Replacing dietary carbohydrate with protein and fat improves lipoprotein subclass profile and liver fat in type 2 diabetes independent of body weight: evidence from 2 randomized controlled trials.

Background: Dyslipidemia with elevated concentrations of triacylglycerol-rich lipoproteins (TRLs), small-dense LDL, and reduced HDL is linked to hepatic steatosis and promotes atherogenesis in type 2 diabetes (T2D).

Objectives: We aimed to analyze whether moderate carbohydrate restriction reduces liver fat in T2D independent of changes in body weight and whether this is accompanied by parallel improvements in plasma lipoprotein subclasses.

Methods: We determined the density profile of circulating lipoproteins in patients with T2D from 2 previous randomized controlled trials.

Centerline-guided reinforcement learning model for pancreatic duct identifications.

Purpose: Pancreatic ductal adenocarcinoma is forecast to become the second most significant cause of cancer mortality as the number of patients with cancer in the main duct of the pancreas grows, and measurement of the pancreatic duct diameter from medical images has been identified as relevant for its early diagnosis.

Approach: We propose an automated pancreatic duct centerline tracing method from computed tomography (CT) images that is based on deep reinforcement learning, which employs an artificial agent to interact with the environment and calculates rewards by combining the distances from the target and the centerline. A deep neural network is implemented to forecast step-wise values for each potential action.

Imaging the pancreas with photon-counting CT - A review of normal pancreatic anatomy.

Purpose: Compared to conventional energy integrating detector CT, Photon-Counting CT (PCCT) has the advantage of increased spatial resolution. The pancreas is a highly complex organ anatomically. The increased spatial resolution of PCCT challenges radiologists' knowledge of pancreatic anatomy.

Three Weeks on a Ketogenic Diet Reduces Free Testosterone and Free Estradiol in Middle-Aged Obese Men and Women.

Background: Beta-hydroxybuturate (-OHB) supplements are commonly utilized in sports by both recreational and professional athletes. In a recent study, we observed a drop in testosterone levels following the oral ingestion of racemic sodium--OHB. In this investigation, we aim to determine whether a single oral dose of ketone ester (study I) and prolonged endogenous ketosis (study II) also reduces testosterone levels.

Elastic wave control in reticulated plates using Schwarz primitive cells.

In this work, the Schwarz primitive unit cell is used as the building block of different types of metastructures for steering and focusing elastic vibrations. The emergence of a Bragg-type bandgap when constructing a two-dimensional plate from such unit cells is experimentally validated. It is demonstrated that increasing both mass and porosity of the Schwarz primitive leads to a decrease in the frequency of the out-of-plane propagating wave targeted in this study.

Reinforcement learning-based anatomical maps for pancreas subregion and duct segmentation.

Background: The pancreas is a complex abdominal organ with many anatomical variations, and therefore automated pancreas segmentation from medical images is a challenging application.

Purpose: In this paper, we present a framework for segmenting individual pancreatic subregions and the pancreatic duct from three-dimensional (3D) computed tomography (CT) images.

Methods: A multiagent reinforcement learning (RL) network was used to detect landmarks of the head, neck, body, and tail of the pancreas, and landmarks along the pancreatic duct in a selected target CT image.

Familywise error for multiple time-to-event endpoints in a group sequential design.

We investigate the familywise error rate (FWER) for time-to-event endpoints evaluated using a group sequential design with a hierarchical testing procedure for secondary endpoints. We show that, in this setup, the correlation between the log-rank test statistics at interim and at end of study is not congruent with the canonical correlation derived for normal-distributed endpoints. We show, both theoretically and by simulation, that the correlation also depends on the level of censoring, the hazard rates of the endpoints, and the hazard ratio.

The Association of Cardiometabolic, Diet and Lifestyle Parameters With Plasma Glucagon-like Peptide-1: An IMI DIRECT Study.

Context: The role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes (T2D) and obesity is not fully understood.

Objective: We investigate the association of cardiometabolic, diet, and lifestyle parameters on fasting and postprandial GLP-1 in people at risk of, or living with, T2D.

Methods: We analyzed cross-sectional data from the two Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohorts, cohort 1 (n = 2127) individuals at risk of diabetes; cohort 2 (n = 789) individuals with new-onset T2D.

Clinical and Metabolic Characterization of Women With Gestational Diabetes Mellitus Within the First Year Postpartum.

Context: Women with gestational diabetes mellitus (GDM) have an increased risk of long-term complications, including impaired glucose metabolism, type 2 diabetes (T2DM), cardiovascular disease, and obesity. In current clinical practice, a 1 size fits all approach to GDM is applied, although heterogeneity among women with GDM has been recognized.

Objective: To give the most adequate preventive care and postpartum (PP) guidance, we aimed to make a metabolic characterization and identify subgroups of women with previous GDM within the first year PP.

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Congenital adrenal hyperplasia (CAH) arises from genetic enzyme defects, often in CYP21A2, causing primary adrenal insufficiency. In this case report, a man in his late 20s with lifelong CAH faced challenges in adhering to medication. Suboptimal treatment led to the development of testicular adrenal rest tumours, diagnosed by ultrasound, and hypogonadism.

Long-term efficacy of a 2-year MRI treat-to-target strategy on disease activity and radiographic progression in patients with rheumatoid arthritis in clinical remission: 5-year follow-up of the IMAGINE-RA randomised trial.

