Evaluating the consequences of critically ill patients with pediatric cancer at Aliasghar Children's Hospital.

Background: Despite significant progress in supportive care and advancements in chemotherapy treatments, cancer remains a leading cause of mortality in children. The objective of this study was to assess the potential correlation between various risk factors and the consequences of patients with pediatric cancer who were admitted to the pediatric intensive care unit (PICU).

Methods: The present investigation is a retrospective cohort study that examined children with cancer who were between the ages of 1 month and 17 years and had been admitted to the PICU.

Factors affecting the incidence of surgical site infections after geriatric hip fracture surgery: a retrospective study during 2017-2020.

Introduction: Geriatric hip fracture are a common and disruptive public health problem worldwide. Surgical Site Infection (SSI) can be a devastating complication of this injury. By identifying these factors, the adverse outcomes of elderly hip fractures can be prevented.

Lymph node swelling combined with temporary effector T cell retention aids T cell response in a model of adaptive immunity.

Swelling of lymph nodes (LNs) is commonly observed during the adaptive immune response, yet the impact on T cell (TC) trafficking and subsequent immune response is not well known. To better understand the effect of macro-scale alterations, we developed an agent-based model of the LN paracortex, describing the TC proliferative response to antigen-presenting dendritic cells alongside inflammation-driven and swelling-induced changes in TC recruitment and egress, while also incorporating regulation of the expression of egress-modulating TC receptor sphingosine-1-phosphate receptor-1. Analysis of the effector TC response under varying swelling conditions showed that swelling consistently aided TC activation.

QSP-IO: A Quantitative Systems Pharmacology Toolbox for Mechanistic Multiscale Modeling for Immuno-Oncology Applications.

Immunotherapy has shown great potential in the treatment of cancer; however, only a fraction of patients respond to treatment, and many experience autoimmune-related side effects. The pharmaceutical industry has relied on mathematical models to study the behavior of candidate drugs and more recently, complex, whole-body, quantitative systems pharmacology (QSP) models have become increasingly popular for discovery and development. QSP modeling has the potential to discover novel predictive biomarkers as well as test the efficacy of treatment plans and combination therapies through virtual clinical trials.

Association of Serum 25-Hydroxyvitamin D Level With Metabolic Phenotypes of Obesity in Children and Adolescents: The CASPIAN-V Study.

Different metabolic phenotypes of obesity are related to cardiometabolic risk factors in children and adolescents. Vitamin D, as one important factor, could be related to different subgroups of metabolic obesity and might affect metabolic disorders. The purpose of this study was to evaluate the relationship between serum 25-hydroxyvitamin D concentration and subsets of metabolic phenotypes of obesity in children and adolescents.

A Quantitative Systems Pharmacology Model of T Cell Engager Applied to Solid Tumor.

Cancer immunotherapy has recently drawn remarkable attention as promising results in the clinic have shown its ability to improve the overall survival, and T cells are considered to be one of the primary effectors for cancer immunotherapy. Enhanced and restored T cell tumoricidal activity has shown great potential for killing cancer cells. Bispecific T cell engagers (TCEs) are a growing class of molecules that are designed to bind two different antigens on the surface of T cells and cancer cells to bring them in close proximity and selectively activate effector T cells to kill target cancer cells.

Conducting a Virtual Clinical Trial in HER2-Negative Breast Cancer Using a Quantitative Systems Pharmacology Model With an Epigenetic Modulator and Immune Checkpoint Inhibitors.

The survival rate of patients with breast cancer has been improved by immune checkpoint blockade therapies, and the efficacy of their combinations with epigenetic modulators has shown promising results in preclinical studies. In this prospective study, we propose an ordinary differential equation (ODE)-based quantitative systems pharmacology (QSP) model to conduct an virtual clinical trial and analyze potential predictive biomarkers to improve the anti-tumor response in HER2-negative breast cancer. The model is comprised of four compartments: central, peripheral, tumor, and tumor-draining lymph node, and describes immune activation, suppression, T cell trafficking, and pharmacokinetics and pharmacodynamics (PK/PD) of the therapeutic agents.

