Ultrasound Evaluation of Upper Limb Sublesional Muscle Morphology in Cervical Spinal Cord Injury.

Introduction/aims: Upper limb paralysis is arguably the most limiting consequence of cervical spinal cord injury (cSCI). There is limited knowledge regarding the early structural changes of muscles implicated in grasp/pinch function and upper extremity nerve transfer surgeries. We evaluated: (1) muscle size and echo intensity (EI) in subacute cSCI (2-6 months) and (2) the influence of lower motor neuron (LMN) damage on these ultrasound parameters.

Multiplex digital PCR enables sensitive detection of resistance to BTK inhibitors.

The advent of BTK inhibitors has been transformative in the management of patients with chronic lymphocytic leukemia or other B-cell lymphoproliferative disorders. However, emergence of BTK or PLCG2 mutations lead to resistance to these compounds and are now a growing concern in clinical practice. Assessing BTK mutations is now becoming a priority to guide the therapeutic decision at further relapse.

Grapevine cell response to carbon deficiency requires transcriptome and methylome reprogramming.

Sugar limitation has dramatic consequences on plant cells, which include cell metabolism and transcriptional reprogramming, and the recycling of cellular components to maintain fundamental cell functions. There is however no description of the contribution of epigenetic regulations to the adaptation of plant cells to limited carbon availability. We investigated this question using nonphotosynthetic grapevine cells (, cv Cabernet Sauvignon) cultured with contrasted glucose concentrations.

Predilection for Perplexion: Preoperative microstructural damage is linked to postoperative delirium.

Postoperative delirium is the most common postsurgical complication in older adults and is associated with an increased risk of long-term cognitive decline and Alzheimer's disease (AD) and related dementias (ADRD). However, the neurological basis of this increased risk- whether postoperative delirium unmasks latent preoperative pathology or leads to AD-relevant pathology after perioperative brain injury-remains unclear. Recent advancements in neuroimaging techniques now enable the detection of subtle brain features or damage that may underlie clinical symptoms.

A randomised double-blind, placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment-resistant bipolar depression (the PAX-BD study).

Background: Options for 'treatment-resistant bipolar depression' (TRBD) are limited. Two small, short-term, trials of pramipexole suggest it might be an option.

Aims: To evaluate the clinical effectiveness and safety of pramipexole in the management of TRBD.

Safety and Efficacy of Thrombectomy for Distal Medium Vessel Occlusions of the Middle Cerebral Artery.

Purpose: Mechanical thrombectomy (MT) for distal medium vessel occlusions (DMVOs) in the middle cerebral artery (MCA) is less established than for large vessel occlusions. This study evaluates the safety and efficacy of MT in DMVOs, comparing it with M1-segment occlusions.

Materials And Methods: This retrospective study analyzed 218 patients who underwent MT for isolated M1 (n=123) or distal M2+M3 (n=35) occlusions between January 2020 and August 2023.

Prognostic value of manual versus automatic methods for assessing extents of resection and residual tumor volume in glioblastoma.

Objective: The extent of resection (EOR) and postoperative residual tumor (RT) volume are prognostic factors in glioblastoma. Calculations of EOR and RT rely on accurate tumor segmentations. Raidionics is an open-access software that enables automatic segmentation of preoperative and early postoperative glioblastoma using pretrained deep learning models.

Expression of PAX6 and Keratocyte-Characteristic Markers in Human Limbal Stromal Cells of Congenital Aniridia and Healthy Subjects, .

Purpose: Our aim was to examine the expression of PAX6 and keratocyte-specific markers in human limbal stromal cells (LSCs) in congenital aniridia (AN) and in healthy corneas, .

Methods: Primary human LSCs were extracted from individuals with aniridia (AN-LSCs) ( = 8) and from healthy corneas (LSCs) ( = 8). The cells were cultured in either normal-glucose serum-containing cell culture medium (NGSC-medium) or low-glucose serum-free cell culture medium (LGSF-medium).

