapies treat conditions such as atopic dermatitis, hidradenitis suppurativa, prurigo nodularis, molluscum contagiosum, and alopecia areata, among others.

Effect of formulation composition on trastuzumab stability.

For monoclonal antibody drug products as for other biologics, while the innovator drug products first becomes commercially available, they are often followed by one or more biosimilar products. These biosimilars often differ from the innovator product, as well as from each other, in their formulation composition. However, the impact of the formulation composition on the stability of the active pharmaceutical ingredient subjected to different 'stresses' is still not understood.

Selective pressure of various levels of erythromycin on the development of antibiotic resistance.

This study evaluated microbial fitness under selective pressure of various erythromycin concentrations and the development of resistance genes in Escherichia coli (E. coli) and Enterococcus faecalis (E. faecalis).

Pitfalls and practical suggestions for using local field potential recordings in DBS clinical practice and research.

Local field potential (LFP) recordings using chronically implanted sensing-enabled stimulators are a powerful tool for indexing symptom presence and severity in neurological and neuropsychiatric disorders, and for enhancing our neurophysiological understanding of brain processes. LFPs have gained interest as input signals for closed-loop deep brain stimulation (DBS) and can be used to inform DBS parameter selection. LFP recordings using chronically implanted sensing-enabled stimulators have various implementational challenges.

Stimulant-involved overdose deaths: Constructing dynamic hypotheses.

The overdose epidemic in the United States is evolving, with a rise in stimulant (cocaine and/or methamphetamine)-only and opioid and stimulant-involved overdose deaths for reasons that remain unclear. We conducted interviews and group model building workshops in Massachusetts and South Dakota. Building on these data and extant research, we identified six dynamic hypotheses, explaining changes in stimulant-involved overdose trends, visualized using causal loop diagrams.

Leveraging Artificial Intelligence to Develop a Decision-Support Tool for Visual Symptom Assessment of Grapevine Leafroll and Red Blotch Diseases.

The timely detection of viral pathogens in vineyards is a critical aspect of management. Diagnostic methods can be labor-intensive and may require specialized training or facilities. The emergence of artificial intelligence (AI) has the potential to provide innovative solutions for disease detection but requires a significant volume of high-quality data as input.

Crop rotation effects on the population density of soybean soilborne pathogens under no-till cropping system.

Soilborne diseases are persistent problems in soybean production. Long-term crop rotation can contribute to soilborne disease management. However, the response of soilborne pathogens to crop rotation is inconsistent, and rotation efficacy is highly variable.

Evaluating oomycete pathogen and community responses to chemical- and Slow Sand Filtration-based water treatment strategies to enable water recycling in nursery production systems.

While recycling irrigation water can reduce water use constraints and costs in nurseries, adoption is hindered by the associated risk of recirculating and spreading waterborne pathogens. To enable regional water re-use, this study assessed oomycete re-circulation risks and recycled water treatment efficacy at organismal and community scales. In culture-based analysis of recycled pond water at two Mid-Atlantic nurseries across three years, diverse oomycetes (12+ species) were detected using culture-based analysis, with Phytopythium helicoides as the dominant species; MiSeq analysis detected eight of these species, plus 24 additional taxa.

Construction of tetrahedral mesh phantom for Chinese women of childbearing age.

Although the Boundary Representation (BREP) method creates detailed surface phantoms of Chinese women of childbearing age, these phantoms cannot be directly used in Monte Carlo simulations. They must first be converted into voxel phantoms, a process that may diminish some of the inherent advantages of the surface phantoms. Therefore, the aim of this study is to construct a tetrahedral mesh (TM) phantom of Chinese women of childbearing age based on the BREP phantom, incorporating micron-level structural refinements to certain organ tissues while maintaining the original model's structure.

Investigation on the Heating Effects of Intra-Tumoral Injectable Magnetic hydrogels (IT-MG) for Cancer Hyperthermia.

Capacitive-based radiofrequency (Rf) radiation at 27 MHz offers a non-invasive approach for inducing hyperthermia, making it a promising technique for thermal cancer therapy applications. To achieve focused and site-specific hyperthermia, external material is required that efficiently convert Rf radiation into localized heat. Nanomaterials capable of absorbing Rf energy and convert into heat for targeted ablation are of critical importance.

Biomechanical and Functional Features of the Carrier Erythrocytes Prolonging Circulation Time of Biotherapeutic Targeted to Glycophorin A.

Red blood cells (RBCs) serve as natural transporters and can be modified to enhance the pharmacokinetics and pharmacodynamics of a protein cargo. Affinity targeting of Factor IX (FIX) to the RBC membrane is a promising approach to improve the (pro)enzyme's pharmacokinetics. For RBC targeting, purified human FIX was conjugated to the anti-mouse glycophorin A monoclonal antibody Ter119.

Bioconjugation of Synthetic Peptides onto Universal Chimeric Antigen Receptor T Cells for Targeted Cancer Immunotherapies.

The recent development of modular universal chimeric antigen receptor (CAR) T-cell platforms that use bifunctional adaptor intermediates to redirect engineered T-cell effector function has greatly expanded the capabilities of adoptive T-cell therapy, enabling safer and more comprehensive cancer treatment. However, universal CAR receptor systems rely on unstable transient recognition of tag-coupled intermediates for T-cell activation, and the array of targeting intermediates has been limited to antibodies and small molecules. Addressing these shortcomings, we engineered universal CAR T-cell receptors that can be covalently modified with synthetic biomaterials by accelerated SpyCatcher003-SpyTag003 chemistry for cancer-cell targeting.

Perspectives on Swedish Regulations for Online Record Access Among Adolescents With Serious Health Issues and Their Parents: Mixed Methods Study.

Background: With the increasing implementation of patient online record access (ORA), various approaches to access to minors' electronic health records have been adopted globally. In Sweden, the current regulatory framework restricts ORA for minors and their guardians when the minor is aged between 13 and 15 years. Families of adolescents with complex health care needs often desire health information to manage their child's care and involve them in their care.

Methods to Adjust for Confounding in Test-Negative Design COVID-19 Effectiveness Studies: Simulation Study.

Background: Real-world COVID-19 vaccine effectiveness (VE) studies are investigating exposures of increasing complexity accounting for time since vaccination. These studies require methods that adjust for the confounding that arises when morbidities and demographics are associated with vaccination and the risk of outcome events. Methods based on propensity scores (PS) are well-suited to this when the exposure is dichotomous, but present challenges when the exposure is multinomial.

Digital Gaming and Subsequent Health and Well-Being Among Older Adults: Longitudinal Outcome-Wide Analysis.

Background: Digital gaming has become increasingly popular among older adults, potentially offering cognitive, social, and physical benefits. However, its broader impact on health and well-being, particularly in real-world settings, remains unclear.

Objective: This study aimed to evaluate the multidimensional effects of digital gaming on health and well-being among older adults, using data from the Japan Gerontological Evaluation Study conducted in Matsudo City, Chiba, Japan.

Establishment and Maintenance of a Digital Therapeutic Alliance in People Living With Negative Symptoms of Schizophrenia: Two Exploratory Single-Arm Studies.

Background: Evidence-based digital therapeutics represent a new treatment modality in mental health, potentially providing cost-efficient, accessible means of augmenting existing treatments for chronic mental illnesses. CT-155/BI 3972080 is a prescription digital therapeutic under development as an adjunct to standard of care treatments for patients 18 years of age and older with experiential negative symptoms (ENS) of schizophrenia. Individual components of CT-155/BI 3972080 are designed based on the underlying principles of face-to-face treatment.