Definitional Challenges in Understanding Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common hereditary cardiomyopathy. It is often caused by mutations of genes encoding for sarcomeric or sarcomere-associated proteins. Despite its clinical importance, divergent definitions are published by major cardiology societies.

Body mass index stratification enables cytokine-based prediction of ACPA status and Power-Doppler disease activity in rheumatoid arthritis.

Objective: Rheumatoid arthritis can be classified according to ACPA and RF status. ACPA status may be associated with other pathophysiological differences, e.g.

Perspectives on Nasal Odorant Metabolism Research.

Olfaction is a multi-step process. At a peripheral level, nasal odorant metabolism contributes to olfaction via signal termination, variation, and regulation. We summarize current techniques used to investigate nasal odorant metabolism and give an outlook on future approaches, such as nasal tissue models and their potential contributions in future research directions.

Outcomes of Alcohol Septal Ablation in Patients With Severe Left Ventricular Outflow Tract Obstruction: A Propensity Score Matching Analysis.

Background: The current ACC/AHA guidelines on hypertrophic cardiomyopathy (HCM) caution that alcohol septal ablation (ASA) might be less effective in patients with left ventricular outflow tract obstruction (LVOTO) ≥ 100 mm Hg.

Methods: We used a multinational registry to evaluate the outcome of ASA patients according to baseline LVOTO.

Results: A total of 1346 ASA patients were enrolled and followed for 5.

LASP1 in Cellular Signaling and Gene Expression: More than Just a Cytoskeletal Regulator.

LIM and SH3 protein 1 was originally identified as a structural cytoskeletal protein with scaffolding function. However, recent data suggest additional roles in cell signaling and gene expression, especially in tumor cells. These novel functions are primarily regulated by the site-specific phosphorylation of LASP1.

Corrigendum to "Degradation of 3D-printed magnesium phosphate ceramics in vitro and a prognosis on their bone regeneration potential" [Bioact. Mater. 19 (2023) 376-391/22].

[This corrects the article DOI: 10.1016/j.bioactmat.

Treosulfan compared with reduced-intensity busulfan improves allogeneic hematopoietic cell transplantation outcomes of older acute myeloid leukemia and myelodysplastic syndrome patients: Final analysis of a prospective randomized trial.

The phase III study was designed to compare event-free survival (EFS) after treosulfan-based conditioning with a widely applied reduced-intensity conditioning (RIC) busulfan regimen in older or comorbid patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplantation (HCT). A previously reported confirmatory interim analysis of the randomized clinical study including 476 patients demonstrated statistically significant noninferiority for treosulfan with clinically meaningful improvement in EFS. Here, the final study results and pre-specified subgroup analyses of all 570 randomized patients with completed longer-term follow-up are presented.

Degradation of 3D-printed magnesium phosphate ceramics and a prognosis on their bone regeneration potential.

Regenerative bone implants promote new bone formation and ideally degrade simultaneously to osteogenesis. Although clinically established calcium phosphate bone grafts provide excellent osseointegration and osteoconductive efficacy, they are limited in terms of bioresorption. Magnesium phosphate (MP) based ceramics are a promising alternative, because they are biocompatible, mechanically extremely stable, and degrade much faster than calcium phosphates under physiological conditions.

Genotype- and Age-Dependent Differences in Ultrasound Vocalizations of SPRED2 Mutant Mice Revealed by Machine Deep Learning.

Vocalization is an important part of social communication, not only for humans but also for mice. Here, we show in a mouse model that functional deficiency of Sprouty-related EVH1 domain-containing 2 (SPRED2), a protein ubiquitously expressed in the brain, causes differences in social ultrasound vocalizations (USVs), using an uncomplicated and reliable experimental setting of a short meeting of two individuals. SPRED2 mutant mice show an OCD-like behaviour, accompanied by an increased release of stress hormones from the hypothalamic-pituitary-adrenal axis, both factors probably influencing USV usage.

Regulation of titin-based cardiac stiffness by unfolded domain oxidation (UnDOx).

The relationship between oxidative stress and cardiac stiffness is thought to involve modifications to the giant muscle protein titin, which in turn can determine the progression of heart disease. In vitro studies have shown that S-glutathionylation and disulfide bonding of titin fragments could alter the elastic properties of titin; however, whether and where titin becomes oxidized in vivo is less certain. Here we demonstrate, using multiple models of oxidative stress in conjunction with mechanical loading, that immunoglobulin domains preferentially from the distal titin spring region become oxidized in vivo through the mechanism of unfolded domain oxidation (UnDOx).

The transcriptome of the newt Cynops orientalis provides new insights into evolution and function of sexual gene networks in sarcopterygians.

Amphibians evolved in the Devonian period about 400 Mya and represent a transition step in tetrapod evolution. Among amphibians, high-throughput sequencing data are very limited for Caudata, due to their largest genome sizes among terrestrial vertebrates. In this paper we present the transcriptome from the fire bellied newt Cynops orientalis.

Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trial.

Background: Further improvement of preparative regimens before allogeneic haemopoietic stem cell transplantation (HSCT) is an unmet medical need for the growing number of older or comorbid patients with acute myeloid leukaemia or myelodysplastic syndrome. We aimed to evaluate the efficacy and safety of conditioning with treosulfan plus fludarabine compared with reduced-intensity busulfan plus fludarabine in this population.