Synthesis of multi-functionalized FeO-NH-SH nanofiber based on chitosan for single and simultaneous adsorption of Pb(II) and Ni(II) from aqueous system.

A multi-functionalized poly ether sulfone (PES)/ chitosan (CS)/FeO-NH-SH nanofiber was applied for single and simultaneous removal of Pb(II) and Ni(II) ions from water systems. The structure of nanofibers was evaluated using FTIR, FESEM, BET, BJH, TGA, EDX and XPS analyses. The characterization results showed that the structure of nanofibers was well maintained after adsorption process.

Quantification of the Whole Lymph Node Vasculature Based on Tomography of the Vessel Corrosion Casts.

Lymph nodes (LN) are crucial for immune function, and comprise an important interface between the blood and lymphatic systems. Blood vessels (BV) in LN are highly specialized, featuring high endothelial venules across which most of the resident lymphocytes crossed. Previous measurements of overall lymph and BV flow rates demonstrated that fluid also crosses BV walls, and that this is important for immune function.

Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma.

Hepatocyte growth factor (HGF) signaling through its receptor Met has been implicated in hepatocellular carcinoma tumorigenesis and progression. Met interaction with integrins is shown to modulate the downstream signaling to Akt and ERK (extracellular-regulated kinase). In this study, we developed a mechanistically detailed systems biology model of HGF/Met signaling pathway that incorporated specific interactions with integrins to investigate the efficacy of integrin-binding peptide, AXT050, as monotherapy and in combination with other therapeutics targeting this pathway.

A QSP Model for Predicting Clinical Responses to Monotherapy, Combination and Sequential Therapy Following CTLA-4, PD-1, and PD-L1 Checkpoint Blockade.

Over the past decade, several immunotherapies have been approved for the treatment of melanoma. The most prominent of these are the immune checkpoint inhibitors, which are antibodies that block the inhibitory effects on the immune system by checkpoint receptors, such as CTLA-4, PD-1 and PD-L1. Preclinically, blocking these receptors has led to increased activation and proliferation of effector cells following stimulation and antigen recognition, and subsequently, more effective elimination of cancer cells.

A Computational Model of Neoadjuvant PD-1 Inhibition in Non-Small Cell Lung Cancer.

Immunotherapy and immune checkpoint blocking antibodies such as anti-PD-1 are approved and significantly improve the survival of advanced non-small cell lung cancer (NSCLC) patients, but there has been little success in identifying biomarkers capable of separating the responders from non-responders before the onset of the therapy. In this study, we developed a quantitative system pharmacology (QSP) model to represent the anti-tumor immune response in human NSCLC that integrated our knowledge of tumor growth, antigen processing and presentation, T cell activation and distribution, antibody pharmacokinetics, and immune checkpoint dynamics. The model was calibrated with the available data and was used to identify potential biomarkers as well as patient-specific response based on the patient parameters.

Computational modeling of synergistic interaction between αVβ3 integrin and VEGFR2 in endothelial cells: Implications for the mechanism of action of angiogenesis-modulating integrin-binding peptides.

Cooperation between VEGFR2 and integrin αVβ3 is critical for neovascularization in wound healing, cardiovascular ischemic diseases, ocular diseases, and tumor angiogenesis. In the present study, we developed a rule-based computational model to investigate the potential mechanism by which the Src-induced integrin association with VEGFR2 enhances VEGFR2 activation. Simulations demonstrated that the main function of integrin is to reduce the degradation of VEGFR2 and hence stabilize the activation signal.

Computer Simulation of TSP1 Inhibition of VEGF-Akt-eNOS: An Angiogenesis Triple Threat.

The matricellular protein thrombospondin-1 (TSP1) is a potent inhibitor of angiogenesis. Specifically, TSP1 has been experimentally shown to inhibit signaling downstream of vascular endothelial growth factor (VEGF). The molecular mechanism of this inhibition is not entirely clear.

