Machine Learning Approach for Care Improvement of Children and Youth with Type 1 Diabetes Treated with Hybrid Closed-Loop System

Type 1 diabetes is a disease affecting beta cells of the pancreas and it’s responsible for a decreased insulin secretion, leading to an increased blood glucose level. The traditional method for glucose treatment is based on finger-stick measurement of the blood glucose concentration and consequent manual insulin injection. Nowadays insulin pumps and continuous glucose monitoring systems are replacing them, being simpler and automatized. This paper focuses on analyzing and improving the knowledge about which Machine Learning algorithms can work best with glycaemic data and tries to find out the relation between insulin pump settings and glycaemic control. The dataset is composed of 90 days of recordings taken from 16 children and adolescents. Three Machine Learning approaches, two for classification, Logistic Regression (LR) and Random Forest (RL), and one for regression, Multivariate Linear Regression (MLR), have been used for the purpose. Specifically, the pump settings analysis was performed based on the Time In Range (TIR) computation and comparison consequent to pump setting changes. RF and MLR have shown the best results, while, for the settings’ analysis, the data show a discrete correlation between changes and TIRs. This study provides an interesting closer look at the data recorded by the insulin pump and a suitable starting point for a thorough and complete analysis of them

Deep structure of the Baikal rift zone revealed by joint inversion of gravity and seismology

International audience[1] The question of plate boundary forces and deep versus shallow asthenospheric uplift has long been debated in intracontinental rift areas, particularly in the Baikal rift zone, Asia, which is colder than other continental rifts. As previous gravity and teleseismic studies support the dominance of opposing mechanisms in the Baikal rift, we reconsidered both data sets and jointly inverted them. This more effective approach brings insight into location of the perturbing bodies related to the extension in this region. Our new joint inversion method allows for inverting the velocity-density relationship with independent model parametrization. We obtain velocity and density models that consistently show (1) crustal heterogeneities that coincide with the main tectonic features at the surface, (2) a faster and denser cratonic mantle NW of Lake Baikal that we relate to the thermal contrast between old and depleted Archean (Siberian platform) and Paleozoic orogenic belt (Sayan-Baikal belt), (3) three-dimensional topographic variations of the crust-mantle boundary with well-located upwarpings, and (4) the lithosphere-asthenosphere boundary uplift up to 70 km depth with a NW dip. Our resulting velocity and density models support the idea of a combined influence of lithospheric extension and inherited lithospheric heterogeneities for the origin of the Baikal rift zone. INDEX TERMS: 1234 Geodesy and Gravity: Regional and global gravity anomalies and Earth structure; 7218 Seismology: Lithosphere and upper mantle; 8122 Citation: Tiberi, C., M. Diament, J. Déverchère, C. Petit-Mariani, V. Mikhailov, S. Tikhotsky, and U. Achauer, Deep structure of the Baikal rift zone revealed by joint inversion of gravity and seismology

252. Prediction of subject-specific SAR distribution in MSK MR exam at 7 T

Purpose we predict SAR during MRI exam using a 7 T 1H 298 MHz eight-channel degenerate birdcage coil1 combining SAR simulations with subject-specific measured (RF) maps. Materials and Methods We simulated the coil1 in CST MW Suite, loaded by a model of human knee (Fig. 1, top). was calculated in an axial slice crossing the patella. The maximum local SAR for an Axial “Zero” Time-of-Echo (ZTE) sequence “SILENT”2 was calculated. We acquired maps of an adult (female) knee with a Bloch-Siegert sequence on 7 axial slices, centered on the same slice of the simulation, on a GE MR950 7T human system. For each slice a coefficient C, proportional to avg, was used to scale the SAR simulated3. Results Fig. 1 shows: bottom left, simulated magnitude; bottom center, local SAR for an input of 1 W per channel; bottom right, simulated magnitude for a FA = 90° (length = 3.2 ms) sinc-pulse in the slice previously chosen. Fig. 2 shows the subject-specific measured for a FA = 90° sinc-pulse. The predicted SAR obtained with scaled maps are 0.50 W/kg (global) and 3.68 W/kg (maximum). Conclusions we obtained a good agreement between simulated and measured in vivo maps, and we were able to calculate the distribution of SAR exposure, a safety MRI parameter not available in current exams, where only global SAR is provided, combining simulations and subject-specific measurements. Limits on global and local SAR (20 W/kg) were met for this sequence [1], [2], [3]

