Targeted degradation of oncogenic KRASG12V triggers antitumor immunity in lung cancer models.

Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most frequently mutated oncogene in lung adenocarcinoma, with G12C and G12V being the most predominant forms. Recent breakthroughs in KRASG12C inhibitors have transformed the clinical management of patients with the G12C mutation and advanced our understanding of the function of this mutation. However, little is known about the targeted disruption of KRASG12V, partly due to a lack of specific inhibitors.

Simultaneous Bilateral T, T, and T Relaxation Mapping of Hip Joint With 3D-MRI Fingerprinting.

Background: Three-dimensional MR fingerprinting (3D-MRF) has been increasingly used to assess cartilage degeneration, particularly in the knee joint, by looking into multiple relaxation parameters. A comparable 3D-MRF approach can be adapted to assess cartilage degeneration for the hip joint, with changes to accommodate specific challenges of hip joint imaging.

Purpose: To demonstrate the feasibility and repeatability of 3D-MRF in the bilateral hip jointly we map proton density (PD), T, T, T, and ∆B in clinically feasible scan times.

Impact of Gender Affirming Vaginoplasty on Lower Urinary Tract Function: A Single-Center Prospective Cohort Study.

Introduction: With increased access to gender affirming care, the rate of vaginoplasties in the US has risen rapidly. Although some retrospective studies report high rates of lower urinary tract symptoms (LUTS) after gender affirming vaginoplasty, the type and severity of symptoms has not been well-described. The purpose of this study was to prospectively characterize postoperative changes in lower urinary tract function after robotic peritoneal flap vaginoplasty as measured by the American Urological Association Symptom Index questionnaire (AUASI), Urogenital Distress Inventory 6 (UDI6), and additional measures.

surtvep: An R package for estimating time-varying effects.

The surtvep package is an open-source software designed for estimating time-varying effects in survival analysis using the Cox non-proportional hazards model in R. With the rapid increase in large-scale time-to-event data from national disease registries, detecting and accounting for time-varying effects in medical studies have become crucial. Current software solutions often face computational issues such as memory limitations when handling large datasets.

Optimal Antithrombotic Regimen After Cryptogenic Stroke: A Systematic Review and Network Meta-Analysis.

Although several antithrombotic strategies have been investigated for the management of cryptogenic strokes, ie, ischemic strokes without known etiologies, an optimal antithrombotic strategy for cryptogenic strokes is unknown. We aim to assess oral antithrombotic agents' comparative efficacy and safety after cryptogenic stroke to identify an optimal treatment.A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Embase Cochrane, Scopus, and Web of Science until February 2024.

Disparities in mortality outcomes among older adults with communication disabilities using the National Health and Aging Trends Study.

Objective: To examine if a nationally representative population of older adults with communication disabilities (CDs) have a higher risk of mortality when compared to older adults without these disabilities, independent of sociodemographic, health, and other disability characteristics.

Design: Retrospective, cohort study. We conducted a survival analysis using multivariable Cox-proportional hazards regression, adjusting for sociodemographic, health, and other disability characteristics.

VGLL-fusions define a new class of intraparenchymal CNS schwannoma.

Background: Intracerebral schwannomas are rare tumors resembling their peripheral nerve sheath counterparts but localized in the CNS. They are not classified as a separate tumor type in the 2021 WHO classification. This study aimed to compile and characterize these rare neoplasms morphologically and molecularly.

Correlation-weighted Na magnetic resonance fingerprinting in the brain.

We developed a new sodium magnetic resonance fingerprinting (Na MRF) method for the simultaneous mapping of and sodium density with built-in (radiofrequency transmission inhomogeneities) and corrections (frequency offsets). We based our Na MRF implementation on a 3D FLORET sequence with 23 radiofrequency pulses. To capture the complex spin dynamics of the Na nucleus, the fingerprint dictionary was simulated using the irreducible spherical tensor operators formalism.

Psilocybin-assisted psychotherapy for methamphetamine dependence: a case report involving daily methamphetamine use.

Methamphetamine (MA) dependence leads to severe physical and psychological issues. Current treatments, including psychosocial therapies and residential rehabilitation, face limitations such as high relapse rates, cost, and accessibility issues. As a result, there is an urgent need for novel approaches to treat MA dependence that are effective, affordable, and accessible to patients.

In Search of Transcriptomic Correlates of Neuronal Firing-Rate Adaptation across Subtypes, Regions and Species: A Patch-seq Analysis.

Can the transcriptomic profile of a neuron predict its physiological properties? Using a Patch-seq dataset of the primary visual cortex, we addressed this question by focusing on spike rate adaptation (SRA), a well-known phenomenon that depends on small conductance calcium (Ca)-dependent potassium (SK) channels. We first show that in parvalbumin-expressing (PV) and somatostatin-expressing (SST) interneurons (INs), expression levels of genes encoding the ion channels underlying action potential generation are correlated with the half-width (HW) of spikes. Surprisingly, the SK encoding gene is not correlated with the degree of SRA (dAdap).

Phosphopeptide Neoantigens as Emerging Targets in Cancer Immunotherapy.

Protein post-translational modifications play a vital role in various cellular events essential for maintaining cellular physiology and homeostasis. In cancer cells, aberrant post-translational modifications such as glycosylation, acetylation, and phosphorylation on proteins can result in the generation of antigenic peptide variants presented in complex with MHC molecules. These modified peptides add to the class of tumorspecific antigens and offer promising avenues for targeted anti- cancer therapies.

Ethical Considerations Regarding Psychedelics for Clinical Pain Research.

