Prediction of chronic postsurgical pain in adults: A protocol for multivariable prediciton model development

INTRODUCTION: Chronic postsurgical pain (CPSP) is a condition that affects an estimated 10%–50% of adults, depending on the surgical procedure. CPSP often interferes with activities of daily living and may have a negative impact on quality of life, emotional and physical well-being. Clinical prediction models can help clinicians target preventive strategies towards patients at high-risk of CPSP. Therefore, the objective of this study is to develop a clinically applicable and generalisable prediction model for CPSP in adults. METHODS AND ANALYSIS: This research will be a prospective single-centre observational cohort study in Denmark spanning approximately 1 year or until a predefined number of patients are recruited (n=1526). Adult patients aged 18 years and older scheduled to undergo surgery will be recruited at Aarhus University Hospital. The primary outcome is CPSP 3 months after surgery defined as average pain intensity at rest or on movement ≥3 on numerical rating scale (NRS) within the past week, and/or average pain interference ≥3 on NRS among any of seven short-form Brief Pain Inventory items in the past week (general activity, mood, walking ability, normal work (including housework), relations with other people, sleep and enjoyment of life). Logistic regression will be used to conduct multivariate analysis. Predictive model performance will be evaluated by discrimination, calibration and model classification. ETHICS AND DISSEMINATION: This research has been approved by Central Region Denmark and will be conducted in accordance with the Danish Data Protection Act and Declaration of Helsinki. Study findings will be disseminated through conference presentations and peer-reviewed publication. A CPSP risk calculator (CPSP-RC) will be developed based on predictors retained in the final models. The CPSP-RC will be made available online and as a mobile application to be easily accessible for clinical use and future research including validation and clinical impact assessments. TRIAL REGISTRATION NUMBER: NCT04866147

Comparison of Fuel Yield of Biomaterials Between Fast Pyrolysis and Gasification

Pyrolysis is a viable method of extracting combustible fuels as gases or liquids from various, high carbon and hydrogen containing biomaterials. This Meta-study attempts to find the ideal combinations of processes for maximising biofuel output by comparing a range of biomaterials (cotton stalks, algae and peach scraps), put through the two primary methods of pyrolysis, through analysis of reactor type, Temperature, particle size and lower heating value achieved from biofuel output. It is proposed that the fast pyrolysis of Algae in a Fluidized bed reactor at a temperature of 550°C is the optimum combination of parameters for maximising biofuel output in terms of bio-oil yield and lower heating value (LHV) in kJ/kg

Global Gene Expression Analysis Identifies Age-Related Differences in Knee Joint Transcriptome during the Development of Post-Traumatic Osteoarthritis in Mice.

Aging and injury are two major risk factors for osteoarthritis (OA). Yet, very little is known about how aging and injury interact and contribute to OA pathogenesis. In the present study, we examined age- and injury-related molecular changes in mouse knee joints that could contribute to OA. Using RNA-seq, first we profiled the knee joint transcriptome of 10-week-old, 62-week-old, and 95-week-old mice and found that the expression of several inflammatory-response related genes increased as a result of aging, whereas the expression of several genes involved in cartilage metabolism decreased with age. To determine how aging impacts post-traumatic arthritis (PTOA) development, the right knee joints of 10-week-old and 62-week-old mice were injured using a non-invasive tibial compression injury model and injury-induced structural and molecular changes were assessed. At six-week post-injury, 62-week-old mice displayed significantly more cartilage degeneration and osteophyte formation compared with young mice. Although both age groups elicited similar transcriptional responses to injury, 62-week-old mice had higher activation of inflammatory cytokines than 10-week-old mice, whereas cartilage/bone metabolism genes had higher expression in 10-week-old mice, suggesting that the differential expression of these genes might contribute to the differences in PTOA severity observed between these age groups

SOST Inhibits Prostate Cancer Invasion.

Inhibitors of Wnt signaling have been shown to be involved in prostate cancer (PC) metastasis; however the role of Sclerostin (Sost) has not yet been explored. Here we show that elevated Wnt signaling derived from Sost deficient osteoblasts promotes PC invasion, while rhSOST has an inhibitory effect. In contrast, rhDKK1 promotes PC elongation and filopodia formation, morphological changes characteristic of an invasive phenotype. Furthermore, rhDKK1 was found to activate canonical Wnt signaling in PC3 cells, suggesting that SOST and DKK1 have opposing roles on Wnt signaling in this context. Gene expression analysis of PC3 cells co-cultured with OBs exhibiting varying amounts of Wnt signaling identified CRIM1 as one of the transcripts upregulated under highly invasive conditions. We found CRIM1 overexpression to also promote cell-invasion. These findings suggest that bone-derived Wnt signaling may enhance PC tropism by promoting CRIM1 expression and facilitating cancer cell invasion and adhesion to bone. We concluded that SOST and DKK1 have opposing effects on PC3 cell invasion and that bone-derived Wnt signaling positively contributes to the invasive phenotypes of PC3 cells by activating CRIM1 expression and facilitating PC-OB physical interaction. As such, we investigated the effects of high concentrations of SOST in vivo. We found that PC3-cells overexpressing SOST injected via the tail vein in NSG mice did not readily metastasize, and those injected intrafemorally had significantly reduced osteolysis, suggesting that targeting the molecular bone environment may influence bone metastatic prognosis in clinical settings

eleanor: An open-source tool for extracting light curves from the TESS Full-Frame Images

