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The MM500 meta-study aims to establish a knowledge basis of the tumor proteome to serve as a complement to genome and transcriptome studies. Somatic mutations and their effect on the transcriptome have been extensively characterized in melanoma. However, the effects of these genetic changes on the proteomic landscape and the impact on cellular processes in melanoma remain poorly understood. In this study, the quantitative mass-spectrometry-based proteomic analysis is interfaced with pathological tumor characterization, and associated with clinical data. The melanoma proteome landscape, obtained by the analysis of 505 well-annotated melanoma tumor samples, is defined based on almost 16 000 proteins, including mutated proteoforms of driver genes. More than 50 million MS/MS spectra were analyzed, resulting in approximately 13,6 million peptide spectrum matches (PSMs). Altogether 13 176 protein-coding genes, represented by 366 172 peptides, in addition to 52 000 phosphorylation sites, and 4 400 acetylation sites were successfully annotated. This data covers 65% and 74% of the predicted and identified human proteome, respectively. A high degree of correlation (Pearson, up to 0.54) with the melanoma transcriptome of the TCGA repository, with an overlap of 12 751 gene products, was found. Mapping of the expressed proteins with quantitation, spatiotemporal localization, mutations, splice isoforms, and PTM variants was proven not to be predicted by genome sequencing alone. The melanoma tumor molecular map was complemented by analysis of blood protein expression, including data on proteins regulated after immunotherapy. By adding these key proteomic pillars, the MM500 study expands the knowledge on melanoma disease., (© 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

The MM500 study is an initiative to map the protein levels in malignant melanoma tumor samples, focused on in-depth histopathology coupled to proteome characterization. The protein levels and localization were determined for a broad spectrum of diverse, surgically isolated melanoma tumors originating from multiple body locations. More than 15,500 proteoforms were identified by mass spectrometry, from which chromosomal and subcellular localization was annotated within both primary and metastatic melanoma. The data generated by global proteomic experiments covered 72% of the proteins identified in the recently reported high stringency blueprint of the human proteome. This study contributes to the NIH Cancer Moonshot initiative combining detailed histopathological presentation with the molecular characterization for 505 melanoma tumor samples, localized in 26 organs from 232 patients., (© 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: Several studies have shown nickel and cobalt release from jewellery by using spot tests, but the metal composition of jewellery is largely unknown., Objectives: To evaluate the metal composition of a large worldwide sample of mainly inexpensive jewellery items, and investigate the release of nickel, cobalt and lead from a subsample by using EN 1811:1998-required methods., Methods: A total of 956 metallic jewellery components were examined with X-ray fluorescence spectroscopy. A subsample of 96 jewellery items purchased in the United States were investigated for nickel, cobalt and lead release by the use of artificial sweat immersion and plasma optical emission spectroscopy., Results: Eighteen elements were detected. The 10 most frequently occurring were, in order of frequency, copper, iron, zinc, nickel, silver, chromium, tin, manganese, lead, and cobalt. Release of nickel was noted from 79 of the 96 US samples (0.01-98 µg/cm(2) /week), release of cobalt from 35 samples (0.02-0.5 µg/cm(2) /week), and release of lead from 37 samples (0.03-2718 µg/cm(2) /week)., Conclusions: We present here a comprehensive list of the most frequently encountered metals in jewellery and fashion accessories. Different allergenic and non-allergenic metals are utilized. We also report the frequent release of nickel, cobalt and lead from these objects, despite legislative restrictions., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The pathogenesis of total joint replacement failure is multifactorial. One hypothesis suggests that corrosion and wear of alloys result in metal ion release, which may then cause sensitization and even implant failure, owing to the acquired immune reactivity., Objectives: To assess cobalt, nickel and chromium(VI) release from, and the metal composition of, failed metal-on-ethylene total hip replacements., Materials/methods: Implant components from 52 revision cases were evaluated with spot tests for free nickel, cobalt, and chromium (VI) ions. Implant composition was determined with X-ray fluorescence spectroscopy, and information on the reason for revision and complications in relation to surgery was collected from the medical charts when possible (72%). For 10 implants, corrosion was further characterized with scanning electron microscopy., Results: We detected cobalt release from three of 38 removed femoral heads and from one of 24 femoral stems. Nickel release was detected from one of 24 femoral stems. No chromium(VI) release was detected., Conclusions: We found that cobalt and nickel were released from some failed total hip arthroplasties, and corrosion