Prognostic impact of expression of CD2, CD25, and/or CD30 in/on mast cells in systemic mastocytosis: a registry study of the European Competence Network on Mastocytosis.

Expression of CD2, CD25 and/or CD30 in extracutaneous mast cells (MC) is a minor diagnostic criterion for systemic mastocytosis (SM) in the classification of the World Health Organization and International Consensus Classification. So far, it remains unknown whether expression of these antigens on MC is of prognostic significance in SM. We performed a retrospective multi-center study of patients with SM using the data set of the registry of the European Competence Network on Mastocytosis, including 5034 patients with various MC disorders.

Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia.

X-linked hypophosphataemia (XLH) is a rare metabolic bone disorder caused by pathogenic variants in the PHEX gene, which is predominantly expressed in osteoblasts, osteocytes and odontoblasts. XLH is characterized by increased synthesis of the bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23), which results in renal phosphate wasting with consecutive hypophosphataemia, rickets, osteomalacia, disproportionate short stature, oral manifestations, pseudofractures, craniosynostosis, enthesopathies and osteoarthritis. Patients with XLH should be provided with multidisciplinary care organized by a metabolic bone expert.

Ancient DNA reveals reproductive barrier despite shared Avar-period culture.

After a long-distance migration, Avars with Eastern Asian ancestry arrived in Eastern Central Europe in 567 to 568 CE and encountered groups with very different European ancestry. We used ancient genome-wide data of 722 individuals and fine-grained interdisciplinary analysis of large seventh- to eighth-century CE neighbouring cemeteries south of Vienna (Austria) to address the centuries-long impact of this encounter. We found that even 200 years after immigration, the ancestry at one site (Leobersdorf) remained dominantly East Asian-like, whereas the other site (Mödling) shows local, European-like ancestry.

Feasibility and potential effect of a pilot blended digital behavior change intervention promoting sustainable diets over a year.

Well-designed effective interventions promoting sustainable diets are urgently needed to benefit both human and planetary health. This study evaluated the feasibility, acceptability, and potential impact of a pilot blended digital intervention aimed at promoting sustainable diets. We conducted a series of ABA n-of-1 trials with baseline, intervention, and follow-up phases over the course of a year, involving twelve participants.

Functional genomics implicates ebony in the black pupae phenotype of tephritid fruit flies.

The remarkable diversity of insect pigmentation offers a captivating avenue for studying evolution and genetics. In tephritids, understanding the molecular basis of mutant traits is also crucial for applied entomology, enabling the creation of genetic sexing strains through genome editing, thus facilitating sex-sorting before sterile insect releases. Here, we present evidence from classical and modern genetics showing that the black pupae (bp) phenotype in the GUA10 strain of Anastrepha ludens is caused by a large deletion at the ebony locus, removing the gene's entire coding region.

Structural basis of Spliced Leader RNA recognition by the Trypanosoma brucei cap-binding complex.

Kinetoplastids are a clade of eukaryotic protozoans that include human parasitic pathogens like trypanosomes and Leishmania species. In these organisms, protein-coding genes are transcribed as polycistronic pre-mRNAs, which need to be processed by the coupled action of trans-splicing and polyadenylation to yield monogenic mature mRNAs. During trans-splicing, a universal RNA sequence, the spliced leader RNA (SL RNA) mini-exon, is added to the 5'-end of each mRNA.

Ethosuximide: Subunit- and Gβγ-dependent blocker and reporter of allosteric changes in GIRK channels.

Background And Purpose: The antiepileptic drug ethosuximide (ETX) suppresses epileptiform activity in a mouse model of GNB1 syndrome, caused by mutations in Gβ protein, likely through the inhibition of G-protein gated K (GIRK) channels. Here, we investigated the mechanism of ETX inhibition (block) of different GIRKs.

Experimental Approach: We studied ETX inhibition of GIRK channels expressed in Xenopus oocytes with or without their physiological activator, the G protein subunit dimer Gβγ.

Association between patient perception of disease status and different components of the Minimal Disease Activity (MDA) criteria in psoriatic arthritis.

Objective: The aim of this analysis was to evaluate the relationship between the criteria met of the Minimal Disease Activity (MDA) score for psoriatic arthritis (PsA) and patient-perceived disease status.

Methods: We analysed data from the ReFlaP study (NCT03119805), a cross-sectional international study of adult patients with PsA. Patients self-reported if they felt their PsA was in remission (REM), low disease activity (LDA) or neither.

Empirical antibiotic therapy improves outcomes in mechanically ventilated patients with COVID-19: An emulated targeted trial within a prospective, multicentre cohort study.

Background: Bacterial pulmonary superinfections develop in a substantial proportion of mechanically ventilated COVID-19 patients and are associated with prolonged mechanical ventilation requirements and an increased mortality. Albeit recommended, evidence supporting the use of empirical antibiotics at intubation is weak and of low quality. The aim of this study was to elucidate the effect of empirical antibiotics, administered within 24hours of endotracheal intubation, on superinfections, duration of mechanical ventilation, and mortality in mechanically ventilated patients with COVID-19.

The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study.

Purpose: To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery.

Background: Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC.

Targeting protein-ligand neosurfaces with a generalizable deep learning tool.

Molecular recognition events between proteins drive biological processes in living systems. However, higher levels of mechanistic regulation have emerged, in which protein-protein interactions are conditioned to small molecules. Despite recent advances, computational tools for the design of new chemically induced protein interactions have remained a challenging task for the field.

Rhythmic categories in horse gait kinematics.

