Heterogeneous and multiple conformational transition pathways between pseudoknots of the SARS-CoV-2 frameshift element.

Frameshifting is an essential mechanism employed by many viruses including coronaviruses to produce viral proteins from a compact RNA genome. It is facilitated by specific RNA folds in the frameshift element (FSE), which has emerged as an important therapeutic target. For SARS-CoV-2, a specific 3-stem pseudoknot has been identified to stimulate frameshifting.

Macromolecular interactions and geometrical confinement determine the 3D diffusion of ribosome-sized particles in live cells.

The crowded bacterial cytoplasm is composed of biomolecules that span several orders of magnitude in size and electrical charge. This complexity has been proposed as the source of the rich spatial organization and apparent anomalous diffusion of intracellular components, although this has not been tested directly. Here, we use biplane microscopy to track the 3D motion of self-assembled bacterial genetically encoded multimeric nanoparticles (bGEMs) with tunable size (20 to 50 nm) and charge (-3,240 to +2,700 e) in live cells.

A split-GAL4 driver line resource for neuron types.

Techniques that enable precise manipulations of subsets of neurons in the fly central nervous system (CNS) have greatly facilitated our understanding of the neural basis of behavior. Split-GAL4 driver lines allow specific targeting of cell types in and other species. We describe here a collection of 3060 lines targeting a range of cell types in the adult CNS and 1373 lines characterized in third-instar larvae.

Eating disorder treatment experiences among racially/ethnically minoritized samples.

Although eating disorders (EDs) affect individuals of all races and ethnicities, racially/ethnically minoritized individuals are less likely to receive ED treatment than White individuals. The present study aimed to compare ED treatment experiences in a sample of racially/ethnically minoritized individuals vs. White participants.

Protocol for real-time assessment of energy metabolism in dissociated mouse retinal photoreceptors using a SeahorseXFe24 analyzer.

Defects in retinal metabolism have been linked to the onset and progression of various retinal diseases. Herein, we provide a protocol for measuring bioenergetics in dissociated mouse retinal photoreceptors. We outline detailed instructions for obtaining morphologically intact and viable photoreceptor cells from adult mice and preparing the cells for metabolic analysis using a SeahorseXFe24 analyzer.

Optimized protocol for single-cell isolation and alkaline comet assay to detect DNA damage in cells of Drosophila wing imaginal discs.

Reduced expression of nucleolar genes induces stress and DNA damage. Here, we present a protocol to analyze DNA fragmentation at the single-cell level in Drosophila imaginal discs using an optimized alkaline comet assay. We describe steps for larvae development, tissue disaggregation, and single-cell dissociation.

Apoptosis in Cancer Biology and Therapy.

Since its inception, the study of apoptosis has been intricately linked to the field of cancer. The term apoptosis was coined more than five decades ago following its identification in both healthy tissues and malignant neoplasms. The subsequent elucidation of its molecular mechanisms has significantly enhanced our understanding of how cancer cells hijack physiological processes to evade cell death.

Role of Fungi in Tumorigenesis: Promises and Challenges.

The mycobiome plays a key role in the host immune responses in homeostasis and inflammation. Recent studies suggest that an imbalance in the gut's fungi contributes to chronic, noninfectious diseases such as obesity, metabolic disorders, and cancers. Pathogenic fungi can colonize specific organs, and the gut mycobiome has been linked to the development and progression of various cancers, including colorectal, breast, head and neck, and pancreatic cancers.

Treatment With Avacopan in Patients With Respiratory Tract Manifestations of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Objective: The ADVOCATE trial demonstrated that treatment of active granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) with avacopan was noninferior in achieving remission at week 26 and superior for sustained remission at week 52 compared with a prednisone taper. This analysis of ADVOCATE evaluated the efficacy and safety of avacopan in patients with ear, nose, throat (ENT), or lung manifestations.

Methods: This post hoc analysis included patients enrolled in ADVOCATE with ENT or lung manifestations at baseline.

Prevalence of Autoimmune Diseases in Patients Treated With Immune Checkpoint Inhibitors: An Epidemiological Study Using A Global Network of Health Care Organizations.

Objective: Evaluate prevalence of new onset autoimmune conditions (ACs) after commencement of immune checkpoint inhibitors (ICIs).

Methods: This retrospective observational study was done using TriNetX. Patients with neoplasm for which ICIs were approved were stratified into two groups based on ICI use.

Biofield Therapies Clinical Research Landscape: A Scoping Review and Interactive Evidence Map.

Biofield Therapies, with a historical lineage spanning millennia and continuing relevance in contemporary practices, have been used to address various health conditions and promote wellbeing. The scientific study and adoption of these therapies have been hindered by cultural challenges and institutional barriers. In addition, the current research landscape for Biofield Therapies is insufficiently documented.

Enhanced Transcriptional Activation in Developing Mouse Photoreceptors.

Purpose: Retinal development in the mouse continues past birth and provides a widely used model system in which photoreceptor formation can be observed and manipulated. This experimental paradigm provides opportunities for both gain-of-function and loss-of-function studies, which can be accomplished through in vivo or ex vivo plasmid delivery and electroporation. However, the cis-regulatory elements used to implement this approach have not been fully evaluated or optimized for the unique transcriptional environment of photoreceptors.

Preferential Sites of Retinal Capillary Occlusion in Sickle Cell Disease.

