| 1. |
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| 2. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
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| 5. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 9. |
- Bauer, M., et al.
(författare)
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Exploratory study of ultraviolet B (UVB) radiation and age of onset of bipolar disorder
- 2023
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Ingår i: International Journal of Bipolar Disorders. - 2194-7511. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample.MethodsData for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P <= 0.001.ResultsThe 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger.ConclusionUVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition.
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| 10. |
- Bauer, M., et al.
(författare)
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Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder
- 2021
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Ingår i: International Journal of Bipolar Disorders. - : Springer Science and Business Media LLC. - 2194-7511. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun's electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.
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| 11. |
- Bauer, M., et al.
(författare)
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Association between polarity of first episode and solar insolation in bipolar I disorder
- 2022
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Ingår i: Journal of Psychosomatic Research. - : Elsevier BV. - 0022-3999 .- 1879-1360. ; 160
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Circadian rhythm disruption is commonly observed in bipolar disorder (BD). Daylight is the most powerful signal to entrain the human circadian clock system. This exploratory study investigated if solar insolation at the onset location was associated with the polarity of the first episode of BD I. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area of the Earth. Methods: Data from 7488 patients with BD I were collected at 75 sites in 42 countries. The first episode occurred at 591 onset locations in 67 countries at a wide range of latitudes in both hemispheres. Solar insolation values were obtained for every onset location, and the ratio of the minimum mean monthly insolation to the maximum mean monthly insolation was calculated. This ratio is largest near the equator (with little change in solar insolation over the year), and smallest near the poles (where winter insolation is very small compared to summer insolation). This ratio also applies to tropical locations which may have a cloudy wet and clear dry season, rather than winter and summer. Results: The larger the change in solar insolation throughout the year (smaller the ratio between the minimum monthly and maximum monthly values), the greater the likelihood the first episode polarity was depression. Other associated variables were being female and increasing percentage of gross domestic product spent on country health expenditures. (All coefficients: P ≤ 0.001). Conclusion: Increased awareness and research into circadian dysfunction throughout the course of BD is warranted.
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| 12. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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| 13. |
- Sumaila, U. Rashid, et al.
(författare)
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WTO must ban harmful fisheries subsidies
- 2021
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 14. |
- Teh, W. -L, et al.
(författare)
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Evolution of a typical ion-scale magnetic flux rope caused by thermal pressure enhancement
- 2017
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Ingår i: Journal of Geophysical Research - Space Physics. - : AMER GEOPHYSICAL UNION. - 2169-9380 .- 2169-9402. ; 122:2, s. 2040-2050
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Tidskriftsartikel (refereegranskat)abstract
- With high time-resolution field and plasma measurements by the Magnetospheric Multiscale spacecraft, interior fine structures of two ion-scale magnetic flux ropes (similar to 5 and similar to 11 ion inertial length radius) separated by similar to 14 s are resolved. These two ion-scale flux ropes (FR1 and FR2) show non-frozen-in ion behavior and consist of a strong axial magnetic field at the reversal of the negative-then-positive bipolar field component. The negative bipolar field component of the FR2 is found to be depressed, where magnetic pressure and total pressure decrease, but ion and electron thermal pressures increase, a feature akin to a crater-like flux rope. The pressure enhancement is due to the magnetosheath plasma feeding into the flux rope along the field lines. Magnetic field draping and energetic electrons are also observed in the trailing part of the FR2. The ratio of perpendicular and parallel currents indicates that the FR1 appears force-free but the FR2 seems not. Moreover, the FR2 is time-dependent as a result of a low correlation coefficient (CC = 0.75) for the derivation of the deHoffmann-Teller frame using the direct measured electric fields, while the FR1 is in quasi-steady conditions (CC = 0.94). It is concluded that the crater formation within the FR2 can be interpreted by the analytical flux rope simulation as the evolution of typical flux rope to crater-like one due to the thermal pressure enhancement, which could be induced by the depression of transverse magnetic fields of the flux rope.
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| 15. |
- Lensen, S., et al.
