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Pam50 intrinsic subtype profiles in primary and metastatic breast cancer show a significant shift toward more aggressive subtypes with prognostic implications

Background: PAM50 breast cancer intrinsic subtyping adds prognostic information in early breast cancer; however, the role in metastatic disease is unclear. We aimed to identify PAM50 subtypes in primary tumors (PTs) and metastases to outline subtype changes and their prognostic role. Methods: RNA was isolated from PTs, lymph node metastases (LNMs), and distant metastases (DMs) in metastatic breast

Permanent pacemaker implantation early and late after heart transplantation : clinical indication, risk factors and prognostic implications

BACKGROUND: Permanent pacemaker implantation (PPM) early after cardiac transplantation has been shown not to predict a worse outcome. However, the requirement for pacing late after transplantation and its prognostic implications are not fully known. We describe the clinical indications, risk factors and long-term outcome in patients who required pacing early and late after transplantation.METHODS:

Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer : 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial

Background: Hypofractionated radiotherapy for prostate cancer has gained increased attention due to its proposed high radiation-fraction sensitivity. Recent reports from studies comparing moderately hypofractionated and conventionally fractionated radiotherapy support the clinical use of moderate hypofractionation. To date, there are no published randomised studies on ultra-hypofractionated radiot

ERS technical standard on bronchial challenge testing : pathophysiology and methodology of indirect airway challenge testing

Recently, this international task force reported the general considerations for bronchial challenge testing and the performance of the methacholine challenge test, a "direct" airway challenge test. Here, the task force provides an updated description of the pathophysiology and the methods to conduct indirect challenge tests. Because indirect challenge tests trigger airway narrowing through the act

Rat alpha 1-microglobulin : co-expression in liver with the light chain of inter-alpha-trypsin inhibitor

A 1162 bp rat liver cDNA clone encoding the immunoregulatory plasma protein alpha 1-microglobulin was isolated and sequenced. The open reading frame encoded a 349 amino acid polyprotein, including alpha 1-microglobulin, 182 amino acids, and bikunin, the light chain of the plasma protein inter-alpha-trypsin inhibitor, 145 amino acids. The alpha 1-microglobulin/bikunin mRNA was found only in the liv

Ig-binding bacterial proteins also bind proteinase inhibitors

Protein G is a streptococcal cell wall protein with separate binding sites for IgG and human serum albumin (HSA). In the present work it was demonstrated that alpha 2-macroglobulin (alpha 2M) and kininogen, two proteinase inhibitors of human plasma, bound to protein G, whereas 23 other human proteins showed no affinity. alpha 2M was found to interact with the IgG-binding domains of protein G, and

In vitro fermentability and antioxidant capacity of the indigestible fraction of cooked black beans (Phaseolus vulgaris L.), lentils (Lens culinaris L.) and chickpeas (Cicer arietinum L.)

BACKGROUND: Pulses represent an important source of protein, as well as digestible and indigestible carbohydrates. Little information is available on the indigestible carbohydrates and antioxidant capacity of legume seeds. The cooked seeds of three pulses (black bean, chickpea and lentil) were evaluated for their indigestible fraction (IF), polyphenols content, antioxidant capacity and in vitro fe

Audible beacons and wearables in schools : Helping young visually impaired children play and move independently

Young children with visual impairments tend to engage less with their surroundings, limiting the benefits from activities at school. We investigated novel ways of using sound from a bracelet, such as speech or familiar noises, to tell children about nearby people, places and activities, to encourage them to engage more during play and help them move independently. We present a series of studies, t

Angiotensin II type 1 receptor autoantibodies in postural tachycardia syndrome

Background--Both the adrenergic and renin-angiotensin systems contribute to orthostatic circulatory homeostasis, which is impaired in postural orthostatic tachycardia syndrome (POTS). Activating autoantibodies to the α1-adrenergic and β1/2-adrenergic receptors have previously been found in sera from patients with POTS. We hypothesized that patients with POTS might also harbor activating autoantibo

Organisational and student characteristics, fidelity, funding models, and unit costs of recovery colleges in 28 countries: a cross-sectional survey

BackgroundRecovery colleges were developed in England to support the recovery of individuals who have mental health symptoms or mental illness. They have been founded in many countries but there has been little international research on recovery colleges and no studies investigating their staffing, fidelity, or costs. We aimed to characterise recovery colleges internationally, to understand organi

CKD-EPI and EKFC GFR Estimating Equations: Performance and Other Considerations for Selecting Equations for Implementation in Adults

