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The use of CRISPR-Cas bacterial adaptive immunity system components for targeted DNA changes has opened broad prospects for programmable genome editing of higher organisms. The most widely used gene editors are based on the Cas9 effectors of the type II CRISPR-Cas systems. In complex with guide RNAs, Cas9 proteins are able to directionally introduce double-stranded breaks into DNA regions that are

Starting with the lead compound roquinimex, a selection of 3-quinolinecarboxamide derivatives were synthesized and evaluated for the treatment of the autoimmune disease multiple sclerosis. Structure-activity relationships were established in animal studies and from these, laquinimod was chosen as the drug candidate due to its superior potency and toxicological profile as compared to roquinimex. Ho

Single-cell technologies have transformed our understanding of cellular heterogeneity through multimodal data acquisition. However, robust cell alignment remains a major challenge for data integration and harmonization, including batch correction, label transfer, and multi-omics integration. Many existing methods constrain alignment based on rigid feature-wise distance metrics, limiting their abil

DNA replication relies on precise coordination between proteins, including the sliding clamp proliferating cell nuclear antigen (PCNA), which encircles DNA to interact with key players in replication and repair. While biochemical studies have demonstrated interactions between PCNA and DNA polymerases δ and ε during DNA synthesis, the functional role of the Pol ε–PCNA interaction in vivo, particula

The testing and safety cases of assisted and automated driving (AAD) functions require considerations for nonideal environmental conditions, such as adverse and extreme weather. In these extreme conditions, perception sensors (e.g., camera, LiDAR, and RADAR), which build the situational awareness of the vehicle, might produce noisy and degraded data. Therefore, it is key to consider: 1) how to rel

Reliable and cost-effective operation of structural systems over their service life depends on the implementation of Structural Health Monitoring (SHM) and maintenance activities, which influence operational costs, the expected costs of failure and downtime. Decision Value Analysis (DVA) provides a framework to quantify the value of such activities by evaluating their effect on total expected life

IntroductionSport-related concussion (SRC) is a pressing issue in Para sport, yet biomechanical mechanisms remain poorly understood. Athletes with visual impairment face elevated risks due to sport-specific demands, such as frequent collisions in blind football. This pilot study examined head acceleration responses in blind football players compared with non-disabled football players, and between

IntroductionSport-related concussion (SRC) is a major health concern in contact sports. Linear head acceleration (LHA) and rotational head acceleration (RHA) are central biomechanical markers, and anticipatory neck muscle activation may mitigate these forces. Evidence on how anticipation influences head kinematics, and whether sex differences exist, remains limited. This study compared head accele

Take Home Message Using Germany as a case example, a comparison between organized mammography screening and contemporary, risk-adapted screening for prostate cancer suggests that prostate-specific antigen–based early detection with incorporation of magnetic resonance imaging and active surveillance can achieve benefits comparable to those of mammography while addressing previous concerns about ove

Background:Trauma patients present with heterogeneous injury patterns that are challenging to represent in statistical models. Traditional approaches either use high-dimensional one-hot encoding, resulting in sparse features, or aggregate injuries into summary scores that lose patient-specific detail.Objective:This study developed data-driven ICD-10 embeddings for trauma injuries and evaluated the

Aim: This paper aims to describe what constitutes good-quality, accessible, affordable and acceptable primary care for migrants. This includes identifying system adaptations and offering evidence- and practice-based recommendations and guidance for primary care organizations and professionals on how to deliver such care.Background: Migration has significantly diversified European populations. Migr

The increasing prevalence of antimicrobial-resistant bacterial infections has ushered in a major global public health crisis. Judicious or restricted antimicrobial use in animal agriculture, aiming to confine the use for the treatment of infections, is the most commonly proposed solution to reduce selection pressure for resistant bacterial strains and resistance genes. However, a multifaceted solu

Purpose: Boys with genetic syndromes have an increased risk of undescended testes (UDT), but laparoscopic findings and outcomes after two-stage Fowler-Stephens orchiopexy (FS2) are rarely reported. This study aims to compare laparoscopic findings and results after FS2 between syndromic and non-syndromic boys. Methods: A retrospective cohort study on boys with UDT who underwent laparoscopy between

Urban freight systems play an indispensable role in contemporary cities. By enabling the continuous flow of goods, they support economic activity and contribute to urban prosperity. At the same time, these activities generate substantial negative externalities, including emissions, noise, congestion and increasing pressures on urban space. As freight activities grow, their impacts intensify, under

Motivation Machine learning offers a powerful approach for building predictive models from high-dimensional molecular data. Omics technologies such as transcriptomics, proteomics, and metabolomics quantify thousands of molecules simultaneously, providing deep insights into disease biology. Integrating multiple modalities can enhance predictive performance, as shown in histology-omics and holter-om

Jerome of Stridon was one of the most important biblical exegetes in early Christianity. Analyzing letters as well as prefaces to biblical commentaries written by Jerome, this article discusses four criteria which he considered to be necessary for orthodox exegesis to take place: 1) education and learning; 2) studying the Scriptures as part of an ascetic lifestyle; 3) divine help; and 4) learning