RECQL4 affects MHC class II-mediated signalling and favours an immune-evasive signature that limits response to immune checkpoint inhibitor therapy in patients with malignant melanoma.

Background: Cancer immunotherapy has transformed metastatic cancer treatment, yet challenges persist regarding therapeutic efficacy. RECQL4, a RecQ-like helicase, plays a central role in DNA replication and repair as part of the DNA damage response, a pathway implicated in enhancing efficacy of immune checkpoint inhibitor (ICI) therapies. However, its role in patient response to ICI remains unclear.

Radiomics-driven spectral profiling of six kidney stone types with monoenergetic CT reconstructions in photon-counting CT.

Objectives: Urolithiasis, a common and painful urological condition, is influenced by factors such as lifestyle, genetics, and medication. Differentiating between different types of kidney stones is crucial for personalized therapy. The purpose of this study is to investigate the use of photon-counting computed tomography (PCCT) in combination with radiomics and machine learning to develop a method for automated and detailed characterization of kidney stones.

Automated Kidney Stone Composition Analysis with Photon-Counting Detector CT, a Performance Study-A Phantom Study.

Background: For treatment of urolithiasis, the stone composition is of particular interest, as uric acid (UA) stones can be treated by chemolitholysis. In this ex vivo study, we employed an advanced composition analysis approach for urolithiasis utilizing spectral data obtained from a photon-counting detector CT (PCDCT) to differentiate UA and non-UA stones. Our primary objective was to assess the accuracy of this analysis method.

From viruses to humans - Exploring the structure-function relationship of the Kesv protein for the future of biomedicine.

Viruses often use ion channel proteins to initialise host infections. Defects in ion channel proteins are also linked to several metabolic disorders in humans. In that instance, modulation of ion channel activities becomes central to development of antiviral therapies and drug design.

Comparison of automated kidney stone size measurement and volumetry in photon counting CT compared to 3rd generation dual energy CT and physically measurements - an ex vivo study.

Purpose: This ex vivo study aimed to compare a newly developed dual-source photon-counting CT (PCCT) with a 3rd generation dual-source dual-energy CT (DECT) for the detection and measurement (stone lengths and volumetrics) of urinary stones.

Methods: 143 urinary stones with a known geometry were physically measured and defined as reference values. Next, urinary stones were placed in an anthropomorphic abdomen-model and were scanned with DECT and PCCT.

Primary Human Papillomavirus Test Uptake and Cervical Cancer Screening Trends in the Midwest, United States.

Introduction/objectives: Despite U.S. Preventive Services Task Force and American Cancer Society endorsement of primary HPV screening, limited published data shows low uptake.

Toward More Selective Antibiotic Inhibitors: A Structural View of the Complexed Binding Pocket of Peptide Deformylase.

Peptide deformylase (PDF) is involved in bacterial protein maturation processes. Originating from the interest in a new antibiotic, tremendous effort was put into the refinement of PDF inhibitors (PDFIs) and their selectivity. We obtained a full NMR backbone assignment the emergent additional protein backbone resonances of ecPDF 1-147 in complex with 2-(5-bromo-1-indol-3-yl)--hydroxyacetamide (), a potential new structural scaffold for more selective PDFIs.

Incorporating recirculation effects into metrics of feeding performance for current-feeding zooplankton.

The feeding performance of zooplankton influences their evolution and can explain their behaviour. A commonly used metric for feeding performance is the volume of fluid that flows through a filtering surface and is scanned for food. Here, we show that such a metric may give incorrect results for organisms that produce recirculatory flows, so that fluid flowing through the filter may have been already filtered of food.

Structural Insights into Antibacterial Payload Release from Gold Nanoparticles Bound to E. coli Peptide Deformylase.

The lack of new antibiotics and the rapidly rising number of pathogens resistant to antibiotics pose a serious problem to mankind. In bacteria, the cell membrane provides the first line of defence to antibiotics by preventing them from reaching their molecular target. To overcome this entrance barrier, it has been suggested that small Gold-Nanoparticles (AuNP) could possibly function as drug delivery systems for antibiotic ligands.

Development and validation of a predictive model of the hospital cost associated with bariatric surgery.

Hospitals are facing difficulties in predicting, evaluating, and managing cost-affecting parameters in patient treatments. Inaccurate cost prediction leads to a deficit in operational revenue. This study aims to determine the ability of Machine Learning (ML) algorithms to predict the cost of care in bariatric and metabolic surgery and develop a predictive tool for improved cost analysis.

Spectroscopically Orthogonal Spin Labels in Structural Biology at Physiological Temperatures.

Electron paramagnetic resonance spectroscopy (EPR) is mostly used in structural biology in conjunction with pulsed dipolar spectroscopy (PDS) methods to monitor interspin distances in biomacromolecules at cryogenic temperatures both in vitro and in cells. In this context, spectroscopically orthogonal spin labels were shown to increase the information content that can be gained per sample. Here, we exploit the characteristic properties of gadolinium and nitroxide spin labels at physiological temperatures to study side chain dynamics via continuous wave (cw) EPR at X band, surface water dynamics via Overhauser dynamic nuclear polarization at X band and short-range distances via cw EPR at high fields.

