Modeling absorbed alpha particle dose from diffusing alpha-emitters radiation therapy in changing tissue volumes.

Background: Diffusing alpha-emitters Radiation Therapy ("Alpha DaRT") is a promising new radiation therapy modality for treating bulky tumors. Ra-carrying sources are inserted intratumorally, producing a therapeutic alpha-dose region with a total size of a few millimeter via the diffusive motion of Ra's alpha-emitting daughters. Clinical studies of Alpha DaRT have reported 100% positive response (30%-100% shrinkage within several weeks), with post-insertion swelling in close to half of the cases.

Automated Integration of AI Results into Radiology Reports Using Common Data Elements.

Integration of artificial intelligence (AI) into radiology practice can create opportunities to improve diagnostic accuracy, workflow efficiency, and patient outcomes. Integration demands the ability to seamlessly incorporate AI-derived measurements into radiology reports. Common data elements (CDEs) define standardized, interoperable units of information.

Screening Young Adult Cancer Patients for Vocational Rehabilitation Services: A Vocational Rehabilitation Readiness Screening Tool.

Purpose: We aimed to develop an online vocational rehabilitation (VR) readiness screening (VRRS) tool for young adults diagnosed with cancer. VR readiness was defined as being physically and cognitively ready to enter or return to work or school.

Methods: We developed an initial VRRS tool informed by previous studies, a scoping review to determine such a tool had not already been developed, and consultation with subject matter experts.

Rethinking the residual approach: leveraging statistical learning to operationalize cognitive resilience in Alzheimer's disease.

Cognitive resilience (CR) describes the phenomenon of individuals evading cognitive decline despite prominent Alzheimer's disease neuropathology. Operationalization and measurement of this latent construct is non-trivial as it cannot be directly observed. The residual approach has been widely applied to estimate CR, where the degree of resilience is estimated through a linear model's residuals.

Multi-level Factors to Build Confidence and Support in Active Surveillance for Low-Risk Prostate Cancer: A Qualitative Study.

Background: Active surveillance (AS) is the guideline-recommended treatment for low-risk prostate cancer and involves routine provider visits, lab tests, imaging, and prostate biopsies. Despite good uptake, adherence to AS, in terms of receiving recommended follow-up testing and remaining on AS in the absence of evidence of cancer progression, remains challenging.

Objective: We sought to better understand urologist, primary care providers (PCPs), and patient experiences with AS care delivery to identify opportunities to improve adherence.

Individual differences in intolerance of uncertainty is primarily linked to the structure of inferior frontal regions.

Increased intolerance of uncertainty (IU), or distress felt when encountering situations with unknown outcomes, occurs transdiagnostically across various forms of psychopathology and is targeted in therapeutic intervention. Increased intolerance of uncertainty shows overlap with symptoms of internalizing disorders, such as depression and anxiety, including negative affect and anxious apprehension (worry). While neuroanatomical correlates of IU have been reported, previous investigations have not disentangled the specific neural substrates of IU above and beyond any overlapping relationships with aspects of internalizing psychopathology.

Biosimilars: A Critical Review of Development, Regulatory Landscape, and Clinical Implications.

The biopharmaceutical industry has witnessed significant growth in the development and approval of biosimilars. These biosimilars aim to provide cost-effective alternatives to expensive originator biosimilars, alleviating financial pressures within healthcare. The manufacturing of biosimilars is a highly complex process that involves several stages, each of which must meet strict regulatory standards to ensure that the final product is highly similar to the reference biologic.

Social epidemiology of early adolescent nutrition.

Background: This study aimed to investigate associations between sociodemographic factors and dietary intake among a diverse population of early adolescents ages 10-13 years in the United States.

Methods: We examined data from the Adolescent Brain Cognitive Development (ABCD) Study in Year 2 (2018-2020, ages 10-13 years, N = 10,280). Multivariable linear regression models were conducted to estimate the adjusted associations between sociodemographic factors (age, sex, race and ethnicity, household income, parental education) and dietary intake of various food groups, measured by the Block Kids Food Screener.

Multistage deep learning methods for automating radiographic sharp score prediction in rheumatoid arthritis.

