Flow Rate Determination of the Nanoflow Sheath Liquid CE-MS-Coupling Applying the nanoCEasy Interface.

In recent years, nanoflow sheath liquid (nanoSL) interfaces have been used more commonly for capillary electrophoresis-mass spectrometry (CE-MS) coupling due to their high sensitivity combined with flexibility in CE separation conditions. So far, the exact amount of sheath liquid (SL) and, thus, the dilution effect remain unknown due to the self-supplying type of the nanoSL interfaces. To quantify the SL flow rates, we present here an approach for the determination of the flow rate based on isotopically labeled standards using the nanoCEasy interface.

Sample size estimates for biomarker-based outcome measures in clinical trials in autosomal dominant Alzheimer's disease.

Introduction: Alzheimer disease (AD)-modifying therapies are approved for treatment of early-symptomatic AD. Autosomal dominant AD (ADAD) provides a unique opportunity to test therapies in presymptomatic individuals.

Methods: Using data from the Dominantly Inherited Alzheimer Network (DIAN), sample sizes for clinical trials were estimated for various cognitive, imaging, and CSF outcomes.

: AI generation of multiplex immunofluorescence staining from histopathology images.

Hematoxylin and eosin (H&E) is a common and inexpensive histopathology assay. Though widely used and information-rich, it cannot directly inform about specific molecular markers, which require additional experiments to assess. To address this gap, we present a deep-learning framework that computationally imputes the expression and localization of dozens of proteins from H&E images.

Chemogenomic Screening in a Patient-Derived 3D Fatty Liver Disease Model Reveals the CHRM1-TRPM8 Axis as a Novel Module for Targeted Intervention.

Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of chronic liver disease with few therapeutic options. To narrow the translational gap in the development of pharmacological MASH treatments, a 3D liver model from primary human hepatocytes and non-parenchymal cells derived from patients with histologically confirmed MASH was established. The model closely mirrors disease-relevant endpoints, such as steatosis, inflammation and fibrosis, and multi-omics analyses show excellent alignment with biopsy data from 306 MASH patients and 77 controls.

Large language models surpass human experts in predicting neuroscience results.

Scientific discoveries often hinge on synthesizing decades of research, a task that potentially outstrips human information processing capacities. Large language models (LLMs) offer a solution. LLMs trained on the vast scientific literature could potentially integrate noisy yet interrelated findings to forecast novel results better than human experts.

Young rat microbiota extracts strongly inhibit fibrillation of α-synuclein and protect neuroblastoma cells and zebrafish against α-synuclein toxicity.

The clinical manifestations of Parkinson's disease (PD) are driven by aggregation of α-Synuclein (α-Syn) in the brain. However, there is increasing evidence that PD may be initiated in the gut and thence spread to the brain, eg, via the vagus nerve. Many studies link PD to changes in the gut microbiome, and bacterial amyloid has been shown to stimulate α-Syn aggregation.

Intact protein barcoding enables one-shot identification of CRISPRi strains and their metabolic state.

Detecting strain-specific barcodes with mass spectrometry can facilitate the screening of genetically engineered bacterial libraries. Here, we introduce intact protein barcoding, a method to measure protein-based library barcodes and metabolites using flow injection mass spectrometry (FI-MS). Protein barcodes are based on ubiquitin with N-terminal tags of six amino acids.

Attention-aware semantic relevance predicting Chinese sentence reading.

In recent years, several influential computational models and metrics have been proposed to predict how humans comprehend and process sentence. One particularly promising approach is contextual semantic similarity. Inspired by the attention algorithm in Transformer and human memory mechanisms, this study proposes an "attention-aware" approach for computing contextual semantic relevance.

Probing the orientation specificity of excitatory and inhibitory circuitries in the primary motor cortex with multi-channel TMS.

Objective: Electric-field orientation is crucial for optimizing neuronal excitation in transcranial magnetic stimulation (TMS). Yet, the stimulus orientation effects on short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) are poorly understood due to technical challenges in manipulating the TMS-induced stimulus orientation within milliseconds. We aimed to assess the orientation sensitivity of SICI and ICF paradigms and identify optimal orientations for motor evoked potential (MEP) facilitation and suppression.

Applying the efficient coding principle to understand encoding of multisensory and multimodality sensory signals.

Sensory neurons often encode multisensory or multimodal signals. For example, many medial superior temporal (MST) neurons are tuned to heading direction of self-motion based on visual (optic flow) signals and vestibular signals. Middle temporal (MT) cortical neurons are tuned to object depth from signals of two visual modalities: motion parallax and binocular disparity.