During its two year prime mission the Transiting Exoplanet Survey Satellite (TESS) will perform a time-series photometric survey covering over 80% of the sky. This survey comprises observations of 26 24 x 96 degree sectors that are each monitored continuously for approximately 27 days. The main goal of TESS is to find transiting planets around 200,000 pre-selected stars for which fixed aperture photometry is recorded every two minutes. However, TESS is also recording and delivering Full-Frame Images (FFIs) of each detector at a 30 minute cadence. We have created an open-source tool, eleanor, to produce light curves for objects in the TESS FFIs. Here, we describe the methods used in eleanor to produce light curves that are optimized for planet searches. The tool performs background subtraction, aperture and PSF photometry, decorrelation of instrument systematics, and cotrending using principal component analysis. We recover known transiting exoplanets in the FFIs to validate the pipeline and perform a limited search for new planet candidates in Sector 1. Our tests indicate that eleanor produces light curves with significantly less scatter than other tools that have been used in the literature. Cadence-stacked images, and raw and detrended eleanor light curves for each analyzed star will be hosted on MAST, with planet candidates on ExoFOP-TESS as Community TESS Objects of Interest (CTOIs). This work confirms the promise that the TESS FFIs will enable the detection of thousands of new exoplanets and a broad range of time domain astrophysics.Comment: 21 pages, 13 figures, 2 tables, Accepted to PAS

Diagnostic agreement between three point-of-care glucose and β-hydroxybutyrate meters and reference laboratory methods in stingrays

Point-of-care (POC) glucose and β-hydroxybutyrate (β-HB) meters can potentially provide rapid insight into an elasmobranch’s metabolic state in clinical and field research settings. This study evaluated the diagnostic agreement of three commercial POC meters against reference laboratory methods for glucose and β-HB concentrations in stingrays. Blood was collected during anesthetized exams from 28 stingrays representing four species: cownose rays (Rhinoptera bonasus), Atlantic stingrays (Hypanus sabina), southern stingrays (Hypanus americanus), and yellow stingrays (Urobatis jamaicensis). Glucose and β-HB concentrations were measured with each POC meter using whole blood and plasma; in parallel, plasma glucose and β-HB concentrations were measured via reference laboratory methods. Agreement between POC meters and reference laboratory methods was assessed using Bland–Altman methods, Passing-Bablok regression, observed total error, percent relative error, and linear mixed effect models. Plasma glucose and β-HB concentrations determined by reference laboratory methods ranged from <20–63 mg/dL to 0.05–5.38 mmol/L, respectively. One human POC meter—the Precision Xtra—showed the greatest agreement with reference laboratory methods when measuring glucose with whole blood [mean bias and 95% CI: 0 (−3–4) mg/dL] and β-HB with plasma [mean bias and 95% CI: 0.1 (−0.04–0.2) mmol/L]. Stingray sex, weight, buffy coat, and packed cell volume did not significantly affect the agreement between POC meters and reference laboratory methods. Across all three POC meters, mean bias and imprecision for plasma β-HB concentrations were relatively small (0–0.1 mmol/L and 0%, respectively). Utilizing POC meters to measure glucose and β-HB in stingrays may be viable when reference methods are unavailable

The transcriptional regulator GalR self-assembles to form highly regular tubular structures

The Gal repressor regulates transport and metabolism of D-galactose in Escherichia coli and can mediate DNA loop formation by forming a bridge between adjacent or distant sites. GalR forms insoluble aggregates at lower salt concentrations in vitro, which can be solubilized at higher salt concentrations. Here, we investigate the assembly and disassembly of GalR aggregates. We find that a sharp transition from aggregates to soluble species occurs between 200 and 400 mM NaCl, incompatible with a simple salting-in effect. The aggregates are highly ordered rod-like structures, highlighting a remarkable ability for organized self-assembly. Mutant studies reveal that aggregation is dependent on two separate interfaces of GalR. The highly ordered structures dissociate to smaller aggregates in the presence of D-galactose. We propose that these self-assembled structures may constitute galactose-tolerant polymers for chromosome compaction in stationary phase cells, in effect linking self-assembly with regulatory function

EMAGE: a spatial database of gene expression patterns during mouse embryo development

EMAGE () is a freely available, curated database of gene expression patterns generated by in situ techniques in the developing mouse embryo. It is unique in that it contains standardized spatial representations of the sites of gene expression for each gene, denoted against a set of virtual reference embryo models. As such, the data can be interrogated in a novel and abstract manner by using space to define a query. Accompanying the spatial representations of gene expression patterns are text descriptions of the sites of expression, which also allows searching of the data by more conventional text-based methods

EMAGE: a spatial database of gene expression patterns during mouse embryo development

EMAGE () is a freely available, curated database of gene expression patterns generated by in situ techniques in the developing mouse embryo. It is unique in that it contains standardized spatial representations of the sites of gene expression for each gene, denoted against a set of virtual reference embryo models. As such, the data can be interrogated in a novel and abstract manner by using space to define a query. Accompanying the spatial representations of gene expression patterns are text descriptions of the sites of expression, which also allows searching of the data by more conventional text-based methods