Effect of providing at-home opioid disposal kits at discharge after an orthopaedic surgery.

Prescription opioids after surgery may pose a risk if left unused. However, prescribers rely on their best judgement in determining how much their patients need, often resulting in over-prescription of these medications. Opioid disposal is a strategy to reduce the risk of persistent use or misuse of opioids.

Explainable Machine Learning to Predict Treatment Response in Advanced Non-Small Cell Lung Cancer.

Purpose: Immune checkpoint inhibitors (ICIs) have demonstrated promise in the treatment of various cancers. Single-drug ICI therapy (immuno-oncology [IO] monotherapy) that targets PD-L1 is the standard of care in patients with advanced non-small cell lung cancer (NSCLC) with PD-L1 expression ≥50%. We sought to find out if a machine learning (ML) algorithm can perform better as a predictive biomarker than PD-L1 alone.

Mitochondrial DNA lineages determine tumor progression through T cell reactive oxygen signaling.

Mitochondrial DNA (mtDNA) is highly polymorphic, and host mtDNA variation has been associated with altered cancer severity. To determine the basis of this mtDNA-cancer association, we analyzed conplastic mice with the C57BL/6J (B6) nucleus but two naturally occurring mtDNA lineages, and , where mitochondria generate more oxidative phosphorylation (OXPHOS)-derived reactive oxygen species (mROS). In a cardiac transplant model, Foxp3+ T regulatory (Treg) cells supported long-term allograft survival, whereas Treg cells failed to suppress host T effector (Teff) cells, leading to acute rejection.

Identification of immune suppressor candidates utilizing comparative transcriptional profiling in histiocytic sarcoma.

Histiocytic sarcoma (HS) is a rare yet lethal malignancy with no established standard of care therapies. A lack of pre-clinical models limits our understanding of HS pathogenesis and identification of therapeutic targets. Canine HS shares multiple clinical and genetic similarities with human HS, supporting its use as a unique translational model.

The hematopoietic niche assembles through collective cell migration controlled by neighbor tissues and Slit-Robo signaling.

Niches are often found in specific positions in tissues relative to the stem cells they support. Consistency of niche position suggests that placement is important for niche function. However, the complexity of most niches has precluded a thorough understanding of how their proper placement is established.

Enhanced Accumulation and Penetration of Magnetic Nanoclusters in Tumors Using an 8-Magnet Halbach Array Leads to Improved Cancer Treatment.

Nanoparticles have gained attention as drug delivery vehicles for cancer treatment, but often struggle with poor tumor accumulation and penetration. Single external magnets can enhance magnetic nanoparticle delivery but are limited to superficial tumors due to the rapid decline in the magnetic field strength with distance. We previously showed that a 2-magnet device could extend targeting to greater tissue depths.

Phenotype Spectrum of TRPM3-Associated Disorders.

Objective: Monoallelic variants in the transient receptor potential melastatin-related type 3 gene (TRPM3) have been associated with neurodevelopmental manifestations, but knowledge on the clinical manifestations and treatment options is limited. We characterized the clinical spectrum, highlighting particularly the epilepsy phenotype, and the effect of treatments.

Methods: We analyzed retrospectively the phenotypes and genotypes of 43 individuals with TRPM3 variants, acquired from GeneMatcher and collaborations (n = 21), and through a systematic literature search (n = 22).

Standardization of Genomic Nomenclature across a Diverse Ecosystem of Stakeholders: Evolution and Challenges.

Background: Genetic testing has traditionally been divided into molecular genetics and cytogenetics, originally driven by the use of different assays and their associated limitations. Cytogenetic technologies such as karyotyping, fluorescent in situ hybridization or chromosomal microarrays are used to detect large "megabase level" copy number variants and other structural variants such as inversions or translocations. In contrast, molecular methodologies are heavily biased toward subgenic "small variants" such as single nucleotide variants, insertions/deletions, and targeted detection of intragenic, exon level deletions or duplications.

Racial, Socioeconomic, and Geographic Disparities in Preamputation Vascular Care for Patients With Chronic Limb-Threatening Ischemia.

Background: Black patients, those with low socioeconomic status (SES), and those living in rural areas have elevated rates of major lower extremity amputation, which may be related to a lack of subspecialty chronic limb-threatening ischemia care. We evaluated the association between race, rurality, SES, and preamputation vascular care.

Methods: Among patients aged 66 to 86 years with fee-for-service Medicare who underwent major lower extremity amputation for chronic limb-threatening ischemia from July 2010 to December 2019, we compared the proportion who received vascular care in the 12 months before amputation by race (Black versus White), rurality, and SES (dual eligibility for Medicaid versus no dual eligibility) using multivariable logistic regression adjusting for clinical and demographic covariates.

