Isoleucine-to-valine substitutions support cellular physiology during isoleucine deprivation.

Aminoacyl-tRNA synthetases (ARSs) couple tRNAs with their corresponding amino acids. While ARSs can bind structurally similar amino acids, extreme specificity is ensured by subsequent editing activity. Yet, we found that upon isoleucine (I) restriction, healthy fibroblasts consistently incorporated valine (V) into proteins at isoleucine codons, resulting from misacylation of tRNAIle with valine by wildtype IARS1.

Information mismatch in PHH3-assisted mitosis annotation leads to interpretation shifts in H&E slide analysis.

The count of mitotic figures (MFs) observed in hematoxylin and eosin (H&E)-stained slides is an important prognostic marker, as it is a measure for tumor cell proliferation. However, the identification of MFs has a known low inter-rater agreement. In a computer-aided setting, deep learning algorithms can help to mitigate this, but they require large amounts of annotated data for training and validation.

mTORC1 restricts TFE3 activity by auto-regulating its presence on lysosomes.

To stimulate cell growth, the protein kinase complex mTORC1 requires intracellular amino acids for activation. Amino-acid sufficiency is relayed to mTORC1 by Rag GTPases on lysosomes, where growth factor signaling enhances mTORC1 activity via the GTPase Rheb. In the absence of amino acids, GATOR1 inactivates the Rags, resulting in lysosomal detachment and inactivation of mTORC1.

Re-identification from histopathology images.

In numerous studies, deep learning algorithms have proven their potential for the analysis of histopathology images, for example, for revealing the subtypes of tumors or the primary origin of metastases. These models require large datasets for training, which must be anonymized to prevent possible patient identity leaks. This study demonstrates that even relatively simple deep learning algorithms can re-identify patients in large histopathology datasets with substantial accuracy.

Prediction of tumor board procedural recommendations using large language models.

Introduction: Multidisciplinary tumor boards are meetings where a team of medical specialists, including medical oncologists, radiation oncologists, radiologists, surgeons, and pathologists, collaborate to determine the best treatment plan for cancer patients. While decision-making in this context is logistically and cost-intensive, it has a significant positive effect on overall cancer survival. METHODS : We evaluated the quality and accuracy of predictions by several large language models for recommending procedures by a Head and Neck Oncology tumor board, which we adapted for the task using parameter-efficient fine-tuning or in-context learning.

Chatbot-supported psychoeducation in adult attention-deficit hyperactivity disorder: randomised controlled trial.

Background: Although psychoeducation is generally recommended for the treatment of adult attention-deficit hyperactivity disorder (ADHD), participation in clinical psychoeducation groups is impeded by waiting times and the constrained number of patients who can simultaneously attend a group. Digital psychoeducation attempts are promising, but the rapidly expanding number of apps lack evidence and are mostly limited to only a few implemented interactive elements.

Aims: To determine the potential of digital, self-guided psychoeducation for adult ADHD, a newly developed interactive chatbot was compared with a previously validated, conventional psychoeducation app.

Macrocephaly and developmental delay caused by missense variants in RAB5C.

Rab GTPases are important regulators of intracellular vesicular trafficking. RAB5C is a member of the Rab GTPase family that plays an important role in the endocytic pathway, membrane protein recycling and signaling. Here we report on 12 individuals with nine different heterozygous de novo variants in RAB5C.

Marine Resources Offer New Compounds and Strategies for the Treatment of Skin and Soft Tissue Infections.

Bioprospecting of the marine environment for drug development has gained much attention in recent years owing to its massive chemical and biological diversity. Drugs for the treatment of skin and soft tissue infections have become part of the search, mainly with respect to enlarging the number of available antibiotics, with a special focus on multidrug-resistant Gram-positive bacteria, being the major causative agents in this field. Marine resources offer novel natural products with distinct biological activities of pharmaceutical importance, having the chance to provide new chemical scaffolds and new modes of action.

A second case of glutaminase hyperactivity: Expanding the phenotype with epilepsy.

Glutaminase (GLS) hyperactivity was first described in 2019 in a patient with profound developmental delay and infantile cataract. Here, we describe a 4-year-old boy with GLS hyperactivity due to a de novo heterozygous missense variant in , detected by trio whole exome sequencing. This boy also exhibits developmental delay without dysmorphic features, but does not have cataract.

Screening of a Thraustochytrid Strain Collection for Carotenoid and Squalene Production Characterized by Cluster Analysis, Comparison of 18S rRNA Gene Sequences, Growth Behavior, and Morphology.

Carotenoids and squalene are important terpenes that are applied in a wide range of products in foods and cosmetics. Thraustochytrids might be used as alternative production organisms to improve production processes, but the taxon is rarely studied. A screening of 62 strains of thraustochytrids for their potential to produce carotenoids and squalene was performed.

Bi-allelic variants in NAE1 cause intellectual disability, ischiopubic hypoplasia, stress-mediated lymphopenia and neurodegeneration.

Neddylation has been implicated in various cellular pathways and in the pathophysiology of numerous diseases. We identified four individuals with bi-allelic variants in NAE1, which encodes the neddylation E1 enzyme. Pathogenicity was supported by decreased NAE1 abundance and overlapping clinical and cellular phenotypes.

