Site-saturation mutagenesis of 500 human protein domains.

Missense variants that change the amino acid sequences of proteins cause one-third of human genetic diseases. Tens of millions of missense variants exist in the current human population, and the vast majority of these have unknown functional consequences. Here we present a large-scale experimental analysis of human missense variants across many different proteins.

The sarcoma ring trial: a case-based analysis of inter-center agreement across 21 German-speaking sarcoma centers.

Purpose: The management of soft tissue sarcoma (STS) at reference centers with specialized multidisciplinary tumor boards (MTB) improves patient survival. The German Cancer Society (DKG) certifies sarcoma centers in German-speaking countries, promoting high standards of care. This study investigated the variability in treatment recommendations for localized STS across different German-speaking tertiary sarcoma centers.

MoCHI: neural networks to fit interpretable models and quantify energies, energetic couplings, epistasis, and allostery from deep mutational scanning data.

We present MoCHI, a tool to fit interpretable models using deep mutational scanning data. MoCHI infers free energy changes, as well as interaction terms (energetic couplings) for specified biophysical models, including from multimodal phenotypic data. When a user-specified model is unavailable, global nonlinearities (epistasis) can be estimated from the data.

Pain After Lower Limb Amputations: Insights from the Heidelberg Amputation Registry.

: The experience of unpleasant sensory phenomena after lower limb amputations (LLAs), including phantom limb pain (PLP), phantom limb sensation (PLS), and residual limb pain (RLP), impacts global healthcare and adversely affects outcomes post-amputation. This study aimed to describe the distribution of PLP, PLS, and RLP among patients with LLAs registered in the Heidelberg Amputation Registry. The primary objective was to determine the prevalence of sensory abnormalities across different amputation levels and causes.

Targeting Bone Tumours with 45S5 Bioactive Glass.

Despite advances in treatment modalities, bone tumour therapies still face significant challenges. Severe side effects of conventional approaches, such as chemo- and radiation therapy, result in poor survival rates and high tumour recurrence rates, which are the most common issues that need to be improved upon. The aim of this study was to evaluate the therapeutic properties of 45S5 bioactive glass (BG) for targeting bone tumours.