Lymph nodes link sex-biased immune aging to compromised antigen recognition.

A diverse naive CD8 T cell repertoire is essential to provide broad protection against infection and cancer. Aging diminishes naive T cells, reducing potential diversity and leading to lymph node contraction. Here, we revealed that this decline occurs earlier in males, resulting in significant sex differences in immunity during middle age.

Probing the physical hallmarks of cancer.

The physical microenvironment plays a crucial role in tumor development, progression, metastasis and treatment. Recently, we proposed four physical hallmarks of cancer, with distinct origins and consequences, to characterize abnormalities in the physical tumor microenvironment: (1) elevated compressive-tensile solid stresses, (2) elevated interstitial fluid pressure and the resulting interstitial fluid flow, (3) altered material properties (for example, increased tissue stiffness) and (4) altered physical micro-architecture. As this emerging field of physical oncology is being advanced by tumor biologists, cell and developmental biologists, engineers, physicists and oncologists, there is a critical need for model systems and measurement tools to mechanistically probe these physical hallmarks.

Clarifying the Qualifications for Nurse Scientists.

The roles of PhD- and DNP-prepared nurses are very different.

Aging-induced changes in lymphatic muscle cell transcriptomes are associated with reduced pumping of peripheral collecting lymphatic vessels in mice.

Lymphatic muscle cells (LMCs) within the wall of collecting lymphatic vessels exhibit tonic and autonomous phasic contractions, which drive active lymph transport to maintain tissue-fluid homeostasis and support immune surveillance. Damage to LMCs disrupts lymphatic function and is related to various diseases. Despite their importance, knowledge of the gene transcriptional signatures in LMCs and how they relate to lymphatic function in normal and disease contexts is largely missing.

The Well-being Coaching Program: An Innovative Approach to Support and Empower Healthcare Workers.

Healthcare workers globally grapple with escalating stress and burnout. This article explores the Well-being Coaching Program (WBCP), designed to boost healthcare worker well-being. The WBCP focuses on Self-leadership using the Compassion, Presence, and Recovery framework.

Solid stress estimations via intraoperative 3D navigation in patients with brain tumors.

Background: Physical forces exerted by expanding brain tumors - specifically the compressive stresses propagated through solid tissue structures - reduces brain perfusion and neurological function, but heretofore has not been directly measured in patients . Solid stress levels estimated from tumor growth patterns are negatively correlated with neurological performance in patients. We hypothesize that measurements of solid stress can be used to inform clinical management of brain tumors.

Job-Related Factors Associated with Burnout and Work Engagement in Emergency Nurses: Evidence to Inform Systems-Focused Interventions.

Introduction: Nurses working in the emergency department experience high rates of burnout. The purpose of this study was to determine job-related factors affecting the well-being of emergency nurses.

Methods: In this cross-sectional study data were collected through multiple methods.

Usability of Light-Linking Technology for Infusion Line Identification: A Simulation Study With ICU Nurses.

Critical care nurses are faced with increasing task loads due to increasing patient complexity. In addition to this complexity, most critical care patients have a maze of infusion and monitoring lines that must be navigated when administering medications. Task load is escalated when a nurse must identify an injection port and administer a medication rapidly.

Compressive stresses in cancer: characterization and implications for tumour progression and treatment.

Beyond their many well-established biological aberrations, solid tumours create an abnormal physical microenvironment that fuels cancer progression and confers treatment resistance. Mechanical forces impact tumours across a range of biological sizes and timescales, from rapid events at the molecular level involved in their sensing and transmission, to slower and larger-scale events, including clonal selection, epigenetic changes, cell invasion, metastasis and immune response. Owing to challenges with studying these dynamic stimuli in biological systems, the mechanistic understanding of the effects and pathways triggered by abnormally elevated mechanical forces remains elusive, despite clear correlations with cancer pathophysiology, aggressiveness and therapeutic resistance.

Fluid dynamics and leukocyte transit in the lymphatic system.

The lymphatic system plays a vital role in maintaining fluid balance in living tissue and serves as a pathway for the transport of antigen, immune cells, and metastatic cancer cells. In this study, we investigate how the movement of cells through a contracting lymphatic vessel differs from steady flow, using a lattice Boltzmann-based computational model. Our model consists of cells carried by flow in a 2D vessel with regularly spaced, bi-leaflet valves that ensure net downstream flow as the vessel walls contract autonomously in response to calcium and nitric oxide levels regulated by stretch and shear stress levels.

Dynamic heterogeneity in COVID-19: Insights from a mathematical model.

Critical illness, such as severe COVID-19, is heterogenous in presentation and treatment response. However, it remains possible that clinical course may be influenced by dynamic and/or random events such that similar patients subject to similar injuries may yet follow different trajectories. We deployed a mechanistic mathematical model of COVID-19 to determine the range of possible clinical courses after SARS-CoV-2 infection, which may follow from specific changes in viral properties, immune properties, treatment modality and random external factors such as initial viral load.

Drivers of hospital nurse practitioner turnover: A national sample survey analysis.

Background: Hospital nurse practitioner (NP) turnover is costly and complex.

Purpose: Provide a pre-COVID-19 pandemic baseline of hospital NP turnover.