Development and validation of reliable astaxanthin quantification from natural sources.

Astaxanthin derived from natural sources occurs in the form of various esters and stereomers, which complicates its quantitative and qualitative analysis. To simplify and standardize astaxanthin measurement with high precision, an enzymolysis-based astaxanthin quantification method was developed to hydrolyze astaxanthin esters and determine free astaxanthin in all its diastereomeric forms. Astaxanthin standards and differently processed Haematococcus pluvialis biomass were investigated.

Smartphone-assisted psychoeducation in adult attention-deficit/hyperactivity disorder: A randomized controlled trial.

Psychoeducation is generally recommended in the treatment of adult Attention-Deficit/Hyperactivity Disorder (ADHD), but only few studies have systematically assessed the effects of structured clinical psychoeducation. Moreover, although a considerable number of psychoeducational mobile applications exist, none have provided scientific evidence for their effectiveness or safety. Therefore, the present randomized controlled trial investigated a newly developed, free-to-use psychoeducation app for adults with ADHD as a support to a clinical psychoeducation group.

Optimization of Astaxanthin Recovery in the Downstream Process of .

Astaxanthin derived from is a valuable metabolite applied in a wide range of products. Its extraction depends on a sophisticated series of downstream process steps, including harvesting, disruption, drying, and extraction, of which some are dependent on each other. To determine the processes that yield maximum astaxanthin recovery, bead milling, high-pressure homogenization, and no disruption of biomass were coupled with spray-drying, vacuum-drying, and freeze-drying in all possible combinations.

FER regulates endosomal recycling and is a predictor for adjuvant taxane benefit in breast cancer.

Elevated expression of non-receptor tyrosine kinase FER is an independent prognosticator that correlates with poor survival of high-grade and basal/triple-negative breast cancer (TNBC) patients. Here, we show that high FER levels are also associated with improved outcomes after adjuvant taxane-based combination chemotherapy in high-risk, HER2-negative patients. In TNBC cells, we observe a causal relation between high FER levels and sensitivity to taxanes.

NAA80 bi-allelic missense variants result in high-frequency hearing loss, muscle weakness and developmental delay.

The recent identification of NAA80/NAT6 as the enzyme that acetylates actins generated new insight into the process of post-translational actin modifications; however, the role of NAA80 in human physiology and pathology has not been clarified yet. We report two individuals from a single family harbouring a homozygous c.389T>C, p.

Are there differences between officers and ratings on merchant vessels concerning effort-reward imbalance: a cross-sectional maritime field study.

Purpose: Today, measures to economise in the operation of ships can cause either an effort-reward imbalance or health impairments. The goal of this study was to assess the risk of effort-reward imbalance including overcommitment among officers and ratings on merchant vessels during their assignments and to evaluate lifestyle factors of seafarers as well as the health-promoting conditions on board.

Methods: A study sample of 308 male seafarers was examined during a total of 20 sea voyages on German container ships (participation rate 91.

Treatment of ARS deficiencies with specific amino acids.

Purpose: Recessive cytosolic aminoacyl-tRNA synthetase (ARS) deficiencies are severe multiorgan diseases, with limited treatment options. By loading transfer RNAs (tRNAs) with their cognate amino acids, ARS are essential for protein translation. However, it remains unknown why ARS deficiencies lead to specific symptoms, especially early life and during infections.

Objective and subjective measures to assess stress among seafarers.

Background: Working and living on board merchant vessels often constitute high psychophysical stress for the crews. In this study, the current stress of seafarers is examined by using observation-based and subjective measures.

Materials And Methods: The workplaces of 70 crew members on board 11 container ships were analysed and evaluated using the objective instrument for the situational screening of mental workload (SMW-S).

Work profile of maritime pilots in Germany.

Long and irregular shifts, unforeseeable operations and high responsibility are still prominent in the job of a pilot and pose high psycho-physical demands. Furthermore, there is a disturbed work-family balance. Working hours of pilots are highly variable and not bound by regulations due to irregularities of vessel traffic.

Physical influences on seafarers are different during their voyage episodes of port stay, river passage and sea passage: A maritime field study.

Introduction: During a sea voyage, crew members of vessels are permanently exposed to physical stress caused by noise, vibration and heat. This study aims to describe the extent of the physical influences on board container ships and the resulting stress.

Methods: Up to four scientific investigators accompanied six sea voyages on container ships under German management.

Simulation of scattered radiation during intraoperative imaging in a virtual reality learning environment.

Purpose: Scattered radiation, which occurs when using a C-arm for intraoperative radiography, can be better understood through interactive visualization. We developed a virtual reality (VR) approach for the simulation of scattered radiation (SSR) as part of a C-arm training system. In VR, it is important to avoid cyber sickness, which is often caused by increased latency between head motion and image presentation inside the head-mounted display.

Spatial separation of metabolic stages in a tube anaerobic baffled reactor: reactor performance and microbial community dynamics.

Spatial separation of metabolic stages in anaerobic digesters can increase the methane content of biogas, as realized in a tube anaerobic baffled reactor. Here, we investigated the performance and microbial community dynamics of a laboratory-scale mesophilic anaerobic baffled reactor with four compartments treating an artificial substrate. Due to the activity of fermentative bacteria, organic acids mostly accumulated in the initial compartments.