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Sökning: WFRF:(Menzies Scott)

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1.
  • Kanai, M, et al. (författare)
  • 2023
  • swepub:Mat__t
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2.
  • Niemi, MEK, et al. (författare)
  • 2021
  • swepub:Mat__t
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3.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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5.
  • Blum, Andreas, et al. (författare)
  • Time to diagnosis, of melanoma: same trend in different continents
  • 2007
  • Ingår i: Journal of Cutaneous Medicine and Surgery. - : SAGE Publications. - 1203-4754 .- 1615-7109. ; 11:4, s. 137-144
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Patients and physicians both play an important role in the diagnosis of malignant melanoma. Objective: The purpose of this study was to assess important factors of delay in diagnosis at different centers and on three continents. Methods: Between October 2001 and October 2002, patients with histologically confirmed invasive melanoma were included in the study and given an established questionnaire. Recorded patients and tumor characteristics included age, sex, anatomic location, Breslow thickness, patients' awareness of the lesion and time with suspicion, and physicians' time (delay) before the operation. Results: The study included 985 patients (486 males, 499 females): 253 from Germany, 464 from Sweden, 58 from Brazil, and 210 from Australia. More females detected their lesions by themselves. The change to a darker color (21%) and enlargement of the area of the lesion (19%) were the major signs. The highest knowledge among patients that early detection may improve the outcome was found in Sweden and Australia. At each center, the media (newspaper, magazine, radio, and television) provided the best sources of information about melanoma. Twenty to 33% of all physicians initially consulted missed the melanoma diagnosis, independent of their specialty. Conclusions: There are still factors for the delay in melanoma diagnosis in different countries and continents, but the differences are rather small. The results should be included in planning prevention campaigns in this specific field and in the education of medical students, physicians of all specialties, and other health professionals.
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6.
  • Campbell, PJ, et al. (författare)
  • Pan-cancer analysis of whole genomes
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
  • 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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7.
  • Liopyris, Konstantinos, et al. (författare)
  • Expert agreement on the presence and spatial localization of melanocytic features in dermoscopy.
  • 2023
  • Ingår i: The Journal of investigative dermatology. - 1523-1747. ; 144:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Dermoscopy aids in melanoma detection; however, agreement on dermoscopic features, including those of high clinical relevance, remains poor. Herein we attempted to evaluate agreement among experts on 'exemplar images' not only for the presence of melanocytic-specific features but also for spatial localization. This was a cross-sectional, multicenter, observational study. Dermoscopy images exhibiting at least one of 31 melanocytic-specific features were submitted by 25 world experts as 'exemplars'. Using a web-based platform that allows for image mark-up of specific contrast-defined regions (superpixels), 20 expert readers annotated 248 dermoscopic images in collections of 62 images. Each collection was reviewed by five independent readers. A total of 4,507 feature observations were performed. Good-to-excellent agreement was found for 14 of 31 features (45.2%), with 8 achieving excellent agreement (Gwet's AC >0.75) and 7 of them being melanoma-specific features. These features were: 'Peppering /Granularity' (0.91); 'Shiny White Streaks' (0.89); 'Typical Pigment network' (0.83); 'Blotch Irregular' (0.82); 'Negative Network' (0.81); 'Irregular Globules' (0.78); 'Dotted Vessels' (0.77) and 'Blue Whitish Veil' (0.76). By utilizing an exemplar dataset, good-to-excellent agreement was found for 14 features that have previously been shown useful in discriminating nevi from melanoma. All images are public (www.isic-archive.com) and can be used for education, scientific communication and machine learning experiments.
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8.
  • Menzies, Scott W, et al. (författare)
  • Dermoscopic evaluation of amelanotic and hypomelanotic melanoma.
  • 2008
  • Ingår i: Archives of dermatology. - : American Medical Association (AMA). - 1538-3652 .- 0003-987X. ; 144:9, s. 1120-7
  • Tidskriftsartikel (refereegranskat)abstract
    • To determine the predictive dermoscopic features of amelanotic and hypomelanotic melanoma.
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9.
  • Menzies, Scott W, et al. (författare)
  • Dermoscopic Evaluation of Nodular Melanoma.
