Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses.

Genetic diagnosis of rare diseases requires accurate identification and interpretation of genomic variants. Clinical and molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree and genomic rare-disease data (94.5% exomes, 5.

Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.

Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated.

An accessible workflow for high-sensitivity proteomics using parallel accumulation-serial fragmentation (PASEF).

Deep and accurate proteome analysis is crucial for understanding cellular processes and disease mechanisms; however, it is challenging to implement in routine settings. In this protocol, we combine a robust chromatographic platform with a high-performance mass spectrometric setup to enable routine yet in-depth proteome coverage for a broad community. This entails tip-based sample preparation and pre-formed gradients (Evosep One) combined with a trapped ion mobility time-of-flight mass spectrometer (timsTOF, Bruker).

Pre-trained artificial intelligence-aided analysis of nanoparticles using the segment anything model.

Complex structures can be understood as compositions of smaller, more basic elements. The characterization of these structures requires an analysis of their constituents and their spatial configuration. Examples can be found in systems as diverse as galaxies, alloys, living tissues, cells, and even nanoparticles.

Spatial analysis and risk mapping of Crimean-Congo hemorrhagic fever (CCHF) in Sub-saharan Africa.

Crimean Congo hemorrhagic fever (CCHF) is a re-emerging tick-borne zoonosis that is caused by CCHF virus (CCHFV). The geographical distribution of the disease and factors that influence its occurrence are poorly known. We analysed historical records on its outbreaks in various countries across the sub-Saharan Africa (SSA) to identify hotspots and determine socioecological and demographicfactors associated with these outbreaks.

Naturally russeted and wound russeted skins of mango (cv. 'Apple') show no differences in anatomy, chemical composition or gene expression.

The mango cultivar 'Apple' is commercially important in Kenya but highly susceptible to russeting. Russeting refers to an area of fruit skin where the primary (epidermal) surface has been replaced by a secondary (peridermal) surface. The objective was to establish histologies, gene expressions and chemical compositions of a natural periderm, a wound-induced periderm and of cuticles of an un-russeted skin.

The Beijing Sentence Corpus II: A cross-script comparison between traditional and simplified Chinese sentence reading.

We introduce a sentence corpus with eye-movement data in traditional Chinese (TC), based on the original Beijing Sentence Corpus (BSC) in simplified Chinese (SC). The most noticeable difference between TC and SC character sets is their visual complexity. There are reaction time corpora in isolated TC character/word lexical decision and naming tasks.

Diffuseness of coronary artery disease impacts on immediate hemodynamic and predicted clinical outcomes.

Diffuse coronary artery disease (CAD) impacts the immediate hemodynamic and clinical outcomes of percutaneous coronary intervention (PCI). We evaluated whether the diffuse pattern of CAD derived from angiographic Quantitative flow ratio (QFR) impacts the immediate hemodynamic outcome post-PCI and the medium term predicted vessel-oriented composite endpoint (VOCE). Paired pre-procedure QFRs were assessed in 503 patients and 1022 vessels in the Multivessel TALENT (MVT) trial.

Acid sphingomyelinase activity suggests a new antipsychotic pharmaco-treatment strategy for schizophrenia.

Schizophrenia is a chronic and severe mental disorder. It is currently treated with antipsychotic drugs (APD). However, APD's work only in a limited number of patients and may have cognition impairing side effects.

Error mitigation in brainbox quantum autoencoders.

Quantum hardware faces noise challenges that disrupt multiqubit entangled states. Quantum autoencoder circuits with a single qubit bottleneck have demonstrated the capability to correct errors in noisy entangled states. By introducing slightly more complex structures in the bottleneck, referred to as brainboxes, the denoising process can occure more quickly and efficiently in the presence of stronger noise channels.

Biochemical failure-free survival of F-rhPSMA-7 and F-flotufolastat PET-guided salvage radiotherapy for patients with recurrent prostate cancer.

Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) has improved localization of prostate cancer (PC) lesions in biochemical recurrence (BCR) for salvage radiotherapy (SRT). We conducted a retrospective review of patients undergoing F-rhPSMA-7 or F-flotufolastat (F-rhPSMA-7.3)-PET-guided SRT compared with conventional-SRT (C-SRT) without PET.

A reproducible representation of healthy tibiofemoral kinematics during stair descent using REFRAME - part I: REFRAME foundations and validation.

In clinical movement biomechanics, kinematic measurements are collected to characterise the motion of articulating joints and investigate how different factors influence movement patterns. Representative time-series signals are calculated to encapsulate (complex and multidimensional) kinematic datasets succinctly. Exacerbated by numerous difficulties to consistently define joint coordinate frames, the influence of local frame orientation and position on the characteristics of the resultant kinematic signals has been previously proven to be a major limitation.