CDK4 inactivation inhibits apoptosis via mitochondria-ER contact remodeling in triple-negative breast cancer.

The energetic demands of proliferating cells during tumorigenesis require close coordination between the cell cycle and metabolism. While CDK4 is known for its role in cell proliferation, its metabolic function in cancer, particularly in triple-negative breast cancer (TNBC), remains unclear. Our study, using genetic and pharmacological approaches, reveals that CDK4 inactivation only modestly impacts TNBC cell proliferation and tumor formation.

Genetic Ancestry-Based Differences in Biomarker-Based Eligibility for Precision Oncology Therapies.

Importance: Although differences in the prevalence of key cancer-specific somatic mutations as a function of genetic ancestry among patients with cancer has been well-established, few studies have addressed the practical clinical implications of these differences for the growing number of biomarker-driven treatments.

Objective: To determine if the approval of precision oncology therapies has benefited patients with cancer from various ancestral backgrounds equally over time.

Design, Setting, And Participants: A retrospective analysis of samples from patients with solid cancers who underwent clinical sequencing using the integrated mutation profiling of actionable cancer targets (MSK-IMPACT) assay between January 2014 and December 2022 was carried out.

Advancing Delirium Treatment Trials in Older Adults: Recommendations for Future Trials From the Network for Investigation of Delirium: Unifying Scientists (NIDUS).

Objectives: To summarize the delirium treatment trial literature, identify the unique challenges in delirium treatment trials, and formulate recommendations to address each in older adults.

Design: A 39-member interprofessional and international expert working group of clinicians (physicians, nurses, and pharmacists) and nonclinicians (biostatisticians, epidemiologists, and trial methodologists) was convened. Four expert panels were assembled to explore key subtopics (pharmacological/nonpharmacologic treatment, methodological challenges, and novel research designs).

Longitudinal Study of SARS-CoV-2 Vaccinations and Infections in Patients with Gastrointestinal Cancer: Stabilizing Immune Responses and Neutralizing Emerging Variants with Variant-Adapted Antigen Exposures.

This longitudinal study examined how active gastrointestinal (GI) cancer types affect immune responses to SARS-CoV-2, focusing on the ability to neutralize the Omicron variants. Patients with GI cancer ( = 168) were categorized into those with hepatocellular carcinoma, hepatic metastatic GI cancer, non-hepatic metastatic GI cancer, and two control groups of patients with and without underlying liver diseases. Humoral and cellular immune responses were evaluated before and after Omicron antigen exposures.

Preparticipation screening in young female elite ice hockey players.

Objectives: The occurrence of sudden cardiac death (SCD) in competitive athletes has led to a discussion about appropriate preparticipation screening models. The role of an electrocardiogram (ECG) in routine testing remains controversial in current guidelines. Furthermore, data on cardiac findings and the prognostic utility of screening strategies in young female elite ice hockey is scarce.

A phase I study of convection-enhanced delivery (CED) of liposomal-irinotecan using real-time magnetic resonance imaging in patients with recurrent high-grade glioma.

Background: Irinotecan demonstrates anti-tumor efficacy in preclinical glioma models but clinical results are modest due to drug delivery limitations. Convection enhanced delivery (CED) improves drug delivery by increasing intratumoral drug concentration. Real-time magnetic resonance imaging of infusate delivery during CED may optimize tumor coverage.

Editorial: Climate change is a children's health hazard.

As temperatures defy heat records, it is difficult to ignore the implications of climate change for public health, including impacts on population health more specifically. In short, climate change is happening now and presents an immediate hazard to human health on a global scale. Age-related health effects are an inalienable truth; physiology is relatively universal, and so are the ways in which our bodies respond to different types and levels of exposures to environmental stressors at different lifestages.

Clinicogenomic landscape of pancreatic adenocarcinoma identifies KRAS mutant dosage as prognostic of overall survival.

Nearly all pancreatic adenocarcinomas (PDAC) are genomically characterized by KRAS exon 2 mutations. Most patients with PDAC present with advanced disease and are treated with cytotoxic therapy. Genomic biomarkers prognostic of disease outcomes have been challenging to identify.

