State-Level Medicaid Reimbursement and Imaging Utilization by Medicaid and Children's Health Insurance Program Patients.

Purpose: To determine if relative Medicaid-to-Medicare reimbursement rates are associated with patient imaging utilization.

Methods: This cross-sectional study estimated the association of diagnostic imaging utilization with the state-level Medicaid-to-Medicare reimbursement ratio (MMRR) of professional payments. State-specific reimbursement ratios were computed for each imaging modality.

High-throughput discovery and deep characterization of cyclin-CDK docking motifs.

Cyclin-CDKs are master regulators of cell division. In addition to directly activating the CDK, the cyclin subunit regulates CDK specificity by binding short peptide "docking" motifs in CDK substrates. Here, we measure the relative binding strength of ~100,000 peptides to 11 human cyclins from five cyclin families (D, E, A, B and F).

A quantitative intracellular peptide binding assay reveals recognition determinants and context dependence of short linear motifs.

Transient protein-protein interactions play key roles in controlling dynamic cellular responses. Many examples involve globular protein domains that bind to peptide sequences known as Short Linear Motifs (SLiMs), which are enriched in intrinsically disordered regions of proteins. Here we describe a novel functional assay for measuring SLiM binding, called Systematic Intracellular Motif Binding Analysis (SIMBA).

CompariPSSM: a PSSM-PSSM comparison tool for motif-binding determinant analysis.

Motivation: Short linear motifs (SLiMs) are compact functional modules that mediate low-affinity protein-protein interactions. SLiMs direct the function of many dynamic signalling and regulatory complexes playing a central role in most biological processes of the cell. Motif-binding determinants describe the contribution of each residue in a motif-containing peptide to the affinity and specificity of binding to the motif-binding partner.

Catalytic and noncatalytic functions of DNA polymerase κ in translesion DNA synthesis.

Translesion DNA synthesis (TLS) is a cellular process that enables the bypass of DNA lesions encountered during DNA replication and is emerging as a primary target of chemotherapy. Among vertebrate DNA polymerases, polymerase κ (Polκ) has the distinctive ability to bypass minor groove DNA adducts in vitro. However, Polκ is also required for cells to overcome major groove DNA adducts but the basis of this requirement is unclear.

GaitKeeper: An AI-Enabled Mobile Technology to Standardize and Measure Gait Speed.

Gait speed is increasingly recognized as an important health indicator. However, gait analysis in clinical settings often encounters inconsistencies due to methodological variability and resource constraints. To address these challenges, GaitKeeper uses artificial intelligence (AI) and augmented reality (AR) to standardize gait speed assessments.

FaSTPACE: a fast and scalable tool for peptide alignment and consensus extraction.

Several novel high-throughput experimental techniques have been developed in recent years that generate large datasets of putative biologically functional peptides. However, many of the computational tools required to process these datasets have not yet been created. In this study, we introduce FaSTPACE, a fast and scalable computational tool to rapidly align short peptides and extract enriched specificity determinants.

Proteome-scale characterisation of motif-based interactome rewiring by disease mutations.

Whole genome and exome sequencing are reporting on hundreds of thousands of missense mutations. Taking a pan-disease approach, we explored how mutations in intrinsically disordered regions (IDRs) break or generate protein interactions mediated by short linear motifs. We created a peptide-phage display library tiling ~57,000 peptides from the IDRs of the human proteome overlapping 12,301 single nucleotide variants associated with diverse phenotypes including cancer, metabolic diseases and neurological diseases.

A Systematic Review of Falls Risk of Frail Patients with Dementia in Hospital: Progress, Challenges, and Recommendations.

This review article assesses the effectiveness and limitations of strategies to reduce falls among hospitalized older adults with frailty and dementia. It explores the efficacy of existing fall prevention strategies for a cohort that is acutely susceptible to falls and fall-related consequences. A systematic literature search was conducted across MEDLINE, Embase, CINAHL, and PsycINFO, employing Medical Subject Headings (MeSH) to identify studies on fall prevention strategies in hospitalized older adults with both dementia and frailty published from 2013 to 2023.

Lessons from the COVID-19 pandemic in paediatric post-discharge care.

The COVID-19 pandemic dictated rapid reform in outpatient paediatric services. To reduce ward footfall and its associated infection risk, a trainee-led outpatient clinic was established with the aim to provide children with continuity of care following discharge from hospital. The service was created as a safe alternative to the long-standing practice of ward attenders while reducing mounting pressures on appointments at consultant-led clinics.

