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Prolonged culture of human pancreatic islets under glucotoxic conditions changes their acute beta cell calcium and insulin secretion glucose response curves from sigmoid to bell-shaped

Aims/hypothesis: The rapid remission of type 2 diabetes by a diet very low in energy correlates with a marked improvement in glucose-stimulated insulin secretion (GSIS), emphasising the role of beta cell dysfunction in the early stages of the disease. In search of novel mechanisms of beta cell dysfunction after long-term exposure to mild to severe glucotoxic conditions, we extensively characterise

International practice heterogeneity in pre-transplant management of pulmonary hypertension related to pediatric left heart disease

BACKGROUND: Elevated pulmonary vascular resistance (PVR) in the setting of left heart failure may contribute to poor outcomes after pediatric heart transplant (HTx), but peri-transplant management is variable.METHODS: We sought to characterize international practice by surveying physicians at pediatric HTx centers.RESULTS: We received 49 complete responses from 39 centers in 16 countries. Most res

New strategies for the conduct of clinical trials in paediatric Pulmonary Arterial Hypertension (PAH): Outcome of a multi-stakeholder meeting with patients, academia, industry and regulators held at EMA on Monday 12th June 2017

Aims: Drug development for paediatric pulmonary arterial hypertension (PAH) ispressingly needed. Experts from the US Food and Drug Administration, EuropeanMedicines Agency, Health Canada, key opinion leaders, academia, patients, and industry representatives held a workshop on 12th June 2017 dedicated to addressing challenges and unmet needs. This report summarises the approaches proposed during th

Lifting with simple gadgets and applications to circuit and proof complexity

We significantly strengthen and generalize the theorem lifting Nullstellensatz degree to monotone span program size by Pitassi and Robere (2018) so that it works for any gadget with high enough rank, in particular, for useful gadgets such as equality and greater-than. We apply our generalized theorem to solve three open problems: •We present the first result that demonstrates a separation in proof

Short-term effect of induced alterations in testosterone levels on fasting plasma amino acid levels in healthy young men

Long term effect of testosterone (T) deficiency impairs metabolism and is associated with muscle degradation and metabolic disease. The association seems to have a bidirectional nature and is not well understood. The present study aims to investigate the early and unidirectional metabolic effect of induced T changes by measuring fasting amino acid (AA) levels in a human model, in which short-term

Temporal changes in the probability of live birth among female survivors of childhood cancer : A population-based Adult Life After Childhood Cancer in Scandinavia (ALiCCS) study in five nordic countries

BACKGROUND: During the past 4 decades, there has been a growing focus on preserving the fertility of patients with childhood cancer; however, no large studies have been conducted of live births across treatment decades during this period. Therefore, the authors estimated the potential birth deficit in female childhood cancer survivors and the probability of live births. METHODS: In total, 8886 wom

The onset of circulation triggers a metabolic switch required for endothelial to hematopoietic transition

Hematopoietic stem cells (HSCs) emerge during development from the vascular wall of the main embryonic arteries. The onset of circulation triggers several processes that provide critical external factors for HSC generation. Nevertheless, it is not fully understood how and when the onset of circulation affects HSC emergence. Here we show that in Ncx1−/− mouse embryos devoid of circulation the HSC l

Gaia Early Data Release 3 : Parallax bias versus magnitude, colour, and position

Context. Gaia Early Data Release 3 (Gaia EDR3) gives trigonometric parallaxes for nearly 1.5 billion sources. Inspection of the EDR3 data for sources identified as quasars reveals that their parallaxes are biased, that is, they are systematically offset from the expected distribution around zero, by a few tens of microarcseconds. Aims. We attempt to map the main dependences of the parallax bias in

Public Key Compression and Fast Polynomial Multiplication for NTRU using the Corrected Hybridized NTT-Karatsuba Method

NTRU is a lattice-based public-key cryptosystem that has been selected as one of the Round III finalists at the NIST Post-Quantum Cryptography Standardization. Compressing the key sizes to increase efficiency has been a long-standing open question for lattice-based cryptosystems. In this paper we provide a solution to three seemingly opposite demands for NTRU cryptosystem: compress the key size, i

Pathological drivers of neurodegeneration in suspected non-Alzheimer’s disease pathophysiology