Psychedelics, substances with a long history of cultural and medicinal use, are experiencing a resurgence in clinical research, particularly in psychiatry. Despite their classification as Schedule I drugs, recent studies suggest therapeutic potential, particularly in treating refractory depression. With chronic pain representing a major health concern and with few non-opioid treatment options available, psychedelics are being explored as alternative treatment modalities.

Racial and ethnic disparities in the burden of non-obese type 2 diabetes using different anthropometric measurements.

Aims: Compare racial/ethnic disparities in the prevalence of non-obese type 2 diabetes (T2D) and the proportion of non-obese individuals among T2D patients.

Methods: This cross-sectional study used ICD-9/10 codes to ascertain T2D. Participants were classified as non-obese by BMI (<25 kg/m for normal weight; <23 kg/m for Asian Americans), waist circumference (<102 cm for males, <88 cm for females), and waist-to-hip ratio (<0.

Examining the relationship between emotion regulation, sleep quality, and anxiety disorder diagnosis.

Anxiety disorders are highly comorbid with sleep disturbance and have also been associated with deficits in emotion regulation, the ability to control and express emotions. However, the extent to which specific dimensions of sleep disturbance and emotion regulation are associated with anxiety diagnosis is not well-explored. This study examined dimensions of emotion regulation and sleep disturbance that may predict greater likelihood of anxiety diagnosis using novel machine learning techniques.

Connectome-based symptom mapping and related gene expression in children with autism and/or attention-deficit/hyperactivity disorder.

Clinical, neuroimaging and genomics evidence have increasingly underscored a degree of overlap between autism and attention-deficit/hyperactivity disorder (ADHD). This study explores the specific contribution of their core symptoms to shared biology in a sample of N=166 verbal children (6-12 years) with rigorously-established primary diagnoses of either autism or ADHD (without autism). We investigated the associations between inter-individual differences in clinician-based dimensional measures of autism and ADHD symptoms and whole-brain low motion intrinsic functional connectivity (iFC).

Depression is Associated with Treatment Response Trajectories in Adults with Prolonged Grief Disorder: A Machine Learning Analysis.

Unlabelled: Although evidence-based treatments for Prolonged Grief Disorder (PGD) exist, pretreatment characteristics associated with differential improvement trajectories have not been identified. To identify clinical factors relevant to optimizing PGD treatment outcomes, we used unsupervised and supervised machine learning to study treatment effects from a double-blinded, placebo-controlled, randomized clinical trial. Participants were randomized into four treatment groups for 20 weeks: citalopram with grief-informed clinical management, citalopram with prolonged grief disorder therapy (PGDT), pill placebo with PGDT, or pill placebo with clinical management.

Change in Grip and Pinch Strength Over the Course of a Game in Professional Baseball Pitchers.

Background: Baseball pitching injuries can be related to fatigue. Changes in grip and pinch strength over the course of professional baseball games are unknown.

Hypothesis: Grip and pinch strength will decrease as the number of innings pitched increases; injured pitchers will have a lower grip strength than uninjured pitchers.

Optimized MR pulse sequence for high-resolution brain 3D-T1ρ mapping with weighted spin-lock acquisitions.

Purpose: To implement and evaluate the feasibility of brain spin-lattice relaxation in the rotating frame (T1ρ) mapping using a novel optimized pulse sequence that incorporates weighted spin-lock acquisitions, enabling high-resolution three-dimensional (3D) mapping.

Methods: The optimized variable flip-angle framework, previously proposed for knee T1ρ mapping, was enhanced by integrating weighted spin-lock acquisitions. This strategic combination significantly boosts signal-to-noise ratio (SNR) while reducing data acquisition time, facilitating high-resolution 3D-T1ρ mapping of the brain.

State-of-the-art narrative review: Mounier-Kuhn syndrome and tracheobronchomegaly.

Mounier-Kuhn syndrome (MKS) or tracheobronchomegaly is an uncommon disease of the central airways. It is characterized by pathological dilatation of the trachea and main bronchi and inevitably leads to recurrent respiratory infections, bronchiectasis, hospitalizations, and results in considerable morbidity and mortality. Despite numerous case reports, there is a shortage of evidence on clinical outcomes and limited data on interventions, thus presenting a significant gap in the literature.

Emerging role of genetics in kidney transplantation.

The advent of more affordable genomic analytical pipelines has facilitated the expansion of genetic studies in kidney transplantation. Advances in genetic sequencing have allowed for a greater understanding of the genetic basis of chronic kidney disease, which has helped to guide transplant management and address issues related to living donation in specific disease settings. Recent efforts have shown significant effects of genetic ancestry and donor APOL1 risk genotypes in determining worse allograft outcomes and increased donation risks.

External Validation of the Neiman Imaging Comorbidity Index in Medicare, Medicaid, and Private Payer Claims Data.

Objective: The Neiman Imaging Comorbidity Index (NICI) was developed and validated in a claims dataset encompassing >10 million privately insured beneficiaries, in which it outperformed the commonly used Charlson Comorbidity Index (CCI) in predicting advanced imaging use. This external validation assessed the broader generalizability of NICI for predicting receipt of advanced imaging in nationally representative populations, including patients insured by Medicare, Medicaid, and private payers.

Methods: All 2018 to 2019 patient-level claims from the CMS Medicare 5% Research Identifiable File, CMS Medicaid 100% Research Identifiable File, and private insurance (commercial and Medicare Advantage) claims from Inovalon Insights, LLC, were included.

Factors associated with placebo response rate in randomized controlled trials of antiseizure medications for focal epilepsy.

Objective: Randomized controlled trials (RCTs) are necessary to evaluate the efficacy of novel treatments for epilepsy. However, there have been concerning increases in the placebo responder rate over time. To understand these trends, we evaluated features associated with increased placebo responder rate.