Stretch-induced endogenous electric fields drive directed collective cell migration in vivo.

Directed collective cell migration is essential for morphogenesis, and chemical, electrical, mechanical and topological features have been shown to guide cell migration in vitro. Here we provide in vivo evidence showing that endogenous electric fields drive the directed collective cell migration of an embryonic stem cell population-the cephalic neural crest of Xenopus laevis. We demonstrate that the voltage-sensitive phosphatase 1 is a key component of the molecular mechanism, enabling neural crest cells to specifically transduce electric fields into a directional cue in vivo.

Choroidal thickness under pilocarpine versus cyclopentolate.

Bruch´s membrane (BM) is firmly connected posteriorly to the optic nerve head through the peripapillary choroidal border tissue, and anteriorly through the longitudinal ciliary muscle to the scleral spur. We assessed, whether a difference in the contractile state of the ciliary muscle influences the position of the posterior BM by lifting the posterior BM pole, i.e.

Evidence of DNA methylation heterogeneity and epipolymorphism in kidney cancer tissue samples.

Clear cell renal cell carcinoma (ccRCC) is characterised by significant genetic heterogeneity, which has diagnostic and prognostic implications. Very limited evidence is available regarding DNA methylation heterogeneity. We therefore generate sequence level DNA methylation data on 136 multi-region tumour and normal kidney tissue from 18 ccRCC patients, along with matched whole exome sequencing (85 samples) and gene expression (47 samples) data on a subset of samples.

Sleep for infants after discharge from a neonatal ward: Expert- and parent endorsed strategies.

Background: This study aims to outline sleep strategies grounded in scientific research and endorsed by sleep experts, integrating parental input into the evaluation process, to assist parents in supporting infant sleep after discharge from a neonatal ward.

Methods: A Delphi method, consisting of three rounds, was employed. Sleep strategies based on scientific literature were presented to sleep experts and parents of infants discharged from a neonatal ward.

Associations of behavioral, motivational, and socioeconomic factors with BMI among children and adolescents.

Background: Higher weight represents a significant health concern in youth and may be influenced by socioeconomic and behavioral factors. We investigated the relationship between BMI and parental education, nutritional health, eating culture, organized and non-organized physical activity (PA), motives for PA (weight loss/maintenance, enjoyment), and screen-time in children and adolescents.

Methods: 677 2- to 11-year-olds (young-age-group) and 464 12- to 20-year-olds (old-age-group) from Leipzig, a city in Germany, participated.

[Implementation of teledermatological consultations at Leipzig University Medical Center].

Background: Numerous patients admitted to a general hospital present skin changes as secondary findings. Approximately 800 dermatological consultations are performed annually at the Leipzig University Medical Center.

Objectives: The aim of this study was, after implementation of teledermatological consulting, the retrospective evaluation of that and the resulting satisfaction of the physicians involved.

How knee muscles and ground reaction forces shape knee buckling and ankle push-off in neuromuscular simulations of human walking.

Ankle push-off is important for efficient, human-like walking, and many prosthetic devices mimic push-off using motors or elastic elements. The knee is extended throughout the stance phase and begins to buckle just before push-off, with timing being crucial. However, the exact mechanisms behind this buckling are still unclear.

Undoped ruthenium oxide as a stable catalyst for the acidic oxygen evolution reaction.

Reducing green hydrogen production cost is critical for its widespread application. Proton-exchange-membrane water electrolyzers are among the most promising technologies, and significant research has been focused on developing more active, durable, and cost-effective catalysts to replace expensive iridium in the anode. Ruthenium oxide is a leading alternative while its stability is inadequate.

Discordance, accuracy and reproducibility study of pathologists' diagnosis of melanoma and melanocytic tumors.

Accurate melanoma diagnosis is crucial for patient outcomes and reliability of AI diagnostic tools. We assess interrater variability among eight expert pathologists reviewing histopathological images and clinical metadata of 792 melanoma-suspicious lesions prospectively collected at eight German hospitals. Moreover, we provide access to the largest panel-validated dataset featuring dermoscopic and histopathological images with metadata.

Comparison of 1D and 3D volume measurement techniques in NF2-associated vestibular schwannoma monitoring.

To compare 1D (linear) tumor volume calculations and classification systems with 3D-segmented volumetric analysis (SVA), focusing specifically on their effectiveness in the evaluation and management of NF2-associated vestibular schwannomas (VS). VS were clinically followed every 6 months with cranial, thin-sliced (< 3 mm) MRI. We retrospectively reviewed and used T1-weighted post-contrast enhanced (gadolinium) images for both SVA and linear measurements.