Mutations disrupting the kinase domain of IKKα lead to immunodeficiency and immune dysregulation in humans.

IKKα, encoded by CHUK, is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKβ. The absence of IKKα causes fetal encasement syndrome in humans, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and causes combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of IKKα in a female patient with hypogammaglobulinemia, recurrent lung infections, and Hay-Wells syndrome-like features.

Circulating Tumor DNA for Prediction of Complete Pathological Response to Neoadjuvant Radiochemotherapy in Locally Advanced Rectal Cancer (NEORECT Trial).

Background/objectives: Locally advanced rectal cancer is treated with neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). As this approach achieves complete pathologic remissions (pCR) in approximately 30% of patients, it raises the question of whether surgery is always necessary. Non-surgical strategies, such as "watch and wait" (W&W), have shown similarly promising outcomes.

Supramolecular multiplexes from collagen mimetic peptide-PNA(GGG) conjugates and C-rich DNA: pH-induced reversible switching from triplex-duplex to triplex--motif.

Peptides are well known for forming nanoparticles, while DNA duplexes, triplexes and tetraplexes create rigid nanostructures. Accordingly, the covalent conjugation of peptides to DNA/RNA produces hybrid self-assembling features and may lead to interesting nano-assemblies distinct from those of their individual components. Herein, we report the preparation of a collagen mimetic peptide incorporating lysine in its backbone, with alkylamino side chains radially conjugated with G-rich PNA [collagen-(PNA-GGG)].

Double Heterozygous Pathogenic Variants in and in Boy with Undifferentiated Embryonal Sarcoma of the Liver.

Undifferentiated embryonal sarcoma of the liver is a rare mesenchymal malignancy that predominantly occurs in children. The relationship between this tumor entity and germline pathogenic variants (PVs) remains undefined. Here, we present the clinical case of a male patient diagnosed with undifferentiated embryonal sarcoma of the liver.

Association of keel bone morphometry with keel bone damage and skeletal quality in the laying hen.

1. The aim of this work was to identify a heritable keel bone phenotype with a correlation to keel bone damage and/or skeletal bone strength that could be easily measured in the living hen to aid selection to prevent welfare issues.2.

3D Cryo-Electron Microscopy Reveals the Structure of a 3-Fluorenylmethyloxycarbonyl Zipper Motif Ensuring the Self-Assembly of Tripeptide Nanofibers.

Short peptide-based supramolecular hydrogels appeared as highly interesting materials for applications in many fields. The optimization of their properties relies mainly on the design of a suitable hydrogelator through an empirical trial-and-error strategy based on the synthesis of various types of peptides. This approach is in part due to the lack of prior structural knowledge of the molecular architecture of the various families of nanofibers.

Model to rationalize and predict the formation of organic patterns originating from an enzyme-assisted self-assembly Liesegang-like process of peptides in a host hydrogel.

Recently, we have investigated the enzyme-assisted self-assembly of precursor peptides diffusing in an enzyme-containing host gel, leading to various self-assembly profiles within the gel. At high enzyme concentrations, the reaction-diffusion self-assembly processes result in the formation of a continuous non-monotonous peptide self-assembly profile. At low enzyme concentrations, they result in the formation of individual self-assembled peptide microglobules and at intermediate enzyme concentrations both kinds of self-assembled structures coexist.

Thickness determination of hydroperoxidized lipid bilayers from medium-resolution cryo-TEM images.

As the primary products of lipid oxidation, lipid hydroperoxides constitute an important class of lipids generated by aerobic metabolism. However, despite several years of effort, the structure of the hydroperoxidized bilayer has not yet been observed under electron microscopy. Here we use a 200 kV Cryo-TEM to image small unilamellar vesicles (SUVs) made (i) of pure POPC or SOPC, (ii) of their pure hydroperoxidized form, and (iii) of their equimolar mixtures.

Tuning the water intrinsic permeability of PEGDA hydrogel membranes by adding free PEG chains of varying molar masses.

We explore the effect of poly(ethylene glycol) (PEG) molar mass on the intrinsic permeability and structural characteristics of poly(ethylene glycol) diacrylate PEGDA/PEG composite hydrogel membranes. We observe that by varying the PEG content and molar mass, we can finely adjust the water intrinsic permeability by several orders of magnitude. Notably, we show the existence of maximum water intrinsic permeability, already identified in a previous study to be located at the critical overlap concentration * of PEG chains, for the highest PEG molar mass studied.

