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Discovery of the 4-aminopiperidine-based compound EM127 for the site-specific covalent inhibition of SMYD3

Recent findings support the hypothesis that inhibition of SMYD3 methyltransferase may be a therapeutic avenue for some of the deadliest cancer types. Herein, active site-selective covalent SMYD3 inhibitors were designed by introducing an appropriate reactive cysteine trap into reversible first-generation SMYD3 inhibitors. The 4-aminopiperidine derivative EM127 (11C) bearing a 2-chloroethanoyl grou

Imaging in gynecological disease (16) : clinical and ultrasound characteristics of serous cystadenofibromas in adnexa

Objective: To describe the clinical and ultrasound characteristics of serous cystadenofibromas in the adnexa. Methods: This was a retrospective study of patients identified in the International Ovarian Tumor Analysis (IOTA) database, who had a histological diagnosis of serous cystadenofibroma and had undergone preoperative ultrasound examination by an experienced ultrasound examiner, between 1999

Inhibition of histone demethylases LSD1 and UTX regulates ERα signaling in breast cancer

In breast cancer, Lysine-specific demethylase-1 (LSD1) and other lysine demethylases (KDMs), such as Lysine-specific demethylase 6A also known as Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), are co-expressed and co-localize with estrogen receptors (ERs), suggesting the potential use of hybrid (epi)molecules to target histone methylation and therefore regulate/redirect hor

Efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases : A systematic literature review for the 2019 update of EULAR recommendations

Aim To present a systematic literature review (SLR) on efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD), aiming to provide a basis for updating the EULAR evidence-based recommendations. Methods An SLR was performed according to the standard operating procedures for EULAR-endorsed recommendations. Outcome was determined by

Hyperspectral fluorescence lifetime fibre probe spectroscopy for use in the study and diagnosis of osteoarthritis and skin cancer

We present the application of two fibre-optic-coupled time-resolved spectrofluorometers and a compact steady-state diffuse reflected light/fluorescence spectrometer to in vivo and ex vivo studies of skin cancer and osteoarthritis. In a clinical study of skin cancer, 27 lesions on 25 patients were investigated in vivo before surgical excision of the region measured. Preliminary analysis reveals a s

Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS

HIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 capsid (p26) amino acid polymorphisms are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific T cell responses common in slower progressors. Lower virus evolutionary rates, and positive selectio

Nuclear magnetic resonance in conjunction with functional genomics suggests mitochondrial dysfunction in a murine model of cancer cachexia

Cancer patients commonly suffer from cachexia, a syndrome in which tumors induce metabolic changes in the host that lead to massive loss in skeletal muscle mass. Using a preclinical mouse model of cancer cachexia, we tested the hypothesis that tumor inoculation causes a reduction in ATP synthesis and genome-wide aberrant expression in skeletal muscle. Mice implanted with Lewis lung carcinomas were

Age-associated differences in the human lung extracellular matrix

Extracellular matrix (ECM) remodeling has been associated with chronic lung diseases. However, information about specific age-associated differences in lung ECM is currently limited. In this study, we aimed to identify and localize age-associated ECM differences in human lungs using comprehensive transcriptomic, proteomic, and immunohistochemical analyses. Our previously identified age-associated

Inconsistent responses of carabid beetles and spiders to land-use intensity and landscape complexity in north-western Europe

Reconciling biodiversity conservation with agricultural production requires a better understanding of how key ecosystem service providing species respond to agricultural intensification. Carabid beetles and spiders represent two widespread guilds providing biocontrol services. Here we surveyed carabid beetles and spiders in 66 winter wheat fields in four northwestern European countries and analyze

ABCC3 is a novel target for the treatment of pancreatic cancer

Pancreatic Ductal Adenocarcinoma (PDAC) is a very aggressive disease, lacking effective therapeutic approaches and leaving PDAC patients with a poor prognosis. The life expectancy of PDAC patients has not experienced a significant change in the last few decades with a five-year survival rate of only 8%. To address this unmet need, novel pharmacological targets must be identified for clinical inter

Precision Prognostics for Cardiovascular Disease in Type 2 Diabetes : A Systematic Review and Meta-analysis

