Genome-wide association study unravels mechanisms of brain glymphatic activity.

Brain glymphatic activity, as indicated by diffusion-tensor imaging analysis along the perivascular space (ALPS) index, is involved in developmental neuropsychiatric and neurodegenerative diseases, but its genetic architecture is poorly understood. Here, we identified 17 unique genome-wide significant loci and 161 candidate genes linked to the ALPS-indexes in a discovery sample of 31,021 individuals from the UK Biobank. Seven loci were replicated in two independent datasets.

Nonlinear exposure-response associations of daytime, nighttime, and day-night compound heatwaves with mortality amid climate change.

Heatwaves are commonly simplified as binary variables in epidemiological studies, limiting the understanding of heatwave-mortality associations. Here we conduct a multi-country study across 28 East Asian cities that employed the Cumulative Excess Heatwave Index (CEHWI), which represents excess heat accumulation during heatwaves, to explore the potentially nonlinear associations of daytime-only, nighttime-only, and day-night compound heatwaves with mortality from 1981 to 2010. Populations exhibited high adaptability to daytime-only and nighttime-only heatwaves, with non-accidental mortality risks increasing only at higher CEHWI levels (75th-90th percentiles).

A truncated variant of the ribosome-associated trigger factor specifically contributes to plant chloroplast ribosome biogenesis.

Molecular chaperones are essential throughout a protein's life and act already during protein synthesis. Bacteria and chloroplasts of plant cells share the ribosome-associated chaperone trigger factor (Tig1 in plastids), facilitating maturation of emerging nascent polypeptides. While typical trigger factor chaperones employ three domains for their task, the here described truncated form, Tig2, contains just the ribosome binding domain.

Early screening of lung function by electrical impedance tomography in people with normal spirometry reveals unrecognized pathological features.

Early detection of lung function impairment is crucial. However, the sensitivity of spirometry in detecting early lung function deterioration is limited. In this study, lungs of 3180 healthy participants scheduled for annual health check were screened.

Evaluation of Drug-Drug Interactions in Pharmacoepidemiologic Research.

Drug-drug interactions (DDIs) represent a significant concern for clinical care and public health, but the health consequences of many DDIs remain largely underexplored. This knowledge gap underscores the critical need for pharmacoepidemiologic research to evaluate real-world health outcomes of DDIs. In this review, we summarize the definitions commonly used in pharmacoepidemiologic DDI studies, discuss common sources of bias, and illustrate through examples how these biases can be mitigated.

Exploring 1-alkene biosynthesis in bacterial antagonists and jeotgalicoccus sp. ATCC 8456.

Terminal olefins are important platform chemicals, drop-in compatible hydrocarbons and also play an important role as biocontrol agents of plant pathogens. Currently, 1-alkenes are derived from petroleum, although microbial biosynthetic routes are known. Jeotgalicoccus sp.

at 50: a data-driven history.

In this paper, we take a data-driven approach to analyse intellectual trends over the first five decades of the (). Our data set, comprising all texts published in the since 1975, reveals not only the most distinctive topics of the in comparison to other key journals with similar profiles but also diachronic fluctuations in the prominence of certain topics. Overall, the distribution of topics shifted gradually, with each editorial period at the showing continuity with its immediate predecessor.

The "HAT-TRICK' technique: A Modification of soft tissue grafting using volume stable collagen matrix and cross-linked hyaluronic acid. Part B: Clinical applications in the esthetic zone.

Soft tissue deficiency around dental implants can negatively impact outcomes in terms of esthetics and long-term stability. While autogenous connective tissue grafting is still considered the gold standard treatment, alternative approaches are being proposed primarily to enhance patient comfort and avoid invasive procedures such as two-sites surgeries using xenogeneic collagen matrices. Despite the advantages, the quality of the regenerated tissues remains unpredictable and, in many cases, questionable, highlighting the need for alternative and innovative approaches.

Altered Neural Responses to Punishment Learning in Conduct Disorder.

Objective: Conduct disorder (CD) is associated with deficits in the use of punishment for reinforcement learning (RL) and subsequent decision-making, contributing to reckless, antisocial, and aggressive behaviors. Here, we used functional magnetic resonance imaging (fMRI) to examine whether differences in behavioral learning rates derived from computational modeling, particularly for punishment, are reflected in aberrant neural responses in youths with CD compared to typically-developing controls (TDCs).

Methods: 75 youths with CD and 99 TDCs (9-18 years, 47% girls) performed a probabilistic RL task with punishment, reward, and neutral contingencies.

Benchmarking R&D success rates of leading pharmaceutical companies: an empirical analysis of FDA approvals (2006-2022).

Previous analyses provide an industry benchmark of ∼10% for the success rate in clinical development. However, prior analyses were limited by a narrow timeframe, a diverse research focus, biases in phase-to-phase transition methodology or a focus on specific use cases. We calculated unbiased input:output ratios (Phase I to FDA new drug approval) to analyze the likelihood of first approval using data from clinicaltrials.

Impact of vial quality on interactions, particle formation, container closure integrity, and gas permeability for frozen drug product storage.

The frozen storage of biopharmaceuticals brings new challenges to the primary packaging material. Due to an increasing demand and the downsides of standard type I glass vials, such as vial breakage, novel vial types for special applications of parenteral drug products have been introduced to the market in the past years. Mechanical stresses due to dimensional changes experienced during freezing and thawing could change the material properties, hence affecting the interaction with the drug product stored in the vial or functionality such as overall integrity.