(författare)
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A Randomized Trial of Endometrial Scratching before In Vitro Fertilization
- 2019
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 380:4, s. 325-334
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Endometrial scratching (with the use of a pipelle biopsy) is a technique proposed to facilitate embryo implantation and increase the probability of pregnancy in women undergoing in vitro fertilization (IVF). We conducted a pragmatic, multicenter, open-label, randomized, controlled trial. Eligible women were undergoing IVF (fresh-embryo or frozen-embryo transfer), with no recent exposure to disruptive intrauterine instrumentation (e.g., hysteroscopy). Participants were randomly assigned in a 1: 1 ratio to either endometrial scratching (by pipelle biopsy between day 3 of the cycle preceding the embryo-transfer cycle and day 3 of the embryo-transfer cycle) or no intervention. The primary outcome was live birth. A total of 1364 women underwent randomization. The frequency of live birth was 180 of 690 women (26.1%) in the endometrial-scratch group and 176 of 674 women (26.1%) in the control group (adjusted odds ratio, 1.00; 95% confidence interval, 0.78 to 1.27). There were no significant between-group differences in the rates of ongoing pregnancy, clinical pregnancy, multiple pregnancy, ectopic pregnancy, or miscarriage. The median score for pain from endometrial scratching (on a scale of 0 to 10, with higher scores indicating worse pain) was 3.5 (interquartile range, 1.9 to 6.0). Endometrial scratching did not result in a higher rate of live birth than no intervention among women undergoing IVF.
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| 16. |
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| 17. |
- Eriksson, S., et al.
(författare)
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Magnetic island formation between large-scale flow vortices at an undulating postnoon magnetopause for northward interplanetary magnetic field
- 2009
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 114:2, s. A00C17-
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Tidskriftsartikel (refereegranskat)abstract
- Time History of Events and Macroscale Interactions during Substorms multispacecraft observations are presented for a similar to 2-h-long postnoon magnetopause event on 8 June 2007 that for the first time indicate that the trailing (sunward) edges of Kelvin-Helmholtz (KH) waves are commonly related to small-scale < 0.56 R-E magnetic islands or flux transfer events (FTE) during the growth phase of these surface waves. The FTEs typically show a characteristic bipolar B-N structure with enhanced total pressure at their center. Most of the small-scale FTEs are not related to any major plasma acceleration. TH-A observations of one small FTE at a transition from the low-latitude boundary layer (LLBL) into a magnetosheath plasma depletion layer were reconstructed using separate techniques that together confirm the presence of a magnetic island within the LLBL adjacent to the magnetopause. The island was associated with a small plasma vortex and both features appeared between two large-scale (similar to 1 R-E long and 2000 km wide) plasma vortices. We propose that the observed magnetic islands may have been generated from a time-varying reconnection process in a low ion plasma beta (beta(i) < 0.2) and low 8.3 degrees field shear environment at the sunward edge of the growing KH waves where the local magnetopause current sheet may be compressed by the converging flow of the large-scale plasma vortices as suggested by numerical simulations of the KH instability.
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| 19. |
- Bi, G., et al.
(författare)
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Feasibility study on the Laser Aided Additive Manufacturing of die inserts for liquid forging
- 2010
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Ingår i: Materials & Design. - : Elsevier BV. - 0261-3069. ; 31:SUPPL. 1, s. S112-S116
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports the Laser Aided Additive Manufacturing of nickel-base alloy Nimonic 80A for the purpose of direct building of die inserts for liquid forging. Low porosity level of 0.01-0.04% with reasonable deposition rate was achieved. The micro-hardness showed very good homogeneity. Directionally solidified cellular micro-structure with an average size of 5Όm was observed. Very fine MC-type carbides were detected at the grain boundaries, which function as the strengthening phase of the alloy. © 2009 Elsevier Ltd.
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| 20. |
- Carpten, JD, et al.
(författare)
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HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome
- 2002
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 32:4, s. 676-680
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Tidskriftsartikel (refereegranskat)abstract
- We report here the identification of a gene associated with the hyperparathyroidism-jaw tumor (HPT-JT) syndrome. A single locus associated with HPT-JT (HRPT2) was previously mapped to chromosomal region 1q25-q32. We refined this region to a critical interval of 12 cM by genotyping in 26 affected kindreds. Using a positional candidate approach, we identified thirteen different heterozygous, germline, inactivating mutations in a single gene in fourteen families with HPT-JT. The proposed role of HRPT2 as a tumor suppressor was supported by mutation screening in 48 parathyroid adenomas with cystic features, which identified three somatic inactivating mutations, all located in exon 1. None of these mutations were detected in normal controls, and all were predicted to cause deficient or impaired protein function. HRPT2 is a ubiquitously expressed, evolutionarily conserved gene encoding a predicted protein of 531 amino acids, for which we propose the name parafibromin. Our findings suggest that HRPT2 is a tumor-suppressor gene, the inactivation of which is directly involved in predisposition to HPT-JT and in development of some sporadic parathyroid tumors.
