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Sökning: WFRF:(Lindskog H.)

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1.
  • Guerova, G., et al. (författare)
  • National Status Reports
  • 2020
  • Ingår i: Advanced GNSS Tropospheric Products for Monitoring Severe Weather Events and Climate. - Cham : Springer International Publishing. - 9783030139001 ; , s. 403-481
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • In this section a summary of the national progress reports is given. GNSS4SWEC Management Committee (MC) members provided outline of the work conducted in their countries combining input from different partners involved. In the COST Action paticipated member from 32 COST countries, 1 Near Neighbour Country and 8 Intrantional Partners from Australia, Canada, Hong Kong and USA. The text reflects the state as of 1 January 2018.
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  • Omenn, Gilbert S., et al. (författare)
  • The 2022 Report on the Human Proteome from the HUPO Human Proteome Project
  • 2023
  • Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 22:4, s. 1024-1042
  • Tidskriftsartikel (refereegranskat)abstract
    • The 2022 Metrics of the Human Proteome from the HUPO Human Proteome Project (HPP) show that protein expression has now been credibly detected (neXtProt PE1 level) for 18 407 (93.2%) of the 19 750 predicted proteins coded in the human genome, a net gain of 50 since 2021 from data sets generated around the world and reanalyzed by the HPP. Conversely, the number of neXtProt PE2, PE3, and PE4 missing proteins has been reduced by 78 from 1421 to 1343. This represents continuing experimental progress on the human proteome parts list across all the chromosomes, as well as significant reclassifications. Meanwhile, applying proteomics in a vast array of biological and clinical studies continues to yield significant findings and growing integration with other omics platforms. We present highlights from the Chromosome-Centric HPP, Biology and Disease-driven HPP, and HPP Resource Pillars, compare features of mass spectrometry and Olink and Somalogic platforms, note the emergence of translation products from ribosome profiling of small open reading frames, and discuss the launch of the initial HPP Grand Challenge Project, “A Function for Each Protein”.
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  • Omenn, Gilbert S., et al. (författare)
  • The 2023 Report on the Proteome from the HUPO Human Proteome Project
  • 2024
  • Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 23:2, s. 532-549
  • Forskningsöversikt (refereegranskat)abstract
    • Since 2010, the Human Proteome Project (HPP), the flagship initiative of the Human Proteome Organization (HUPO), has pursued two goals: (1) to credibly identify the protein parts list and (2) to make proteomics an integral part of multiomics studies of human health and disease. The HPP relies on international collaboration, data sharing, standardized reanalysis of MS data sets by PeptideAtlas and MassIVE-KB using HPP Guidelines for quality assurance, integration and curation of MS and non-MS protein data by neXtProt, plus extensive use of antibody profiling carried out by the Human Protein Atlas. According to the neXtProt release 2023-04-18, protein expression has now been credibly detected (PE1) for 18,397 of the 19,778 neXtProt predicted proteins coded in the human genome (93%). Of these PE1 proteins, 17,453 were detected with mass spectrometry (MS) in accordance with HPP Guidelines and 944 by a variety of non-MS methods. The number of neXtProt PE2, PE3, and PE4 missing proteins now stands at 1381. Achieving the unambiguous identification of 93% of predicted proteins encoded from across all chromosomes represents remarkable experimental progress on the Human Proteome parts list. Meanwhile, there are several categories of predicted proteins that have proved resistant to detection regardless of protein-based methods used. Additionally there are some PE1–4 proteins that probably should be reclassified to PE5, specifically 21 LINC entries and ∼30 HERV entries; these are being addressed in the present year. Applying proteomics in a wide array of biological and clinical studies ensures integration with other omics platforms as reported by the Biology and Disease-driven HPP teams and the antibody and pathology resource pillars. Current progress has positioned the HPP to transition to its Grand Challenge Project focused on determining the primary function(s) of every protein itself and in networks and pathways within the context of human health and disease.
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  • Tanskanen, T., et al. (författare)
  • Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci
  • 2018
  • Ingår i: International Journal of Cancer. - Stockholm : Wiley. - 0020-7136 .- 1097-0215. ; 142:3, s. 540-546
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer (CRC), but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 CRC cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism (SNP) rs992157 (2q35) and CRC was independently replicated (p=2.08 x 10(-4); OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p=1.50 x 10(-9); OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3 and 20q13.33 were associated with CRC in the Finnish population (false discovery rate<0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of CRC and identify shared risk alleles between the Finnish population isolate and outbred populations.
