| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Drake, Thomas M., et al.
(author)
-
Outcomes following small bowel obstruction due to malignancy in the national audit of small bowel obstruction
- 2019
-
In: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 45:12, s. 2319-2324
-
Journal article (peer-reviewed)abstract
- © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology Introduction: Patients with cancer who develop small bowel obstruction are at high risk of malnutrition and morbidity following compromise of gastrointestinal tract continuity. This study aimed to characterise current management and outcomes following malignant small bowel obstruction. Methods: A prospective, multicentre cohort study of patients with small bowel obstruction who presented to UK hospitals between 16th January and 13th March 2017. Patients who presented with small bowel obstruction due to primary tumours of the intestine (excluding left-sided colonic tumours) or disseminated intra-abdominal malignancy were included. Outcomes included 30-day mortality and in-hospital complications. Cox-proportional hazards models were used to generate adjusted effects estimates, which are presented as hazard ratios (HR) alongside the corresponding 95% confidence interval (95% CI). The threshold for statistical significance was set at the level of P ≤ 0.05 a-priori. Results: 205 patients with malignant small bowel obstruction presented to emergency surgery services during the study period. Of these patients, 50 had obstruction due to right sided colon cancer, 143 due to disseminated intraabdominal malignancy, 10 had primary tumours of the small bowel and 2 patients had gastrointestinal stromal tumours. In total 100 out of 205 patients underwent a surgical intervention for obstruction. 30-day in-hospital mortality rate was 11.3% for those with primary tumours and 19.6% for those with disseminated malignancy. Severe risk of malnutrition was an independent predictor for poor mortality in this cohort (adjusted HR 16.18, 95% CI 1.86 to 140.84, p = 0.012). Patients with right-sided colon cancer had high rates of morbidity. Conclusions: Mortality rates were high in patients with disseminated malignancy and in those with right sided colon cancer. Further research should identify optimal management strategy to reduce morbidity for these patient groups.
|
|
| 5. |
- Brevini, T, et al.
(author)
-
FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2
- 2023
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7950, s. 134-
-
Journal article (peer-reviewed)abstract
- Preventing SARS-CoV-2 infection by modulating viral host receptors, such as angiotensin-converting enzyme 2 (ACE2)1, could represent a new chemoprophylactic approach for COVID-19 that complements vaccination2,3. However, the mechanisms that control the expression of ACE2 remain unclear. Here we show that the farnesoid X receptor (FXR) is a direct regulator of ACE2 transcription in several tissues affected by COVID-19, including the gastrointestinal and respiratory systems. We then use the over-the-counter compound z-guggulsterone and the off-patent drug ursodeoxycholic acid (UDCA) to reduce FXR signalling and downregulate ACE2 in human lung, cholangiocyte and intestinal organoids and in the corresponding tissues in mice and hamsters. We show that the UDCA-mediated downregulation of ACE2 reduces susceptibility to SARS-CoV-2 infection in vitro, in vivo and in human lungs and livers perfused ex situ. Furthermore, we reveal that UDCA reduces the expression of ACE2 in the nasal epithelium in humans. Finally, we identify a correlation between UDCA treatment and positive clinical outcomes after SARS-CoV-2 infection using retrospective registry data, and confirm these findings in an independent validation cohort of recipients of liver transplants. In conclusion, we show that FXR has a role in controlling ACE2 expression and provide evidence that modulation of this pathway could be beneficial for reducing SARS-CoV-2 infection, paving the way for future clinical trials.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Contreras, ZA, et al.
(author)
-
Does early onset asthma increase childhood obesity risk? A pooled analysis of 16 European cohorts
- 2018
-
In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 52:3
-
Journal article (peer-reviewed)abstract
- The parallel epidemics of childhood asthma and obesity over the past few decades have spurred research into obesity as a risk factor for asthma. However, little is known regarding the role of asthma in obesity incidence. We examined whether early-onset asthma and related phenotypes are associated with the risk of developing obesity in childhood.This study includes 21 130 children born from 1990 to 2008 in Denmark, France, Germany, Greece, Italy, The Netherlands, Spain, Sweden and the UK. We followed non-obese children at 3–4 years of age for incident obesity up to 8 years of age. Physician-diagnosed asthma, wheezing and allergic rhinitis were assessed up to 3–4 years of age.Children with physician-diagnosed asthma had a higher risk for incident obesity than those without asthma (adjusted hazard ratio (aHR) 1.66, 95% CI 1.18–2.33). Children with active asthma (wheeze in the last 12 months and physician-diagnosed asthma) exhibited a higher risk for obesity (aHR 1.98, 95% CI 1.31–3.00) than those without wheeze and asthma. Persistent wheezing was associated with increased risk for incident obesity compared to never wheezers (aHR 1.51, 95% CI 1.08–2.09).Early-onset asthma and wheezing may contribute to an increased risk of developing obesity in later childhood.
|
|
| 11. |
|
|
| 12. |
- Polyakov, A., et al.
