Generation of binder-format-payload conjugate-matrices by antibody chain-exchange.

The generation of antibody-drug conjugates with optimal functionality depends on many parameters. These include binder epitope, antibody format, linker composition, conjugation site(s), drug-to-antibody ratio, and conjugation method. The production of matrices that cover all possible parameters is a major challenge in identifying optimal antibody-drug conjugates.

A UV-Vis method for investigation of gallium(III) complexation kinetics with NOTA and TRAP chelators: advantages, limitations and comparison with radiolabelling.

An easy and cheap method for measurement of Ga complexation kinetics was developed. The method is based on UV-Vis quantification of non-complexed chelators after the addition of Cu ions at individual time points. The method was evaluated using established ligands, Hnota and HnotP, and was utilized to study the kinetics of Ga complexation with four new symmetric derivatives of 1,4,7-triazacyclononane bearing methylphosphonate/phosphinate pendant arms - TRAP ligands.

DNA methylation profiling identifies TBKBP1 as potent amplifier of cytotoxic activity in CMV-specific human CD8+ T cells.

Epigenetic mechanisms stabilize gene expression patterns during CD8+ T cell differentiation. Although adoptive transfer of virus-specific T cells is clinically applied to reduce the risk of virus infection or reactivation in immunocompromised individuals, the DNA methylation pattern of virus-specific CD8+ T cells is largely unknown. Hence, we here performed whole-genome bisulfite sequencing of cytomegalovirus-specific human CD8+ T cells and found that they display a unique DNA methylation pattern consisting of 79 differentially methylated regions (DMRs) when compared to memory CD8+ T cells.

Impact of coating type on structure and magnetic properties of biocompatible iron oxide nanoparticles: insights into cluster organization and oxidation stability.

Superparamagnetic iron oxide nanoparticles (SPIONs) are a promising tool for biomedical applications, including drug delivery, imaging, and magnetic hyperthermia. However, their tendency to agglomerate limits their performance efficiency. To overcome this limitation, a coating can be applied during or after synthesis.

Measuring Kinetics under Vibrational Strong Coupling: Testing for a Change in the Nucleophilicity of Water and Alcohols.

Vibrational Strong Coupling (VSC) has been reported to change the rate of organic reactions. However, a lack of convenient and reliable methods to measure reaction kinetics under VSC makes it challenging to obtain mechanistic insight into its influence, hindering progress in the field. Here, we use recently developed fixed-width optical cavities to obtain large kinetic datasets under VSC with small errors (±1-5 %) in an operationally simple manner using UV/Vis spectroscopy.

Hypoxia-driven heterogeneous expression of α5 integrin in glioblastoma stem cells is linked to HIF-2α.

Despite numerous molecular targeted therapies tested in glioblastoma (GBM), no significant progress in patient survival has been achieved in the last 20 years in the overall population of GBM patients except with TTfield setup associated with the standard of care chemoradiotherapy. Therapy resistance is associated with target expression heterogeneity and plasticity between tumors and in tumor niches. We focused on α5 integrin implicated in aggressive GBM in preclinical and clinical samples.

Comprehensive genetic profiling and molecularly guided treatment for patients with primary CNS tumors.

Despite major advances in molecular profiling and classification of primary brain tumors, personalized treatment remains limited for most patients. Here, we explored the feasibility of individual molecular profiling and the efficacy of biomarker-guided therapy for adult patients with primary brain cancers in the real-world setting within the molecular tumor board Freiburg, Germany. We analyzed genetic profiles, personalized treatment recommendations, and clinical outcomes of 102 patients with 21 brain tumor types.

Evaluating the modulation of peripheral immune profile in people living with HIV and (Neuro)cysticercosis.

Background: The parasitic infection caused by Taenia solium represents a significant public health concern in developing countries. Larval invasion of body tissues leads to cysticercosis (CC), while central nervous system (CNS) involvement results in neurocysticercosis (NCC). Both conditions exhibit diverse clinical manifestations, and the potential impact of concomitant HIV infection especially prevalent in sub-Saharan Africa on peripheral and CNS immune responses remains poorly understood.

Unraveling the mechanism of small molecule induced activation of Staphylococcus aureus signal peptidase IB.

Staphylococcus aureus signal peptidase IB (SpsB) is an essential enzyme for protein secretion. While inhibition of its activity by small molecules is a well-precedented mechanism to kill bacteria, the mode of activation is however less understood. We here investigate the activation mechanism of a recently introduced activator, the antibiotic compound PK150, and demonstrate by combined experimental and Molecular Dynamics (MD) simulation studies a unique principle of enzyme stimulation.

