| 1. |
- Adhikari, Subash, et al.
(författare)
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A high-stringency blueprint of the human proteome
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Forskningsöversikt (refereegranskat)abstract
- The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP’s tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases.
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| 2. |
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| 3. |
- Berndsen, Marta, 1986, et al.
(författare)
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Long-term outcome after surgical resection of non-high-risk gastrointestinal stromal tumours without adjuvant therapy
- 2023
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Ingår i: The British journal of surgery. - 1365-2168. ; 110:12, s. 1857-1862
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gastrointestinal stromal tumour (GIST) is the most common intra-abdominal sarcoma. Risk classification systems, commonly the modified National Institutes of Health consensus criteria, identify tumour properties relating to patient outcomes. However, owing to limited long-term evidence, most guidelines recommend up to 10-year follow-up for all risk groups except very low-risk GIST. METHODS: This retrospective multicentre study included patients who had complete resection of primary, non-metastatic GIST from three Scandinavian sarcoma centres: Gothenburg (2004-2020), Stockholm (2000-2019), and Oslo (2000-2017). Medical records were reviewed for clinical details regarding diagnosis, treatment, and follow-up, and recurrence-free and disease-specific survival evaluated. RESULTS: The total cohort consisted of 1213 patients with GIST. High-risk patients and those treated with tyrosine kinase inhibitors were excluded. The remaining 649 patients were included in the present analysis: 118 with very low-, 381 with low-, and 150 with intermediate-risk GISTs. Five-year recurrence-free survival rates were 100, 98.5, and 100 per cent for the intermediate-, low-, and very low-risk groups respectively (P = 0.246). Disease-specific survival rates 10 years after surgery were 100, 98.4, and 100 per cent for the intermediate-, low-, and very low-risk groups respectively (P = 0.262). CONCLUSION: Patients with completely resected non-high-risk GISTs have an excellent long-term outcome, irrespective of risk group. Follow-up programmes to detect disease recurrences in these patients are probably not indicated.
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| 4. |
- Carreras-Puigvert, Jordi, et al.
(författare)
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A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family
- 2017
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- The NUDIX enzymes are involved in cellular metabolism and homeostasis, as well as mRNA processing. Although highly conserved throughout all organisms, their biological roles and biochemical redundancies remain largely unclear. To address this, we globally resolve their individual properties and inter-relationships. We purify 18 of the human NUDIX proteins and screen 52 substrates, providing a substrate redundancy map. Using crystal structures, we generate sequence alignment analyses revealing four major structural classes. To a certain extent, their substrate preference redundancies correlate with structural classes, thus linking structure and activity relationships. To elucidate interdependence among the NUDIX hydrolases, we pairwise deplete them generating an epistatic interaction map, evaluate cell cycle perturbations upon knockdown in normal and cancer cells, and analyse their protein and mRNA expression in normal and cancer tissues. Using a novel FUSION algorithm, we integrate all data creating a comprehensive NUDIX enzyme profile map, which will prove fundamental to understanding their biological functionality.
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| 5. |
- Dalin, Frida, 1984-, et al.
(författare)
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Clinical and immunological characteristics of Autoimmune Addison's disease : a nationwide Swedish multicenter study
- 2017
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:2, s. 379-389
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.
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| 6. |
- Enblom, Anneli, et al.
(författare)
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High rate of abnormal blood values and vascular complications before diagnosis of myeloproliferative neoplasms
- 2015
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Ingår i: European journal of internal medicine. - : Elsevier. - 0953-6205 .- 1879-0828. ; 26:5, s. 344-347
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Tidskriftsartikel (refereegranskat)abstract
- Background: Vascular complications occurring before the diagnosis of myeloproliferative neoplasms (MPN) in 612 patients from four centers in Sweden, Denmark and France were retrospectively studied.Results: Vascular complications were observed in 151 (25%) of the 612 patients. Of these, 66% occurred during the two years preceding diagnosis. The majority of events were thromboembolic (95%), and included myocardial infarction (n = 46), ischemic stroke (n = 43), transient ischemic attack (TIA) (n = 22), deep vein thrombosis/pulmonary embolism (n = 19), splanchnic vein thrombosis (n = 7), and peripheral embolism (n = 7). Bleeding was observed in only 7 (5%) of the 151 patients with vascular events (3 with intracranial bleeding, 2 with epistaxis and 2 with gastrointestinal bleeding). Full blood counts obtained at least 3 months prior to the MPN diagnosis showed that 269 (44%) had abnormal blood values, fulfilling the diagnostic criteria for MPN. During the time from the abnormal blood test to the diagnosis of MPN, 50 patients suffered from a vascular complication.Conclusion: We therefore conclude that a large proportion of MPN patients suffer severe thromboembolic complications prior to diagnosis. If MPN were diagnosed earlier, a large proportion of these events might be prevented. An MPN should always be suspected and ruled out in patients with unexplained elevated hematocrit, leukocyte and/or platelet counts.
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| 7. |
- Ericsson, Emma, et al.
(författare)
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Har egen upplevd sorg någon betydelse i mötet med personer i sorg inom hemsjukvården?
