| 61. |
- Chowdhury, Susmita, et al.
(författare)
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Thermoelectric properties and electronic structure of Cr(Mo,V)Nx thin films studied by synchrotron and lab-based x-ray spectroscopy
- 2023
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Ingår i: Physical Review B. - : AMER PHYSICAL SOC. - 2469-9950 .- 2469-9969. ; 108:20
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Tidskriftsartikel (refereegranskat)abstract
- Chromium-based nitrides are used in hard, resilient coatings and show promise for thermoelectric applications due to their combination of structural, thermal, and electronic properties. Here, we investigate the electronic structures and chemical bonding correlated to the thermoelectric properties of epitaxially grown chromium-based multicomponent nitride Cr(Mo,V)Nx thin films. The small amount of N vacancies causes Cr 3d and N 2p states to appear at the Fermi level and reduces the band gap in Cr0.51N0.49. Incorporating holes by alloying of V in N-deficient CrN results in an enhanced thermoelectric power factor with marginal change in the charge transfer of Cr to N compared with Cr0.51N0.49. Further alloying of Mo, isoelectronic to Cr, increases the density of states at the Fermi level due to hybridization of the (Cr, V) 3d and Mo 4d-N 2p states in Cr(Mo,V)Nx. This hybridization and N off-stoichiometry result in more metal-like electrical resistivity and reduction in Seebeck coefficient. The N deficiency in Cr(Mo,V)Nx also depicts a critical role in reduction of the charge transfer from metal to N site compared with Cr0.51N0.49 and Cr0.50V0.03N0.47. In this paper, we envisage ways for enhancing thermoelectric properties through electronic band engineering by alloying and competing effects of N vacancies.
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| 62. |
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| 63. |
- Crippa, Alessio, et al.
(författare)
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The ProBio trial : molecular biomarkers for advancing personalized treatment decision in patients with metastatic castration-resistant prostate cancer
- 2020
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Ingår i: Trials. - : BioMed Central. - 1745-6215. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple therapies exist for patients with metastatic castration-resistant prostate cancer (mCRPC). However, their improvement on progression-free survival (PFS) remains modest, potentially explained by tumor molecular heterogeneity. Several prognostic molecular biomarkers have been identified for mCRPC that may have predictive potential to guide treatment selection and prolong PFS. We designed a platform trial to test this hypothesis.Methods: The Prostate-Biomarker (ProBio) study is a multi-center, outcome-adaptive, multi-arm, biomarker-driven platform trial for tailoring treatment decisions for men with mCRPC. Treatment decisions in the experimental arms are based on biomarker signatures defined as mutations in certain genes/pathways suggested in the scientific literature to be important for treatment response in mCRPC. The biomarker signatures are determined by targeted sequencing of circulating tumor and germline DNA using a panel specifically designed for mCRPC.Discussion: Patients are stratified based on the sequencing results and randomized to either current clinical practice (control), where the treating physician decides treatment, or to molecularly driven treatment selection based on the biomarker profile. Outcome-adaptive randomization is implemented to early identify promising treatments for a biomarker signature. Biomarker signature-treatment combinations graduate from the platform when they demonstrate 85% probability of improving PFS compared to the control arm. Graduated combinations are further evaluated in a seamless confirmatory trial with fixed randomization. The platform design allows for new drugs and biomarkers to be introduced in the study.Conclusions: The ProBio design allows promising treatment-biomarker combinations to quickly graduate from the platform and be confirmed for rapid implementation in clinical care.
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| 64. |
- Dadaev, T, et al.
(författare)
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Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2256-
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.
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| 65. |
- Dembrower, Karin, et al.
(författare)
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Effect of artificial intelligence-based triaging of breast cancer screening mammograms on cancer detection and radiologist workload : a retrospective simulation study
- 2020
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Ingår i: The Lancet Digital Health. - : Elsevier. - 2589-7500. ; 2:9, s. E468-E474
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Tidskriftsartikel (refereegranskat)abstract
- Background We examined the potential change in cancer detection when using an artificial intelligence (AI) cancer-detection software to triage certain screening examinations into a no radiologist work stream, and then after regular radiologist assessment of the remainder, triage certain screening examinations into an enhanced assessment work stream. The purpose of enhanced assessment was to simulate selection of women for more sensitive screening promoting early detection of cancers that would otherwise be diagnosed as interval cancers or as next-round screen-detected cancers. The aim of the study was to examine how AI could reduce radiologist workload and increase cancer detection. Methods In this retrospective simulation study, all women diagnosed with breast cancer who attended two consecutive screening rounds were included. Healthy women were randomly sampled from the same cohort; their observations were given elevated weight to mimic a frequency of 0.7% incident cancer per screening interval. Based on the prediction score from a commercially available AI cancer detector, various cutoff points for the decision to channel women to the two new work streams were examined in terms of missed and additionally detected cancer. Findings 7364 women were included in the study sample: 547 were diagnosed with breast cancer and 6817 were healthy controls. When including 60%, 70%, or 80% of women with the lowest AI scores in the no radiologist stream, the proportion of screen-detected cancers that would have been missed were 0, 0.3% (95% CI 0.0-4.3), or 2.6% (1.1-5.4), respectively. When including 1% or 5% of women with the highest AI scores in the enhanced assessment stream, the potential additional cancer detection was 24 (12%) or 53 (27%) of 200 subsequent interval cancers, respectively, and 48 (14%) or 121 (35%) of 347 next-round screen-detected cancers, respectively. Interpretation Using a commercial AI cancer detector to triage mammograms into no radiologist assessment and enhanced assessment could potentially reduce radiologist workload by more than half, and pre-emptively detect a substantial proportion of cancers otherwise diagnosed later.