  • 2013
  • Ingår i: JAMA dermatology (Chicago, Ill.). - : American Medical Association (AMA). - 2168-6084 .- 2168-6068. ; 149:6, s. 699-709
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE Nodular melanoma (NM) is a rapidly progressing potentially lethal skin tumor for which early diagnosis is critical. OBJECTIVE To determine the dermoscopy features of NM. DESIGN Eighty-three cases of NM, 134 of invasive non-NM, 115 of nodular benign melanocytic tumors, and 135 of nodular nonmelanocytic tumors were scored for dermoscopy features using modified and previously described methods. Lesions were separated into amelanotic/hypomelanotic or pigmented to assess outcomes. SETTING Predominantly hospital-based clinics from 5 continents. MAIN OUTCOME MEASURES Sensitivity, specificity, and odds ratios for features/models for the diagnosis of melanoma. RESULTS Nodular melanoma occurred more frequently as amelanotic/hypomelanotic (37.3%) than did invasive non-NM (7.5%). Pigmented NM had a more frequent (compared with invasive non-NM; in descending order of odds ratio) symmetrical pigmentation pattern (5.8% vs 0.8%), large-diameter vessels, areas of homogeneous blue pigmentation, symmetrical shape, predominant peripheral vessels, blue-white veil, pink color, black color, and milky red/pink areas. Pigmented NM less frequently displayed an atypical broadened network, pigment network or pseudonetwork, multiple blue-gray dots, scarlike depigmentation, irregularly distributed and sized brown dots and globules, tan color, irregularly shaped depigmentation, and irregularly distributed and sized dots and globules of any color. The most important positive correlating features of pigmented NM vs nodular nonmelanoma were peripheral black dots/globules, multiple brown dots, irregular black dots/globules, blue-white veil, homogeneous blue pigmentation, 5 to 6 colors, and black color. A model to classify a lesion as melanocytic gave a high sensitivity (>98.0%) for both nodular pigmented and nonnodular pigmented melanoma but a lower sensitivity for amelanotic/hypomelanotic NM (84%). A method for diagnosing amelanotic/hypomelanotic malignant lesions (including basal cell carcinoma) gave a 93% sensitivity and 70% specificity for NM. CONCLUSIONS AND RELEVANCE When a progressively growing, symmetrically patterned melanocytic nodule is identified, NM needs to be excluded.
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11.
  • Russo, Teresa, et al. (författare)
  • Indications for Digital Monitoring of Patients With Multiple Nevi: Recommendations from the International Dermoscopy Society
  • 2022
  • Ingår i: Dermatology Practical and Conceptual. - : Mattioli1885. - 2160-9381. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: In patients with multiple nevi, sequential imaging using total body skin photography (TBSP) coupled with digital dermoscopy (DD) documentation reduces unnecessary excisions and improves the early detection of melanoma. Correct patient selection is essential for optimizing the efficacy of this diagnostic approach. Objectives: The purpose of the study was to identify, via expert consensus, the best indications for TBSP and DD follow-up. Methods: This study was performed on behalf of the International Dermoscopy Society (IDS). We attained consensus by using an e-Delphi methodology. The panel of participants included international experts in dermoscopy. In each Delphi round, experts were asked to select from a list of indications for TBSP and DD. Results: Expert consensus was attained after 3 rounds of Delphi. Participants considered a total nevus count of 60 or more nevi or the presence of a CDKN2A mutation sufficient to refer the patient for digital monitoring. Patients with more than 40 nevi were only considered an indication in case of personal history of melanoma or red hair and/or a MC1R mutation or history of organ transplantation. Conclusions: Our recommendations support clinicians in choosing appropriate follow-up regimens for patients with multiple nevi and in applying the time-consuming procedure of sequential imaging more efficiently. Further studies and real-life data are needed to confirm the usefulness of this list of indications in clinical practice.
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13.
  • Sinz, Christoph, et al. (författare)
  • Accuracy of dermatoscopy for the diagnosis of nonpigmented cancers of the skin.
  • 2017
  • Ingår i: Journal of the American Academy of Dermatology. - : Elsevier BV. - 1097-6787 .- 0190-9622. ; 77:6, s. 1100-1109
  • Tidskriftsartikel (refereegranskat)abstract
    • Nonpigmented skin cancer is common, and diagnosis with the unaided eye is error prone.To investigate whether dermatoscopy improves the diagnostic accuracy for nonpigmented (amelanotic) cutaneous neoplasms.We collected a sample of 2072 benign and malignant neoplastic lesions and inflammatory conditions and presented close-up images taken with and without dermatoscopy to 95 examiners with different levels of experience.The area under the curve was significantly higher with than without dermatoscopy (0.68 vs 0.64, P<.001). Among 51 possible diagnoses, the correct diagnosis was selected in 33.1% of cases with and 26.4% of cases without dermatoscopy (P<.001). For experts, the frequencies of correct specific diagnoses of a malignant lesion improved from 40.2% without to 51.3% with dermatoscopy. For all malignant neoplasms combined, the frequencies of appropriate management strategies increased from 78.1% without to 82.5% with dermatoscopy.The study deviated from a real-life clinical setting and was potentially affected by verification and selection bias.Dermatoscopy improves the diagnosis and management of nonpigmented skin cancer and should be used as an adjunct to examination with the unaided eye.