Calcium and electrical dynamics in lymphatic endothelium.

Key Points: Endothelial cell function in resistance arteries integrates Ca signalling with hyperpolarization to promote relaxation of smooth muscle cells and increase tissue blood flow. Whether complementary signalling occurs in lymphatic endothelium is unknown. Intracellular calcium and membrane potential were evaluated in endothelial cell tubes freshly isolated from mouse collecting lymphatic vessels of the popliteal fossa.

Demonstration and Analysis of the Suction Effect for Pumping Lymph from Tissue Beds at Subatmospheric Pressure.

Many tissues exhibit subatmospheric interstitial pressures under normal physiologic conditions. The mechanisms by which the lymphatic system extracts fluid from these tissues against the overall pressure gradient are unknown. We address this important physiologic issue by combining experimental measurements of contractile function and pressure generation with a previously validated mathematical model.

The passive biomechanics of human pelvic collecting lymphatic vessels.

The lymphatic system has a major significance in the metastatic pathways in women's cancers. Lymphatic pumping depends on both extrinsic and intrinsic mechanisms, and the mechanical behavior of lymphatic vessels regulates the function of the system. However, data on the mechanical properties and function of human lymphatics are lacking.

A Novel Computational Model Predicts Key Regulators of Chemokine Gradient Formation in Lymph Nodes and Site-Specific Roles for CCL19 and ACKR4.

The chemokine receptor CCR7 drives leukocyte migration into and within lymph nodes (LNs). It is activated by chemokines CCL19 and CCL21, which are scavenged by the atypical chemokine receptor ACKR4. CCR7-dependent navigation is determined by the distribution of extracellular CCL19 and CCL21, which form concentration gradients at specific microanatomical locations.

Epigenetic Modifications and Therapy in Multiple Sclerosis.

Breakthroughs in genetic studies, like whole human genome sequencing and genome-wide association studies (GWAS), have richened our knowledge of etiopathology of autoimmune diseases (AID) through discovery of genetic patterns. Nonetheless, the precise etiology of autoimmune diseases remains largely unknown. The lack of complete concordance of autoimmune disease in identical twins suggests that non-genetic factors also play a major role in determining disease susceptibility.

Modeling Lymph Flow and Fluid Exchange with Blood Vessels in Lymph Nodes.

Background: Lymph nodes (LNs) are positioned strategically throughout the body as critical mediators of lymph filtration and immune response. Lymph carries cytokines, antigens, and cells to the downstream LNs, and their effective delivery to the correct location within the LN directly impacts the quality and quantity of immune response. Despite the importance of this system, the flow patterns in LN have never been quantified, in part because experimental characterization is so difficult.

Measurement of shear stress-mediated intracellular calcium dynamics in human dermal lymphatic endothelial cells.

The shear stress applied to lymphatic endothelial cells (LEC) by lymph flow changes dramatically under normal conditions as well as in response to disease conditions and immune reactions. In general, LEC are known to regulate the contraction frequency and strength of lymphatic pumping in response to shear stress. Intracellular calcium concentration ([Ca(2+)]i) is an important factor that regulates lymphatic contraction characteristics.

The relationship between helicobacter pylori infection and myocardial infarction.

Background: Coronary Artery Disease is known as the main cause of death in industrialized countries. Relation between this disease and some infections such as Helicobacter pylori (H.pylori) has been shown in several studies.

Chlamydia pneumoniae infection and cardiac risk factors in patients with myocardial infection.

Background: Evidences support the possible involvement of microorganisms such as Chlamydia pneumonia in the pathogenesis of ischemic heart diseases through a chronic inflammatory process. The aim of this study was to determine the relation between Chlamydia pneumoniae seropositivity with acute myocardial infarction and its related risk factors.

Methods: In this case-control study, 88 patients admitted in CCU with a diagnosis of acute coronary syndrome, without a history of chronic diseases including cancers were selected as cases and 49 surgical patients without an evidence of cardiovascular disease according to clinical examinations and ECG were selected as controls.