The inhibitory receptor PVRIG is dominantly expressed in the bone marrow of patients with multiple myeloma and its blockade enhances T-cell engager's immune activation.

Therapeutic advances in treating patients with multiple myeloma (MM), including novel immunotherapies, have improved the disease control, but it remains incurable. Although traditional immune check point inhibitors have shown limited clinical benefit, targeting alternative immune-inhibitory pathways may offer a novel way to address relapsed disease. Blockade of the immune regulator TIGIT was shown to enhance antitumor immunity in preclinical MM models.

Primary inferior vena cava synovial sarcoma treated with caval replacement during cardiopulmonary bypass and liver perfusion.

Primary inferior vena cava (IVC) tumors are rare. Most are leiomyosarcomas. The prognosis is poor with those involving and superior to the hepatic veins faring worse than those isolated within the retrohepatic cava.

[CANCER SURVIVORS - QUESTIONS, CONSIDERATIONS AND POSSIBLE SOLUTIONS].

Objectives: To describe and evaluate the gaps in cancer survivors' treatment in Israel and suggest possible methods of meeting their needs.

Methods: This narrative review explores cancer survivors' unmet needs and global methodologies aiming at meeting them within various health systems.

Results: Cancer survivorship has become a topic of great interest in the past few years.

Dual-energy subtraction radiography (DESR): a systematic review and meta-analysis of pulmonary nodule detection.

Purpose: This study examined the literature to compare the accuracy, sensitivity, and specificity of dual-energy subtraction radiography (DESR) with conventional radiography (CR) in the detection of pulmonary nodules. To our knowledge, no meta-analysis has been conducted to compare DESR with CR.

Material And Methods: The authors searched Pubmed using the terms "Dual-energy subtraction radiography," and "Dual-Energy Chest Radiography.

Polyvalvular Dysplasia and Vascular Abnormalities in a Neonate With an Variant.

There is growing appreciation for inherited structural heart diseases and their genetic causes. One causal gene for congenital cardiac and vascular lesions is which encodes a critical protein for cytoskeletal and extracellular matrix development. A newborn infant male, with prenatally diagnosed polyvalvular dysfunction, presented with low cardiac output and postnatally detected aortic arch hypoplasia and coarctation.

Current opportunities and challenges of immersive virtual reality for psychological research and application.

Immersive virtual reality (iVR), that is, digital stereoscopic 360° scenarios usually presented in head-mounted displays, has gained much popularity in medical, educational, and consumer contexts in the last years. Recently, psychological research started to utilize the theoretical and methodological advantages of iVR. Furthermore, understanding cognitive, emotional, and behavioral processes in iVR similar to real-life is a genuinely psychological, currently understudied topic.

Inverse Phase Transition in Droplet Clusters Levitating over the Locally Heated Water Layer.

Self-assembled microdroplet clusters can levitate above a locally heated water surface. Normally, the temperature of droplets is in the range of 50-95 °C. However, it is possible to generate clusters at lower temperatures.

Eliminating residual neuromuscular blockade: a literature review.

Background And Objective: Although millions of patients receive neuromuscular blocking agents (NMBAs) each year as part of an anesthetic, residual neuromuscular blockade (NMB) remains a too-frequent occurrence and its adverse consequences continue to negatively impact patient outcomes. The goal of this manuscript is to provide clinicians with the information they need to decrease the incidence of residual NMB.

Methods: Published literature was reviewed and incorporated into the narrative as appropriate.

Large-scale discovery of chromatin dysregulation induced by oncofusions and other protein-coding variants.

Population-scale databases have expanded to millions of protein-coding variants, yet insight into their mechanistic consequences has lagged. Here we present PROD-ATAC, a high-throughput method for discovering the effects of protein-coding variants on chromatin regulation. A pooled variant library is expressed in a disease-agnostic cell line, and single-cell assay for transposase-accessible chromatin resolves each variant's effect on the chromatin landscape.

PVRIG is Expressed on Stem-Like T Cells in Dendritic Cell-Rich Niches in Tumors and Its Blockade May Induce Immune Infiltration in Non-Inflamed Tumors.

Cancers that are poorly immune infiltrated pose a substantial challenge, with current immunotherapies yielding limited clinical success. Stem-like memory T cells (TSCM) have been identified as a subgroup of T cells that possess strong proliferative capacity and that can expand and differentiate following interactions with dendritic cells (DCs). In this study, we explored the pattern of expression of a recently discovered inhibitory receptor poliovirus receptor-related immunoglobulin domain protein (PVRIG) and its ligand, poliovirus receptor-related ligand 2 (PVRL2), in the human tumor microenvironment.

Discovering mechanisms of human genetic variation and controlling cell states at scale.

