Bariatric Surgery in Patients With Prader-Willi Syndrome.

Prader-Willi Syndrome (PWS) is a genetic disorder characterized by insatiable hyperphagia, resulting in severe, early-onset obesity that is often refractory to conventional management. The associated comorbidities and reduced life expectancy in PWS present a significant therapeutic challenge. This review synthesizes the existing literature on the controversial role, outcomes, and complexities of bariatric surgery in patients with PWS.

Isocitrate dehydrogenase mutation and microenvironment in gliomas: do immunotherapy approaches matter?

Purpose Of Review: Gliomas with mutations in the gene for isocitrate dehydrogenase (IDH) display a unique immune microenvironment that is distinct from IDH-wildtype gliomas. This unique immune microenvironment is shaped by 2-hydroxyglutarate (2-HG), an oncometabolite produced by mutant IDH. These features provide an opportunity to develop and test targeted immunotherapies for IDH-mutant gliomas.

Food, Built and Socio-Economic Environments and Maternal-Infant Outcomes: A Geospatial and Structural Equation Modelling of 163 000 Births.

Objectives: To examine the combined influence of food environment, built environment, socio-economic status and individual factors (maternal age, parity, smoking status and need for an interpreter) on maternal overweight, gestational diabetes mellitus (GDM) and large-for-gestational age (LGA) births in Australia.

Design: Retrospective cohort study.

Setting: Melbourne, Australia.

Oleandrin-mediated suppression of MELK induces apoptosis, autophagy, and ferroptosis in human non-small cell lung cancer cells.

Background: Non-small-cell lung cancer NSCLC is the major diagnosed type of lung cancers in the USA and Europe. It is generally related to poor prognosis and low rates of survival. Oleandrin is a cardiac glycoside occurring naturally in Nerium oleander (Apocynaceae).

Chronic kidney disease and incident cancer risk: an individual participant data meta-analysis.

Background: Studies examining the association of chronic kidney disease (CKD) with cancer risk have demonstrated conflicting results.

Methods: This was an individual participant data meta-analysis including 54 international cohorts contributing to the CKD Prognosis Consortium. Included cohorts had data on albuminuria [urine albumin-to-creatinine ratio (ACR)], estimated glomerular filtration rate (eGFR), overall and site-specific cancer incidence, and established risk factors for cancer.

Single-step, chloroform-free Extraction of Lysophosphatidylcholine from Plasma for Cancer Biomarker Analysis.

Lysophosphatidylcholine (LPC) has been the subject of research for many years, but its role in lipid turnover is still not fully understood, neither its role in cancer development and progression. A crucial aspect in LPC research is its efficient and fast extraction from plasma and tissues to use LPC as a biomarker in clinical settings. The extraction methods commonly in use like Bligh & Dyer require the use of toxic halogenated solvents and are time consuming due to multiple extraction steps and subsequent solvent evaporation.

Predicting Treatment Response in Retinal Vein Occlusions Using Baseline Optical Coherence Tomography Biomarkers: A Systematic Review.

This systematic review examines the prognostic value of baseline optical coherence tomography (OCT) biomarkers in predicting visual acuity (VA) outcomes for eyes with macular edema secondary to retinal vein occlusions (RVO) treated with anti-VEGF therapies, steroids, laser photocoagulation, or combination treatments. VA predictions at 6, 12, and 24 months post-treatment were assessed using a narrative synthesis approach and vote counting based on effect direction relative to a minimal clinically important difference. Certainty of evidence was evaluated using GRADE guidelines.

HT SpaceM: A high-throughput and reproducible method for small-molecule single-cell metabolomics.

Single-cell metabolomics (SCM) promises to reveal metabolism in its complexity and heterogeneity, yet current methods struggle with detecting small-molecule metabolites, throughput, and reproducibility. Addressing these gaps, we developed HT SpaceM, a high-throughput SCM method combining cell preparation on custom glass slides, small-molecule matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (MS), and batch processing. We propose a unified framework covering quality control, characterization, structural validation, and differential and functional analyses.

Prognostic factors for very early recurrence after neoadjuvant treatment and curative resection in pancreatic ductal adenocarcinoma.

Introduction: Very early recurrence in pancreatic ductal adenocarcinoma has been defined as recurrence ≤3 months after resection. Besides others, neoadjuvant treatment is delivered based on the assumption of preoperative eradication of micrometastasis as well as local downstaging. Prognostic factors of very early recurrence after neoadjuvant treatment remain largely unexplored.

Artificial intelligence-assisted assessment of metabolic response to tebentafusp in metastatic uveal melanoma: a long axial field-of-view [F]FDG PET/CT study.

Purpose: Tebentafusp has emerged as the first systemic therapy to significantly prolong survival in treatment-naïve HLA-A*02:01 + patients with unresectable or metastatic uveal melanoma (mUM). Notably, a survival benefit has been observed even in the absence of radiographic response. This study aims to investigate the feasibility and prognostic value of artificial intelligence (AI)-assisted quantification and metabolic response assessment of [F]FDG long axial field-of-view (LAFOV) PET/CT in mUM patients undergoing tebentafusp therapy.

Comparison of prognostication by IPSS-M, IPSS-R and AIPSS-MDS in the context of limited availability of molecular data in daily clinical practice.

The IPSS-M was developed to revolutionize the prediction of MDS patients' survival by incorporating molecular data. To compensate for lack of access to molecular analyses, the AIPSS-MDS, a supervised machine learning algorithm exclusively based on clinical and cytogenetic data, was developed by the Spanish MDS Group. We used data of the Düsseldorf MDS Registry and included 207 of more than 8500 registry patients whose IPSS-M-requested complete molecular data were known to compare and validate prognostication regarding OS and LFS of the IPSS-M, IPSS-R and AIPSS-MDS.