Methods: We did an open-label, randomised, non-inferiority, phase 3 trial in 31 transplantation centres in France, Germany, Hungary, Italy, and Poland.

Correction to: Differing X-ray patterns in seronegative and seropositive rheumatoid arthritis.

The first and family names of the authors were interchanged and are now presented correctly. The original article has been corrected.

Differing X-ray patterns in seronegative and seropositive rheumatoid arthritis.

Introduction: Anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) status are important predictors for rheumatoid arthritis (RA) erosivity. Qualitative differences on hand/feet radiographs have been described, indicating more carpal fusion in seronegative RA. This study explores these differences further using the total Sharp/van der Heijde score (TSS), digital X-ray radiogrammetry (DXR), and qualitative description.

Analysis of the Role of the Mc4r System in Development, Growth, and Puberty of Medaka.

In mammals the melanocortin 4 receptor (Mc4r) signaling system has been mainly associated with the regulation of appetite and energy homeostasis. In fish of the genus (platyfish and swordtails) puberty onset is genetically determined by a single locus, which encodes the . Wild populations of are polymorphic for early and late-maturing individuals.

A Comparative View on Sex Differentiation and Gametogenesis Genes in Lungfish and Coelacanths.

Gonadal sex differentiation and reproduction are the keys to the perpetuation of favorable gene combinations and positively selected traits. In vertebrates, several gonad development features that differentiate tetrapods and fishes are likely to be, at least in part, related to the water-to-land transition. The collection of information from basal sarcopterygians, coelacanths, and lungfishes, is crucial to improve our understanding of the molecular evolution of pathways involved in reproductive functions, since these organisms are generally regarded as "living fossils" and as the direct ancestors of tetrapods.

The Colorful Sex Chromosomes of Teleost Fish.

Teleost fish provide some of the most intriguing examples of sexually dimorphic coloration, which is often advantageous for only one of the sexes. Mapping studies demonstrated that the genetic loci underlying such color patterns are frequently in tight linkage to the sex-determining locus of a species, ensuring sex-specific expression of the corresponding trait. Several genes affecting color synthesis and pigment cell development have been previously described, but the color loci on the sex chromosomes have mostly remained elusive as yet.

Activity alterations in the bed nucleus of the stria terminalis and amygdala during threat anticipation in generalized anxiety disorder.

Sustained anticipatory anxiety is central to Generalized Anxiety Disorder (GAD). During anticipatory anxiety, phasic threat responding appears to be mediated by the amygdala, while sustained threat responding seems related to the bed nucleus of the stria terminalis (BNST). Although sustained anticipatory anxiety in GAD patients was proposed to be associated with BNST activity alterations, firm evidence is lacking.

Myocardial aging as a T-cell-mediated phenomenon.

In recent years, the myocardium has been rediscovered under the lenses of immunology, and lymphocytes have been implicated in the pathogenesis of cardiomyopathies with different etiologies. Aging is an important risk factor for heart diseases, and it also has impact on the immune system. Thus, we sought to determine whether immunological activity would influence myocardial structure and function in elderly mice.

The small non-coding RNA processing machinery of two living fossil species, lungfish and coelacanth, gives new insights into the evolution of the Argonaute protein family.

Argonaute (AGO) family proteins play many roles in epigenetic programming, genome rearrangement, mRNA breakdown, inhibition of translation, and transposon silencing. Despite being a hotspot in current scientific research, their evolutionary history is still poorly understood and consequently the identification of evolutionary conserved structural features should also generate useful information for better understanding their functions. We report here for the first time the transcript sets of the two subfamilies, and , in the West African lungfish and in the Indonesian coelacanth , two key species in the evolutionary lineage leading to tetrapods.

Anti-CCP status determines the power Doppler oscillation pattern in rheumatoid arthritis: a prospective study.

Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction. Serologically, it can be differentiated according to rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (anti-CCP), or both. This differentiation is prognostically and therapeutically relevant.

Transposable elements and early evolution of sex chromosomes in fish.

In many organisms, the sex chromosome pair can be recognized due to heteromorphy; the Y and W chromosomes have often lost many genes due to the absence of recombination during meiosis and are frequently heterochromatic. Repetitive sequences are found at a high proportion on such heterochromatic sex chromosomes and the evolution and emergence of sex chromosomes has been connected to the dynamics of repeats and transposable elements. With an amazing plasticity of sex determination mechanisms and numerous instances of independent emergence of novel sex chromosomes, fish represent an excellent lineage to investigate the early stages of sex chromosome differentiation, where sex chromosomes often are homomorphic and not heterochromatic.

Animal models of ischemic stroke and their application in clinical research.

This review outlines the most frequently used rodent stroke models and discusses their strengths and shortcomings. Mimicking all aspects of human stroke in one animal model is not feasible because ischemic stroke in humans is a heterogeneous disorder with a complex pathophysiology. The transient or permanent middle cerebral artery occlusion (MCAo) model is one of the models that most closely simulate human ischemic stroke.