(author)
-
Instability of the topological surface state in Bi2Se3 upon deposition of gold
- 2017
-
In: Physical Review B. - : American Physical Society. - 2469-9950 .- 2469-9969. ; 95:18
-
Journal article (peer-reviewed)abstract
- Momentum-resolved photoemission spectroscopy indicates the instability of the Dirac surface state upon deposition of gold on the (0001) surface of the topological insulator Bi2Se3. Based on the structure model derived from extended x-ray absorption fine structure experiments showing that gold atoms substitute bismuth atoms, first-principles calculations provide evidence that a gap appears due to hybridization of the surface state with gold d states near the Fermi level. Our findings provide insights into the mechanisms affecting the stability of the surface state.
|
|
| 13. |
- Polyakov, A., et al.
(author)
-
Reply to Comment on 'Instability of the topological surface state in Bi2Se3 upon deposition of gold'
- 2018
-
In: Physical Review B. - : American Physical Society. - 2469-9950 .- 2469-9969. ; 98:13
-
Journal article (peer-reviewed)abstract
- In the Comment on our publication [Phys. Rev. B 95, 180202(R) (2017)], R. A. Gordon claims that our main conclusion is not valid, namely that gold atoms deposited in situ on the (0001) surface of single-crystalline Bi2Se3 reside in substitutional sites, i.e., replacing bismuth atoms within the topmost quintuple layer (QL). Based on x-ray absorption near-edge (XANES) spectra and a re-evaluation of extended x-ray absorption fine structure (EXAFS) data above the Au L-III edge, R. A. Gordon concludes that Au resides in a twofold environment as a result of an interface reaction leading to an Au2S-type local structure, in which gold adopts an Au(I) state and is linearly coordinated by selenium atoms. In this Reply, we will confirm the results published in the original paper and their interpretation that Au atoms reside in the substitutional site.
|
|
| 14. |
- Tohnak, S., et al.
(author)
-
Dental CT metal artefact reduction based on sequential substitution
- 2011
-
In: Dentomaxillofacial Radiology. - : British Institute of Radiology. - 0250-832X .- 1476-542X. ; 40:3, s. 184-190
-
Journal article (peer-reviewed)abstract
- Objective: Metal artefacts can seriously degrade the visual quality and interpretability of dental CT images. Existing image processing algorithms for metal artefact reduction (MAR) are either too computationally expensive to be used in clinical scanners or effective only in correcting mild artefacts. The aim of the present study was to investigate whether it is possible to improve the efficacy of the computationally efficient projection-correction approach to MAR by exploiting the spatial dependency or autocorrelation between adjacent CT slices. Methods: A new projection-correction algorithm [MAR by sequential substitution (MARSS)] was developed based on the idea that the corrupted portions of the projection data can be substituted with the corresponding portions from an unaffected adjacent slice. The performance of MARSS was evaluated relative to the projection-correction method of Watzke and Kalendar using a two-alternative forced choice (2AFC) visual trial involving 20 observers and 20 clinical CT data sets.(16) Results: The Cochran Q test revealed no significant difference in the responses across all observers. The data were then pooled and analysed using a one-tailed exact binomial test. This revealed that the proportion of responses in favour of MARSS was significant (P
|
|
| 15. |
- Tohnak, S., et al.
(author)
-
Synthesizing dental radiographs for human identification
- 2007
-
In: Journal of Dental Research. - 0022-0345 .- 1544-0591. ; 86:11, s. 1057-1062
-
Journal article (peer-reviewed)abstract
- The task of identifying human remains based on dental comparisons of post mortem (PM) and ante mortem (AM) radiographs is labor-intensive, subjective, and has several drawbacks, including: inherently poor image quality, difficulty matching the viewing angles in PM radiographs to those taken AM, and the fact that the state of the dental remains may entirely preclude the possibility of obtaining certain types of radiographs PM. The aim of the present study was to investigate the feasibility of using radiograph-like images reconstructed from PM x-ray computed tomography (CT) data to overcome the shortcomings of conventional radiographic comparison. Algorithms for computer synthesis of panoramic, periapical, and bitewing images are presented. The algorithms were evaluated with data from clinical examinations of two persons. The results demonstrate the efficacy of the CT-based approach and that, in comparison with conventional radiographs, the synthesized images exhibit minimal geometric distortion, reduced blurring, and reduced superimposition of oral structures.
|
|
| 16. |
- Bayani, Jane, et al.