was frequently observed. Metal ions and particles corroded from metal-on-polyethylene may play a role in the complex aetiopathology of implant failure., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Man-made vitreous fibres (MMVFs) are used in products for insulation and as reinforcement in materials. Contamination of the skin may arise through direct or indirect contact, and from the deposition of airborne fibres. The scientific basis regarding the effects on skin of MMVFs dates from 1970-1980., Objectives: To investigate whether currently used insulation MMVF products still cause skin discomfort., Methods: Focus group interviews and structured interviews were performed among workers engaged in insulation tasks and among do-it-yourself consumers with a recent experience of MMVF products., Results: A majority of interviewees experienced skin discomfort when handling MMVF products. Complaints caused by traditional (yellow) glass fibre products were more severe than those caused by products of rock or slag wool fibres. The wrists, forearms, neck and face were the locations where the skin was most affected. The situations causing problems varied between occupational tasks, but working with the hands over the head or in narrow spaces were described as the worst situations. Building construction apprentices performed insulation tasks more often than senior workers., Conclusions: MMVF insulation products do still cause skin discomfort. Updated knowledge about people's experiences of work with such products should influence legislation., (© 2014 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Background: The objectives and goals of the Southern Swedish Malignant Melanoma (SSMM) are to develop, build and utilize cutting edge biobanks and OMICS platforms to better understand disease pathology and drug mechanisms. The SSMM research team is a truly cross-functional group with members from oncology, surgery, bioinformatics, proteomics, and genomics initiatives. Within the research team there are members who daily diagnose patients with suspect melanomas, do follow-ups on malignant melanoma patients and remove primary or metastatic lesions by surgery. This inter-disciplinary clinical patient care ensures a competence build as well as a best practice procedure where the patient benefits., Methods: Clinical materials from patients before, during and after treatments with clinical end points are being collected. Tissue samples as well as bio-fluid samples such as blood fractions, plasma, serum and whole blood will be archived in 384-high density sample tube formats. Standardized approaches for patient selections, patient sampling, sample-processing and analysis platforms with dedicated protein assays and genomics platforms that will hold value for the research community are used. The patient biobank archives are fully automated with novel ultralow temperature biobank storage units and used as clinical resources., Results: An IT-infrastructure using a laboratory information management system (LIMS) has been established, that is the key interface for the research teams in order to share and explore data generated within the project. The cross-site data repository in Lund forms the basis for sample processing, together with biological samples in southern Sweden, including blood fractions and tumor tissues. Clinical registries are associated with the biobank materials, including pathology reports on disease diagnosis on the malignant melanoma (MM) patients., Conclusions: We provide data on the developments of protein profiling and targeted protein assays on isolated melanoma tumors, as well as reference blood standards that is used by the team members in the respective laboratories. These pilot data show biobank access and feasibility of performing quantitative proteomics in MM biobank repositories collected in southern Sweden. The scientific outcomes further strengthen the build of healthcare benefit in the complex challenges of malignant melanoma pathophysiology that is addressed by the novel personalized medicines entering the market.

Background: The accuracy of the dimethylglyoxime (DMG) nickel spot test has been questioned because of false negative and positive test reactions. The EN 1811, a European standard reference method developed by the European Committee for Standardization (CEN), is fine-tuned to estimate nickel release around the limit value of the EU Nickel Directive from products intended to come into direct and prolonged skin contact. Because assessments according to EN 1811 are expensive to perform, time consuming, and may destruct the test item, it should be of great value to know the accuracy of the DMG screening test., Objectives: To evaluate the sensitivity and specificity of the DMG test., Methods: DMG spot testing, chemical analysis according to the EN 1811 reference method, and X-ray fluorescence spectroscopy (XRF) were performed concomitantly on 96 metallic components from earrings recently purchased in San Francisco., Results: The sensitivity of the DMG test was 59.3% and the specificity was 97.5% based on DMG-test results and nickel release concentrations determined by the EN 1811 reference method., Conclusions: The DMG test has a high specificity but a modest sensitivity. It may serve well for screening purposes. Past exposure studies may have underestimated nickel release from consumer items.