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| 66. |
- Edsfeldt, Sara, et al.
(författare)
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Prognostic factors for digital range of motion after intrasynovial flexor tendon injury and repair : Long-term follow-up on 273 patients treated with active extension-passive flexion with rubber bands.
- 2019
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Ingår i: Journal of Hand Therapy. - : Elsevier BV. - 0894-1130 .- 1545-004X. ; 32:3, s. 328-333
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Tidskriftsartikel (refereegranskat)abstract
- Study Design: Observational cohort study.Introduction: Investigating prognostic factors using population-based data may be used to improve functional outcome after flexor tendon injury and repair.Purpose of the Study: The aim of this study is to investigate the effect of concomitant nerve transection, combined flexor digitorum profundus (FDP) and flexor digitorum superficialis (FDS) tendon transection and the age of the patient, on digital range of motion (ROM) more than 1 year after FDP tendon transection and repair in zone I and II.Methods: Two hundred seventy-three patients with a total of 311 fingers admitted for FDP injury in zone I and II were treated with active extension-passive flexion with rubber bands and followed for at least 1 year. We compared outcome by evaluating digital mobility using Strickland's evaluation system.Results: At 12 months 72% of patients aged > 50 had fair or poor ROM compared to 17% of patients aged 0-25 years. At 24 months the results for patients aged > 50 had improved to 33% with fair or poor ROM, whereas no improvement had occurred for patients aged 0-25 (17% with fair or poor ROM). Concomitant nerve transection and FDS tendon transection had no negative effects on digital mobility.Discussion: Age above 50 was significantly associated with impaired digital ROM during the first year after flexor tendon injury and repair but not at 2 years follow-up. Concomitant nerve transection and combined transection of FDP and FDS do not affect digital mobility.Conclusions: Older patients are likely to have a slower healing process and impaired digital ROM during the first year after surgery.
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| 67. |
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| 68. |
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| 69. |
- Egeblad, Louise, et al.
(författare)
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Structural and functional studies of the human phosphoribosyltransferase domain containing protein 1
- 2010
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Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 277:23, s. 4920-30
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Tidskriftsartikel (refereegranskat)abstract
- Human hypoxanthine-guanine phosphoribosyltransferase (HPRT) (EC 2.4.2.8) catalyzes the conversion of hypoxanthine and guanine to their respective nucleoside monophosphates. Human HPRT deficiency as a result of genetic mutations is linked to both Lesch-Nyhan disease and gout. In the present study, we have characterized phosphoribosyltransferase domain containing protein 1 (PRTFDC1), a human HPRT homolog of unknown function. The PRTFDC1 structure has been determined at 1.7 Å resolution with bound GMP. The overall structure and GMP binding mode are very similar to that observed for HPRT. Using a thermal-melt assay, a nucleotide metabolome library was screened against PRTFDC1 and revealed that hypoxanthine and guanine specifically interacted with the enzyme. It was subsequently confirmed that PRTFDC1 could convert these two bases into their corresponding nucleoside monophosphate. However, the catalytic efficiency (k(cat)/K(m)) of PRTFDC1 towards hypoxanthine and guanine was only 0.26% and 0.09%, respectively, of that of HPRT. This low activity could be explained by the fact that PRTFDC1 has a Gly in the position of the proposed catalytic Asp of HPRT. In PRTFDC1, a water molecule at the position of the aspartic acid side chain position in HPRT might be responsible for the low activity observed by acting as a weak base. The data obtained in the present study indicate that PRTFDC1 does not have a direct catalytic role in the nucleotide salvage pathway.
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| 70. |
- Egevad, Lars, et al.
(författare)
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Interobserver reproducibility of perineural invasion of prostatic adenocarcinoma in needle biopsies
- 2021
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Ingår i: Virchows Archiv. - : Springer Nature. - 0945-6317 .- 1432-2307. ; 478:6, s. 1109-1116
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Tidskriftsartikel (refereegranskat)abstract
- Numerous studies have shown a correlation between perineural invasion (PNI) in prostate biopsies and outcome. The reporting of PNI varies widely in the literature. While the interobserver variability of prostate cancer grading has been studied extensively, less is known regarding the reproducibility of PNI. A total of 212 biopsy cores from a population-based screening trial were included in this study (106 with and 106 without PNI according to the original pathology reports). The glass slides were scanned and circulated among four pathologists with a special interest in urological pathology for assessment of PNI. Discordant cases were stained by immunohistochemistry for S-100 protein. PNI was diagnosed by all four observers in 34.0% of cases, while 41.5% were considered to be negative for PNI. In 24.5% of cases, there was a disagreement between the observers. The kappa for interobserver variability was 0.67-0.75 (mean 0.73). The observations from one participant were compared with data from the original reports, and a kappa for intraobserver variability of 0.87 was achieved. Based on immunohistochemical findings among discordant cases, 88.6% had PNI while 11.4% did not. The most common diagnostic pitfall was the presence of bundles of stroma or smooth muscle. It was noted in a few cases that collagenous micronodules could be mistaken for a nerve. The distance between cancer and nerve was another cause of disagreement. Although the results suggest that the reproducibility of PNI may be greater than that of prostate cancer grading, there is still a need for improvement and standardization.
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