(author)
-
Evaluation of multiple transcriptomic gene risk signatures in male breast cancer
- 2021
-
In: npj Breast Cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 7:1
-
Journal article (peer-reviewed)abstract
- Male breast cancer (BCa) is a rare disease accounting for less than 1% of all breast cancers and 1% of all cancers in males. The clinical management is largely extrapolated from female BCa. Several multigene assays are increasingly used to guide clinical treatment decisions in female BCa, however, there are limited data on the utility of these tests in male BCa. Here we present the gene expression results of 381 M0, ER+ve, HER2-ve male BCa patients enrolled in the Part 1 (retrospective analysis) of the International Male Breast Cancer Program. Using a custom NanoString™ panel comprised of the genes from the commercial risk tests Prosigna®, OncotypeDX®, and MammaPrint®, risk scores and intrinsic subtyping data were generated to recapitulate the commercial tests as described by us previously. We also examined the prognostic value of other risk scores such as the Genomic Grade Index (GGI), IHC4-mRNA and our prognostic 95-gene signature. In this sample set of male BCa, we demonstrated prognostic utility on univariate analysis. Across all signatures, patients whose samples were identified as low-risk experienced better outcomes than intermediate-risk, with those classed as high risk experiencing the poorest outcomes. As seen with female BCa, the concordance between tests was poor, with C-index values ranging from 40.3% to 78.2% and Kappa values ranging from 0.17 to 0.58. To our knowledge, this is the largest study of male breast cancers assayed to generate risk scores of the current commercial and academic risk tests demonstrating comparable clinical utility to female BCa.
|
|
| 17. |
- Di Pede, Giuseppe, et al.
(author)
-
Revisiting the bioavailability of flavan-3-ols in humans: A systematic review and comprehensive data analysis
- 2023
-
In: Molecular Aspects of Medicine. - : Elsevier BV. - 1872-9452 .- 0098-2997. ; 89
-
Research review (peer-reviewed)abstract
- This systematic review summarizes findings from human studies investigating the different routes of absorption, metabolism, distribution and excretion (ADME) of dietary flavan-3-ols and their circulating metabolites in healthy subjects. Literature searches were performed in PubMed, Scopus and the Web of Science. Human intervention studies using single and/or multiple intake of flavan-3-ols from food, extracts, and pure compounds were included. Forty-nine human intervention studies met inclusion criteria. Up to 180 metabolites were quantified from blood and urine samples following intake of flavan-3-ols, mainly as phase 2 conjugates of microbial catabolites (n = 97), with phenyl-γ-valerolactones being the most representative ones (n = 34). Phase 2 conjugates of monomers and phenyl-γ-valerolactones, the main compounds in both plasma and urine, reached two peak plasma concentrations (Cmax) of 260 and 88 nmol/L at 1.8 and 5.3 h (Tmax) after flavan-3-ol intake. They contributed to the bioavailability of flavan-3-ols for over 20%. Mean bioavailability for flavan-3-ols was moderate (31 ± 23%, n bioavailability values = 20), and it seems to be scarcely affected by the amount of ingested compounds. While intra- and inter-source differences in flavan-3-ol bioavailability emerged, mean flavan-3-ol bioavailability was 82% (n = 1) and 63% (n = 2) after (−)-epicatechin and nut (hazelnuts, almonds) intake, respectively, followed by 25% after consumption of tea (n = 7), cocoa (n = 5), apples (n = 3) and grape (n = 2). This highlights the need to better clarify the metabolic yield with which monomer flavan-3-ols and proanthocyanidins are metabolized in humans. This work clarified in a comprehensive way for the first time the ADME of a (poly)phenol family, highlighting the pool of circulating compounds that might be determinants of the putative beneficial effects linked to flavan-3-ol intake. Lastly, methodological inputs for implementing well-designed human and experimental model studies were provided.
|
|
| 18. |
- Gal, Y., et al.