The Sharp-van der Heijde score (SvH) is crucial for assessing joint damage in rheumatoid arthritis (RA) through radiographic images. However, manual scoring is time-consuming and subject to variability. This study proposes a multistage deep learning model to predict the Overall Sharp Score (OSS) from hand X-ray images.

Who is American? A comprehensive analysis of the American = White/Foreign = Asian stereotype (2007-2023).

Against the backdrop of increasing ethnic diversity in the U.S., we replicate, extend, and challenge previous examinations of the American = White/Foreign = Asian stereotype in the largest sample to date (N = 666,623 respondents) over 17 years (2007-2023).

Short-term evolutionary implications of an introgressed size-determining supergene in a vulnerable population.

The Thorny Skate (Amblyraja radiata) is a vulnerable species displaying a discrete size-polymorphism in the northwest Atlantic Ocean (NWA). We conducted whole genome sequencing of samples collected across its range. Genetic diversity was similar at all sampled sites, but we discovered a ~ 31 megabase bi-allelic supergene associated with the size polymorphism, with the larger size allele having introgressed in the last ~160,000 years B.

Integrating representation learning, permutation, and optimization to detect lineage-related gene expression patterns.

Recent barcoding technologies allow reconstructing lineage trees while capturing paired single-cell RNA-sequencing (scRNA-seq) data. Such datasets provide opportunities to compare gene expression memory maintenance through lineage branching and pinpoint critical genes in these processes. Here we develop Permutation, Optimization, and Representation learning based single Cell gene Expression and Lineage ANalysis (PORCELAN) to identify lineage-informative genes or subtrees where lineage and expression are tightly coupled.

Propidium Monoazide is Unreliable for Quantitative Live-Dead Molecular Assays.

Propidium monoazide (PMA) is a dye that distinguishes between live and dead cells in molecular assays like the Polymerase Chain Reaction (PCR). It works by cross-linking to the DNA of cells that have compromised membranes or extracellular DNA upon photoactivation, making the DNA inaccessible for amplification. Currently, PMA is used to detect viable pathogens and alleviate systemic bias in the microbiome analysis of samples using 16S rRNA gene sequencing.

New insights into the goals of transgender male versus non-binary individuals considering metoidioplasty and phalloplasty gender-affirming surgery.

Background: Understanding patient goals for metoidioplasty and phalloplasty gender-affirming surgery (MaPGAS) is paramount to achieving satisfactory, preference-sensitive outcomes, yet there is a lack of understanding of MaPGAS priorities and how these may vary between transgender men and non-binary individuals assigned female at birth (AFAB).

Aim: To understand the surgical goals of transgender men and non-binary individuals AFAB considering MaPGAS.

Methods: An online survey was created following literature review and qualitative interviews and distributed via social media and a community health center to participants AFAB aged ≥18 years who had considered but not yet undergone MaPGAS.

Interplay between Two Structure Types in the Incommensurately Modulated ATaSe Compounds (A = Rb, Cs).

Incommensurately modulated crystals are a rare class of materials that are notoriously difficult to characterize properly. We have synthesized two new incommensurately modulated compounds, RbTaSe and CsTaSe, based on the MQ (M = Nb, Ta; Q = S, Se) unit using high-temperature solid-state synthesis. Using superspace crystallography in combination with second harmonic generation measurements, we confirmed both materials to be noncentrosymmetric, falling into the superspace group 1(αβγ)0, while the basic cell suggests 2/.

A Qualitative Study of Primary Care Physicians' Approaches to Caring for Adult Adopted Patients.

Purpose: Adoption has lifelong health implications for 7.8 million adopted people and their families in the United States. The majority of adoptees have limited family medical history (LFMH).

Intervention Stage Completion and Behavioral Health Outcomes: An Integrated Behavioral Health and Primary Care Randomized Pragmatic Trial.

Purpose: We performed a pragmatic, cluster randomized controlled trial of a comprehensive practice-level, multistage practice transformation intervention aiming to increase behavioral health integration in primary care practices and improve patient outcomes. We examined associations between completion of intervention stages and patient outcomes across a heterogeneous national sample of primary care practices.

Methods: Forty-two primary care practices across the United States with colocated behavioral health and 2,945 patients with multiple chronic medical and behavioral health conditions completed surveys at baseline, midpoint, and 2-year follow-up.