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| 21. |
- Hasegawa, H., et al.
(författare)
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Kelvin-Helmholtz waves at the Earth's magnetopause : Multiscale development and associated reconnection
- 2009
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 114:12, s. A12207-
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Tidskriftsartikel (refereegranskat)abstract
- We examine traversals on 20 November 2001 of the equatorial magnetopause boundary layer simultaneously at similar to 1500 magnetic local time (MLT) by the Geotail spacecraft and at similar to 1900 MLT by the Cluster spacecraft, which detected rolled-up MHD-scale vortices generated by the Kelvin-Helmholtz instability (KHI) under prolonged northward interplanetary magnetic field conditions. Our purpose is to address the excitation process of the KHI, MHD-scale and ion-scale structures of the vortices, and the formation mechanism of the low-latitude boundary layer (LLBL). The observed KH wavelength (>4 x 10(4) km) is considerably longer than predicted by the linear theory from the thickness (similar to 1000 km) of the dayside velocity shear layer. Our analyses suggest that the KHI excitation is facilitated by combined effects of the formation of the LLBL presumably through high-latitude magnetopause reconnection and compressional magnetosheath fluctuations on the dayside, and that breakup and/or coalescence of the vortices are beginning around 1900 MLT. Current layers of thickness a few times ion inertia length similar to 100 km and of magnetic shear similar to 60 degrees existed at the trailing edges of the vortices. Identified in one such current sheet were signatures of local reconnection: Alfvenic outflow jet within a bifurcated current sheet, nonzero magnetic field component normal to the sheet, and field-aligned beam of accelerated electrons. Because of its incipient nature, however, this reconnection process is unlikely to lead to the observed dusk-flank LLBL. It is thus inferred that the flank LLBL resulted from other mechanisms, namely, diffusion and/or remote reconnection unidentified by Cluster.
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| 22. |
- Mino-Kenudson, Mari, et al.
(författare)
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The International Association for the Study of Lung Cancer Global Survey on Programmed Death-Ligand 1 Testing for NSCLC
- 2021
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Ingår i: Journal of Thoracic Oncology. - : Elsevier. - 1556-0864 .- 1556-1380. ; 16:4, s. 686-696
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) is required to determine the eligibility for pembrolizumab monotherapy in advanced NSCLC worldwide and for several other indications depending on the country. Four assays have been approved/Communaute Europeene-In vitro Diagnostic (CV-IVD)-marked, but PD-L1 IHC seems diversely implemented across regions and laboratories with the application of laboratory-developed tests (LDTs).Method: To assess the practice of PD-L1 IHC and identify issues and disparities, the International Association for the Study of Lung Cancer Pathology Committee conducted a global survey for pathologists from January to May 2019, comprising multiple questions on preanalytical, analytical, and postanalytical conditions.Result: A total of 344 pathologists from 64 countries participated with 41% from Europe, 24% from North America, and 18% from Asia. Besides biopsies and resections, cellblocks were used by 75% of the participants and smears by 11%. The clone 22C3 was most often used (69%) followed by SP263 (51%). They were applied as an LDT by 40% and 30% of the users, respectively, and 76% of the participants developed at least one LDT. Half of the participants reported a turnaround time of less than or equal to 2 days, whereas 13% reported that of greater than or equal to 5 days. In addition, quality assurance (QA), formal training for scoring, and standardized reporting were not implemented by 18%, 16%, and 14% of the participants, respectively.Conclusions: Heterogeneity in PD-L1 testing is marked across regions and laboratories in terms of antibody clones, IHC assays, samples, turnaround times, and QA measures. The lack of QA, formal training, and standardized reporting stated by a considerable minority identifies a need for additional QA measures and training opportunities.
