Preexisting Skin-Resident CD8 and γδ T-cell Circuits Mediate Immune Response in Merkel Cell Carcinoma and Predict Immunotherapy Efficacy.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with a ∼50% response rate to immune checkpoint blockade (ICB) therapy. To identify predictive biomarkers, we integrated bulk and single-cell RNA sequencing (RNA-seq) with spatial transcriptomics from a cohort of 186 samples from 116 patients, including bulk RNA-seq from 14 matched pairs pre- and post-ICB. In nonresponders, tumors show evidence of increased tumor proliferation, neuronal stem cell markers, and IL1.

Dextrose Prolotherapy for the Treatment of Chronic Shoulder Pain in Patients With Joint Hypermobility: A Case Series.

Hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are common causes of chronic musculoskeletal pain. Current practices rely on analgesics, physical therapy, bracing, and assistive devices. Dextrose prolotherapy (DPT) is a regenerative injection modality used to treat chronic painful musculoskeletal conditions through stimulation of tissue proliferation.

Implementation of Digital Pathology and Artificial Intelligence in Routine Pathology Practice.

The advent of affordable technology has significantly influenced the practice of digital pathology, leading to its growing adoption within the pathology community. This review article aimed to outline the latest developments in digital pathology, the cutting-edge advancements in artificial intelligence (AI) applications within this field, and the pertinent United States regulatory frameworks. The content is based on a thorough analysis of original research articles and official United States Federal guidelines.

Engineered Proteins and Materials Utilizing Residue-Specific Noncanonical Amino Acid Incorporation.

The incorporation of noncanonical amino acids into proteins and protein-based materials has significantly expanded the repertoire of available protein structures and chemistries. Through residue-specific incorporation, protein properties can be globally modified, resulting in the creation of novel proteins and materials with diverse and tailored characteristics. In this review, we highlight recent advancements in residue-specific incorporation techniques as well as the applications of the engineered proteins and materials.

Provider and administrator attitudes and experiences with implementing telebuprenorphine during the COVID-19 pandemic: a mixed-methods survey.

Introduction: This mixed-methods study assessed buprenorphine provider and administrator perceptions and experiences in offering telebuprenorphine during the COVID-19 pandemic.

Methods: Semi-structured interviews were conducted between June 2021 and September 2021 among telebuprenorphine providers and administrators (N=16) and assessed for program design and implementation strategies, clinical workflow, patient-level factors influencing program entry and retention, and challenges and solutions to improving clinical care.

Results: Clinician (n=15) and administrator (n=1) participants identified changes to clinical workflow, including increased administrative tasks to confirm patient receipt of prescribed medications, completion of referrals to community- or specialty treatment, and locating available pharmacies and laboratory services.

Development and Characterization of 50 nanometer diameter Genetically Encoded Multimeric Nanoparticles.

The mechanisms that regulate the physical properties of the cell interior remain poorly understood, especially at the mesoscale (10nm-100nm). Changes in these properties have been suggested to be crucial for both normal physiology and disease. Many crucial macromolecules and molecular assemblies such as ribosomes, RNA polymerase, and biomolecular condensates span the mesoscale size range.

Composite Pulmonary Embolism Shock Score and Risk of Adverse Outcomes in Patients With Pulmonary Embolism.

Background: In hemodynamically stable patients with acute pulmonary embolism (PE), the Composite Pulmonary Embolism Shock (CPES) score predicts normotensive shock. However, it is unknown if CPES predicts adverse clinical outcomes. The objective of this study was to determine whether the CPES score predicts in-hospital mortality, resuscitated cardiac arrest, or hemodynamic deterioration.

Complex intracranial aneurysms: a DELPHI study to define associated characteristics.

Purpose: Intracranial aneurysms present significant health risks, as their rupture leads to subarachnoid haemorrhage, which in turn has high morbidity and mortality rates. There are several elements affecting the complexity of an intracranial aneurysm. However, criteria for defining a complex intracranial aneurysm (CIA) in open surgery and endovascular treatment could differ, and actually there is no consensus on the definition of a "complex" aneurysm.

Trauma care in crisis: war trauma and mental health funding.

Israel is currently under a state of continued unrest and state of war. There has been an influx of financial aid to treat the mental health fallout both from within Israel and abroad. Despite increased research into resilience, treatment and wide-scale interventions, there is a concern that this is not significantly influencing mental health aid allocation.

Impaired immune responses in the airways are associated with poor outcome in critically ill COVID-19 patients.