Heparan Sulfate Proteoglycan Affinity of Adeno-Associated Virus Vectors: Implications for Retinal Gene Delivery.

Adeno-associated virus (AAV)-based vectors have emerged as an effective and widely used technology for somatic gene therapy approaches, including those targeting the retina. A major advantage of the AAV technology is the availability of a large number of serotypes that have either been isolated from nature or produced in the laboratory. These serotypes have different properties in terms of sensitivity to neutralizing antibodies, cellular transduction profile and efficiency.

Local effective connectivity changes after transcranial direct current stimulation in obsessive-compulsive disorder patients.

Aim: This study investigates the effects of transcranial direct current stimulation (tDCS) on brain network connectivity in individuals with obsessive-compulsive disorder (OCD).

Methods: In a randomized, double-blind, sham-controlled experimental design anodal tDCS (vs. sham) was applied in a total of 43 right-handed patients with OCD, targeting the right pre-supplementary motor area (pre-SMA).

Long-Term Success and Survival of Post-Endodontic Restorations Without Posts After up to18 Years: A Practice-Based Study.

Objectives: The aim of this non-interventional, multi-center, prospective, practice-based study was, firstly, to evaluate the longevity of composite build-ups in endodontically treated teeth, treated with root canal therapy (ETT), without post placement and secondly, to identify and analyze factors influencing the success of these reconstructions.

Methods: Each of seven general dental practitioners placed up to 50 composite build-ups without additional posts in ETT. Teeth were restricted to incisors, canines and premolars.

Heterotypic spheroids as a strategy for 3D culture of cryopreserved primary human hepatocytes in stirred-tank systems.

Primary human hepatocytes (PHHs) are the preferred cell source to address liver function. Despite originating from the native tissue, one of the bottlenecks when using primary material is the donor-to-donor variability. Cryopreserved PHHs offer a high number of cells from the same donor and standardization of cell isolation and cryopreservation procedures, mitigating some of the inter-donor variability.

Characterization of cell membrane fragments containing muscle type nAChR from Tetronarce californica after preparation using high pressure homogenization.

The nicotinic acetylcholine receptor (nAChR) is a pentameric ligand-gated ion channel (pLGIC) commonly used as a model for receptors belonging to the Cys-loop superfamily. Members of pLGICs are standardly used in numerous toxicological investigations e.g.

Medication reviews in hospitalised patients for reduced hospital readmission and mortality. Systematic review, meta-analysis and meta-regression of RCTs.

Efforts to reduce preventable medication-related harm through medication reviews have increased, but interventions often yield null-results regarding clinical outcomes. We conducted a systematic literature search in four data bases and summarised the available evidence from randomised controlled trials (RCTs) comparing medication reviews and usual care in hospitalised patients regarding hospital readmissions and all-cause mortality by random-effects meta-analyses. Effect size differences by methodological study differences were of special interest.

Hydrolysis of chitin and chitosans by the human chitinolytic enzymes: Chitotriosidase, acidic mammalian chitinase, and lysozyme.

Human chitinolytic enzymes trigger growing interest, not only because a wide range of diseases and allergic responses are linked to chitinous components of pathogens, including their interplay with human enzymes, but also due to the increasing use of chitosans in biomedical applications. Here, we present a detailed side-by-side analysis of the only two human chitinases, chitotriosidase and acidic mammalian chitinase, as well as human lysozyme. By analyzing the cleavage of well-characterized chitosan polymers and defined chitin and chitosan oligomers, we report mild processivity and a quantitative subsite preference typical for GH18 chitinases for chitotriosidase and acidic mammalian chitinase.

Type 1 diabetes incidence curves differ by age for girls and boys between 1996 and 2022: Results from the North Rhine-Westphalia diabetes Registry, Germany.

Type 1 diabetes incidence was analyzed in 0- to 14-year-old children in North Rhine-Westphalia, Germany, from 1996 to 2022. The data revealed an overall increasing trend, with variations by age and sex. The incidence increased in boys across age groups but peaked in girls in the 5-9-year age group.

Roles of acyl carrier proteins in ladderane fatty acid producing-organisms.

Ladderanes are highly strained hydrocarbons consisting of two or more linearly concatenated cyclobutane rings. Strikingly, ladderane moieties are part of unique fatty acids and fatty alcohols that are exclusively found in the membrane lipids of anaerobic ammonium-oxidizing (anammox) bacteria. These bacteria express a distinctive gene cluster (cluster I) that has been suggested to be responsible for ladderane fatty acid (FA) biosynthesis in addition to a cluster likely involved in canonical FA biosynthesis (cluster III).

Nerve transfer of the median flexor pollicis brevis branch to the deep branch of the ulnar nerve for ulnar nerve palsy: a cadaveric feasibility study.

An ulnar nerve (UN) palsy is devastating for hand function, resulting in an intrinsic minus position or claw hand with a loss of pinch grip. Distal nerve transfers facilitate faster reinnervation of hand intrinsic muscles in cases of proximal ulnar nerve lesions. The traditional anterior interosseous nerve (AIN) to UN motor transfer is commonly used, however, this still leads to long reinnervation times for the distal intrinsic muscles, important for the thumb to index pinch grip.

Clinical Guidelines for Canine Transmissible Venereal Tumour Treatment: Systematic Review and Meta-Analysis.

The treatment of canine transmissible venereal tumour (CTVT) has evolved since its initial description in 1810. Initially considered untreatable in the early 20th century, extensive research over time has significantly advanced our understanding of its aetiopathogenesis. This led to successful chemotherapy treatments, which have shown superior outcomes compared to surgical interventions.