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  • Edlund, Karolina, et al. (författare)
  • CD99 is a novel prognostic stromal marker in non-small cell lung cancer
  • 2012
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 131:10, s. 2264-2273
  • Tidskriftsartikel (refereegranskat)abstract
    • The complex interaction between cancer cells and the microenvironment plays an essential role in all stages of tumourigenesis. Despite the significance of this interplay, alterations in protein composition underlying tumourstroma interactions are largely unknown. The aim of this study was to identify stromal proteins with clinical relevance in non-small cell lung cancer (NSCLC). A list encompassing 203 stromal candidate genes was compiled based on gene expression array data and available literature. The protein expression of these genes in human NSCLC was screened using the Human Protein Atlas. Twelve proteins were selected that showed a differential stromal staining pattern (BGN, CD99, DCN, EMILIN1, FBN1, PDGFRB, PDLIM5, POSTN, SPARC, TAGLN, TNC and VCAN). The corresponding antibodies were applied on tissue microarrays, including 190 NSCLC samples, and stromal staining was correlated with clinical parameters. Higher stromal expression of CD99 was associated with better prognosis in the univariate (p = 0.037) and multivariate (p = 0.039) analysis. The association was independent from the proportion of tumour stroma, the fraction of inflammatory cells and clinical and pathological parameters like stage, performance status and tumour histology. The prognostic impact of stromal CD99 protein expression was confirmed in an independent cohort of 240 NSCLC patients (p = 0.008). Furthermore, double-staining confocal fluorescence microscopy showed that CD99 was expressed in stromal lymphocytes as well as in cancer-associated fibroblasts. Based on a comprehensive screening strategy the membrane protein CD99 was identified as a novel stromal factor with clinical relevance. The results support the concept that stromal properties have an important impact on tumour progression.
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  • Fagerberg, Linn, et al. (författare)
  • Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics
  • 2014
  • Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 13:2, s. 397-406
  • Tidskriftsartikel (refereegranskat)abstract
    • Global classification of the human proteins with regards to spatial expression patterns across organs and tissues is important for studies of human biology and disease. Here, we used a quantitative transcriptomics analysis (RNA-Seq) to classify the tissue-specific expression of genes across a representative set of all major human organs and tissues and combined this analysis with antibody- based profiling of the same tissues. To present the data, we launch a new version of the Human Protein Atlas that integrates RNA and protein expression data corresponding to 80% of the human protein-coding genes with access to the primary data for both the RNA and the protein analysis on an individual gene level. We present a classification of all human protein-coding genes with regards to tissue-specificity and spatial expression pattern. The integrative human expression map can be used as a starting point to explore the molecular constituents of the human body.
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  • Fischer Hübner, Simone, et al. (författare)
  • Self-determination in the Mobile Internet
  • 2002
  • Konferensbidrag (refereegranskat)abstract
    • Mobile Internet environments will offer a whole new range of services that might revolutionize our way of life. However, with these new technologies and services new risks to the users privacy arise, and both legal and technical privacy safeguards are needed to protect the user. This paper discusses privacy and privacy risks in the mobile Internet and presents the result of the PiMI prototype project, in which one browser built-in, and one proxy- based P3P user agent for mobile Internet environments have been developed. The PiMI prototype enhances the users control over the dissemination of user and user-device related information and thus protects their right for informational self-determination.
