Effects of Dietary Protein and Fat Content on Intrahepatocellular and Intramyocellular Lipids during a 6-Day Hypercaloric, High Sucrose Diet: A Randomized Controlled Trial in Normal Weight Healthy Subjects.

Sucrose overfeeding increases intrahepatocellular (IHCL) and intramyocellular (IMCL) lipid concentrations in healthy subjects. We hypothesized that these effects would be modulated by diet protein/fat content. Twelve healthy men and women were studied on two occasions in a randomized, cross-over trial. On each occasion, they received a 3-day 12% protein weight maintenance diet (WM) followed by a 6-day hypercaloric high sucrose diet (150% energy requirements). On one occasion the hypercaloric diet contained 5% protein and 25% fat (low protein-high fat, LP-HF), on the other occasion it contained 20% protein and 10% fat (high protein-low fat, HP-LF). IHCL and IMCL concentrations (magnetic resonance spectroscopy) and energy expenditure (indirect calorimetry) were measured after WM, and again after HP-LF/LP-HF. IHCL increased from 25.0 ± 3.6 after WM to 147.1 ± 26.9 mmol/kg wet weight (ww) after LP-HF and from 30.3 ± 7.7 to 57.8 ± 14.8 after HP-LF (two-way ANOVA with interaction: p < 0.001 overfeeding x protein/fat content). IMCL increased from 7.1 ± 0.6 to 8.8 ± 0.7 mmol/kg ww after LP-HF and from 6.2 ± 0.6 to 6.9 ± 0.6 after HP-LF, (p < 0.002). These results indicate that liver and muscle fat deposition is enhanced when sucrose overfeeding is associated with a low protein, high fat diet compared to a high protein, low fat diet

Federated learning enables big data for rare cancer boundary detection.

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing

Impact of sleep restriction on metabolic outcomes induced by overfeeding: a randomized controlled trial in healthy individuals.

Overconsumption of energy-dense foods and sleep restriction are both associated with the development of metabolic and cardiovascular diseases, but their combined effects remain poorly evaluated. The aim of this study was to assess whether sleep restriction potentiates the effects of a short-term overfeeding on intrahepatocellular lipid (IHCL) concentrations and on glucose homeostasis. Ten healthy subjects were exposed to a 6-d overfeeding period (130% daily energy needs, with 15% extra energy as sucrose and 15% as fat), with normal sleep (8 h sleep opportunity time) or sleep restriction (4 h sleep opportunity time), according to a randomized, crossover design. At baseline and after intervention, IHCL concentrations were measured by proton magnetic resonance spectroscopy, and a dual intravenous [6,6-2H2]-, oral 13C-labeled glucose tolerance test and a polysomnographic recording were performed. Overfeeding significantly increased IHCL concentrations (Poverfeeding < 0.001; overfeeding + normal sleep: +53% ± 16%). During the oral glucose tolerance test, overfeeding significantly increased endogenous glucose production (Poverfeeding = 0.034) and the oxidation of 13C-labeled glucose load (Poverfeeding = 0.038). Sleep restriction significantly decreased total sleep time, and the duration of stages 1 and 2 and rapid eye movement sleep (all P < 0.001), whereas slow-wave sleep duration was preserved (Poverfeeding × sleep = 0.809). Compared with overfeeding, overfeeding + sleep restriction did not change IHCL concentrations (Poverfeeding × sleep = 0.541; +83% ± 33%), endogenous glucose production (Poverfeeding × sleep = 0.567), or exogenous glucose oxidation (Poverfeeding × sleep = 0.118). Sleep restriction did not significantly alter blood pressure, heart rate, or plasma cortisol concentrations (all Poverfeeding × sleep = NS). Six days of a high-sucrose, high-fat overfeeding diet significantly increased IHCL concentrations and increased endogenous glucose production, suggesting hepatic insulin resistance. These effects of overfeeding were not altered by sleep restriction. This trial was registered at clinicaltrials.gov as NCT02075723. Other study ID numbers: SleepDep 02/14

Analysis of 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia

Pregnancy in women with inherited thrombocytopenias is a major matter of concern as both the mothers and the newborns are potentially at risk of bleeding. However, medical management of this condition cannot be based on evidence because of the lack of consistent information in the literature. To advance knowledge on this matter, we performed a multicentric, retrospective study evaluating 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia. Neither the degree of thrombocytopenia nor the severity of bleeding tendency worsened during pregnancy and the course of pregnancy did not differ from that of healthy subjects in terms of miscarriages, fetal bleeding and pre-term births. The degree of thrombocytopenia in the babies was similar to that in the mother. Only 7 of 156 affected newborns had delivery-related bleeding, but 2 of them died of cerebral hemorrhage. The frequency of delivery-related maternal bleeding ranged from 6.8% to 14.2% depending on the definition of abnormal blood loss, suggesting that the risk of abnormal blood loss was increased with respect to the general population. However, no mother died or had to undergo hysterectomy to arrest bleeding. The search for parameters predicting delivery-related bleeding in the mother suggested that hemorrhages requiring blood transfusion were more frequent in women with history of severe bleedings before pregnancy and with platelet count at delivery below 50 7 109/L