Background: Little is known about the heterogeneous etiology of suspected non-Alzheimer’s pathophysiology (SNAP), a group of subjects with neurodegeneration in the absence of β-amyloid. Using antemortem MRI and pathological data, we investigated the etiology of SNAP and the association of neurodegenerative pathologies with structural medial temporal lobe (MTL) measures in β-amyloid-negative subjec

The new educational project Televascular Games during the Coronavirus Disease 2019 pandemic

Objective: To report methodology and first-year results of a new educational project called Televascular Games,” which took place during coronavirus disease 2019 pandemic. Methods: Complex aneurysmal aortic disease was discussed during a 2-hour competition webinar, according to three modalities. (1) Planning case competition (PCC): Two to four preoperative computed tomography angiography (CTA) sca

Chromosome-scale genome assembly of the brown anole (Anolis sagrei), an emerging model species

Rapid technological improvements are democratizing access to high quality, chromosome-scale genome assemblies. No longer the domain of only the most highly studied model organisms, now non-traditional and emerging model species can be genome-enabled using a combination of sequencing technologies and assembly software. Consequently, old ideas built on sparse sampling across the tree of life have re

The Long Non-Coding Antisense RNA JHDM1D-AS1 Regulates Inflammatory Responses in Human Monocytes

Monocytes are key players in innate immunity, with their ability to regulate inflammatory responses and combat invading pathogens. There is a growing body of evidence indicating that long non-coding RNA (lncRNA) participate in various cellular biological processes, including the innate immune response. The immunoregulatory properties of numerous lncRNAs discovered in monocytes remain largely unexp

Human genes for the alpha and beta chains of complement C4b-binding protein are closely linked in a head-to-tail arrangement

C4b-binding protein (C4BP) is an important component in the regulation of the complement system and also binds the anticoagulant vitamin K-dependent protein S. These activities are performed by distinct, although structurally related, polypeptides of 70 kDa (alpha chain) and 45 kDa (beta chain), respectively. In this report we have investigated the genetic relationships between these polypeptides.

Kynurenine metabolites predict survival in pulmonary arterial hypertension : A role for IL-6/IL-6Rα

Activation of the kynurenine pathway (KP) has been reported in patients with pulmonary arterial hypertension (PAH) undergoing PAH therapy. We aimed to determine KP-metabolism in treatment-naïve PAH patients, investigate its prognostic values, evaluate the effect of PAH therapy on KP-metabolites and identify cytokines responsible for altered KP-metabolism. KP-metabolite levels were determined in pl

Quality Controls in Digital Mammography protocol of the EFOMP Mammo Working group

This article aims to present the protocol on Quality Controls in Digital Mammography published online in 2015 by the European Federation of Organisations for Medical Physics (EFOMP) which was developed by a Task Force under the Mammo Working Group. The main objective of this protocol was to define a minimum set of easily implemented quality control tests on digital mammography systems that can be

Parkin absence accelerates microtubule aging in dopaminergic neurons

Loss-of-function caused by mutations in the parkin gene (PARK2) lead to early-onset familial Parkinson's disease. Recently, mechanistic studies proved the ability of parkin in regulating mitochondria homeostasis and microtubule (MT) stability. Looking at these systems during aging of PARK2 knockout mice, we found that loss of parkin induced an accelerated (over)acetylation of MT system both in dop

TANGO2 deficiency as a cause of neurodevelopmental delay with indirect effects on mitochondrial energy metabolism

Exome sequencing has recently identified mutations in the gene TANGO2 (transport and Golgi organization 2) as a cause of developmental delay associated with recurrent crises involving rhabdomyolysis, cardiac arrhythmias, and metabolic derangements. The disease is not well understood, in part as the cellular function and subcellular localization of the TANGO2 protein remain unknown. Furthermore, th

Assessment of the appropriate use criteria for amyloid PET in an unselected memory clinic cohort : The ABIDE project

Introduction: The objective of this study was to assess the usefulness of the appropriate use criteria (AUC) for amyloid imaging in an unselected cohort. Methods: We calculated sensitivity and specificity of appropriate use (increased confidence and management change), as defined by Amyloid Imaging Taskforce in the AUC, and other clinical utility outcomes. Furthermore, we compared differences in p