IGLV3-21-directed bispecific antibodies activate T cells and promote killing in a high-risk subset of chronic lymphocytic leukemia.

We previously used a disease-specific B cell receptor (BCR) point mutation (IGLV3-21R110) for selective targeting of a high-risk subset of chronic lymphocytic leukemia (CLL) with chimeric antigen receptor (CAR) T cells. Since CLL is a disease of the elderly and a significant fraction of patients is not able to physically tolerate CAR T cell treatment, we explored bispecific antibodies as an alternative for precision targeting of this tumor mutation. Heterodimeric IgG1-based antibodies consisting of a fragment crystallizable region (Fc) attached to both an anti-IGLV3-21R110 Fab and an anti-CD3 (UCHT1) single chain variable fragment (R110-bsAb) selectively killed cell lines engineered to express high levels of the neoepitope as well as primary CLL cells using healthy donor and CLL patient-derived T cells as effectors.

Molecular Plasmonic Cavities.

Graphene-based photonic structures have emerged as fertile ground for the controlled manipulation of surface plasmon polaritons (SPPs), providing a two-dimensional platform with low optoelectronic losses. In principle, nanostructuring graphene can enable further confinement of nanolight─enhancing light-matter interactions in the form of SPP cavity modes. In this study, we engineer nanoscale plasmonic cavities composed of self-assembled C arrays on graphene.

Preclinical Ischemic Stroke Multicenter (PRISM) Trials Collective Statement: Opportunities, Challenges, and Recommendations for a New Era.

Preclinical stroke research faces a critical translational gap, with animal studies failing to reliably predict clinical efficacy. To address this, the field is moving toward rigorous, multicenter preclinical randomized controlled trials (mpRCTs) that mimic phase 3 clinical trials in several key components. This collective statement, derived from experts involved in mpRCTs, outlines considerations for designing and executing such trials.

Severe course of tick-borne encephalitis (TBE) in a patient with relapsing multiple sclerosis (MS) treated with ocrelizumab.

Description of a patient with multiple sclerosis (MS) who underwent immunotherapy with ocrelizumab and suffered a severe course of tick-borne encephalitis (TBE): A 33-year-old man presented with acute cerebellitis with tonsillar herniation. The initial suspected diagnosis of TBE was confirmed after a significant diagnostic delay, likely caused by negative serological testing due to B-cell depletion from ocrelizumab treatment for underlying MS. TBE diagnosis was made using polymerase chain reaction (PCR) and oligo-hybrid capture metagenomic next-generation sequencing (mNGS) of cerebral spinal fluid and brain biopsy samples which yielded a near-full length TBE Virus (TBEV) genome.

Factors influencing diagnostic yield and complication risk in computed tomography fluoroscopy-guided lung biopsies: a 10-year single-center study.

Purpose: Computed tomography fluoroscopy (CTF)-guided biopsy is an established technique for sampling pulmonary lesions, particularly with the growing prevalence of lung nodule screening programs. This study investigated procedural and lesion-related factors affecting success and complication rates in routine CTF-guided lung core-needle biopsies at a tertiary center.

Methods: Consecutive patients undergoing percutaneous CTF-guided lung biopsies over a 10-year period (2007-2016) were retrospectively analyzed.

Geometrical Isotope Effects on Chemical Bonding in Hydrogen Bonded Systems: Combining Nuclear-Electronic Orbital DFT and Energy Decomposition Analysis.

We investigated primary and secondary geometric isotope effects (H, D, T) on charge-inverted hydrogen bonds (CIHB) and dihydrogen bonds (DHB) using nuclear-electronic orbital density functional theory (NEO-DFT). The dianionic but electrophilic boron cluster [BH] served as a bonding partner, exhibiting a negatively polarized hydrogen atom in the BH bond. CIHB systems included interactions with Lewis acids (AlH, BH, GaH) and carbenes (CF, CCl, CBr), while DHBs were analyzed with NH, HF, HCl, and HBr.

Risk factors and trajectories for self-harm, neurodevelopmental disorders and mental health conditions in pupils in alternative education provision in Wales: population-based electronic cohort study.

Background: Pupils in alternative education provision, known as 'Educated in Other Than At School' (EOTAS) in Wales, UK, are among the most vulnerable learners and who, for reasons such as mental health or behavioural challenges, do not attend a mainstream or special school.

Aims: We compared self-harm, neurodevelopmental disorders and mental health conditions between EOTAS pupils and controls with similar characteristics, before and after being in EOTAS provision.