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| 23. |
- Moreira, Andre L., et al.
(författare)
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A Grading System for Invasive Pulmonary Adenocarcinoma : A Proposal From the International Association for the Study of Lung Cancer Pathology Committee
- 2020
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Ingår i: Journal of Thoracic Oncology. - : ELSEVIER SCIENCE INC. - 1556-0864 .- 1556-1380. ; 15:10, s. 1599-1610
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: A grading system for pulmonary adenocarcinoma has not been established. The International Association for the Study of Lung Cancer pathology panel evaluated a set of histologic criteria associated with prognosis aimed at establishing a grading system for invasive pulmonary adenocarcinoma. Methods: A multi-institutional study involving multiple cohorts of invasive pulmonary adenocarcinomas was conducted. A cohort of 284 stage I pulmonary adenocarcinomas was used as a training set to identify histologic features associated with patient outcomes (recurrence-free survival [RFS] and overall survival [OS]). Receiver operating characteristic curve analysis was used to select the best model, which was validated (n = 212) and tested (n = 300, including stage I-III) in independent cohorts. Reproducibility of the model was assessed using kappa statistics. Results: The best model (area under the receiver operating characteristic curve [AUC] = 0.749 for RFS and 0.787 for OS) was composed of a combination of predominant plus high-grade histologic pattern with a cutoff of 20% for the latter. The model consists of the following: grade 1, lepidic predominant tumor; grade 2, acinar or papillary predominant tumor, both with no or less than 20% of high-grade patterns; and grade 3, any tumor with 20% or more of high-grade patterns (solid, micropapillary, or complex gland). Similar results were seen in the validation (AUC = 0.732 for RFS and 0.787 for OS) and test cohorts (AUC = 0.690 for RFS and 0.743 for OS), confirming the predictive value of the model. Interobserver reproducibility revealed good agreement (k = 0.617). Conclusions: A grading system based on the predominant and high-grade patterns is practical and prognostic for invasive pulmonary adenocarcinoma. (C) 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
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| 24. |
- Tsao, Ming Sound, et al.
(författare)
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PD-L1 Immunohistochemistry Comparability Study in Real-Life Clinical Samples : Results of Blueprint Phase 2 Project
- 2018
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Ingår i: Journal of Thoracic Oncology. - : Elsevier BV. - 1556-0864 .- 1556-1380. ; 13:9, s. 1302-1311
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The Blueprint (BP) Programmed Death Ligand 1 (PD-L1) Immunohistochemistry Comparability Project is a pivotal academic/professional society and industrial collaboration to assess the feasibility of harmonizing the clinical use of five independently developed commercial PD-L1 immunohistochemistry assays. The goal of BP phase 2 (BP2) was to validate the results obtained in BP phase 1 by using real-world clinical lung cancer samples.Methods: BP2 were conducted using 81 lung cancer specimens of various histological and sample types, stained with all five trial-validated PD-L1 assays (22C3, 28-8, SP142, SP263, and 73-10); the slides were evaluated by an international panel of pathologists. BP2 also assessed the reliability of PD-L1 scoring by using digital images, and samples prepared for cytological examination. PD-L1 expression was assessed for percentage (tumor proportional score) of tumor cell (TC) and immune cell areas showing PD-L1 staining, with TCs scored continuously or categorically with the cutoffs used in checkpoint inhibitor trials.Results: The BP2 results showed highly comparable staining by the 22C3, 28-8 and SP263 assays; less sensitivity with the SP142 assay; and higher sensitivity with the 73-10 assay to detect PD-L1 expression on TCs. Glass slide and digital image scorings were highly concordant (Pearson correlation >0.96). There was very strong reliability among pathologists in TC PD-L1 scoring with all assays (overall intraclass correlation coefficient [ICC] = 0.86–0.93), poor reliability in IC PD-L1 scoring (overall ICC = 0.18–0.19), and good agreement in assessing PD-L1 status on cytological cell block materials (ICC = 0.78–0.85).Conclusion: BP2 consolidates the analytical evidence for interchangeability of the 22C3, 28-8, and SP263 assays and lower sensitivity of the SP142 assay for determining tumor proportion score on TCs and demonstrates greater sensitivity of the 73-10 assay compared with that of the other assays.
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