Introduction: Mounting evidence indicates that an individual's humoral adaptive immune response plays a critical role in the setting of SARS-CoV-2 infection, and that the efficiency of the response correlates with disease severity. The relationship between the adaptive immune dynamics in the lower airways with those in the systemic circulation, and how these relate to an individual's clinical response to SARS-CoV-2 infection, are less understood and are the focus of this study.

Material And Methods: We investigated the adaptive immune response to SARS-CoV-2 in paired samples from the lower airways and blood from 27 critically ill patients during the first wave of the pandemic (median time from symptom onset to intubation 11 days).

CD73 Is an Immunometabolic Biomarker of Poor Prognosis in Patients With Primary Cutaneous Squamous Cell Carcinoma and Hematologic Malignancy.

Background: Impaired immunity may drive the increased incidence and aggression of cutaneous squamous cell carcinoma (cSCC) in patients with hematologic malignancy; however, precise mechanisms and prognostic biomarkers remain undefined. CD73 maintains elevated immunosuppressive adenosine levels and is associated with poor prognosis in several tumor microenvironments.

Objective: Identify poor outcome biomarkers in patients with cSCC and hematologic malignancy.

Clinical prediction for surgical versus nonsurgical interventions in patients with vertebral osteomyelitis and discitis.

Background: Vertebral osteomyelitis and discitis (VOD), an infection of intervertebral discs, often requires spine surgical intervention and timely management to prevent adverse outcomes. Our study aims to develop a machine learning (ML) model to predict the indication for surgical intervention (during the same hospital stay) versus nonsurgical management in patients with VOD.

Methods: This retrospective study included adult patients (≥18 years) with VOD (ICD-10 diagnosis codes M46.

The method in the madness: Transcriptional control from stochastic action at the single-molecule scale.

Cell states result from the ordered activation of gene expression by transcription factors. Transcription factors face opposing design constraints: they need to be dynamic to trigger rapid cell state transitions, but also stable enough to maintain terminal cell identities indefinitely. Recent progress in live-cell single-molecule microscopy has helped define the biophysical principles underlying this paradox.

Nanopore guided annotation of transcriptome architectures.

Unlabelled: Nanopore direct RNA sequencing (DRS) enables the capture and full-length sequencing of native RNAs, without recoding or amplification bias. Resulting data sets may be interrogated to define the identity and location of chemically modified ribonucleotides, as well as the length of poly(A) tails, on individual RNA molecules. The success of these analyses is highly dependent on the provision of high-resolution transcriptome annotations in combination with workflows that minimize misalignments and other analysis artifacts.

The Risk for Readmission to Juvenile Detention: The Role of Trauma Exposure and Trauma-related Mental Health Disorders.

The purpose of this study was to examine the impact of childhood trauma exposure, posttraumatic stress disorder, and trauma-related comorbid diagnoses on the risk for readmission to juvenile detention among youth in a large metropolitan area ( = 1282). The following research questions were addressed: 1) Does a greater number of childhood traumas increase the risk for readmission to detention following release? 2) Does the risk for readmission differ by type of trauma? 3) Do PTSD and other co-morbid diagnoses increase the risk for readmission? and 4) What role do demographic factors play in the relationship between trauma-related variables and risk for readmission? This study utilized the screening results of 1282 youth who were voluntarily screened for PTSD, depressive symptoms and substance use during their initial intake to detention. More than half of the sample was readmitted during the three-year study period, with readmissions most likely to occur within one year of release.

Stroma-derived neoplasms and pseudoneoplastic lesions of the spleen: a select review of pathologic and CT/MRI findings.

A wide spectrum of benign and malignant primary mesenchymal tumors and tumor-like lesions of the spleen has been recently included under the umbrella term 'stroma-derived' neoplasms and tumor-like lesions. These include dendritic cell neoplasms such as follicular dendritic cell sarcoma, EBV-positive inflammatory follicular dendritic cell sarcoma, and fibroblastic reticular cell tumor; smooth muscle and myofibroblastic lesions such as inflammatory pseudotumor, EBV-associated smooth muscle tumor and undifferentiated pleomorphic sarcoma as well as a diverse spectrum of vascular and vascular-stromal tumors and tumor-like lesions. While some tumor and tumor-like lesions are unique to the spleen, others may also occur in diverse extra-splenic viscera.

Neutrophils insert elastase into hepatocytes to regulate calcium signaling in alcohol-associated hepatitis.

Neutrophil infiltration occurs in a variety of liver diseases, but it is unclear how neutrophils and hepatocytes interact. Neutrophils generally use granule proteases to digest phagocytosed bacteria and foreign substances or neutralize them in neutrophil extracellular traps. In certain pathological states, granule proteases play a destructive role against the host as well.