Flow cytometry-based monitoring of myeloid-derived suppressor cells in the peripheral blood of patients with solid tumors.

Myeloid-derived suppressor cells (MDSCs) ameliorate inflammation by inhibiting T cell responses. In pathological conditions, such as autoimmunity, chronic infections or cancer they accumulate in the periphery. In cancer, MDSCs can also be part of the tumor microenvironment and are associated with a worse prognosis and limited response to immunotherapy.

Pancreatic cancer cell-intrinsic transglutaminase-2 promotes T cell suppression through microtubule-dependent secretion of immunosuppressive cytokines.

Background: Pancreatic ductal adenocarcinoma (PDAC) is mostly refractory to immunotherapy due to immunosuppression in the tumor microenvironment and cancer cell-intrinsic T cell tolerance mechanisms. PDAC is described as a "cold" tumor type with poor infiltration by T cells and factors leading to intratumoral T cell suppression have thus received less attention. Here, we identify a cancer cell-intrinsic mechanism that contributes to a T cell-resistant phenotype and describes potential combinatorial therapy.

Advances in the understanding and therapeutic manipulation of cancer immune responsiveness: a Society for Immunotherapy of Cancer (SITC) review.

Cancer immunotherapy-including immune checkpoint inhibition (ICI) and adoptive cell therapy (ACT)-has become a standard, potentially curative treatment for a subset of advanced solid and liquid tumors. However, most patients with cancer do not benefit from the rapidly evolving improvements in the understanding of principal mechanisms determining cancer immune responsiveness (CIR); including patient-specific genetically determined and acquired factors, as well as intrinsic cancer cell biology. Though CIR is multifactorial, fundamental concepts are emerging that should be considered for the design of novel therapeutic strategies and related clinical studies.

On-Surface Synthesis and Characterization of Pentadecacene and Its Gold Complexes.

Acenes are an important class of polycyclic aromatic hydrocarbons that have gained considerable attention from chemists, physicists, and material scientists, due to their exceptional potential for organic electronics. They serve as an ideal platform for studying the physical and chemical properties of sp carbon frameworks in the one-dimensional limit and also provide a fertile playground to explore magnetism in graphenic nanostructures due to their zigzag edge topology. While higher acenes up to tridecacene have been successfully generated by means of on-surface synthesis, it is imperative to extend their synthesis toward even longer homologues to comprehensively understand the evolution of their electronic ground state.

T follicular helper cell expansion and hyperimmunoglobulinemia with spontaneous IgE production to dietary antigens in IgA-deficient mice.

Immunoglobulin A (IgA), the most abundantly produced antibody at mucosal surfaces, is thought to play key roles in immune responses to respiratory and enteric pathogens and in the regulation of commensal colonization. Low IgA levels have been associated with recurrent infections and immune dysregulation, including inflammatory bowel disease and autoimmunity. Levels of IgA in maternal breast milk and infant stool are both inversely associated with the emergence of immune responses to food antigens in infants and, in naturally resolving food sensitivity and immunotherapy protocols, the induction of IgA antibodies to dietary antigens has been associated with the acquisition of food tolerance.

Rationale and Design of the HERZCHECK trial: Detection of Early Heart Failure Using Telemedicine and CMR in Structurally Weak Regions (NCT05122793).

Background And Aims: Heart failure (HF) is an imminent global health problem. Yet established screening algorithms for asymptomatic pre-HF, allowing for early and effective preventive interventions, are largely lacking. The HERZCHECK trial, conducted in structurally underserved rural regions of North-Eastern Germany, aims to close this gap by evaluating the feasibility, diagnostic efficacy, and cost-effectiveness of a fully mobile, telemedically-supervised screening approach, combining cardiac magnetic resonance imaging (CMR) and laboratory testing as central elements.

The investigation of the interaction of warangalone with transferrin as a therapeutic biological macromolecule and the formation of a protein-ligand nanocomplex with superior anticancer activity against lung cancer cells.