The WERA cancer center matrix: Strategic management of patient access to precision oncology in a large and mostly rural area of Germany.

Purpose: Providing patient access to precision oncology (PO) is a major challenge of clinical oncologists. Here, we provide an easily transferable model from strategic management science to assess the outreach of a cancer center.

Methods: As members of the German WERA alliance, the cancer centers in Würzburg, Erlangen, Regensburg and Augsburg merged care data regarding their geographical impact.

Supramolecular Heterodimer Peptides Assembly for Nanoparticles Functionalization.

Nanoparticle (NP) surface functionalization with proteins, including monoclonal antibodies (mAbs), mAb fragments, and various peptides, has emerged as a promising strategy to enhance tumor targeting specificity and immune cell interaction. However, these methods often rely on complex chemistry and suffer from batch-dependent outcomes, primarily due to limited control over the protein orientation and quantity on NP surfaces. To address these challenges, a novel approach based on the supramolecular assembly of two peptides is presented to create a heterotetramer displaying VHs on NP surfaces.

Predicting Hypoxia Using Machine Learning: Systematic Review.

Background: Hypoxia is an important risk factor and indicator for the declining health of inpatients. Predicting future hypoxic events using machine learning is a prospective area of study to facilitate time-critical interventions to counter patient health deterioration.

Objective: This systematic review aims to summarize and compare previous efforts to predict hypoxic events in the hospital setting using machine learning with respect to their methodology, predictive performance, and assessed population.

Elaboration and rheological characterization of nanocomposite hydrogels containing C fullerene nanoplatelets.

Nanocomposite hydrogels were elaborated that consisted of a physical network formed by an amphiphilic polymer in which C fullerene nanoplatelets were embedded. Characterization showed that the nanoplatelets within the polymer network were aggregated. The presence of these nanoplatelets led to an increase of the shear modulus of the hydrogels, that cannot be explained by a filler effect alone.

[NGS-based molecular genetics of leukemia-a powerful and decentralized approach].

The diagnosis of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), originally based on morphological assessment alone, has to bring together more and more disciplines. Today, modern AML/MDS diagnostics rely on cytomorphology, cytochemistry, immunophenotyping, cytogenetics, and molecular genetics. Only the integration of all these methods allows a comprehensive and complementary characterization of each case, which is a prerequisite for optimal AML/MDS diagnosis and treatment.

Individualized targeted treatment in a case of a rare TFG::ROS1 fusion positive inflammatory myofibroblastic tumor (IMT).

Background: Inflammatory myofibroblastic tumor (IMTs) are rare mesenchymal neoplasms with slow growth. Resection is considered as therapeutic standard, with chemotherapy being insufficiently effective in advanced disease. ALK translocations are present in 50% of cases, ROS1 fusions (YWHAE::ROS1, TFG::ROS1) are extremely rare.

Predictive value of DNA methylation patterns in AML patients treated with an azacytidine containing induction regimen.

Background: Acute myeloid leukemia (AML) is a heterogeneous disease with a poor prognosis. Dysregulation of the epigenetic machinery is a significant contributor to disease development. Some AML patients benefit from treatment with hypomethylating agents (HMAs), but no predictive biomarkers for therapy response exist.

Sieving and Clogging in PEG-PEGDA Hydrogel Membranes.

Hydrogels are promising systems for separation applications due to their structural characteristics (i.e., hydrophilicity and porosity).

In Situ Monitoring of Block Copolymer Self-Assembly via Solvent Exchange through Controlled Dialysis with Light and Neutron Scattering Detection.

Solution self-assembly of amphiphilic block copolymers (BCs) is typically performed by a solvent-to-water exchange. However, BC assemblies are often trapped in metastable states depending on the mixing conditions such as the magnitude and rate of water addition. BC self-assembly can be performed under near thermodynamic control by dialysis, which accounts for a slow and gradual water addition.

Genome wide association analysis of cuticle deposition in laying hens.

The cuticle is an invisible barrier that protects the internal egg contents from microorganisms entering through gas exchange pores. Eggs which have a good cuticle are least likely to be penetrated by microorganisms and improved cuticle cover should reduce vertical transmission of microorganisms and improve biosecurity. The aim was to carry out a genome wide association study for cuticle deposition in 3 independent populations of laying hens using tartrazine and lissamine green staining.