Molecularly matched targeted therapies plus radiotherapy in glioblastoma: the phase 1/2a NM umbrella trial.

Advances in molecular understanding and diagnostic precision of glioblastoma enable the identification of key genetic alterations in a timely manner and, in principle, allow treatments with targeted compounds based on molecular markers. Here we report the results of the phase 1/2 umbrella trial NCT Neuro Master Match (NM), which evaluated targeted treatments in 228 patients with newly diagnosed glioblastoma without O6-methylguanine DNA-methyltransferase promoter hypermethylation. Stratification for treatment was conducted by a trial-specific molecular tumor board across five subtrials, each evaluating a targeted therapy-alectinib, idasanutlin, palbociclib, vismodegib or temsirolimus-selected according to the best-matching molecular alteration.

National survey on the presence of multidisciplinary meetings for interstitial lung diseases (ILD-MDM) in hospitals in Germany.

Background: Interstitial lung diseases (ILD) represent an interdisciplinary clinical challenge and are not uncommonly associated with rheumatological diseases. Interstitial lung disease multidisciplinary meetings (ILD-MDM) provide a structured platform for interdisciplinary case discussions and decision making. Despite their great importance in patient care, data on the prevalence, structure and function of ILD-MDM in Germany are lacking.

Impulsivity and neuroticism share distinct functional connectivity signatures with alcohol-use risk in youth.

Increases in impulsivity and negative affect (e.g., neuroticism) are common during adolescence and are both associated with risk for alcohol-use initiation and other risk behaviors.

[Health services research as a job market: A document analysis of job advertisements].

Introduction: Since the mid-2010s, health services research (HSR) in Germany has been increasingly institutionalized. However, little is known about actual career paths within the field. The aim of this study was to describe the HSR job market in Germany, both in general terms and specifically for graduates of health services research master degree programs.

Resolving leukemic stem cell heterogeneity and plasticity with single-cell multiomics.

Acute myeloid leukemia (AML) is an aggressive blood cancer in which disease initiation and relapse are driven by leukemic cells with stem-like properties, known as leukemic stem cells (LSCs). The LSC compartment is highly heterogenous and this contributes to differences in therapy response. This heterogeneity is determined by genetic and nongenetic factors including somatic mutations, the cell of origin, transcriptional and epigenetic states as well as phenotypic plasticity.

The art of diagnosing rare skin tumors: Can DL-CNNs enhance dermatologists' diagnostic accuracy?

Importance: Deep learning convolutional neural networks (DL-CNN) achieved diagnostic accuracies comparable to dermatologists in controlled test environments. However, their performance in diagnosing rare skin tumors (RST) remains unclear. This study aimed to evaluate a binary DL-CNN's diagnostic performance in RST and assess the level of support for an international group of dermatologists.

Outcome of systemic therapy in patients with advanced rare skin cancers: A retrospective multicenter DeCOG study of 209 patients.

Introduction: For rare skin cancers, few data exist on the outcome of systemic therapies, particularly immune checkpoint inhibition (ICI). The present study analysed the real-world use of different systemic therapies including ICI, and its outcome in patients with advanced rare skin cancers.

Methods: This retrospective multicenter study included patients who received systemic therapy for advanced, non-resectable cutaneous angiosarcoma (AS), Kaposi sarcoma (KS), pleomorphic dermal sarcoma (PDS), or cutaneous adnexal carcinoma (CAC).

Advancing preclinical biology for Ewing Sarcoma: an international effort.

Ewing sarcoma (EwS) is an aggressive bone and soft tissue cancer affecting adolescents and young adults. In vitro and in vivo models of EwS have been instrumental in advancing our understanding of EwS biology and essential in evaluating potential therapies, particularly for metastatic or relapsed disease where effective treatment options remain limited. Through an international collaborative effort between the Children's Oncology Group (COG) Bone Tumor Committee and the Euro Ewing Consortium (EEC), we review the current landscape of preclinical modeling used in EwS research encompassing both in vitro (cell lines and tumor organoids) and in vivo (mouse and non-mammalian xenografts) model systems.

Computational design of potent and selective binders of BAK and BAX.

Potent and selective binders of the key proapoptotic proteins BAK and BAX have not been described. We use computational protein design to generate high affinity binders of BAK and BAX with greater than 100-fold specificity for their target. Both binders activate their targets when at low concentration, driving pore formation, but inhibit membrane permeabilization when in excess.

Differential regulation of calcium-activated plant kinases in Arabidopsis thaliana.

The decoding of calcium signals by plant calcium-dependent kinases (CPKs) is not fully understood yet. Based on kinetic in vitro measurements of the activity of several CPK proteins, their individual activity profile was modeled and coupled to cytosolic calcium concentration changes from in vivo measurements of guard cells and epidermal leaf cells. In addition, computationally produced surrogate data were used.

Approaches for the treatment of perforated peptic ulcers: a network meta-analysis of randomized controlled trials.

Purpose: This network meta-analysis (NMA) aims to evaluate surgical and alternative treatment strategies for perforated peptic ulcers (PPU) with respect to mortality and other clinically relevant outcomes.

Methods: An NMA was conducted in accordance with PRISMA guidelines to assess treatment approaches for PPU. Randomized controlled trials (RCT) were identified through systematic searches of PubMed/MEDLINE, Cochrane Library, Embase, CINAHL, ClinicalTrials.