Development of mutated β-catenin gene signature to identify mutations from whole and spatial transcriptomic data in patients with HCC.

Background & Aims: Patients with β-catenin (encoded by )-mutated hepatocellular carcinoma (HCC) demonstrate heterogenous responses to first-line immune checkpoint inhibitors (ICIs). Precision-medicine based treatments for this subclass are currently in clinical development. Here, we report derivation of the Mutated β-catenin Gene Signature (MBGS) to predict -mutational status in patients with HCC for future application in personalized medicine treatment regimens.

Anthrax lethal toxin exerts potent metabolic inhibition of the cardiovascular system.

causes anthrax through a combination of bacterial infection and toxemia. As a major virulence factor of , anthrax lethal toxin (LT) is a zinc-dependent metalloproteinase, exerting its cytotoxicity through proteolytic cleavage of the mitogen-activated protein kinase kinases, thereby shutting down the MAPK pathways. Anthrax lethal toxin induces host lethality mostly by targeting the cardiovascular system.

Adipocyte-specific Nrf2 deletion negates nitro-oleic acid benefits on glucose tolerance in diet-induced obesity.

Obesity is commonly linked with white adipose tissue (WAT) dysfunction, setting off inflammation and oxidative stress, both key contributors to the cardiometabolic complications associated with obesity. To improve metabolic and cardiovascular health, countering these inflammatory and oxidative signaling processes is crucial. Offering potential in this context, the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by nitro-fatty acids (NO-FA) promote diverse anti-inflammatory signaling and counteract oxidative stress.

Automated Quantitative CD8+ Tumor-Infiltrating Lymphocytes and Tumor Mutation Burden as Independent Biomarkers in Melanoma Patients Receiving Front-Line Anti-PD-1 Immunotherapy.

Background: CD8+ tumor-infiltrating lymphocyte (TIL) predicts response to anti-PD-(L)1 therapy. However, there remains no standardized method to assess CD8+ TIL in melanoma, and developing a specific, cost-effective, reproducible, and clinically actionable biomarker to anti-PD-(L)1 remains elusive. We report on the development of automatic CD8+ TIL density quantification via whole slide image (WSI) analysis in advanced melanoma patients treated with front-line anti-PD-1 blockade, and correlation immunotherapy response.

Impact of autophagy inhibition on intervertebral disc cells and extracellular matrix.

Background: Intervertebral disc degeneration (IDD) is a leading contributor to low back pain (LBP). Autophagy, strongly activated by hypoxia and nutrient starvation, is a vital intracellular quality control process that removes damaged proteins and organelles to recycle them for cellular biosynthesis and energy production. While well-established as a major driver of many age-related diseases, autophagy dysregulation or deficiency has yet been confirmed to cause IDD.

3-D real-time ultrasound tracking of acoustically actuated swimming microdrone.

Maneuverable microswimmers/microdrones that navigate in hard-to-reach spaces inside human bodies hold a great potential for various biomedical applications. Acoustically actuated microswimmers have already demonstrated feasibility. However, for eventual translation of this technology, a robust 3-D tracking strategy for the microswimmer is particularly required.

Best clinical practice in the treatment of juvenile systemic sclerosis: expert panel guidance - the result of the International Hamburg Consensus Meeting December 2022.

Introduction: Juvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence of 3 in 1,000,000 children. Currently there is only one consensus treatment guideline concerning skin, pulmonary and vascular involvement for jSSc, the jSSc SHARE (Single Hub and Access point for pediatric Rheumatology in Europe) initiative, which was based on data procured up to 2014. Therefore, an update of these guidelines, with a more recent literature and expert experience, and extension of the guidance to more aspects of the disease is needed.

Prevalence and Clinical Outcomes of Respiratory Syncytial Virus vs Influenza in Adults Hospitalized With Acute Respiratory Illness From a Prospective Multicenter Study.

Background: Current understanding of severe respiratory syncytial virus (RSV) infections in adults is limited by clinical underrecognition. We compared the prevalence, clinical characteristics, and outcomes of RSV infections vs influenza in adults hospitalized with acute respiratory illnesses (ARIs) in a prospective national surveillance network.

Methods: Hospitalized adults who met a standardized ARI case definition were prospectively enrolled across 3 respiratory seasons from hospitals participating across all sites of the US Hospitalized Adult Influenza Vaccine Effectiveness Network (2016-2019).

ERK and c-Myc signaling in host-derived tumor endothelial cells is essential for solid tumor growth.

The limited efficacy of the current antitumor microenvironment strategies is due in part to the poor understanding of the roles and relative contributions of the various tumor stromal cells to tumor development. Here, we describe a versatile in vivo anthrax toxin protein delivery system allowing for the unambiguous genetic evaluation of individual tumor stromal elements in cancer. Our reengineered tumor-selective anthrax toxin exhibits potent antiproliferative activity by disrupting ERK signaling in sensitive cells.

Agent-based model of the impact of higher influenza vaccine efficacy on seasonal influenza burden.

Introduction: Current influenza vaccines have limited effectiveness. COVID-19 vaccines using mRNA technology have demonstrated very high efficacy, suggesting that mRNA vaccines could be more effective for influenza. Several such influenza vaccines are in development.

Asynchronous training for ultrasound-guided peripheral IV placement among critical care nurses.

Objective: Teaching ultrasound (US) guidance for placement of peripheral intravenous (PIV) catheters requires significant time for synchronous didactic and hands-on training. The investigators assessed the feasibility of an asynchronous model for critical care nurses to learn the novel skill of US-guided PIV placement. Secondary outcomes included the percentage of successful attempts and number of sticks per attempt for anatomy versus US-guided approaches.