Though warangalone has shown anticancer properties against breast cancer cells, its colloidal stability and therapeutic index ought to be improved using a potential strategy, especially via protein-based (nano)carriers. In this research, transferrin was used as a plasma protein for the development of the warangalone-transferrin NPs. To investigate the mechanism underlying the formation of this complex, the interaction between warangalone and transferrin, as well as transferrin NPs, was analyzed using spectroscopic methods.

Meta-analysis of prospective longitudinal cohort studies on the impact of childhood traumas on anxiety disorders.

Objects: Childhood trauma is an early pathogenic factor that increases individuals' vulnerability to mental illness. This systematic review aims to explore the evidence regarding the association between childhood trauma and the subsequent occurrence of anxiety disorders.

Methods: Embase, Scopus, and PubMed databases were searched for peer-reviewed longitudinal cohort studies published in English between January 1, 1995, and November 15, 2022.

AN IMMUNOHISTOCHEMICAL AND MOLECULAR GENETIC STUDY OF 60 COLORECTAL CARCINOMA BRAIN METASTASES IN PURSUIT OF PREDICTIVE BIOMARKERS FOR CANCER THERAPY.

Colorectal carcinoma brain metastases (n=60) were studied using next-generation sequencing and immunohistochemistry. RAS and BRAF mutations were detected in 58.2% and 7.

Intimal Sarcoma of the Lower Pulmonary Vein Diagnosed by Endobronchial Ultrasound-Guided Fine-Needle Aspiration (EBUS-FNA): A Case Report and Comprehensive Literature Review.

Intimal sarcoma of blood vessels is a rare, aggressive tumor originating from vascular endothelial cells. This report presents a 22-year-old male diagnosed with an intimal sarcoma of the lower pulmonary vein, detailing diagnosis, treatment, and prognosis information. Additionally, this report explores the application application of Endobronchial Ultrasound-Guided Fine-Needle Aspiration (EBUS-FNA) alongside with Rapid Remote Online Evaluation (ROLE) for identifying a mass-like lesion in the pulmonary vein.

Associations of blood-based biomarkers of neurodegenerative diseases with mortality, cardio- and cerebrovascular events in persons with chronic coronary syndrome.

Background: In light of growing evidence highlighting interactions between cardiac and brain health, we investigated associations of biomarkers of neurodegenerative diseases with adverse outcomes (all-cause and cardiovascular mortality, major cardiovascular events, and stroke) in persons with chronic coronary syndrome (CCS).

Methods: We used data from a cohort of persons with CCS for whom major adverse events were recorded over a follow-up of 20 years. We measured biomarkers of neurodegenerative diseases in baseline blood samples, using the Single-Molecule Array Technology on a HD-1 Analyzer.

[Access to and Transitions within the Medical Care Process of Persons with Down Syndrome and Dementia: A Qualitative Analysis].

Compared to the general population, individuals with Down syndrome carry a much higher genetic risk of developing early onset Alzheimer's dementia. This leads to unique challenges and the need for a targeted patient journey.In a qualitative interview study with medical professionals, patient organisations and formal and informal care persons, we assessed barriers within the medical care process of this patient group as well as current approaches to overcome these problems.

Sonography of Salivary Gland Tumors and Disorders.

Diseases of the salivary glands are as common as they are diverse and can have different causes. Clinicians can differentiate salivary gland changes based on chronic systemic diseases, congenital and vascular malformations, and benign and malignant tumors. Acute infectious pathologies can also arise as a result of obstructive pathologies.

A biodegradable polymer plug for liver tract embolization after percutaneous or surgical placement of transhepatic biliary drainage tubes: a feasibility study.

To evaluate the feasibility of liver tract embolization after transhepatic biliary drainage using a biodegradable polymer plug (IMPEDE-FX, Shape Memorial Medical, Santa Clara, CA, USA).In a retrospective observational study, 15 plug embolizations were performed in 13 patients at risk for tract-related adverse events (AEs). Risk factors included coagulopathy, cirrhosis, central bile duct puncture, previous drain-related bleeding, malignant obstruction, large tract diameter, or multilevel strictures.

