Naphtho[1,2-][1,4]diazepinedione-Based P2X4 Receptor Antagonists from Structure-Activity Relationship Studies toward PET Tracer Development.

The P2X4 receptor is implicated in various pathological conditions, including neuropathic pain and cancer. This study reports the development of 1,4-naphthodiazepinedione-based P2X4 receptor antagonists aimed at both therapeutic applications and potential use as PET tracers for imaging P2X4 receptor expression in cancer. Structure-activity relationship studies aided by docking studies and molecular dynamics simulations led to a series of compounds with potent P2X4 receptor antagonism, promising inhibition of interleukin-1β release in THP-1 cells and suitability for radiolabeling with fluorine-18.

ZNFX1 functions as a master regulator of epigenetically induced pathogen mimicry and inflammasome signaling in cancer.

DNA methyltransferase and poly (ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon genes (STING)-dependent pathogen mimicry response (PMR) in ovarian and other cancers. Here, we showed that combining DNMTis and PARPis upregulates expression of the nucleic-acid sensor NFX1-type zinc finger-containing 1 protein (ZNFX1). ZNFX1 mediated induction of PMR in mitochondria, serving as a gateway for STING-dependent interferon/inflammasome signaling.

Correction: Peisen et al. Can Delta Radiomics Improve the Prediction of Best Overall Response, Progression-Free Survival, and Overall Survival of Melanoma Patients Treated with Immune Checkpoint Inhibitors? 2024, , 2669.

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Long-Term Outcomes and Quality of Life of High-Risk Neuroblastoma Patients Treated with a Multimodal Treatment Including Anti-GD2 Immunotherapy: A Retrospective Cohort Study.

Background: The incorporation of anti-GD2 antibodies such as ch14.18/SP2/0 into the multimodal treatment of high-risk neuroblastoma (HR-NB) patients has improved their outcomes. As studies assessing the long-term outcomes, long-term sequelae, and health-related quality of life (HRQoL) of this treatment are limited, this retrospective analysis aimed to explore these.

Oral Maintenance Therapy in Early Breast Cancer-How Many Patients Are Potential Candidates?

Background/objectives: This single-center analysis evaluated the number of potential candidates for endocrine-based oral maintenance therapy in a real-world setting, focusing on three therapeutic agents, namely, olaparib, abemaciclib, and ribociclib, for patients with hormone receptor-positive HER2-negative early breast cancer.

Methods: All breast cancer cases from the past 10 years ( = 3230) that underwent treatment at the certified Breast Cancer Center of the Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Lübeck Campus, were analyzed.

Results: Of a total of 2038 patients with HR+ HER2- eBC, 685 patients (33.

Comparison of GFR estimation in patients with diabetes mellitus using the EKFC and CKD-EPI equations.

Background: The estimation of glomerular filtration rate (eGFR) is essential in the early detection of diabetic nephropathy. We herein compare the performance of common eGFR formulas against a gold standard measurement of GFR in patients with diabetes mellitus.

Methods: GFR was measured in 93 patients with diabetes mellitus using iohexol clearance as the reference standard.

Everolimus with or without mycophenolate mofetil for GVHD prophylaxis after allogeneic HSCT in children with acute kidney injury - a single-center retrospective analysis.

Background: Hematopoietic stem cell transplantation (HSCT) serves as a therapeutic intervention for various pediatric diseases. Acute and chronic graft-versus-host disease (GVHD) are decisive determinants for allogeneic HSCT success. The immunosuppressive agent, ciclosporin A, is most often used to prevent GVHD in pediatric patients, but is known to be nephrotoxic.

Recipient sex and donor leukemic cell characteristics determine leukemogenesis in patient-derived models.

In acute myeloid leukemia (AML), leukemogenesis depends on cell-intrinsic genetic aberrations and thus, studies on AML require investigations in an in vivo setting as provided by patient derived xenografts (PDX) models. Here we report that, next to leukemic cell characteristics, recipient sex highly influences the outgrowth of AML cells in PDX models, with females being much better repopulated than males in primary as well as secondary transplantation assays. Testosterone may be the more important player since, strikingly, better engraftment was seen in castrated versus control male recipients, while ovariectomy did not significantly impair engraftment in females.

Cardiotoxicity as important differential diagnosis for reduced myocardial blood flow during Rubidium cardiac PET/CT : Cardiotoxicity in Rubidium PET/CT.

A 65-year-old woman with a history of ductal mammary carcinoma and recent autonomic dysfunction underwent a Rb-82 chloride (RbCl) cardiac PET/CT scan that showed no ischemia or scarring, but significantly reduced myocardial flow reserve (MFR) (global: 1.5) and a CAC-Score of 0. The patient's chemotherapy history (paclitaxel, carboplatin, epirubicin, pembrolizumab 2 years before) with elevated Troponin T and NT-pro-BNP levels at that time, and now reduced MFR with 0 CAC suggests cancer-therapy-related cardiotoxicity.

Longitudinal association between nailfold capillaroscopy and incident interstitial lung disease: A EUSTAR database analysis.

Objectives: To evaluate (1) the association between nailfold capillaroscopy pattern and 5-year risk for incident interstitial lung disease and (2) the association between transition in nailfold capillaroscopy pattern and risk of incident interstitial lung disease.

Methods: Data of adult patients from the EUSTAR database fulfilling the ACR-EULAR criteria with a disease duration ⩽5 years, having a scleroderma pattern at nailfold capillaroscopy with high-resolution computed tomography confirmed absence of interstitial lung disease (i.e.

SarkoLife: quality of life in patients undergoing multimodal soft tissue sarcoma treatment.

Objective: To assess the tolerability of multimodal therapy in soft tissue sarcoma patients, particularly with regard to their quality of life and level of distress.