(author)
-
Denoising of Dynamic Contrast-Enhanced MR Images Using Dynamic Nonlocal Means
- 2010
-
In: IEEE Transactions on Medical Imaging. - 0278-0062. ; 29:2, s. 302-310
-
Journal article (peer-reviewed)abstract
- This paper presents a new algorithm for denoising dynamic contrast-enhanced (DCE) MR images. It is a novel variation on the nonlocal means (NLM) algorithm. The algorithm, called dynamic nonlocal means (DNLM), exploits the redundancy of information in the temporal sequence of images. Empirical evaluations of the performance of the DNLM algorithm relative to seven other denoising methods-simple Gaussian filtering, the original NLM algorithm, a trivial extension of NLM to include the temporal dimension, bilateral filtering, anisotropic diffusion filtering, wavelet adaptive multiscale products threshold, and traditional wavelet thresholding-are presented. The evaluations include quantitative evaluations using simulated data and real data (20 DCE-MRI data sets from routine clinical breast MRI examinations) as well as qualitative evaluations using the same real data (24 observers: 14 image/signal-processing specialists, 10 clinical breast MRI radiographers). The results of the quantitative evaluation using the simulated data show that the DNLM algorithm consistently yields the smallest MSE between the denoised image and its corresponding original noiseless version. The results of the quantitative evaluation using the real data provide evidence, at the alpha = 0.05 level of significance, that the DNLM algorithm yields the smallest MSE between the denoised image and its corresponding original noiseless version. The results of the qualitative evaluation provide evidence, at the alpha = 0.05 level of significance, that the DNLM algorithm performs visually better than all of the other algorithms. Collectively the qualitative and quantitative results suggest that the DNLM algorithm more effectively attenuates noise in DCE MR images than any of the other algorithms.
|
|
| 19. |
|
|
| 20. |
- Hill, A., et al.
(author)
-
Evaluating the Accuracy and Impact of Registration in Dynamic Contrast-Enhanced Breast MRI
- 2009
-
In: Concepts in Magnetic Resonance Part B: Magnetic Resonance Engineering. - 1552-5031. ; 35B:2, s. 106-120
-
Journal article (peer-reviewed)abstract
- This article presents a quantitative evaluation framework-incorporating a novel heterogeneous biomechanical model-for objectively comparing the accuracy of registration algorithms in dynamic contrast-enhanced (DCE) MRI of the breast; an evaluation of several algorithms using this framework; and several clinical examples where accurate registration significantly changes the shape of the enhancement curves associated with suspicious regions of interest (ROIs) identified by a radiologist. The experimental results demonstrate: (i) the efficacy of the evaluation framework; (ii) that a good registration algorithm can accurately recover the shapes of voxel enhancement curves from breast DCE-MRI data containing motion; (iii) that motion of as little as I mm can significantly change the shape of the mean enhancement curve for an ROI; and (iv) that accurate registration can significantly change the shape of enhancement curves estimated for small and large ROIs even when there is little or no visible evidence of motion. This suggests that all DCE-MRI breast data should be spatially aligned using a nonrigid registration algorithm before the analysis of contrast enhancement. (C) 2009 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 3513: 106-120, 2009
|
|
| 21. |
- McClymont, D., et al.
(author)
-
Fully Automatic Lesion Segmentation in Breast MRI Using Mean-Shift and Graph-Cuts on a Region Adjacency Graph
- 2014
-
In: Journal of Magnetic Resonance Imaging. - : Wiley. - 1053-1807 .- 1522-2586. ; 39:4, s. 795-804
-
Journal article (peer-reviewed)abstract
- PurposeTo present and evaluate a fully automatic method for segmentation (i.e., detection and delineation) of suspicious tissue in breast MRI. Materials and MethodsThe method, based on mean-shift clustering and graph-cuts on a region adjacency graph, was developed and its parameters tuned using multimodal (T1, T2, DCE-MRI) clinical breast MRI data from 35 subjects (training data). It was then tested using two data sets. Test set 1 comprises data for 85 subjects (93 lesions) acquired using the same protocol and scanner system used to acquire the training data. Test set 2 comprises data for eight subjects (nine lesions) acquired using a similar protocol but a different vendor's scanner system. Each lesion was manually delineated in three-dimensions by an experienced breast radiographer to establish segmentation ground truth. The regions of interest identified by the method were compared with the ground truth and the detection and delineation accuracies quantitatively evaluated. ResultsOne hundred percent of the lesions were detected with a mean of 4.5 1.2 false positives per subject. This false-positive rate is nearly 50% better than previously reported for a fully automatic breast lesion detection system. The median Dice coefficient for Test set 1 was 0.76 (interquartile range, 0.17), and 0.75 (interquartile range, 0.16) for Test set 2. ConclusionThe results demonstrate the efficacy and accuracy of the proposed method as well as its potential for direct application across different MRI systems. It is (to the authors' knowledge) the first fully automatic method for breast lesion detection and delineation in breast MRI. J. Magn. Reson. Imaging 2014;39:795-804. (c) 2013 Wiley Periodicals, Inc.
|
|