Objective: To investigate whether a 2-year MRI treat-to-target strategy targeting the absence of osteitis combined with clinical remission, compared with a conventional treat-to-target strategy targeting clinical remission only (IMAGINE-rheumatoid arthritis (RA) trial) improves clinical and radiographic outcomes over 5 years in patients with RA in clinical remission.

Methods: IMAGINE-more was an observational extension study of the original 2-year IMAGINE-RA randomised trial (NCT01656278). Clinical examinations and radiographs (hands and feet) were obtained yearly.

Interactive training workshop to improve prostate mpMRI knowledge: results from the ESOR Nicholas Gourtsoyiannis teaching fellowship.

Purpose: Prostate MRI is established for the investigation of patients presenting with suspected early prostate cancer. Outcomes are dependent on both image quality and interpretation. This study assessed the impact of an educational intervention on participants' theoretical knowledge of the technique.

Nutrient sensing: LEAP2 concentration in response to fasting, glucose, lactate, and β-hydroxybutyrate in healthy young males.

Background: The appetite-suppressing potential of liver-expressed antimicrobial peptide 2 (LEAP2), and its antagonistic effects on the hunger-inducing hormone ghrelin have attracted scientific interest. It is unclear how LEAP2 is influenced by fasting and how it responds to specific nutrients.

Objectives: The purpose of this investigation was to assess whether LEAP2 concentration 1) decreases after fasting, 2) increases postprandially, and 3) is regulated by nutrient sensing in the splanchnic bed.

Markers of Glucagon Resistance Improve With Reductions in Hepatic Steatosis and Body Weight in Type 2 Diabetes.

Context: Hyperglucagonemia may develop in type 2 diabetes due to obesity-prone hepatic steatosis (glucagon resistance). Markers of glucagon resistance (including the glucagon-alanine index) improve following diet-induced weight loss, but the partial contribution of lowering hepatic steatosis vs body weight is unknown.

Objective: This work aimed to investigate the dependency of body weight loss following a reduction in hepatic steatosis on markers of glucagon resistance in type 2 diabetes.

Towards a Precise NMR Quantification of Acute Phase Inflammation Proteins from Human Serum.

Nuclear Magnetic Resonance (NMR) spectra of human serum and plasma show, besides metabolites and lipoproteins, two characteristic signals termed GlycA and B arising from the acetyl groups of glycoprotein glycans from acute phase proteins, which constitute good markers for inflammatory processes. Here, we report a comprehensive assignment of glycoprotein glycan NMR signals observed in human serum, showing that GlycA and GlycB signals originate from Neu5Ac and GlcNAc moieties from N-glycans, respectively. Diffusion-edited NMR experiments demonstrate that signal components can be associated with specific acute phase proteins.

An adult-based genetic risk score for liver fat associates with liver and plasma lipid traits in children and adolescents.

Background & Aims: Genome-wide association studies have identified steatogenic variants that also showed pleiotropic effects on cardiometabolic traits in adults. We investigated the effect of eight previously reported genome-wide significant steatogenic variants, individually and combined in a weighted genetic risk score (GRS), on liver and cardiometabolic traits, and the predictive ability of the GRS for hepatic steatosis in children and adolescents.

Approach & Results: Children and adolescents with overweight (including obesity) from an obesity clinic group (n = 1768) and a population-based group (n = 1890) were included.

Extreme hyperferritinemia in restrictive type anorexia nervosa.

Summary: Iron metabolism and markers hereof are altered in anorexia nervosa (AN) but far from completely understood. We report a case of extreme hyperferritinemia in a patient with AN and discuss the possible mechanisms and current knowledge about the association between hyperferritinemia and AN. A 20-year-old woman with a history of AN presented with bradycardia, weariness, and malaise in addition to an incidentally very high ferritin level.

Discovery of drug-omics associations in type 2 diabetes with generative deep-learning models.

The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium.

Was There Something Rotten in Denmark: Nephrogenic System Fibrosis Cases Occurring in Copenhagen.

More than half of all serious adverse drug reactions are identified seven years after FDA approval. One recent and unusual example involves a syndrome initially termed nephrogenic dermatopathic fibrosis, and then called nephrogenic systemic fibrosis (NSF).

Comparison of PSA density and lesion volume strategies for selecting men with equivocal PI-RADS 3 lesions on bpMRI for biopsies.

Purpose: To compare two strategies: Prostate-specific antigen density (PSAd) and lesion volume measurement in ruling out significant prostate cancer (sPCa) in men with equivocal Prostate Imaging Reporting and Data System (PI-RADS) category 3 index lesions on biparametric magnetic resonance imaging.

Methods: In total, 130 men from our database had index lesions with PI-RADS scores of 3. Prostate volume was measured using the ellipsoid method, in accordance with PI-RADS version 2.

Real life evaluation of sodium-glucose cotransporter 2 inhibition in type 1 diabetes and the risk of diabetic ketoacidosis.

Background: The indication for treatment of type 1 diabetes(T1D) with the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin has been withdrawn in Europe likely because of concern for diabetic ketoacidosis (DKA). We calculated the incidence of DKA in people with T1D treated with SGLT2i in Denmark.

Methods: Clinical data from adults with T1D in Denmark were collected from nine outpatient clinics.