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  • Fischer Hübner, Simone, et al. (författare)
  • Teaching Privacy-Enhancing Technologies
  • 2001
  • Konferensbidrag (refereegranskat)abstract
    • This paper discusses the increasing relevance of privacy-enhancing technologies (PET) and the importance of teaching PET within IT-security curricula. A structure for a PET course is presented, which can be used for designing PET overview courses or PET introductory lectures
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  • Ghanipour, Lana, et al. (författare)
  • Efficacy of hyperthermic intraperitoneal chemotherapy in colorectal cancer : A phase I and III open label randomized controlled registry-based clinical trial protocol
  • 2024
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 19:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Standard treatment for patient with peritoneal metastases from colorectal cancer is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In recent years, the efficacy of oxaliplatin-based HIPEC has been challenged. An intensified HIPEC (oxaliplatin+irinotecan) in combination with early postoperative intraperitoneal chemotherapy (EPIC) has shown increased recurrence-free survival in retrospective studies. The aim of this trial is to develop a new HIPEC/EPIC regimen and evaluate its effect on morbidity, oncological outcome, and quality-of-life (QoL). This study is designed as a combined phase I/III multicenter randomized trial (RCT) of patients with peritoneal metastases from colorectal cancer eligible for CRS-HIPEC. An initial phase I dose escalation study, designed as a 3+3 stepwise escalation, will determine the maximum tolerable dose of 5-Fluorouracil (5-FU) as 1-day EPIC, enrolling a total of 15–30 patients in 5 dose levels. In the phase III efficacy study, patients are randomly assigned intraoperatively to either the standard treatment with oxaliplatin HIPEC (control arm) or oxaliplatin/irinotecan-HIPEC in combination with single dose of 1-day 5-FU EPIC (experimental arm). 5-FU is administered intraoperatively after CRS-HIPEC and closure of the abdomen. The primary endpoint is 12-month recurrence-free survival. Secondary endpoints include 5-year overall survival, 5-year recurrence-free survival (registry based), postoperative complications, and QoL up to 3 years after study treatment. This phase I/III trial aims to identify a more effective treatment of colorectal peritoneal metastases by combination of HIPEC and EPIC.
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  • Iwaya, Leonardo H., et al. (författare)
  • Firewall Usability and Visualization : A Systematic Literature Review
  • 2016
  • Rapport (refereegranskat)abstract
    • Firewalls are network security components that allow administrators to handle incoming and outgoing traffic based on a set of rules. Such security appliances are typically the first line of defense, creating a barrier between organization’s internal network and the outside network (e.g., Internet). The process of correctly configuring a firewall is complex and error prone, and it only gets worse as the complexity of the network grows. A vulnerable firewall configuration will very likely result in major threats to the organization’s security. In this report we aim to investigate how to make administrator task of planning and implementing firewall solutions easier, from the stand points of usability and visualization. Our scientific investigation starts with the understanding of the state-of-the-art on this specific field. To do so, we conducted a Systematic Literature Review (SLR), a strict methodology to plan a literature review, to gather relevant information, to synthesize and compare approaches, and to report findings. During the initial search process thousands of papers were screened, leading us to 125 papers carefully selected for further readings. In the secondary study, ten relevant works were identified and assessed, in which authors tackled the issues of usability and visualization for Firewalls and Personal Firewalls. Among the main findings, we perceive that there is a lack (or even absence) of user studies to validate the proposed models. This leads us to a series of unwarranted solutions, that need to be prototyped and tested with real users. We also see an huge opportunity for integrative approaches, that could combine firewall research areas, such as automatic anomaly detection, advisory systems, and varying visualization schemes.
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  • Jounger, SL, et al. (författare)
  • Repeated buffered acidic saline infusion in the human masseter muscle as a putative experimental pain model
  • 2019
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 15474-
  • Tidskriftsartikel (refereegranskat)abstract
    • This study investigated if repeated buffered acidic saline infusions into the masseter muscles induced muscle pain and mechanical sensitization. Fourteen healthy men participated in this double-blind, randomized, and placebo-controlled study. Two repeated infusions (day 1 and 3) were given in the masseter muscles with either a buffered acidic saline solution (pH 5.2) or an isotonic saline solution (pH 6) as control. After 10 days of wash-out, the experiment was repeated with the other substance. Pressure pain thresholds (PPT), pain intensity, maximum unassisted mouth opening (MUO), and pain drawings were assessed before, directly following, and after each infusion at 5, 15, and 30 min and on day 4 and 7. Fatigue and pain intensity were assessed after a one-minute chewing test 30 min after infusions and day 4 and 7. Acidic saline induced higher pain intensity than control day 3 up to 5 min after infusions, but did not affect PPT. The chewing test did not evoke higher fatigue during chewing or MUO or after acidic saline infusion compared to control. Repeated acidic saline infusions in the masseter muscles induced a short-lasting muscle pain without mechanical hyperalgesia or functional pain. Hence, this model might not be superior to already existing experimental muscle pain models.