Anecdotally, horses' gaits sound rhythmic. Are they really? In this study, we quantified the motor rhythmicity of horses across three different gaits (walk, trot, and canter). For the first time, we adopted quantitative tools from bioacoustics and music cognition to quantify locomotor rhythmicity.

Antigenic determinants underlying IgE-mediated anaphylaxis to peanut.

Background: Studies of human IgE and its targeted epitopes on allergens have been very limited. We have an established method to immortalize IgE encoding B cells from allergic individuals.

Objective: To develop an unbiased and comprehensive panel of peanut-specific human IgE mAbs to characterize key immunodominant antigenic regions and epitopes on peanut allergens to map the molecular interactions responsible for inducing anaphylaxis.

Restimulation by macrophages exhausts T cells.

Inhibiting T cell exhaustion is an attractive cancer immunotherapy strategy. In this issue of Immunity, Waibl Polania et al. examine the microenvironmental signals regulating terminal T cell exhaustion and find that antigen presentation by tumor-associated macrophages, not tumor cells, drives terminal T cell exhaustion in glioblastoma.

Enormous Out-of-Plane Charge Rectification and Conductance through Two-Dimensional Monolayers.

Heterogeneous integration of emerging two-dimensional (2D) materials with mature three-dimensional (3D) silicon-based semiconductor technology presents a promising approach for the future development of energy-efficient, function-rich nanoelectronic devices. In this study, we designed a mixed-dimensional junction structure in which a 2D monolayer (e.g.

Targeting TRPC channels for control of arthritis-induced bone erosion.

Arthritis leads to bone erosion due to an imbalance between osteoclast and osteoblast function. Our prior investigations revealed that the Ca-selective ion channel, Orai1, is critical for osteoclast maturation. Here, we show that the small-molecule ELP-004 preferentially inhibits transient receptor potential canonical (TRPC) channels.

Epithelial OPA1 links mitochondrial fusion to inflammatory bowel disease.

Dysregulation at the intestinal epithelial barrier is a driver of inflammatory bowel disease (IBD). However, the molecular mechanisms of barrier failure are not well understood. Here, we demonstrate dysregulated mitochondrial fusion in intestinal epithelial cells (IECs) of patients with IBD and show that impaired fusion is sufficient to drive chronic intestinal inflammation.

Multi-tissue characterization of the constitutive heterochromatin proteome in Drosophila identifies a link between satellite DNA organization and transposon repression.

Noncoding satellite DNA repeats are abundant at the pericentromeric heterochromatin of eukaryotic chromosomes. During interphase, sequence-specific DNA-binding proteins cluster these repeats from multiple chromosomes into nuclear foci known as chromocenters. Despite the pivotal role of chromocenters in cellular processes like genome encapsulation and gene repression, the associated proteins remain incompletely characterized.

Maternal characteristics and their relation to early mother-child interaction and cognitive development in toddlers.

Early mother-infant interaction is believed to have a significant impact on the social, cognitive, and emotional development of children. These interactions are not only influenced by child and contextual factors but also by the mother's personality traits and strain. In this study, we investigated the relation between maternal factors such as personality, depressive symptoms, or experiencing of emotions, and (i) children's early cognitive development and (ii) interaction patterns in a sample of 116 mother-child dyads (mean child age = 18.

Short-term impact of low air pressure on plants' functional traits.

Lower atmospheric pressure affects biologically relevant physical parameters such as gas partial pressure and concentration, leading to increased water vapor diffusivity and greater soil water content loss through evapotranspiration. This might impact plant photosynthetic activity, resource allocation, water relations, and growth. However, the direct impact of low air pressure on plant physiology is largely unknown.

Effectiveness and Safety of Adalimumab in Patients With Very Early-Onset Inflammatory Bowel Disease: A Retrospective Study on Behalf of the Porto Inflammatory Bowel Disease Working Group of European Society for Pediatric Gastroenterology Hepatology and Nutrition.

Background And Aims: Patients with very early-onset inflammatory bowel disease (VEO-IBD), with an age of onset < 6 years, can present with severe manifestations and may require biologic therapy. Infliximab and adalimumab are approved for induction and maintenance in pediatric IBD patients but are licensed only above the age of 6 years. Effectiveness and safety data on adalimumab in this patient population are lacking.

Outcomes of mechanical thrombectomy for medium vessel occlusion in acute ischemic stroke patients with ASPECTS 4-5 vs. 6-7: a retrospective, multicenter, and multinational study.

Introduction: Mechanical thrombectomy (MT) efficacy in medium vessel occlusion (MeVO) stroke, particularly in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS), remains less explored.

Methods: This retrospective study analyzed data from 443 AIS patients treated with MT for MeVO and low ASPECTS (4-7) at 37 centers across North America, Asia, and Europe, from September 2017 to July 2021. Patients were categorized into ASPECTS of 4-5 and 6-7.

Impact of fluorination on membrane-protein stabilization and extraction by lactobionamide detergents.

We report the synthesis of a series of detergents with a lactobionamide polar head group and a tail containing four to seven perfluorinated carbon atoms. Critical micellar concentrations (CMCs) were determined using isothermal titration calorimetry (ITC) and surface tension (SFT) measurements, showing a progressive decrease from 27 mM to about 0.2 mM across the series.

Fabrication of nanoparticles with precisely controllable plasmonic properties as tools for biomedical applications.

Metal nanoparticles are established tools for biomedical applications due to their unique optical properties, primarily attributed to localized surface plasmon resonances. They show distinct optical characteristics, such as high extinction cross-sections and resonances at specific wavelengths, which are tunable across the wavelength spectrum by modifying the nanoparticle geometry. These attributes make metal nanoparticles highly valuable for sensing and imaging in biology and medicine.