Characterization of a fold in TANGO1 evolved from SH3 domains for the export of bulky cargos.

Bulky cargos like procollagens, apolipoproteins, and mucins exceed the size of conventional COPII vesicles. During evolution a process emerged in metazoans, predominantly governed by the TANGO1 protein family, that organizes cargo at the exit sites of the endoplasmic reticulum and facilitates export by the formation of tunnel-like connections between the ER and Golgi. Hitherto, cargo-recognition appeared to be mediated by an SH3-like domain.

A Reinvestigation of the Role of the Sorbic Acid Tail on the Antibacterial and Anti-Tuberculosis Properties of Moiramide B.

Due to worldwide increasing resistances, there is a considerable need for antibacterial compounds with modes of action not yet realized in commercial antibiotics. One such promising structure is the acetyl-CoA carboxylase (ACC) inhibitor moiramide B which shows strong antibacterial activity against gram-positive bacteria such as Bacillus subtilis and weaker activities against gram-negative bacteria. However, the narrow structure-activity relationship of the pseudopeptide unit of moiramide B represents a formidable challenge for any optimization strategy.

The second PI(3,5)P binding site in the helix of KCNQ1 stabilizes PIP-at the primary site with potential consequences on intermediate-to-open state transition.

The Phosphatidylinositol 3-phosphate 5-kinase Type III PIKfyve is the main source for selectively generated phosphatidylinositol 3,5-bisphosphate (PI(3,5)P), a known regulator of membrane protein trafficking. PI(3,5)P facilitates the cardiac KCNQ1/KCNE1 channel plasma membrane abundance and therewith increases the macroscopic current amplitude. Functional-physical interaction of PI(3,5)P with membrane proteins and its structural impact is not sufficiently understood.

Streamlined pediatric anxiety program for school mental health services.

There needs to be serious transformation of evidence-based interventions (EBIs) into real-world solutions; otherwise, EBIs will never achieve the intended public health impact. In a randomized trial, we reported effects of a redesigned anxiety program. Herein, we described the redesign process that led to the program.

Potassium viroporins as model systems for understanding eukaryotic ion channel behaviour.

Ion channels are membrane proteins essential for a plethora of cellular functions including maintaining cell shape, ion homeostasis, cardiac rhythm and action potential in neurons. The complexity and often extensive structure of eukaryotic membrane proteins makes it difficult to understand their basic biological regulation. Therefore, this article suggests, viroporins - the miniature versions of eukaryotic protein homologs from viruses - might serve as model systems to provide insights into behaviour of eukaryotic ion channels in general.

Design, synthesis, and molecular docking study of novel cinnoline derivatives as potential inhibitors of tubulin polymerization.

The preparation of a novel 4-methylbenzo[] cinnolines entity via a three-step synthetic protocol is described. Cyclization of the naphthylamidrazones, in the presence of polyphosphoric acid (PPA), furnishes the respective target benzo[]cinnolines directly. This one-pot synthesis involves intramolecular Friedel-Crafts acylation followed by instant elimination under heating conditions.

Synthesis, Biological Evaluation, and Binding Mode of a New Class of Oncogenic K-Ras4b Inhibitors.

Ras proteins are implicated in some of the most common life-threatening cancers. Despite intense research during the past three decades, progress towards small-molecule inhibitors of mutant Ras proteins still has been limited. Only recently has significant progress been made, in particular with ligands for binding sites located in the switch II and between the switch I and switch II region of K-Ras4B.

Deciphering the Emulsification Process to Create an Albumin-Perfluorocarbon-(o/w) Nanoemulsion with High Shelf Life and Bioresistivity.

This work aimed at the development of a stable albumin-perfluorocarbon (o/w) emulsion as an artificial oxygen carrier suitable for clinical application. So far, albumin-perfluorocarbon-(o/w) emulsions have been successfully applied in preclinical trials. Cross-linking a variety of different physical and chemical methods for the characterization of an albumin-perfluorocarbon (PFC)-(o/w) emulsion was necessary to gain a deep understanding of its specific emulsification processes during high-pressure homogenization.

Synthesis and Cytotoxic Activity Study of Novel 2-(Aryldiazenyl)-3-methyl-1-benzo[]indole Derivatives.

A novel series of 2-(aryldiazenyl)-3-methyl-1-benzo[]indole derivatives (-) were prepared through the cyclization of the corresponding arylamidrazones, employing polyphosphoric acid (PPA) as a cyclizing agent. All of the compounds (-) were characterized using H NMR, C NMR, MS, elemental analysis, and melting point techniques. The synthesized compounds were evaluated for cytotoxic activity against diverse human cancer cell lines by the National Cancer Institute.