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  • Larsson, Karin, et al. (författare)
  • Novel antigen design for the generation of antibodies to G-protein-coupled receptors
  • 2011
  • Ingår i: JIM - Journal of Immunological Methods. - : Elsevier BV. - 0022-1759 .- 1872-7905. ; 370:1-2, s. 14-23
  • Tidskriftsartikel (refereegranskat)abstract
    • Antibodies are important tools for the study of G-protein-coupled receptors, key proteins in cellular signaling. Due to their large hydrophobic membrane spanning regions and often very short loops exposed on the surface of the cells, generation of antibodies able to recognize the receptors in the endogenous environment has been difficult. Here, we describe an antigen-design method where the extracellular loops and N-terminus are combined to a single antigen for generation of antibodies specific to three selected GPCRs: NPY5R, B2ARN and GLP1R. The design strategy enabled straightforward antigen production and antibody generation. Binding of the antibodies to intact receptors was analyzed using flow cytometry and immunofluorescence based confocal microscopy on A-431 cells overexpressing the respective GPCR. The antibody-antigen interactions were characterized using epitope mapping, and the antibodies were applied in immunohistochemical staining of human tissues. Most of the antibodies showed specific binding to their respective overexpressing cell line but not to the non-transfected cells, thus indicating binding to their respective target receptor. The epitope mapping showed that sub-populations within the purified antibody pool recognized different regions of the antigen. Hence, the genetic combination of several different epitopes enables efficient generation of specific antibodies with potential use in several applications for the study of endogenous receptors.
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  • Lindskog, Annika, 1979, et al. (författare)
  • Risk-taking and others Does the social reference point matter?
  • 2022
  • Ingår i: Journal of Risk and Uncertainty. - : Springer Science and Business Media LLC. - 0895-5646 .- 1573-0476. ; 64, s. 287-307
  • Tidskriftsartikel (refereegranskat)abstract
    • Real-life risk decisions are taken in a social context. However, we still know little about how that affects risk decisions. We have experimentally investigated the effect of social comparison on risk taking. We designed an experiment that allows us to isolate social comparison from other channels whereby the social context can affect risk decisions. The design also allows us to find impacts of the social reference point both if the individual cares about the distance to the social reference point and if she cares about her rank. Thus, we compare risk-taking in isolation to risk-taking with various exogenously imposed social reference points. We find that risk-taking is affected by the desire to get ahead of others, both when the social reference point is within reach (rank can be affected) and when it is out of reach (rank cannot be affected). Our results suggest that people do not only care about rank but also care about the distance to the social reference point.
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  • Lindskog, H., et al. (författare)
  • Taking Charge of Profile Conveyance
  • 2002
  • Konferensbidrag (refereegranskat)abstract
    • The Mobile Internet offers a new range of services that revolutionize the way we use the Internet. In order to cater for these services, personal information is used extensively, which raises new risks to the users' privacy. Managing these risks require a holistic approach - comprising technical solutions and a comprehensive legal framework. This paper discusses legal privacy requirements for the Mobile Internet, the potential risks, and describes how the Platform for Privacy Preferences Project (P3P) Protocol can be used to meet the legal and ethical requirement of the user's prior informed consent for data delivery, processing, collection and redistribution, which will not only enhance the user's privacy and particularly her right to informational self-determination, but also ease data delivery
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  • Lindskog, Magnus, et al. (författare)
  • Ilixadencel, a Cell-based Immune Primer, plus Sunitinib Versus Sunitinib Alone in Metastatic Renal Cell Carcinoma: A Randomized Phase 2 Study
  • 2022
  • Ingår i: European Urology Open Science. - : Elsevier BV. - 2666-1691 .- 2666-1683. ; 40, s. 38-45
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The prognosis of patients with synchronous metastatic renal cell carcinoma (mRCC) is poor. Whereas single-agent tyrosine kinase inhibition (TKI) is clearly insufficient, the effects can be enhanced by combinations with immune checkpoint inhibitors. Innovative treatment options combining TKI and other immune-stimulating agents could prove beneficial. Objective: To evaluate the clinical effects on metastatic disease when two doses of allogeneic monocyte-derived dendritic cells (ilixadencel) are administrated intratumorally followed by nephrectomy and treatment with sunitinib compared with nephrectomy and sunitinib monotherapy, in patients with synchronous mRCC. Design, setting, and participants: A randomized (2:1) phase 2 multicenter trial enrolled 88 