Population-scale sequencing efforts have catalogued substantial genetic variation in humans such that variant discovery dramatically outpaces interpretation. We discuss how single-cell sequencing is poised to reveal genetic mechanisms at a rate that may soon approach that of variant discovery. The functional genomics toolkit is sufficiently modular to systematically profile almost any type of variation within increasingly diverse contexts and with molecularly comprehensive and unbiased readouts.

Unleashing Natural IL18 Activity Using an Anti-IL18BP Blocker Induces Potent Immune Stimulation and Antitumor Effects.

Recombinant cytokines have limited anticancer efficacy mostly due to a narrow therapeutic window and systemic adverse effects. IL18 is an inflammasome-induced proinflammatory cytokine, which enhances T- and NK-cell activity and stimulates IFNγ production. The activity of IL18 is naturally blocked by a high-affinity endogenous binding protein (IL18BP).

Establishing an Integrative Oncology Service: Essential Aspects of Program Development.

Purpose Of Review: Over the last 2 decades, integrative oncology (IO) has seen exponential growth within cancer care. It aims to combine evidence-based complementary therapies with conventional treatments to improve the well-being and quality of life for individuals dealing with cancer. The proliferation of integrative medicine programs in major cancer centers globally reflects varying approaches shaped by cultural, demographic, and resource-based factors.

Addressing Patient Requests to Add Dietary Supplements to Their Cancer Care-A Suggested Approach.

Dietary supplements are widely utilized by cancer patients as part of a complementary and integrative approach to their healthcare. However, a significant portion of patients refrain from discussing their supplement use with their physicians, often due to the perceived indifference or negativity of their healthcare providers. This communication gap exposes patients to unreliable information sources and potential risks associated with uninformed supplementation.

Fermat Principle, Ramsey Theory and Metamaterials.

Reinterpretation of the Fermat principle governing the propagation of light in media within the Ramsey theory is suggested. Complete bi-colored graphs corresponding to light propagation in media are considered. The vertices of the graphs correspond to the points in real physical space in which the light sources or sensors are placed.

Testing the hormesis hypothesis on motor behavior under stress.

While much research has focused on the deleterious effects of stress on goal-directed behavior in recent decades, current views increasingly discuss growth under stress, often assuming dose-dependent effects of stress in a curvilinear association. This is based on the concept of hormesis, which postulates a strengthening effect of stress at low-to-moderate doses. Leveraging this approach, hormetic curves indicate under which stress dose an individual is able to maintain or even increase goal-directed behavior.

Shannon Entropy of Ramsey Graphs with up to Six Vertices.

Shannon entropy quantifying bi-colored Ramsey complete graphs is introduced and calculated for complete graphs containing up to six vertices. Complete graphs in which vertices are connected with two types of links, labeled as α-links and -links, are considered. Shannon entropy is introduced according to the classical Shannon formula considering the fractions of monochromatic convex α-colored polygons with -sides or edges, and the fraction of monochromatic β-colored convex polygons with -sides in the given complete graph.

Discovering chromatin dysregulation induced by protein-coding perturbations at scale.

Although population-scale databases have expanded to millions of protein-coding variants, insight into variant mechanisms has not kept pace. We present PROD-ATAC, a high-throughput method for discovering the effects of protein-coding variants on chromatin. A pooled library of variants is expressed in a disease-agnostic cell line, and single-cell ATAC resolves each variant's effect on chromatin.

An oligogenic case of severe neonatal thrombocytopenia and a purportedly benign variant in requiring reinterpretation.

Although thrombocytopenia in neonatal intensive care patients is rarely due to inherited disorders, the number of genetic variants implicated in platelet defects has grown dramatically with increasing genome-wide sequencing. Here we describe a case of severe, oligogenic neonatal thrombocytopenia and reinterpret a reportedly benign mutation that is likely pathogenic. Despite this patient's synonymous mutation ( 576 C>T, Phe192=) being annotated as benign, GFI1B is a well-known regulator of megakaryopoiesis, this variant alters splicing and megakaryocyte maturation, and our analysis of existing genome-wide associated studies demonstrates that it likely causes gray platelet syndrome.

Improved HIV-1 neutralization breadth and potency of V2-apex antibodies by in silico design.

Broadly neutralizing antibodies (bNAbs) against HIV can reduce viral transmission in humans, but an effective therapeutic will require unusually high breadth and potency of neutralization. We employ the OSPREY computational protein design software to engineer variants of two apex-directed bNAbs, PGT145 and PG9RSH, resulting in increases in potency of over 100-fold against some viruses. The top designed variants improve neutralization breadth from 39% to 54% at clinically relevant concentrations (IC < 1 μg/mL) and improve median potency (IC) by up to 4-fold over a cross-clade panel of 208 strains.