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14.
  • Tschandl, Philipp, et al. (författare)
  • Expert-Level Diagnosis of Nonpigmented Skin Cancer by Combined Convolutional Neural Networks.
  • 2019
  • Ingår i: JAMA dermatology. - : American Medical Association (AMA). - 2168-6084 .- 2168-6068. ; 55:1, s. 58-65
  • Tidskriftsartikel (refereegranskat)abstract
    • Convolutional neural networks (CNNs) achieve expert-level accuracy in the diagnosis of pigmented melanocytic lesions. However, the most common types of skin cancer are nonpigmented and nonmelanocytic, and are more difficult to diagnose.To compare the accuracy of a CNN-based classifier with that of physicians with different levels of experience.A CNN-based classification model was trained on 7895 dermoscopic and 5829 close-up images of lesions excised at a primary skin cancer clinic between January 1, 2008, and July 13, 2017, for a combined evaluation of both imaging methods. The combined CNN (cCNN) was tested on a set of 2072 unknown cases and compared with results from 95 human raters who were medical personnel, including 62 board-certified dermatologists, with different experience in dermoscopy.The proportions of correct specific diagnoses and the accuracy to differentiate between benign and malignant lesions measured as an area under the receiver operating characteristic curve served as main outcome measures.Among 95 human raters (51.6% female; mean age, 43.4 years; 95% CI, 41.0-45.7 years), the participants were divided into 3 groups (according to years of experience with dermoscopy): beginner raters (<3 years), intermediate raters (3-10 years), or expert raters (>10 years). The area under the receiver operating characteristic curve of the trained cCNN was higher than human ratings (0.742; 95% CI, 0.729-0.755 vs 0.695; 95% CI, 0.676-0.713; P<.001). The specificity was fixed at the mean level of human raters (51.3%), and therefore the sensitivity of the cCNN (80.5%; 95% CI, 79.0%-82.1%) was higher than that of human raters (77.6%; 95% CI, 74.7%-80.5%). The cCNN achieved a higher percentage of correct specific diagnoses compared with human raters (37.6%; 95% CI, 36.6%-38.4% vs 33.5%; 95% CI, 31.5%-35.6%; P=.001) but not compared with experts (37.3%; 95% CI, 35.7%-38.8% vs 40.0%; 95% CI, 37.0%-43.0%; P=.18).Neural networks are able to classify dermoscopic and close-up images of nonpigmented lesions as accurately as human experts in an experimental setting.
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15.
  • van Akkooi, Alexander C. J., et al. (författare)
  • Neoadjuvant Systemic Therapy (NAST) in Patients with Melanoma: Surgical Considerations by the International Neoadjuvant Melanoma Consortium (INMC)
  • 2022
  • Ingår i: ANNALS OF SURGICAL ONCOLOGY. - : Springer Science and Business Media LLC. - 1068-9265 .- 1534-4681. ; 29:6, s. 3694-3708
  • Tidskriftsartikel (refereegranskat)abstract
    • Exciting advances in melanoma systemic therapies have presented the opportunity for surgical oncologists and their multidisciplinary colleagues to test the neoadjuvant systemic treatment approach in high-risk, resectable metastatic melanomas. Here we describe the state of the science of neoadjuvant systemic therapy (NAST) for melanoma, focusing on the surgical aspects and the key role of the surgical oncologist in this treatment paradigm. This paper summarizes the past decade of developments in melanoma treatment and the current evidence for NAST in stage III melanoma specifically. Issues of surgical relevance are discussed, including the risk of progression on NAST prior to surgery. Technical aspects, such as the definition of resectability for melanoma and the extent and scope of routine surgery are presented. Other important issues, such as the utility of radiographic response evaluation and method of pathologic response evaluation, are addressed. Surgical complications and perioperative management of NAST related adverse events are considered. The International Neoadjuvant Melanoma Consortium has the goal of harmonizing NAST trials in melanoma to facilitate rapid advances with new approaches, and facilitating the comparison of results across trials evaluating different treatment regimens. Our ultimate goals are to provide definitive proof of the safety and efficacy of NAST in melanoma, sufficient for NAST to become an acceptable standard of care, and to leverage this platform to allow more personalized, biomarker-driven, tailored approaches to subsequent treatment and surveillance.
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