Method: This population-based electronic cohort study included pupils in Wales aged 7-18 years, from the academic years 2010-11 to 2018-19.

Structure-Guided Engineering of a Bacterial Sesterterpene Synthase for Sesterviridene Diversification.

Terpene synthases produce a remarkable structural diversity from acyclic precursors through complex carbocation cascades. Here, we report the crystal structure of the bacterial sesterterpene synthase StvirS bound to geranylfarnesyl thiopyrophosphate (GFSPP), revealing a preorganized active site that enforces a defined folding of the C25 backbone. Guided by this structure, active-site engineering at 11 positions yielded 23 enzyme variants and 13 new sesterterpenes.

The Role of Deep Cerebral Tracts in Predicting Postoperative Aphasia: An nTMS-Based Investigation of the Corticothalamic Fibers.

Postoperative aphasia (POA) is a common complication in patients undergoing surgery for language-eloquent lesions. This study aimed to enhance the prediction of POA by leveraging preoperative navigated transcranial magnetic stimulation (nTMS) language mapping and diffusion tensor imaging (DTI)-based tractography, incorporating deep learning (DL) algorithms. One hundred patients with left-hemispheric lesions were retrospectively enrolled (43 developed postoperative aphasia, as the POA group; 57 did not, as the non-aphasia (NA) group).

Characterization of the N-Hydroxylating Monooxygenase TheA from Thermocrispum agreste Reveals a Broad Substrate Spectrum.

The N-hydroxylating monooxygenase (NMO) TheA from Thermocrispum agreste catalyzes the N-hydroxylation step of l-ornithine, which is the first step in the thermochelin siderophore biosynthesis. Characterization of this enzyme revealed a significant thermostability up to 50 °C and activity with the non-native substrate d-ornithine with kinetic parameters (K = 4.06 ± 0.

The Linear Arginoketides Neotetrafibricin A, B, and C have Algicidal and Signal Function in Microbial Interactions.

Soils harbor some of the most diverse microbiomes on Earth. Interactions within these microbial communities are often mediated by natural products, many functioning as chemical signals. Specialized metabolites known as arginoketides, or arginine-derived polyketides, have been linked to mediate these interactions.

Diagnosis of Quinolone Hypersensitivity: An EAACI Position Paper.

Hypersensitivity reactions to quinolones (QHRs) have been increasing in frequency, thus classifying them as the second most frequently implicated class of antibiotics in hypersensitivity reactions (HRs). It is noteworthy that quinolones (Qs) have been observed to predominantly trigger immediate hypersensitivity reactions (IHRs). These reactions are categorized as either IgE-mediated or non-IgE-mediated, attributable to the off-target occupation of the recently described receptor, Mas-related G-protein coupled receptor member X2 (MRGPRX2), on effector cells.

Diversity and Dosage Determine the Efficacy of the Probiotic SYN-53 in Allergic Rhinoconjunctivitis: A Randomized, Double-Blind, Placebo-Controlled Trial.

SYN-53, a multi-strain probiotic food supplement, was recently shown to significantly alleviate allergic rhinoconjunctivitis (ARC) and its symptoms. The diversity and dosage of bacterial strains administered via SYN-53 have been proposed as key drivers of its efficacy. The aim of this study was to assess the role of bacterial diversity and dosage by comparing SYN-53 to a low dose variant (SYN-53-LD), a low diversity variant (SYN-4), and a placebo in the management of ARC.

Relevance of nonessential amino acids in low crude protein diets for broiler chickens - an updated review.

Reducing crude protein in amino acid-adequate diets for broiler chickens is effective in reducing nitrogenous emissions and competition for resources between the food and feed sectors. This review provides a comprehensive analysis of the literature on the relevance of nonessential amino acids in low-protein diets for broiler chickens. Glycine and serine, due to their interconvertibility summarized as glycine equivalents ( ), limit growth when dietary crude protein is reduced below 19% in up to 3-week-old birds.

A phylogenomic study of African Impatiens (Balsaminaceae) using nuclear and chloroplast sequences.

Background And Aims: The large genus, Impatiens, is well known to vary excessively, presenting extensive modifications in floral structure among its 1100+ species. Phylogenetic relationships in the genus have historically been difficult to intuit based on morphology, given numerous occurrences of convergent evolution, but they are also difficult to determine based on molecular characters. In this study we focus on resolving the phylogentic relationships within the genus Impatiens, with an emphasis on continental African taxa.