Protocol for the Tallaght University Hospital Institute for Memory and Cognition-Biobank for Research in Ageing and Neurodegeneration.

Introduction: Alzheimer's disease and other dementias affect >50 million individuals globally and are characterised by broad clinical and biological heterogeneity. Cohort and biobank studies have played a critical role in advancing the understanding of disease pathophysiology and in identifying novel diagnostic and treatment approaches. However, further discovery and validation cohorts are required to clarify the real-world utility of new biomarkers, facilitate research into the development of novel therapies and advance our understanding of the clinical heterogeneity and pathobiology of neurodegenerative diseases.

ELM-the Eukaryotic Linear Motif resource-2024 update.

Short Linear Motifs (SLiMs) are the smallest structural and functional components of modular eukaryotic proteins. They are also the most abundant, especially when considering post-translational modifications. As well as being found throughout the cell as part of regulatory processes, SLiMs are extensively mimicked by intracellular pathogens.

Phosphatase specificity principles uncovered by MRBLE:Dephos and global substrate identification.

Phosphoprotein phosphatases (PPPs) regulate major signaling pathways, but the determinants of phosphatase specificity are poorly understood. This is because methods to investigate this at scale are lacking. Here, we develop a novel in vitro assay, MRBLE:Dephos, that allows multiplexing of dephosphorylation reactions to determine phosphatase preferences.

Identification of motif-based interactions between SARS-CoV-2 protein domains and human peptide ligands pinpoint antiviral targets.

The virus life cycle depends on host-virus protein-protein interactions, which often involve a disordered protein region binding to a folded protein domain. Here, we used proteomic peptide phage display (ProP-PD) to identify peptides from the intrinsically disordered regions of the human proteome that bind to folded protein domains encoded by the SARS-CoV-2 genome. Eleven folded domains of SARS-CoV-2 proteins were found to bind 281 peptides from human proteins, and affinities of 31 interactions involving eight SARS-CoV-2 protein domains were determined (K ∼ 7-300 μM).

Minimum information guidelines for experiments structurally characterizing intrinsically disordered protein regions.

An unambiguous description of an experiment, and the subsequent biological observation, is vital for accurate data interpretation. Minimum information guidelines define the fundamental complement of data that can support an unambiguous conclusion based on experimental observations. We present the Minimum Information About Disorder Experiments (MIADE) guidelines to define the parameters required for the wider scientific community to understand the findings of an experiment studying the structural properties of intrinsically disordered regions (IDRs).

xProtCAS: A Toolkit for Extracting Conserved Accessible Surfaces from Protein Structures.

The identification of protein surfaces required for interaction with other biomolecules broadens our understanding of protein function, their regulation by post-translational modification, and the deleterious effect of disease mutations. Protein interaction interfaces are often identifiable as patches of conserved residues on a protein's surface. However, finding conserved accessible surfaces on folded regions requires an understanding of the protein structure to discriminate between functional and structural constraints on residue conservation.

Large-scale phosphomimetic screening identifies phospho-modulated motif-based protein interactions.

Phosphorylation is a ubiquitous post-translation modification that regulates protein function by promoting, inhibiting or modulating protein-protein interactions. Hundreds of thousands of phosphosites have been identified but the vast majority have not been functionally characterised and it remains a challenge to decipher phosphorylation events modulating interactions. We generated a phosphomimetic proteomic peptide-phage display library to screen for phosphosites that modulate short linear motif-based interactions.

The next wave of interactomics: Mapping the SLiM-based interactions of the intrinsically disordered proteome.

Short linear motifs (SLiMs) are a unique and ubiquitous class of protein interaction modules that perform key regulatory functions and drive dynamic complex formation. For decades, interactions mediated by SLiMs have accumulated through detailed low-throughput experiments. Recent methodological advances have opened this previously underexplored area of the human interactome to high-throughput protein-protein interaction discovery.

Driving communication forward: improving communication for palliative care patients around driving and opioids - a quality improvement report.

Introduction: The number of people requiring palliative care is increasing with an ageing comorbid population. Pain is a prevalent symptom for palliative care patients and is often managed with opioids. Opioids reduce reaction time and can cause drowsiness and visual disturbance.