Novick Meets Bayes: Improving the Assessment of Individual Students in Educational Practice and Research by Capitalizing on Assessors' Prior Beliefs.

The assessment of individual students is not only crucial in the school setting but also at the core of educational research. Although classical test theory focuses on maximizing insights from student responses, the Bayesian perspective incorporates the assessor's prior belief, thereby enriching assessment with knowledge gained from previous interactions with the student or with similar students. We propose and illustrate a formal Bayesian approach that not only allows to form a stronger belief about a student's competency but also offers a more accurate assessment than classical test theory.

Diversity of Neurotransmitter-Producing Human Skin Commensals.

Recent findings indicate that human microbiota can excrete trace amines, dopamine, and serotonin. These neurotransmitters (NTs) can either affect classical neurotransmitter signaling or directly trigger trace amine-associated receptors (TAARs), with still unclear consequences for host physiology. Compared to gut microbiota, less information is available on the role of skin microbiota in NT production.

PSMA-Guided Imaging and Therapy of Advanced Adenoid Cystic Carcinomas and Other Salivary Gland Carcinomas.

SGCs are rare malignancies, accounting for less than 1% of all head and neck cancers [...

Perioperative Observations and Outcome in Surgical Treatment of Malignant Peripheral Nerve Sheath Tumors.

Background/objectives: This retrospective observational study aimed to investigate the perioperative outcome in Malignant Peripheral Nerve Sheath Tumors (MPNSTs) with and without relation to Neurofibromatosis Type 1 (NF1) and to detect possible influencing factors.

Methods: Clinical reports, histopathological evaluations, imaging, and treatment characteristics were reviewed in 35 operated MPNSTs in 33 patients. Possible predictive valuables included disease type, preoperative tumor volume, SUV and MIB-1 proliferation index, resection margins, the presence of metastasis, and whether radio-/chemotherapy was received.

Continuous Tuning of Intersystem Crossing Times in Rose Bengal Water/Methanol Solutions.

We use femtosecond transient broadband absorption spectroscopy (TAS) to characterize Rose Bengal in water/methanol solutions and reveal a continuous tunability of intersystem crossing (ISC) times by changing the mole fraction of the solvents. We find that the transients of excited state absorptions (ESAs) in Rose Bengal at ∼430 nm can be attributed to transitions from the singlet state S, with decay times of 74 ps via ISC in pure water and up to 405 ps in pure methanol. TA measurements at near-infrared wavelengths, on the other hand, reveal the rise of an ESA at ∼1080 nm from the triplet state T with time constants of 68 and 491 ps in pure water and methanol, respectively, strongly supporting the associated UV-vis TAS data.

Carrageenan and insulin resistance in humans: a randomised double-blind cross-over trial.

Background: The potential impact of specific food additives, common in Western diets, on the risk of developing type 2 diabetes is not well understood. This study focuses on carrageenan, a widely used food additive known to induce insulin resistance and gut inflammation in animal models, and its effects on human health.

Methods: In a randomised, double-blind, placebo-controlled, cross-over trial conducted at a university hospital metabolic study centre, 20 males (age 27.

Roles for primary cilia in synapses and neurological disorders.

The role of primary cilia has recently garnered significant attention in the field of neurodegeneration. This review explores the diversity of primary cilia in the mature brain and their interrelationships with a multitude of cellular structures, including axons and synapses. Importantly, an overview of the growing prominence of ciliary-related dysfunctions in neurodegenerative diseases is summarized, with a special emphasis on Parkinson's disease (PD) and neuropsychiatric disorders.

STAR LIGHT Study: XBB.1.5 COVID-19 mRNA Vaccines Boost Systemic but Not Mucosal Immunity Against the SARS-CoV-2 JN.1 Variant in Patients with Chronic Liver Disease.

Background: Patients with chronic liver disease (CLD) have impaired vaccine immunogenicity and an excess risk of severe COVID-19. While variant-adapted COVID-19 mRNA vaccines are recommended for vulnerable individuals, their efficacy in patients with CLD has not been studied.

Methods: We present the first evaluation of XBB.

Gram-negative bloodstream infections in six German university hospitals, 2016-2020: clinical and microbiological features.

Purpose: To analyze the longitudinal epidemiology and antimicrobial resistance (AMR) patterns of Gram-negative bloodstream infections (BSI) in Germany.

Methods: Post-hoc analysis of prospectively documented BSI due to Escherichia coli, Klebsiella spp., Enterobacter spp.