Video-based Informed Consent in Radiology - Acceptance, Satisfaction, and Effectiveness.

Before any medical procedure, including computed tomography (CT), it is crucial to ensure patients are fully informed about the risks and alternative options. Video-based informed consent offers an increased transfer of information in less time.In a monocentric, prospective, questionnaire-based study, video-based informed consent, which included a digital medical history form, was compared to the traditional paper-based consent form.

Outcomes after medical treatment for primary aldosteronism: an international consensus and analysis of treatment response in an international cohort.

Background: Primary aldosteronism can be treated medically but there is no standardised method to evaluate treatment outcomes. We aimed to develop criteria for assessing the outcomes of targeted medical treatment of primary aldosteronism, analyse outcomes across an international cohort, and identify factors associated with a complete treatment response.

Methods: An international panel of 31 primary aldosteronism experts used the Delphi method to reach consensus on the definition of complete, partial, or absent biochemical and clinical outcomes of medical treatment of primary aldosteronism.

Bi-allelic KICS2 mutations impair KICSTOR complex-mediated mTORC1 regulation, causing intellectual disability and epilepsy.

Nutrient-dependent mTORC1 regulation upon amino acid deprivation is mediated by the KICSTOR complex, comprising SZT2, KPTN, ITFG2, and KICS2, recruiting GATOR1 to lysosomes. Previously, pathogenic SZT2 and KPTN variants have been associated with autosomal recessive intellectual disability and epileptic encephalopathy. We identified bi-allelic KICS2 variants in eleven affected individuals presenting with intellectual disability and epilepsy.

Repeat Procedures After Pulsed Field Ablation for Atrial Fibrillation: MANIFEST-REDO Study.

Background: Initial clinical studies of pulsed field ablation (PFA) to treat atrial fibrillation (AF) indicated a >90% durability rate of pulmonary vein isolation (PVI). However, these studies were largely conducted in single centers and involved a limited number of operators. The electrophysiological findings and outcomes in patients undergoing repeat ablation after an initial PF ablation for AF are incompletely understood.

Molecular determinants of condensate composition.

Cells use membraneless compartments to organize their interiors, and recent research has begun to uncover the molecular principles underlying their assembly. Here, we explore how site-specific and chemically specific interactions shape the properties and functions of condensates. Site-specific recruitment involves precise interactions at specific sites driven by partially or fully structured interfaces.

Bridging the gap: How enhancers cooperate to regulate gene expression over large genomic distances.

By building synthetic regulatory landscapes, Jensen et al. and Thomas et al. demonstrate in this issue of Molecular Cell that gene expression levels strongly depend on the genomic distance between enhancers and promoters and that enhancer cooperation can compensate for reduced enhancer activity over large genomic distances.

Combining steric exclusion with anion exchange - development of a universal and scalable adeno-associated virus downstream process.

Adeno-associated viruses (AAV) are among the leading vectors for in vivo gene therapy. The purification of AAV remains a bottleneck as it typically requires multiple individual process steps, often resulting in product loss and high costs. Current downstream processes are usually serotype-specific and rely primarily on expensive affinity resins.

Regulatory workshop on standardisation of clinical procedures, endpoints and data robustness of human challenge studies - A stakeholder meeting report.

Inno4Vac, a public-private partnership funded by the IMI2/EU/EFPIA Joint Undertaking (IMI2 JU), brings together academic institutions, SMEs, and pharmaceutical companies to accelerate and de-risk vaccine development. The project has made significant strides in the selection and production of challenge agents for influenza, respiratory syncytial virus (RSV), and toxigenic Clostridioides difficile for controlled human infection model studies (CHIMs). A regulatory workshop held on March 20, 2024, addressed the standardisation of clinical procedures, ethical considerations, endpoints, and data integrity, highlighting the ongoing initiatives related to these CHIMs.