Healthcare Use in the Year Following Bronchiolitis Hospitalization.

Objectives: Healthcare utilization after bronchiolitis hospitalization is incompletely understood. We aimed to characterize readmissions and outpatient visits within 1 year after hospital discharge.

Methods: Retrospective multicenter observational cohort study of children under 24-months old admitted with bronchiolitis between January 1, 2010 and December 12, 2019 to the Pediatric Health Information Systems database.

Performance of High Throughput SARS-CoV-2 Antigen Testing Compared to Nucleic Acid Testing.

Objective: Independent assessment of SARS-CoV-2 antigen (COV2Ag) tests remains important as varying performance between assays is common. We assessed the performance of a new high-throughput COV2Ag test compared to SARS-CoV-2 nucleic acid amplification tests (NAAT).

Methods: A total of 347 nasopharyngeal samples collected from January to October 2021 were assessed by NAAT as part of standard-of-care testing (CDC LDT or GeneXpert System, Cepheid) and COV2Ag using the ADVIA Centaur CoV2Ag assay (Siemens Healthineers).

A potent tumor-selective ERK pathway inactivator with high therapeutic index.

FDA-approved BRAF and MEK small molecule inhibitors have demonstrated some level of efficacy in patients with metastatic melanomas. However, these "targeted" therapeutics have a very low therapeutic index, since these agents affect normal cells, causing undesirable, even fatal, side effects. To address these significant drawbacks, here, we have reengineered the anthrax toxin-based protein delivery system to develop a potent, tumor-selective MEK inactivator.

Clinical Presentation and Severity of Adenovirus Detection Alone vs Adenovirus Co-detection With Other Respiratory Viruses in US Children With Acute Respiratory Illness from 2016 to 2018.

Background: Human adenovirus (HAdV) is commonly associated with acute respiratory illnesses (ARI) in children and is also frequently co-detected with other viral pathogens. We compared clinical presentation and outcomes in young children with HAdV detected alone vs co-detected with other respiratory viruses.

Methods: We used data from a multicenter, prospective, viral surveillance study of children seen in the emergency department and inpatient pediatric settings at seven US sites.

Development of a multisystem point of care ultrasound skills assessment checklist.

Background: Many institutions are training clinicians in point-of-care ultrasound (POCUS), but few POCUS skills checklists have been developed and validated. We developed a consensus-based multispecialty POCUS skills checklist with anchoring references for basic cardiac, lung, abdominal, and vascular ultrasound, and peripheral intravenous line (PIV) insertion.

Methods: A POCUS expert panel of 14 physicians specializing in emergency, critical care, and internal/hospital medicine participated in a modified-Delphi approach to develop a basic POCUS skills checklist by group consensus.

Perspectives on Anti-Black Racism and Mitigation Strategies Among Faculty Experts at Academic Medical Centers.

Importance: Black faculty and trainees remain underrepresented in academic medicine because of systemic racism. Years of diversity and inclusion efforts have not succeeded in eliminating the unique challenges faced by Black faculty in academic medicine.

Objectives: To elicit expert faculty perspectives on anti-Black racism in academic medicine based on lived and/or professional experience and to solicit recommendations for an intervention for faculty to dismantle anti-Black racism within academic medical centers.

Semi-Automated Graphical System for Calculating Pulmonary Vascular Impedances in a Clinical Setting.

Create a semi-automated, graphical, stand-alone application that uses clinically available asynchronous pressure and Doppler velocity captures to rapidly calculate, display, and interpret the pulmonary vascular impedance (PVZ) spectra. MATLAB-based software was written to analyze PVZ by creating a composite PVZ (cPVZ) spectra comprised of asynchronous screen captures of pulmonary arterial pressure and pulmonary arterial pulsed-wave Doppler velocity waveforms obtained during standard of care procedures. The pressure waveform, Doppler frequency envelopes, and ECG signals were re-digitized via automated border detection.

The Clinical Impact of Anti-HLA Donor Specific Antibody Detection Through First Year Screening on Stable Kidney Transplant Recipients.

Anti-HLA Donor Specific Antibody (DSA) detection post kidney transplant has been associated with adverse outcomes, though the impact of early DSA screening on stable patients remain unclear. We analyzed impact of DSA detection through screening in 1st year stable patients ( = 736) on subsequent estimated glomerular filtration rate (eGFR), death censored graft survival (DCGS), and graft failure (graft loss including return to dialysis or re-transplant, patient death, or eGFR < 20 ml/min at last follow up). Patients were grouped using 1st year screening into DSA+ (Class I, II; = 131) or DSA- ( = 605).

The Effects of Healthy Aging on Right Ventricular Structure and Biomechanical Properties: A Pilot Study.

Healthy aging has been associated with alterations in pulmonary vascular and right ventricular (RV) hemodynamics, potentially leading to RV remodeling. Despite the current evidence suggesting an association between aging and alterations in RV function and higher prevalence of pulmonary hypertension in the elderly, limited data exist on age-related differences in RV structure and biomechanics. In this work, we report our preliminary findings on the effects of healthy aging on RV structure, function, and biomechanical properties.

Role of YAP1 Signaling in Biliary Development, Repair, and Disease.

Yes-associated protein 1 (YAP1) is a transcriptional coactivator that activates transcriptional enhanced associate domain transcription factors upon inactivation of the Hippo signaling pathway, to regulate biological processes like proliferation, survival, and differentiation. YAP1 is most prominently expressed in biliary epithelial cells (BECs) in normal adult livers and during development. In the current review, we will discuss the multiple roles of YAP1 in the development and morphogenesis of bile ducts inside and outside the liver, as well as in orchestrating the cholangiocyte repair response to biliary injury.