Background: New CKD-EPI and EKFC estimated GFR (eGFR) equations usingcreatinine (eGFRcr), cystatin C (eGFRcys) and both (eGFRcr-cys) have sufficientaccuracy for use in clinical practice. A better understanding of the equations, includingtheir performance in race, sex and age subgroups, is important for selection of eGFRequations for global implementation.Methods: We evaluated performance (bias and

Interferon Alpha-Inducible Protein 27 Expression Is Linked to Disease Severity in Chronic Infection of Both HIV-1 and HIV-2

Disease progression is slower in HIV-2, as compared with HIV-1 infection, in accordance with low or undetectable plasma viremia at viral setpoint. However, it is unclear why most HIV-2 infected individuals are still at risk of developing AIDS. To explore if specific host responses are linked to HIV disease severity, we have compared blood gene expression profiles between HIV seronegative and HIV-1

Twenty‐Four‐Hour Ambulatory Blood Pressure Profile in Patients With Reflex Syncope and Matched Controls

BackgroundAmbulatory blood pressure (BP) monitoring has long been used to monitor BP in hypertension and lately emerged as a useful tool to detect hypotensive susceptibility in reflex syncope. However, hemodynamic characteristics in reflex syncope have not been sufficiently explored. The present study investigated the differences between ambulatory BP monitoring profiles associated with reflex syn

Establishing conversion of the 16-item Informant Questionnaire on Cognitive Decline in the Elderly scores into interval-level data across multiple samples using Rasch methodology

Background: The 16-item Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE-16) is a well-validated and widely-used measure of cognitive changes (CCs) among older adults. This study aimed to use Rasch methodology to establish psychometric properties of the IQCODE-16 and validate the existing ordinal-to-interval transformation algorithms across multiple large samples. Methods: A Par

Improved distances and ages for stars common to TGAS and RAVE

We combine parallaxes from the first Gaia data release with the spectrophotometric distance estimation framework for stars in the fifth RAVE survey data release. The combined distance estimates aremore accurate than either determination in isolation - uncertainties are on average two times smaller than for RAVE-only distances (three times smaller for dwarfs), and 1.4 times smaller than TGAS parall

Severe Congenital Thrombocytopenia Characterized by Decreased Platelet Sialylation and Moderate Complement Activation Caused by Novel Compound Heterozygous Variants in GNE

Background: Hereditary thrombocytopenias constitute a genetically heterogeneouscause of increased bleeding. We report a case of a 17-year-old boy suffering fromsevere macrothrombocytopenia throughout his life. Whole genome sequencing revealed the presence of two compound heterozygous variants in GNE encoding the enzyme UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase, crucial for si

Microbial Regulation of Enteric Eosinophils and Its Impact on Tissue Remodeling and Th2 Immunity

Eosinophils have emerged as multifaceted cells that contribute to tissue homeostasis. However, the impact of the microbiota on their frequency and function at mucosal sites remains unclear. Here, we investigated the role of the microbiota in the regulation of enteric eosinophils. We found that small intestinal (SI) eosinophilia was significantly greater in germ-free (GF) mice compared to specific

A Human IgE Antibody Binding Site on Der p 2 for the Design of a Recombinant Allergen for Immunotherapy

Der p 2 is one of the most important allergens from the house dust mite Dermatophagoides pteronyssinus Identification of human IgE Ab binding epitopes can be used for rational design of allergens with reduced IgE reactivity for therapy. Antigenic analysis of Der p 2 was performed by site-directed mutagenesis based on the x-ray crystal structure of the allergen in complex with a Fab from the murine

Galectin-1 induces a tumor-associated macrophage phenotype and upregulates indoleamine 2,3-dioxygenase-1

Galectins are a group of carbohydrate-binding proteins with a presumed immunomodulatory role and an elusive function on antigen-presenting cells. Here we analyzed the expression of galectin-1 and found upregulation of galectin-1 in the extracellular matrix across multiple tumors. Performing an in-depth and dynamic proteomic and phosphoproteomic analysis of human macrophages stimulated with galecti

Identification of pathogenic GCK variants in patients with common type 2 diabetes can lead to discontinuation of pharmacological treatment

Background: Functionally disruptive variants in the glucokinase gene (GCK) cause a form of mild non-progressive hyperglycemia, which does not require pharmacological treatment. A substantial proportion of patients with type 2 diabetes (T2D) carry GCK variants. We aimed to investigate whether carriers of rare GCK variants diagnosed with T2D have a glycemic phenotype and treatment response consisten