Treatment Strategies for Filamentous Fungi Keratitis.

Introduction: This research aims to describe clinical findings, epidemiology and treatment outcomes in patients with filamentous fungi keratitis of a tertiary centre in Germany over a 7-year period and to compare the efficacy of different antifungal treatments and the effect of additive topical steroids.

Methods: This retrospective study included 25 eyes of 23 patients from October 2013 to December 2020 with cultural isolates of filamentous fungi and corresponding keratitis. Best-corrected visual acuity (BCVA), clinical signs, symptoms, risk factors and outcome were extracted from medical records.

Crossing-Point Estimation in Human-Robot Navigation-Statistical Linearization versus Sigma-Point Transformation.

Interactions between mobile robots and human operators in common areas require a high level of safety, especially in terms of trajectory planning, obstacle avoidance and mutual cooperation. In this connection, the crossings of planned trajectories and their uncertainty based on model fluctuations, system noise and sensor noise play an outstanding role. This paper discusses the calculation of the expected areas of interactions during human-robot navigation with respect to fuzzy and noisy information.

When is it appropriate to ask a question? The role of age, social context, and personality.

How do children decide when it is appropriate to ask a question? In Study 1 (preregistered), 50 4- and 5-year-olds, 50 7- and 8-year-olds, and 100 adults watched vignettes featuring a child who had a question, and participants indicated whether they thought the child should ask the question "right now." Both adults and children endorsed more question-asking to a well-known informant than to an acquaintance and to someone doing nothing than to someone busy working or busy socializing. However, younger children endorsed asking questions to someone who was busy more often than older children and adults.

Adjuvant Treatment with S-1 in Patients after R0-Resection of Adenocarcinoma of the Stomach and Esophagogastric Junction: A Multicenter Phase I/II Feasibility Study (GMBH-STO-0114).

Introduction: S-1 has been shown to be an effective adjuvant treatment option for East Asian patients who underwent gastrectomy for stage II/III gastric cancer. We conducted a phase I/II study to evaluate the feasibility, tolerability, and efficacy of administering S-1 in the adjuvant setting after R0-resection of adenocarcinoma of the stomach and esophagogastric junction (EGJ) in Caucasian patients.

Methods: In this single-cohort, open-label, phase I/II trial, we enrolled patients with locally advanced adenocarcinoma of the stomach or EGJ having undergone R0-resection with or without neoadjuvant treatment.

Characterization of clumpy adhesion of to human cells and associated factors influencing antibiotic sensitivity.

Unlabelled: intestinal infection pathotypes are characterized by distinct adhesion patterns, including the recently described clumpy adhesion phenotype. Here, we identify and characterize the genetic factors contributing to the clumpy adhesion of strain 4972. In this strain, the transcriptome and proteome of adhered bacteria were found to be distinct from planktonic bacteria in the supernatant.

The role of molecular tumor boards in neuro-oncology: a nationwide survey.

Background: In neuro-oncology, the inclusion of tumor patients in the molecular tumor board has only become increasingly widespread in recent years, but so far there are no standards for indication, procedure, evaluation, therapy recommendations and therapy implementation of neuro-oncological patients. The present work examines the current handling of neuro-oncological patients included in molecular tumor boards in Germany.

Methods: We created an online based survey with questions covering the handling of neuro-oncologic patient inclusion, annotation of genetic analyses, management of target therapies and the general role of molecular tumor boards in neuro-oncology in Germany.

LASER FLARE PHOTOMETRY IN PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT: An Evaluation of 2,487 Cases.

Purpose: Exploratory analysis associated with the prospective, multicenter, randomized PRIVENT trial. To characterize the associations between laser flare photometry and anatomical and epidemiological features of rhegmatogenous retinal detachment (RRD).

Methods: The authors measured laser flare values of all 3,048 prescreened patients excluding those with comorbidities.

Protocol of the HISTOTHERM study: assessing the response to hyperthermia and hypofractionated radiotherapy in recurrent breast cancer.

Introduction: Breast cancer is globally the leading cancer in women, and despite the high 5-year survival rate the most frequent cause of cancer related deaths. Surgery, systemic therapy and radiotherapy are the three pillars of curative breast cancer treatment. However, locoregional recurrences frequently occur after initial treatment and are often challenging to treat, amongst others due to high doses of previous radiotherapy treatments.