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.

High-throughput determination of exchange rates of unmodified and PTM-containing peptides using HX-MS.

Despite the widespread use of MS for hydrogen/deuterium exchange measurements, no systematic, large-scale study has been conducted to compare the observed exchange rates in protein-derived, unstructured peptides measured by MS to the predicted exchange rates calculated from NMR-derived values and how neighboring residues and post-translational modifications influence those exchange rates. In this study, we sought to test the accuracy of predicted values by performing hydrogen exchange measurements on whole cell digests to generate an unbiased dataset of 563 unique peptides derived from naturally-occurring protein sequences. A remarkable 97% of observed exchange rates of peptides are within two-fold of predicted values.

Periapical cysts in dogs: 10 cases (2000-2020).

Objective: To characterize the clinical, diagnostic imaging, and histologic features with description of treatment outcome of periapical cysts in dogs.

Animals: Ten client-owned dogs diagnosed with periapical cysts biopsied between July 1, 2000 and June 30, 2020.

Procedures: Medical records of the Matthew J.

A social information processing perspective on social connectedness.

Social connectedness (SC) is one of the most important predictors for physical and mental health. Consequently, SC is addressed in an increasing number of studies, providing evidence for the multidimensionality of the construct, and revealing several factors that contribute to individual differences in SC. However, a unified model that can address SC subcomponents is yet missing.

Trends and Outcomes in Elective Pediatric Surgery During Weekends.

Purpose: Limited operating room availability constrains hospital scheduling capacity for elective surgical cases. Leveraging weekends for elective surgical cases could increase operative capacity but must be balanced with practical considerations. Our study aimed to characterize trends and outcomes for elective pediatric surgeries performed during weekends.

Comparative Analytical Evaluation of the Proposed Biosimilar FYB206 and its Reference Medicinal Product Keytruda.

Background And Objective: Biological medicinal products improve patients' lives, but access is limited, mainly due to high costs. Patents for many existing biological products are expiring, and generic versions, which are referred to as biosimilars, are produced to serve as an alternative to the reference medicinal product (RMP) cutting down the costs and expanding access. The present paper assesses the analytical similarity between Formycon's FYB206 pembrolizumab biosimilar candidate and Keytruda, an RMP that is approved to treat various types of cancer, with the intention of determining FYB206's suitability to enter clinical biosimilar trials.

Nuclear ATP-citrate lyase regulates chromatin-dependent activation and maintenance of the myofibroblast gene program.

Differentiation of cardiac fibroblasts to myofibroblasts is necessary for matrix remodeling and fibrosis in heart failure. We previously reported that mitochondrial calcium signaling drives α-ketoglutarate-dependent histone demethylation, promoting myofibroblast formation. Here we investigate the role of ATP-citrate lyase (ACLY), a key enzyme for acetyl-CoA biosynthesis, in histone acetylation regulating myofibroblast fate and persistence in cardiac fibrosis.

Fidelity of Enhanced Recovery Protocol Implementation With Assessment of Hospital-Specific Materials.

Introduction: Variability in implementation of enhanced recovery protocols (ERPs) often reduces the effects of an intervention on clinical outcomes. This study aimed to evaluate hospital-level implementation fidelity to a pediatric gastrointestinal surgery ERP by assessing site-specific implementation materials.

Methods: This document analysis study operationalized implementation fidelity as adherence to the creation of specified materials at each study site.

Age differences in prosociality across the adult lifespan: A meta-analysis.

Lifespan developmental theories and research suggest a positive effect of adult age on prosociality. However, this effect lacks consistency, with many studies excluding the period of midlife. This study summarized cross-sectional studies on adult age and prosociality, combining 120 (independent) samples (n = 103,829) in a lifespan meta-analysis approach.

An integrative framework of conflict and control.

People regularly encounter various types of conflict. Here, we ask if, and, if so, how, different types of conflict, from lab-based Stroop conflicts to everyday-life self-control or moral conflicts, are related to one other. We present a framework that assumes that action-goal representations are hierarchically organized, ranging from concrete actions to abstract goals.

Validation of the hind feet position score and its association with heel height difference in dairy cows.

Hind feet position scoring (HFPS) categorizes the outward rotation of the hind feet from the line parallel to the midline of the body in standing dairy cows. It has previously been used as an indication of both differences in heel height between the lateral and medial hind claw (to determine the need of hoof trimming) and the presence of claw lesions in sound cattle. In this observational study, the agreement of HFPS with other types of hoof angle measurements, as well as its association with the heel height difference (HHD) between the claws were investigated.