Legacy of the Lost and Pressure of the Present: Malagasy Plant Seeds Retain Megafauna Dispersal Signatures but Downsize Under Human Pressure.

Ongoing declines of large-bodied frugivores limit the dispersal of large-seeded plants, contributing to their (local) demise and 'downsizing' of seeds across assemblages. However, the extent to which human pressure leads to contemporary seed downsizing, and whether extinct megafrugivores have left imprints on seed size, remains unclear. Here, we integrate trait and distribution data for 2852 endozoochorous plant species, 48 extant and 15 extinct frugivore species across 361 assemblages on Madagascar.

Bioavailability of Magnesium and Potassium Salts Used as Potential Substitutes for Sodium Chloride in Human Nutrition - A Review.

Hypertension represents a major risk factor for cardiovascular diseases. As a diet high in sodium chloride is associated with hypertension, so-called "blood pressure salts" are attracting increasing scientific interest. These are characterized by a partial replacement of sodium chloride by other salts, mainly potassium and magnesium compounds.

Dissecting the Causal Association Between Bulimia Nervosa and Structural Brain Abnormalities: A Two-Sample Bidirectional Mendelian Randomization Study.

Background: Diverse correlations between structural brain abnormalities and the clinical feature of bulimia nervosa (BN) have been identified in previous observational studies.

Objective: To explore the bidirectional causality between BN and brain structural magnetic resonance imaging (MRI) phenotypes.

Methods: Genome-wide association studies (GWAS) of 2441 participants identified genetic variants associated with disordered eating and predicted BN, whereas UK Biobank 3D-T1 MRI data were used to analyze brain structural phenotypes.

PATJ deficiency leads to cystic kidney disease and related ciliopathies.

Cystic kidney disease and related ciliopathies are caused by pathogenic variants in genes that commonly result in ciliary dysfunction. For a substantial number of individuals affected by those cilia-related diseases, the causative gene still remains unknown. Using massively parallel sequencing, we here identified a pathogenic bi-allelic variant in the gene encoding PALS1-Associated Tight Junction Protein (PATJ; also known as Inactivation-No-Afterpotential D-Like, INADL) in an individual with ciliopathy.

Redefining agroecological zones in China to mitigate climate change impacts on maize production.

This study introduces Multi-Dimensional Environment (MDE) zoning to enhance maize resilience and improve stagnant yields in China amidst climate change. Utilizing comprehensive environmental and yield data, MDE zoning accurately identifies areas for targeted, climate-adaptive breeding. The tool provides a flexible framework for updates using annual variety testing and daily environmental data, optimizing production and resource allocation.

16th German Endocrine-Brain-Immune Network (GEBIN) Conference 2025 with the European Psychoneuroimmunology Network (EPN) and the Working Group Neuroimmunology of the German Society for Immunology (AKNI) Satellite Symposia, September 2-6, 2025, Giessen, Germany: Abstracts.

There is no abstract GEBIN 2025 Conference.

Tailoring the Magnetic Properties of 2D Metal-Organic Networks by Harnessing the Coordination Sphere.

Achieving magnetic ordering in low-dimensional materials remains a key objective in the field of magnetism. Herein, coordination chemistry emerges as a powerful discipline to promote the stabilization of magnetism at the nanoscale. We present a thorough study of exemplary two-dimensional metal-organic nanoarchitectures synthesized on a Au(111) substrate, which are rationalized by using surface-science techniques and theoretical calculations.

Use of Muscle Relaxants in Emergency Medicine: A Review.

Modern anesthesia, intensive care, and emergency medicine rely heavily on neuromuscular blocking agents (NMBAs), first introduced in 1942. These agents not only facilitate endotracheal intubation but also improve surgical conditions by suppressing muscle responses to stimuli. NMBAs function via depolarizing (eg, succinylcholine) or non-depolarizing mechanisms.

On the structural and practical identifiability of multi-echo BBB-ASL tracer kinetic models.

Purpose: Tracer kinetic models are used in arterial spin labeling (ASL); however, deciding which model parameters to fix or fit is not always trivial. The identifiability of the resultant system of equations is useful to consider, since it will likely impact parameter uncertainty. Here, we analyze the identifiability of two-compartment models used in multi-echo (ME) blood-brain-barrier (BBB)-ASL and evaluate the reliability of the fitted water-transfer rate ).