Extraspinal articular tuberculosis: An 11-year retrospective study of demographic features and clinical outcomes in East London

OBJECTIVES: To describe demographic features, clinical outcomes and diagnostic delay amongst patients with extra-spinal articular tuberculosis (TB) in a low-incidence setting. METHODS: Cases of TB treated at our institution between 2004 and 2014 were identified via the London TB register (LTBR). Demographic features of extra-spinal articular TB cases were compared to controls with TB at all other sites. For articular cases (excluding individuals <16 years or with spinal TB without peripheral joint involvement) clinical data were retrospectively collected. RESULTS: 6,146 TB patients were identified over the study period; 146 (2.4%) cases had extra-spinal articular infection. There was no difference in median age between extra-spinal articular TB cases and controls with TB at other sites (31 vs 32 years, p = 0.57). Articular cases were more likely to be male (70.6% vs 59.5%, p = 0.007), Bangladeshi (28.7% vs 18.0%) or Pakistani (24.0% vs 16.1%) and were less likely to be Black-African (9.5% vs 19.8%) (p < 0.001). 93 cases were included in the case series; 85 (88.5%) were migrants and 83 (89.2%) were South Asian. Knee and elbow joints were affected in 22 (23.7%) and 18 (19.4%) cases respectively. The median durations of pre-healthcare and healthcare associated delay were 16 and 6 weeks respectively. Where mycobacterial culture was performed, 57/75 (76%) were positive for Mycobacterium tuberculosis. 86 (92.5%) cases received standard quadruple therapy for a median of 6 months (IQR 6–9). Recurrence of TB infection occurred in 4 (4.3%) cases and there were no TB related deaths. Seven (7.6%) cases required surgical intervention. CONCLUSIONS: Extra-spinal articular TB more commonly affected men and people of South Asian ethnicity. Significant diagnostic delays were identified, including avoidable healthcare-associated delays

Exploring a combined biomarker for tuberculosis treatment response: protocol for a prospective observational cohort study.

INTRODUCTION: An improved understanding of factors explaining tuberculosis (TB) treatment response is urgently needed to help clinicians optimise and personalise treatment and assist scientists undertaking novel treatment regimen trials. Promising outcome proxy measures, including sputum bacillary load and host immune response, are widely reported with variable results. However, they have not been studied together in combination with antibiotic exposure. The aim of this observational cohort study is to investigate which antibiotic exposures correlate with sputum bacillary load and which with the host immune response. Subsequently, we will explore if these correlations can be used to inform a candidate combined biomarker predicting cure. METHODS AND ANALYSIS: All patients aged ≥ 18, diagnosed with drug-sensitive pulmonary TB (culture or molecular test), eligible for standard anti-TB treatment, at selected London, UK TB Services, will be invited to participate in this observational cohort study (target sample size=210). Patients will be asked to give blood for host transcriptomics and antibiotic plasma exposure, in addition to standard of care sputum samples for bacillary load. Antibiotic plasma concentrations will be quantified using a validated liquid chromatograph triple quadrupole mass spectrometer (LC-MS/MS) assay and sputum bacillary load by mycobacterial growth incubator tube time to positivity. Expression from a total of 35 prespecified host blood genes will be quantified using NanoString®. Antibiotic exposure, sputum bacillary load and host blood transcriptomic time series data will be analysed using nonlinear mixed-effects models. Correlations between combinations of longitudinal biomarkers and microbiological cure at the end of treatment and remaining relapse free for 1 year thereafter will be analysed using logistic regression and Cox proportional hazard models. ETHICS AND DISSEMINATION: The observational cohort study has been approved by the UK's HRA REC (20/SW/0007). Written informed consent will be obtained. Results will be disseminated via publication, presentation and through engagement with institutes/companies developing novel anti-TB treatment combinations