Materials And Methods: A retrospective cohort study enrolled individuals receiving sarcoma therapy at the sarcoma center of the University of Tuebingen between 2017 and 2022. Participants completed an online survey that included the EORTC's questionnaire (QLQ-C30), coupled with the distress thermometer and demographic inquiries.

Metabolic Biomarkers of Liver Failure in Cell Models and Patient Sera: Toward Liver Damage Evaluation In Vitro.

Recent research has concentrated on the development of suitable in vitro cell models for the early identification of hepatotoxicity during drug development in order to reduce the number of animal models and to obtain a better predictability for hepatotoxic reactions in humans. The aim of the presented study was to identify translational biomarkers for acute liver injury in human patients that can serve as biomarkers for hepatocellular injury in vivo and in vitro in simple cell models. Therefore, 188 different metabolites from patients with acute-on-chronic liver failure before and after liver transplantation were analyzed with mass spectrometry.

Brolucizumab and Platelet Activation and Reactivity.

Purpose: This study explores the potential interaction of brolucizumab with platelets and its effects on platelet activation and reactivity, crucial in retinal vasculitis and retinal vascular occlusion. Safety concerns remain of interest, although brolucizumab showed superior retinal efficacy and reduced injection frequency compared to other licensed anti-VEGF agents.

Methods: Resting and activated platelets of healthy volunteers were pretreated with brolucizumab at the following concentrations 0.

Patient's Perception of Primary Health Care Provision With Respect to Access, Continuity and Coordination-InCept: An International Qualitative Perspective.

Health care systems are confronted with an increasing burden of (multi-)morbidity and a shortfall of healthcare providers. Coordination and continuity of care in chronic and multi-morbid patient is especially important. As qualitative patient experience data within care processes is scarce, we aim to increase the understanding of chronically ill patient's perspectives by assessing patient experiences in different health systems while treated in primary care.

EEFSEC deficiency: A selenopathy with early-onset neurodegeneration.

Inborn errors of selenoprotein expression arise from deleterious variants in genes encoding selenoproteins or selenoprotein biosynthetic factors, some of which are associated with neurodegenerative disorders. This study shows that bi-allelic selenocysteine tRNA-specific eukaryotic elongation factor (EEFSEC) variants cause selenoprotein deficiency, leading to progressive neurodegeneration. EEFSEC deficiency, an autosomal recessive disorder, manifests with global developmental delay, progressive spasticity, ataxia, and seizures.

Real-World-Data of Treatment-Naïve and Previously Treated Patients Receiving Up to 3 Injections of Faricimab in Neovascular Age-Related Macular Degeneration.

Purpose: To evaluate visual and anatomical outcome of consecutive patients who received intravitreal injections (IVI) of faricimab for the treatment of neovascular age-related macular degeneration (nAMD).

Patients And Methods: A retrospective study of patients treated for nAMD with one to three IVIs of faricimab from October 2022 to January 2024. Demographic data, treatment history, best corrected visual acuity (BCVA), anatomic parameters, and adverse events (AEs) were collected.

Real-world management of patients with complete response under immune-checkpoint inhibition for advanced melanoma.

Background: Up to now, the optimal duration of immune checkpoint inhibitors (ICI) has not been evaluated in prospective studies. However, current clinical practice requires decisions to be made regarding the duration of ICI in complete responders.

Material And Methods: A survey was sent to 80 DeCOG skin cancer centers to assess how decisions are made on treatment duration of ICI in melanoma after having reached complete response, and staging intervals after ICI discontinuation.

SARS-CoV-2 immune responses in patients with multiple myeloma and lenalidomide maintenance therapy.

Introduction: Multiple myeloma (MM) is an uncontrolled plasma cell proliferation in the bone marrow, leading to immune dysregulation with impaired humoral immune responses. Conversely, cellular-based responses play a vital role in MM patients. However, the extent and duration of cellular-induced protection remain unclear to date.

The joint memory effect: challenging the selfish stigma in Huntington's disease?

The prevalent belief that individuals with Huntington's disease exhibit selfish behaviour, disregarding the thoughts, feelings and actions of others, has been challenged by patient organizations and clinical experts. To further investigate this issue and study whether participants with Huntington's disease can pay attention to others, a joint memory task was carried out in patients with Huntington's disease with and without a partner. This study involved 69 participants at an early stage of Huntington's disease and 56 healthy controls from the UK, France and Germany, who participated in the international Repair-HD multicentre study (NCT03119246).

Subphenotypes of body composition and their association with cardiometabolic risk - Magnetic resonance imaging in a population-based sample.

Background: For characterizing health states, fat distribution is more informative than overall body size. We used population-based whole-body magnetic resonance imaging (MRI) to identify distinct body composition subphenotypes and characterize associations with cardiovascular disease (CVD) risk.

Methods: Bone marrow, visceral, subcutaneous, cardiac, renal, hepatic, skeletal muscle and pancreatic adipose tissue were measured by MRI in n = 299 individuals from the population-based KORA cohort.

Developing Gingerol-Based Analogs against Infections.

(), a Gram-negative opportunistic pathogen, produces virulent factors and forms biofilms through a quorum sensing (QS) mechanism. Modulating QS networks is considered an effective strategy for treating infections. Particularly, the system, one of the QS networks, can be a potential target in treating patients with chronic infections.

Wilms tumor primary cultures capture phenotypic heterogeneity and facilitate preclinical screening.

Wilms tumors (WT) are characterized by variable contributions of blastemal, epithelial and stromal elements, reflecting their diverse cellular origins and genetic drivers. In vitro models remain rare, despite a growing need to better characterize tumor biology and evaluate new treatments. Using three approaches, we have now established a large collection of long-term cultures that represent this diversity.