Methods: A secondary analysis of NSSRN18 data on 6,558 (67,863 weighted) NPs employed in hospitals on 12/31/2017.

Neovascularization by DPSC-ECs in a Tube Model for Pulp Regeneration Study.

The process of neovascularization during cell-based pulp regeneration is difficult to study. Here we developed a tube model that simulates root canal space and allows direct visualization of the vascularization process in vitro. Endothelial-like cells (ECs) derived from guiding human dental pulp stem cells (DPSCs) into expressing endothelial cell markers CD144, vWF, VEGFR1, and VEGFR2 were used.

A Multiresolution Approach with Method-Informed Statistical Analysis for Quantifying Lymphatic Pumping Dynamics.

Despite significant strides in lymphatic system imaging, the timely diagnosis of lymphatic disorders remains elusive. One main cause for this is the absence of standardized, quantitative methods for real-time analysis of lymphatic contractility. Here, we address this unmet need by combining near-infrared lymphangiography imaging with an innovative analytical workflow.

Mechanics of Lymphatic Pumping and Lymphatic Function.

The lymphatic system plays a crucial role in maintaining tissue fluid balance, immune surveillance, and the transport of lipids and macromolecules. Lymph is absorbed by initial lymphatics and then driven through lymph nodes and to the blood circulation by the contraction of collecting lymphatic vessels. Intraluminal valves in collecting lymphatic vessels ensure the unidirectional flow of lymph centrally.

Experimental and theoretical model of microvascular network remodeling and blood flow redistribution following minimally invasive microvessel laser ablation.

Overly dense microvascular networks are treated by selective reduction of vascular elements. Inappropriate manipulation of microvessels could result in loss of host tissue function or a worsening of the clinical problem. Here, experimental, and computational models were developed to induce blood flow changes via selective artery and vein laser ablation and study the compensatory collateral flow redistribution and vessel diameter remodeling.

In silico clinical studies for optimal COVID-19 vaccination schedules in patients with cancer.

This study introduces a tailored COVID-19 model for patients with cancer, incorporating viral variants and immune-response dynamics. The model aims to optimize vaccination strategies, contributing to personalized healthcare for vulnerable groups.

Reprogramming the Intrahepatic Cholangiocarcinoma Immune Microenvironment by Chemotherapy and CTLA-4 Blockade Enhances Anti-PD-1 Therapy.

Intrahepatic cholangiocarcinoma (ICC) has limited therapeutic options and a dismal prognosis. Adding blockade of the anti-programmed cell death protein (PD)-1 pathway to gemcitabine/cisplatin chemotherapy has recently shown efficacy in biliary tract cancers but with low response rates. Here, we studied the effects of anti-cytotoxic T lymphocyte antigen (CTLA)-4 when combined with anti-PD-1 and gemcitabine/cisplatin in orthotopic murine models of ICC.

Wnt inhibition alleviates resistance to immune checkpoint blockade in glioblastoma.

Wnt signaling plays a critical role in the progression and treatment outcome of glioblastoma (GBM). Here, we identified WNT7b as a heretofore unknown mechanism of resistance to immune checkpoint inhibition (αPD1) in GBM patients and murine models. Acquired resistance to αPD1 was found to be associated with the upregulation of Wnt7b and β-catenin protein levels in GBM in patients and in a clinically relevant, stem-rich GBM model.

Experimental and Theoretical Model of Single Vessel Minimally Invasive Micro-Laser Ablation: Inducing Microvascular Network Remodeling and Blood Flow Redistribution Without Compromising Host Tissue Function.

Overly dense microvascular networks are treated by selective reduction of vascular elements. Inappropriate manipulation of microvessels could result in loss of host tissue function or a worsening of the clinical problem. Here, experimental, and computational models were developed to induce blood flow changes via selective artery and vein laser ablation and study the compensatory collateral flow redistribution and vessel diameter remodeling.

Dissecting the Impact of the Gut Microbiome on Cancer Immunotherapy.

The gut microbiome has emerged as a key regulator of response to cancer immunotherapy. However, there is a gap in our understanding of the underlying mechanisms by which the microbiome influences immunotherapy. To this end, we developed a mathematical model based on i) gut microbiome data derived from preclinical studies on melanomas after fecal microbiota transplant, ii) mechanistic modeling of antitumor immune response, and iii) robust association analysis of murine and human microbiome profiles with model-predicted immune profiles.

Transport Barriers Influence the Activation of Anti-Tumor Immunity: A Systems Biology Analysis.

Effective anti-cancer immune responses require activation of one or more naïve T cells. If the correct naïve T cell encounters its cognate antigen presented by an antigen presenting cell, then the T cell can activate and proliferate. Here, mathematical modeling is used to explore the possibility that immune activation in lymph nodes is a rate-limiting step in anti-cancer immunity and can affect response rates to immune checkpoint therapy.

A study of error reporting by nurses: the significant impact of nursing team dynamics.

Background: Error reporting is crucial for organisational learning and improving patient safety in hospitals, yet errors are significantly underreported.

Aims: The aim of this study was to understand how the nursing team dynamics of leader inclusiveness, safety climate and psychological safety affected the willingness of hospital nurses to report errors.

Methods: The study was a cross-sectional design.