Butyrate prevents visceral adipose tissue inflammation and metabolic alterations in a Friedreich's ataxia mouse model

Friedreich's ataxia (FA) is a neurodegenerative disease resulting from a mutation in the FXN gene, leading to mitochondrial frataxin deficiency. FA patients exhibit increased visceral adiposity, inflammation, and heightened diabetes risk, negatively affecting prognosis. We investigated visceral white adipose tissue (vWAT) in a murine model (KIKO) to understand its role in FA-related metabolic complications. RNAseq analysis revealed altered expression of inflammation, angiogenesis, and fibrosis genes. Diabetes like traits, including larger adipocytes, immune cell infiltration, and increased lactate production, were observed in vWAT. FXN downregulation in cultured adipocytes mirrored vWAT diabetes-like features, showing metabolic shifts toward glycolysis and lactate production. Metagenomic analysis indicated a reduction in fecal butyrate-producing bacteria, known to exert antidiabetic effects. A butyrate-enriched diet restrained vWAT abnormalities and mitigated diabetes features in KIKO mice. Our work emphasizes the role of vWAT in FA-related metabolic issues and suggests butyrate as a safe and promising adjunct for FA management

Bedaquiline as part of combination therapy in adults with pulmonary multi-drug resistant tuberculosis

Introduction: Few innovative anti-microbial products have been brought to market in recent years to combat the global multidrug resistant-tuberculosis (MDR-TB) epidemic. Bedaquiline, a novel oral diarylquinoline, was approved by the US FDA as a part of combination therapy in adults with pulmonary MDR-TB based on phase II trials.Area covered: Pubmed searches were conducted using search terms bedaquiline, diarylquinoline, R207910, and TMC207 was performed. Supplementary sources included World Health Organization, Clinicaltrial.gov, US Food and Drug Administration. Bedaquiline is an ATP synthase inhibitor specific for M. tuberculosis and some nontuberculous mycobacteria. It is metabolized by CYP3A4 and it's drug exposure can be influenced by inducers and inhibitors of this enzyme. Phase II studies showed promising results on efficacy of bedaquiline when being used in combination with a background regimen for MDR-TB. Main safety concerns include QTc prolongation and hepatotoxicity. Phase III trials are ongoing to confirm efficacy findings from phase II studies and provide additional evidence of safety and efficacy.Expert commentary: Critical data for long-term efficacy and safety are incomplete and scarce, supporting the cautious use of bedaquiline

Prokineticin 1 induces Dickkopf 1 expression and regulates cell proliferation and decidualization in the human endometrium

Prokineticin 1 (PROK1) signalling via prokineticin receptor 1 (PROKR1) regulates the expression of several genes with important roles in endometrial receptivity and implantation. This study investigated PROK1 regulation of Dickkopf 1 (DKK1) expression, a negative regulator of canonical Wnt signalling, and its function in the non-pregnant endometrium and first trimester decidua. DKK1 mRNA expression is elevated during the mid-secretory phase of the menstrual cycle and expression increases further in first trimester decidua. DKK1 protein expression is localized to glandular epithelial and stromal cells during the proliferative, early- and mid-secretory phases, whereas expression is confined to the stroma in the late-secretory phase and first trimester decidua. PROK1 induces the expression of DKK1 in endometrial epithelial cells stably expressing PROKR1 and in first trimester decidua explants, via a Gq-calcium-calcineurin-nuclear factor of activated T-cells-mediated pathway. Endometrial epithelial cell proliferation is negatively regulated by PROK1-PROKR1 signalling. We demonstrate that this effect on cell proliferation occurs via DKK1 expression, as siRNA targeted against DKK1 reduces the PROK1-induced decrease in proliferation. Furthermore, decidualization of primary human endometrial stromal cells with progesterone and cyclic adenosine monophosphate is inhibited by miRNA knock down of PROK1 or DKK1. These data demonstrate important roles for PROK1 and DKK1 during endometrial receptivity and early pregnancy, which include regulation of endometrial cell proliferation and decidualization