Purpose: To assess the preferential sites of retinal capillary occlusion at the parafovea in patients with sickle cell disease (SCD) using optical coherence tomography angiography (OCT-A).

Methods: OCT-A scans from 107 patients with SCD and 51 race-matched unaffected controls were obtained using a commercial spectral domain-OCT system. At least eight sequential 3 × 3 mm scans centered at the fovea were acquired and averaged for image analysis.

COVID-19 Pandemic and Racial and Ethnic Disparities in Long-Term Nursing Home Stay or Death Following Hospital Discharge.

Importance: Long-term nursing home stay or death (long-term NH stay or death), defined as new long-term residence in a nursing home or death following hospital discharge, is an important patient-centered outcome.

Objective: To examine whether the COVID-19 pandemic was associated with changes in long-term NH stay or death among older adults with sepsis, and whether these changes were greater in individuals from racial and ethnic minoritized groups.

Design, Setting, And Participants: This cross-sectional study used patient-level data from the Medicare Provider Analysis and Review File, the Master Beneficiary Summary File, and the Minimum Data Set.

Exploring Developmental Connections: Sleep Patterns, Self-Locomotion, and Vocabulary Growth in Early Childhood.

Current research indicates likely developmental connections between the evolution of sleep patterns, motor skills progression, and the expansion of vocabulary. These connections are grounded in the well-established role of sleep in memory and learning, as well as in the cascading effects on language development of the acquisition of new motor skills. However, no study has so far undertaken a comprehensive and systematic examination of these connections or explored their developmental trajectory over time.

Baseline Imaging Derived Factors of Response Following [225Ac]Ac-J591 Therapy in Metastatic Castration-Resistant Prostate Cancer: A Lesion Level Analysis.

Purpose: Actinium-225 labeled prostate-specific membrane antigen (PSMA) targeted radionuclide therapy has emerged as a potential treatment option in the management of men with metastatic castrate-resistant prostate cancer (mCRPC). This study investigated molecular imaging-derived parameters and compared imaging response of lesions categorized by tumor site.

Methods: Men with mCRPC treated with [225Ac]Ac-J591 from 2017 to 2022 at our center on two prospective trials (NCT03276572 and NCT04506567) with pre- and post-treatment [68Ga]Ga-PSMA-11 Positron Emission Tomography (PET) imaging studies available were included.

Prophylactic Use of Cardiac Medications and Survival in Duchenne Muscular Dystrophy.

Introduction/aims: Prophylactic treatment of left ventricular dysfunction (LVD) in Duchenne muscular dystrophy (DMD) delays onset of LVD, but there is limited data showing impact on survival. Our aim was to describe survival among treated and untreated individuals with DMD.

Methods: Retrospective, population-based surveillance data from the Muscular Dystrophy Surveillance, Tracking and Research Network (MD STARnet) were used.

Symptomatic Improvement in Adults and Adolescents With Eosinophilic Esophagitis Requires Higher Systemic Dupilumab Exposure Than Histologic Response.

Introduction: We assessed potential mechanisms behind the requirement for more frequent dupilumab dosing in eosinophilic esophagitis (EoE) compared with other approved indications.

Methods: Results for the phase 3 LIBERTY EoE TREET study coprimary endpoints (proportion of patients achieving a peak intraepithelial eosinophil count of ≤6 eosinophils per high-power field and absolute change from baseline in Dysphagia Symptom Questionnaire total score) were pooled in exposure-response analyses.

Results: A steep initial relationship then plateau was observed between higher dupilumab steady-state trough concentrations and decreased eosinophilic infiltration at week 24, whereas a graded exposure-response relationship was observed for symptomatic improvement at week 24.

Gender Differences in Barriers in Career Development Among a Cohort of Dental Researchers. A Cross-Sectional Study.

Background: This cross-sectional study investigated gender differences in barriers to career development among dental researchers and between academic and non-academic women.

Methods: An anonymous 34-item survey assessing barriers to career development and workplace obstacles (14 items), along with demographic/occupation characteristics (22 items), was distributed among dental researchers at the Women In Science Network meetings at 2024 AADOCR/IADR General Session (QR code) and through AADOCR/IADR discussion board (online platform). Differences in barriers and workplace obstacles were analyzed between women and men with chi-square tests; comparisons were repeated among women working within versus outside academia.

Nutraceuticals and Headache 2024: Riboflavin, Coenzyme Q10, Feverfew, Magnesium, Melatonin, and Butterbur.

Nutraceuticals are not regulated by the US Food and Drug Administration, so a careful literature review is essential to make clinical decisions. Riboflavin or vitamin B2 can be recommended for migraine prevention in adults, but pediatric use is not proven. Adverse events are minimal.

Remote Food Security Research Project: Applying an Indigenist Research Lens.

This paper aimed to reflect on how Rigney's model of Indigenist research informed the research design of a project which explored community-led solutions to improve food security in remote Aboriginal and Torres Strait Islander communities. The project was conducted in partnership with two Aboriginal Community Controlled Health Organisations (ACCHOs); Apunipima Cape York Health Council (Apunipima) and Central Australian Aboriginal Congress (Congress), communities in Central Australia and Cape York, Queensland and researchers from the University of Queensland, Monash University, Dalhousie University and Menzies School of Health Research. On reflection the principles of Indigenist research were evident providing a means of resistance to oppression through Indigenous stakeholders being in control of research to address social determinants, in this case food security.