- 2022
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Bakgrund: I princip alla människor kommer någon gång i livet att drabbas av sorg. Sorg är en av våra starkaste känslor. Distriktssköterskan ska arbeta för att främja hälsa, förebygga ohälsa, återställa hälsa samt lindralidande. En distriktssköterska inom hemsjukvården träffar på människor i olika utsatta situationer och behöver ha en empatisk förmåga för att kunna bemöta personer i sorg. Syfte: Att belysa distriktssköterskors erfarenhet av vilken betydelse egen upplevd sorg har i mötet med personer i sorg inom hemsjukvården. Metod: Semistrukturerade intervjuer genomfördes med nio distriktssköterskor. Kvalitativ innehållsanalys med induktiv ansats har använts. Resultat: Studien resulterade i ett övergripande tema, tvåkategorier och tre underkategorier. Temat blev ” Distriktssköterskans egen erfarenhet av sorg innebär främst en tillgång i att möta sörjande men kan även vara en utmaning”, kategorierna var; Egen sorg som professionell tillgång och; Egensorg som professionell utmaning. Distriktssköterskorna upplevde främst fördelarmed egen upplevd sorg då det gav en annan förståelse för vad personer i sorg går igenom. Erfarenheten skapade en medvetenhet som underlättade fördistriktssköterskorna vid möten med personer i sorg. Dock kunde egen erfarenhet i vissa fall utgöra en utmaning. Slutsats: Distriktssköterskor förväntas ha en förmåga att vårda patienter professionellt och ur ett holistiskt perspektiv. Genom egenerfarenhet ökade medvetenheten om egna känslor, och de kunde tillåta sig bli känslosamma i mötet med personer i sorg. Det bidrar till att samtalet kan bli mer genuint. Distriktssköterskor och vårdpersonal behöver tid för reflektion och samtal kollegor emellan för att orka med arbetet i svåra situationer. Det kan bidra till hållbar utveckling, minskad risk för sjukskrivningar och att personalen i högre grad stannar kvar på sin arbetsplats.
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| 8. |
- Gnann, Christian, et al.
(författare)
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Widespread enzyme expression variations underlie diverse metabolic capacities within cell types
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Metabolic enzymes perform life-sustaining functions in various compartments of the cell. Recent studies have shown some enzymes to exhibit varied expression or localization between genetically identical cells and that this heterogeneity impacts drug resistance, metastasis, differentiation, and immune cell activation. However, no systematic analysis of metabolic cellular heterogeneity has been performed. Here, we leverage imaging-based single-cell spatial proteomic data to reveal the extent of non-genetic partitioning of the metabolic proteome. Over half of all enzymes localize to multiple cellular compartments, hinting at moonlighting potential. In addition, nearly two fifths of metabolic enzymes exhibit cell-to-cell variable expression. We demonstrate that individual cells reproduce these highly heterogeneous cell populations using clonal expansion, establishing that cells recapitulate myriad metabolic phenotypes over just a few cell divisions. To identify multifunctional moonlighting enzymes, we mine protein-protein interaction datasets to find interacting proteins with distinct functional roles, and using a timeresolved transcriptomic dataset, we find that metabolic heterogeneity arises largely independently of cell cycle progression and is established mostly post-transcriptionally or posttranslationally. Taken together, our data suggest that the heterogeneity of metabolic enzymes establish diverse cellular phenotypes, which are reflected in tissues, and which may ultimately allow targeted studies of their roles in health and disease.
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| 9. |
- Jain, Yashvardhan, et al.
(författare)
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Segmenting functional tissue units across human organs using community-driven development of generalizable machine learning algorithms
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The development of a reference atlas of the healthy human body requires automated image segmentation of major anatomical structures across multiple organs based on spatial bioimages generated from various sources with differences in sample preparation. We present the setup and results of the Hacking the Human Body machine learning algorithm development competition hosted by the Human Biomolecular Atlas (HuBMAP) and the Human Protein Atlas (HPA) teams on the Kaggle platform. We create a dataset containing 880 histology images with 12,901 segmented structures, engaging 1175 teams from 78 countries in community-driven, open-science development of machine learning models. Tissue variations in the dataset pose a major challenge to the teams which they overcome by using color normalization techniques and combining vision transformers with convolutional models. The best model will be productized in the HuBMAP portal to process tissue image datasets at scale in support of Human Reference Atlas construction.
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| 10. |
- Mahdessian, Diana, et al.
(författare)
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Spatiotemporal dissection of the cell cycle regulated human proteome
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Here we present a spatiotemporal dissection of proteome single cell heterogeneity in human cells, performed with subcellular resolution over the course of a cell cycle. We identify 17% of the human proteome to display cell-to-cell variability, of which we could attribute 25% as correlated to cell cycle progression, and present the first evidence of cell cycle association for 258 proteins. A key finding is that the variance, of many of the cell cycle associated proteins, is only partially explained by the cell cycle, which hints at cross-talk between the cell cycle and other signaling pathways. We also demonstrate that several of the identified cell cycle regulated proteins may be clinically significant in proliferative disorders. This spatially resolved proteome map of the cell cycle, integrated into the Human Protein Atlas, serves as a valuable resource to accelerate the molecular knowledge of the cell cycle and opens up novel avenues for the understanding of cell proliferation.
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