Impact of Financial Incentives and Department Size on Scholarly Activity Output.

Purpose: Family medicine research is essential to improving population health. It has the unique ability to answer questions about health care outcomes and use those insights to impact communities. Increasing research capacity continues to be a challenge; however, recent literature has touted the success of incentivization in several academic medicine specialties.

EndoVIA for quantifying A-to-I editing and mapping the subcellular localization of edited transcripts.

Adenosine-to-inosine (A-to-I) editing, catalyzed by adenosine deaminases acting on RNA (ADARs), is a prevalent post-transcriptional modification that is vital for numerous biological functions. Given that this modification impacts global gene expression, RNA localization, and innate cellular immunity, dysregulation of A-to-I editing has unsurprisingly been linked to a variety of cancers and other diseases. However, our current understanding of the underpinning mechanisms that connect dysregulated A-to-I editing and disease processes remains limited.

A probe-based capture enrichment method for detection of A-to-I editing in low abundance transcripts.

Exactly two decades ago, the ability to use high-throughput RNA sequencing technology to identify sites of editing by ADARs was employed for the first time. Since that time, RNA sequencing has become a standard tool for researchers studying RNA biology and led to the discovery of RNA editing sites present in a multitude of organisms, across tissue types, and in disease. However, transcriptome-wide sequencing is not without limitations.

CellREADR: An ADAR-based RNA sensor-actuator device.

RNAs are central mediators of genetic information flow and gene regulation that underlie diverse cell types and cell states across species. Thus, methods that can sense and respond to RNA profiles in living cells will have broad applications in biology and medicine. CellREADR - Cell access through RNA sensing by Endogenous ADAR (adenosine deaminase acting on RNA), is a programmable RNA sensor-actuator technology that couples the detection of a cell-defining RNA to the translation of an effector protein to monitor and manipulate the cell.

En masse evaluation of RNA guides (EMERGe) for ADARs.

Adenosine Deaminases Acting on RNA (ADARs) convert adenosine to inosine in duplex RNA, and through the delivery of guide RNAs, can be directed to edit specific adenosine sites. As ADARs are endogenously expressed in humans, their editing capacities hold therapeutic potential and allow us to target disease-relevant sequences in RNA through the rationale design of guide RNAs. However, current design principles are not suitable for difficult-to-edit target sites, posing challenges to unlocking the full therapeutic potential of this approach.

Retinoids and retinoid-binding proteins: Unexpected roles in metabolic disease.

Alterations in tissue expression levels of both retinol-binding protein 2 (RBP2) and retinol-binding protein 4 (RBP4) have been associated with metabolic disease, specifically with obesity, glucose intolerance and hepatic steatosis. Our laboratories have shown that this involves novel pathways not previously considered as possible linkages between impaired retinoid metabolism and metabolic disease development. We have established both biochemically and structurally that RBP2 binds with very high affinity to very long-chain unsaturated 2-monoacylglycerols like the canonical endocannabinoid 2-arachidonoyl glycerol (2-AG) and other endocannabinoid-like substances.

The multifaceted roles of retinoids in eye development, vision, and retinal degenerative diseases.

Vitamin A (all-trans-retinol; at-Rol) and its derivatives, known as retinoids, have been adopted by vertebrates to serve as visual chromophores and signaling molecules, particularly in the eye/retina. Few tissues rely on retinoids as heavily as the retina, and the study of genetically modified mouse models with deficiencies in specific retinoid-metabolizing proteins has allowed us to gain insight into the unique or redundant roles of these proteins in at-Rol uptake and storage, or their downstream roles in retinal development and function. These processes occur during embryogenesis and continue throughout life.

Retinoic acid homeostasis and disease.

Retinoids, particularly all-trans-retinoic acid (ATRA), play crucial roles in various physiological processes, including development, immune response, and reproduction, by regulating gene transcription through nuclear receptors. This review explores the biosynthetic pathways, homeostatic mechanisms, and the significance of retinoid-binding proteins in maintaining ATRA levels. It highlights the intricate balance required for ATRA homeostasis, emphasizing that both excess and deficiency can lead to severe developmental and health consequences.