Maximizing the clinical utility and performance of cytology samples for comprehensive genetic profiling.

Comprehensive molecular profiling by next-generation sequencing has revolutionized tumor classification and biomarker evaluation. However, routine implementation is challenged by the scant nature of diagnostic material obtained through minimally invasive procedures. Here, we describe our long-term experience in profiling cytology samples with an in-depth assessment of the performance, quality metrics, biomarker identification capabilities, and potential pitfalls.

A deep multiple instance learning framework improves microsatellite instability detection from tumor next generation sequencing.

Microsatellite instability (MSI) is a critical phenotype of cancer genomes and an FDA-recognized biomarker that can guide treatment with immune checkpoint inhibitors. Previous work has demonstrated that next-generation sequencing data can be used to identify samples with MSI-high phenotype. However, low tumor purity, as frequently observed in routine clinical samples, poses a challenge to the sensitivity of existing algorithms.

Deciphering metabolic shifts in Gaucher disease type 1: a multi-omics study.

Gaucher disease (GD), an autosomal recessive lysosomal disorder, primarily affects the lysosomal enzyme β-glucocerebrosidase (GCase), leading to glucosylceramide accumulation in lysosomes. GD presents a wide spectrum of clinical manifestations. This study deploys immune-based proteomics and mass spectrometry-based metabolomics technologies to comprehensively investigate the biochemical landscape in 43 deeply phenotyped type 1 GD patients compared to 59 controls.

Lysosphingolipid Quantitation in Plasma and Dried-Blood Spots Using Targeted High-Resolution Mass Spectrometry.

Background: Sphingolipidoses are rare inherited metabolic diseases belonging to lysosomal diseases. Early and accurate diagnosis is crucial for effective management and treatment. In this study, we aimed to develop a robust method to accelerate the diagnosis of these sphingolipidoses using dried blood spots and plasma.

Molecular Testing for the World Health Organization Classification of Central Nervous System Tumors: A Review.

Importance: Molecular techniques, including next-generation sequencing, genomic copy number profiling, fusion transcript detection, and genomic DNA methylation arrays, are now indispensable tools for the workup of central nervous system (CNS) tumors. Yet there remains a great deal of heterogeneity in using such biomarker testing across institutions and hospital systems. This is in large part because there is a persistent reluctance among third-party payers to cover molecular testing.

Systematic assessment of COVID-19 host genetics using whole genome sequencing data.

Courses of SARS-CoV-2 infections are highly variable, ranging from asymptomatic to lethal COVID-19. Though research has shown that host genetic factors contribute to this variability, cohort-based joint analyses of variants from the entire allelic spectrum in individuals with confirmed SARS-CoV-2 infections are still lacking. Here, we present the results of whole genome sequencing in 1,220 mainly vaccine-naïve individuals with confirmed SARS-CoV-2 infection, including 827 hospitalized COVID-19 cases.

Effects of a Digital Intervention to Improve DASH and Blood Pressure Among US Adults.

Background: Dietary Approaches to Stop Hypertension (DASH) is a recommended first-line treatment for adults with hypertension, yet adherence to DASH is low. To evaluate the efficacy of a digital health intervention (DHI), compared with attention control, on changes in DASH adherence and blood pressure among adults with hypertension.

Methods: Nourish was a 12-month, parallel, 2-arm, randomized controlled trial of a virtually delivered DHI.

Vagus nerve stimulation in treatment-resistant depression: A one-year, randomized, sham-controlled trial.

Background: Few treatments are available for individuals with marked treatment-resistant depression (TRD).

Objective: Evaluate the safety and effectiveness of FDA-approved adjunctive vagus nerve stimulation (VNS) in patients with marked TRD.

Methods: This 12-month, multicenter, double-blind, sham-controlled trial included 493 adults with marked treatment-resistant major depression who were randomized to active or no-stimulation sham VNS for 12 months.