BACKGROUND: Precision medicine has the potential to improve cardiovascular disease (CVD) risk prediction in individuals with type 2 diabetes (T2D).METHODS: We conducted a systematic review and meta-analysis of longitudinal studies to identify potentially novel prognostic factors that could improve CVD risk prediction in T2D. Out of 9380 studies identified, 416 studies met inclusion criteria. Outco

Translational opportunities of single-cell biology in atherosclerosis

The advent of single-cell biology opens a new chapter for understanding human biological processes and for diagnosing, monitoring, and treating disease. This revolution now reaches the field of cardiovascular disease (CVD). New technologies to interrogate CVD samples at single-cell resolution are allowing the identification of novel cell communities that are important in shaping disease developmen

The Early neo2 Registry : Transcatheter Aortic Valve Implantation With ACURATE neo2 in a European Population

BACKGROUND: ACURATE neo2 is a transcatheter aortic valve implantation system consisting of a self-expanding bioprosthetic valve with supra-annular leaflet position and featuring innovations to facilitate placement accuracy and reduce paravalvular regurgitation. METHODS AND RESULTS: The goal of the Early neo2 (Early neo2 Registry of the ACURATE neo2 TAVI Prosthesis) was to gather real-life data on

Low levels of WRAP53 predict decreased efficacy of radiotherapy and are prognostic for local recurrence and death from breast cancer : a long-term follow-up of the SweBCG91RT randomized trial

Downregulation of the DNA repair protein WD40-encoding RNA antisense to p53 (WRAP53) has been associated with radiotherapy resistance and reduced cancer survival. The aim of this study was to evaluate WRAP53 protein and RNA levels as prognostic and predictive markers in the SweBCG91RT trial, in which breast cancer patients were randomized for postoperative radiotherapy. Using tissue microarray and

Occupational therapy gender imbalance; : revisiting a lingering issue

BackgroundRecently, it has been suggested that gender disparity in Occupational Therapy has to do with segregated gendered job norms that position female dominated professions as a ‘step down’ for many males. Interestingly, this suggestion was not underpinned by experiences of males in the profession.Aims and MethodsThirteen male Occupational Therapists with a variety of backgrounds were invited t

GATA2 mitotic bookmarking is required for definitive haematopoiesis

In mitosis, most transcription factors detach from chromatin, but some are retained and bookmark genomic sites. Mitotic bookmarking has been implicated in lineage inheritance, pluripotency and reprogramming. However, the biological significance of this mechanism in vivo remains unclear. Here, we address mitotic retention of the hemogenic factors GATA2, GFI1B and FOS during haematopoietic specifica

Randomized Controlled Early versus Late Ventricular Intervention Study in Posthemorrhagic Ventricular Dilatation : Outcome at 2 Years

OBJECTIVE: To compare the effect of intervention at low vs high threshold of ventriculomegaly in preterm infants with posthemorrhagic ventricular dilatation on death or severe neurodevelopmental disability.STUDY DESIGN: This multicenter randomized controlled trial reviewed lumbar punctures initiated after either a low threshold (ventricular index of >p97 and anterior horn width of >6 mm) or high t

European stroke organisation (ESO) guideline on cerebral small vessel disease, part 2, lacunar ischaemic stroke

A quarter of ischaemic strokes are lacunar subtype, typically neurologically mild, usually resulting from intrinsic cerebral small vessel pathology, with risk factor profiles and outcome rates differing from other stroke subtypes. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations to assist with clinical decisions about management of lacunar ischaemic stroke

Pre-asthma : a useful concept for prevention and disease-modification? A EUFOREA paper. Part 1—allergic asthma

Asthma, which affects some 300 million people worldwide and caused 455,000 deaths in 2019, is a significant burden to suffers and to society. It is the most common chronic disease in children and represents one of the major causes for years lived with disability. Significant efforts are made by organizations such as WHO in improving the diagnosis, treatment and monitoring of asthma. However asthma

Distance decay effects predominantly shape spider but not carabid community composition in crop fields in north-western Europe

Agricultural intensification and expansion are regarded as main drivers of biodiversity loss. This conclusion is mainly based on observed declines of local diversity (α-diversity), while effects on community composition homogenization (decrease of β-diversity) at a larger spatial scale are less well understood. Carabid beetles and spiders represent two widespread guilds and are important predators