Correlates of multidimensional sleep in premenopausal women: The BioCycle study.

Purpose: To identify sleep dimensions (characteristics) that co-occur in premenopausal women. The second aim was to examine associations between multiple dimensions of sleep and a set of demographic, lifestyle, and health correlates. The overarching goal was to uncover patterns of poor-sleep correlates that might inform interventions to improve sleep health of women in this age group.

Factors associated with cognitive flexibility in people with opioid-use disorder: a pilot study.

The ability to adapt to changing circumstances has strong survival value. Individuals with substance use disorders tend to get "stuck" over-responding to drug-reward signals and pursuing drugs despite negative consequences. A lack of flexibility may be tied to impairments in neurocognition, including learning, memory, and executive function.

Application of the revised criteria for diagnosis and staging of Alzheimer's disease: Drug development and clinical practice.

Unlabelled: The newly proposed revised criteria for diagnosis and staging of Alzheimer's disease (AD) by the Alzheimer's Association (AA) Workgroup represent a significant milestone in the field. These criteria offer objective measures for diagnosing and staging biological AD, bridging the gap between research and clinical care. Although implementation feasibility may vary across regions and settings, improving the availability and accuracy of biomarkers, especially plasma biomarkers, is expected to enhance the applicability of these criteria in clinical practice.

Sepsis-induced cardiogenic shock: controversies and evidence gaps in diagnosis and management.

Sepsis often leads to vasoplegia and a hyperdynamic cardiac state, with treatment focused on restoring vascular tone. However, sepsis can also cause reversible myocardial dysfunction, particularly in the elderly with pre-existing heart conditions. The Surviving Sepsis Campaign Guidelines recommend using dobutamine with norepinephrine or epinephrine alone for patients with septic shock with cardiac dysfunction and persistent hypoperfusion despite adequate fluid resuscitation and stable blood pressure.

The impact of common and rare genetic variants on bradyarrhythmia development.

To broaden our understanding of bradyarrhythmias and conduction disease, we performed common variant genome-wide association analyses in up to 1.3 million individuals and rare variant burden testing in 460,000 individuals for sinus node dysfunction (SND), distal conduction disease (DCD) and pacemaker (PM) implantation. We identified 13, 31 and 21 common variant loci for SND, DCD and PM, respectively.

Nuclear speckles regulate functional programs in cancer.

Nuclear speckles are dynamic nuclear bodies characterized by high concentrations of factors involved in RNA production. Although the contents of speckles suggest multifaceted roles in gene regulation, their biological functions are unclear. Here we investigate speckle variation in human cancer, finding two main signatures.

Two-hit mouse model of heart failure with preserved ejection fraction combining diet-induced obesity and renin-mediated hypertension.

Heart failure with preserved ejection fraction (HFpEF) is increasingly common but its pathogenesis is poorly understood. The ability to assess genetic and pharmacologic interventions is hampered by the lack of robust preclinical mouse models of HFpEF. We developed a novel "two-hit" model, which combines obesity and insulin resistance with chronic pressure overload to recapitulate clinical features of HFpEF.

Fortilin binds CTNNA3 and protects it against phosphorylation, ubiquitination, and proteasomal degradation to guard cells against apoptosis.

Fortilin, a 172-amino acid polypeptide, is a multifunctional protein that interacts with various protein molecules to regulate their functions. Although fortilin has been shown to interact with cytoskeleton proteins such as tubulin and actin, its interactions with the components of adherens junctions remained unknown. Using co-immunoprecipitation western blot analyses, the proximity ligation assay, microscale thermophoresis, and biolayer interferometry, we here show that fortilin specifically interacts with CTNNA3 (α-T-catenin), but not with CTNNA1, CTNNA2, or CTNNB.

The heterogeneity of neutrophils in cancer and its implication for therapeutic targeting.

Neutrophils have a pivotal role in safeguarding the host against pathogens and facilitating tissue remodeling. They possess a large array of tools essential for executing these functions. Neutrophils have a critical role in cancer, where they are largely associated with negative clinical outcome and resistance to therapy.

Dopaminergic signaling to ventral striatum neurons initiates sniffing behavior.

Sniffing is a motivated behavior displayed by nearly all terrestrial vertebrates. While sniffing is associated with acquiring and processing odors, sniffing is also intertwined with affective and motivated states. The systems which influence the display of sniffing are unclear.

ATLAS-seq: a microfluidic single-cell TCR screen for antigen-reactive TCRs.

Discovering antigen-reactive T cell receptors (TCRs) is central to developing effective engineered T cell immunotherapies. However, the conventional technologies for isolating antigen-reactive TCRs (i.e.