How I (Diagnose and) Treat Myeloid / Lymphoid Neoplasms with Tyrosine Kinase Gene Fusions.

The fifth edition of the WHO classification and the International Consensus Classification (ICC) both include a category "myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase (TK) gene fusions" (WHO, MLN-TK; ICC, M/LN-eo-TK). This rare group comprises phenotypically and prognostically heterogeneous disorders that present a significant diagnostic challenge. The rapid and reliable identification of patients with MLN-TK may be delayed due to genetic complexity and significant phenotypic differences, which include chronic phase and primary/secondary blast phase (BP) of myeloid, or lymphoid or mixed phenotype in the bone marrow (BP-BM) and/or at extramedullary sites (extramedullary disease, EMD).

Approach to the patient with eosinophilia in the era of tyrosine kinase inhibitors and biologicals.

Purpose Of Review: In this review, we aim to explore the optimal approach to patients presenting with eosinophilia, considering recent advances in diagnostic and therapeutic strategies. Specifically, we focus on the integration of novel therapies into clinical practice to improve patient outcomes.

Recent Findings: Advanced insights into the clinical and genetic features of eosinophilic disorders have prompted revisions in diagnostic criteria by the World Health Organization classification (WHO-HAEM5) and the International Consensus Classification (ICC).

Loss of Kmt2c or Kmt2d drives brain metastasis via KDM6A-dependent upregulation of MMP3.

KMT2C and KMT2D, encoding histone H3 lysine 4 methyltransferases, are among the most commonly mutated genes in triple-negative breast cancer (TNBC). However, how these mutations may shape epigenomic and transcriptomic landscapes to promote tumorigenesis is largely unknown. Here we describe that deletion of Kmt2c or Kmt2d in non-metastatic murine models of TNBC drives metastasis, especially to the brain.

Neurocomputational Mechanisms Underlying Differential Reinforcement Learning From Wins and Losses in Obesity With and Without Binge Eating.

Background: Binge-eating disorder (BED) is thought of as a disorder of cognitive control, but evidence regarding its neurocognitive mechanisms is inconclusive. Key limitations of previous research include a lack of consistent separation between effects of BED and obesity and a disregard for self-report evidence suggesting that neurocognitive alterations may emerge primarily in loss- or harm-avoidance contexts.

Methods: To address these gaps, in this longitudinal study we investigated behavioral flexibility and its underlying neurocomputational processes in reward-seeking and loss-avoidance contexts.

An autoinhibitory switch of the LSD1 disordered region controls enhancer silencing.

Transcriptional coregulators and transcription factors (TFs) contain intrinsically disordered regions (IDRs) that are critical for their association and function in gene regulation. More recently, IDRs have been shown to promote multivalent protein-protein interactions between coregulators and TFs to drive their association into condensates. By contrast, here we demonstrate how the IDR of the corepressor LSD1 excludes TF association, acting as a dynamic conformational switch that tunes repression of active cis-regulatory elements.

Genetic alterations in myeloproliferative and myelodysplastic/myeloproliferative neoplasms - a practical guide to WHO-HAEM5.

Within the World Health Organization (WHO) classification of haematopoietic neoplasms, particularly its fifth version from 2022 (WHO-HAEM5), myeloid neoplasms are not only grouped into myeloproliferative (MPN) and myelodysplastic neoplasms (MDS). There is also a group of haematological disorders that share features of both categories termed myelodysplastic /myeloproliferative neoplasms (MDS/MPN). In this article, we aim to provide a comprehensive and practical guide to WHO-HAEM5 highlighting the genetic alterations that underlie MPN and MDS/MPN.

Effects of astaxanthin on gut microbiota of polo ponies during deconditioning and reconditioning periods.

To determine the effects of astaxanthin (ASTX) supplementation on the equine gut microbiota during a deconditioning-reconditioning cycle, 12 polo ponies were assigned to a control (CON; n = 6) or supplemented (ASTX; 75 mg ASTX daily orally; n = 6) group. All horses underwent a 16-week deconditioning period, with no forced exercise, followed by a 16-week reconditioning program where physical activity gradually increased. Fecal samples were obtained at the beginning of the study (Baseline), after deconditioning (PostDecon), after reconditioning (PostRecon), and 16 weeks after the cessation of ASTX supplementation (Washout).