patients with newly diagnosed mRCC to treatment with the combination ilixadencel/sunitinib (ILIXA/SUN; 58 patients) or sunitinib alone (SUN; 30 patients).Outcome measurements and statistical analysis: The primary endpoints were 18mo survival rate and overall survival (OS). A secondary endpoint was objective response rate (ORR) assessed up to 18 mo after enrollment. Statistic evaluations included Kaplan-Meier estimates, log-rank tests, Cox regression, and stratified Cochran-Mantel-Haenszel tests.Results and limitations: The median OS was 35.6 mo in the ILIXA/SUN arm versus 25.3 mo in the SUN arm (hazard ratio 0.73, 95% confidence interval 0.42-1.27; p = 0.25), while the 18-mo OS rates were 63% and 66% in the ILIXA/SUN and SUN arms, respectively. The confirmed ORR in the ILIXA/SUN arm were 42.2% (19/45), including three patients with complete response, versus 24.0% (six/25) in the SUN arm (p = 0.13) without complete responses. The study was not adequately powered to detect modest differences in survival. Conclusions: The study failed to meet its primary endpoints. However, ilixadencel in combination with sunitinib was associated with a numerically higher, nonsignificant, confirmed response rate, including complete responses, compared with sunitinib monotherapy.Patient summary: We studied the effects of intratumoral vaccination with ilixadencel followed by sunitinib versus sunitinib only in a randomized phase 2 study. The combination treatment showed numerically higher numbers of confirmed responses, suggesting an immunologic effect.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).
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  • Lindskog, Stefan, et al. (författare)
  • [Phenotypic expression of a mutation in MEN 2A documented in a family in the western part of Sweden]. : Fenotypiskt uttryck av mutation vid MEN 2A kartlagd i västsvensk familj.
  • 2001
  • Ingår i: Lakartidningen. - 0023-7205. ; 98:35
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • A missense mutation at codon 618 of the RET proto-oncogene is a rather unusual cause of multiple endocrine neoplasia 2A. We report the phenotypic expression of this specific RET mutation in a large Swedish family. The family was mapped back to the 18th century. Since 1971 the family has been included in a biochemical screening program, and since 1994 has undergone genetic screening. Twenty-seven individuals were found to have medullary thyroid carcinoma (MTC). Eighteen were detected by screening. The incidence of pheochromocytoma (4%) and hyperparathyroidism (7%) was low. Five individuals died of MTC, but of these none had been included in the screening program. One patient underwent prophylactic thyroidectomy after positive genetic screening. MTC tumor aggressivity differed markedly between gene carriers. The screening program shows that the clinical aggressivity of MTC can be mitigated by early and adequate surgical intervention.
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  • Mahdessian, Diana, et al. (författare)
  • Spatiotemporal dissection of the cell cycle with single-cell proteogenomics
  • 2021
  • Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 590:7847
  • Tidskriftsartikel (refereegranskat)abstract
    • Spatial and temporal variations among individual human cell proteomes are comprehensively mapped across the cell cycle using proteomic imaging and transcriptomics. The cell cycle, over which cells grow and divide, is a fundamental process of life. Its dysregulation has devastating consequences, including cancer(1-3). The cell cycle is driven by precise regulation of proteins in time and space, which creates variability between individual proliferating cells. To our knowledge, no systematic investigations of such cell-to-cell proteomic variability exist. Here we present a comprehensive, spatiotemporal map of human proteomic heterogeneity by integrating proteomics at subcellular resolution with single-cell transcriptomics and precise temporal measurements of individual cells in the cell cycle. We show that around one-fifth of the human proteome displays cell-to-cell variability, identify hundreds of proteins with previously unknown associations with mitosis and the cell cycle, and provide evidence that several of these proteins have oncogenic functions. Our results show that cell cycle progression explains less than half of all cell-to-cell variability, and that most cycling proteins are regulated post-translationally, rather than by transcriptomic cycling. These proteins are disproportionately phosphorylated by kinases that regulate cell fate, whereas non-cycling proteins that vary between cells are more likely to be modified by kinases that regulate metabolism. This spatially resolved proteomic map of the cell cycle is integrated into the Human Protein Atlas and will serve as a resource for accelerating molecular studies of the human cell cycle and cell proliferation.
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  • Naguib, Mahmoud, et al. (författare)
  • A Comparison of Host Responses to Infection with Wild-Type Avian Influenza Viruses in Chickens and Tufted Ducks
  • 2023
  • Ingår i: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497. ; 11:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Cross-species transmission of influenza A virus (IAV) from wild waterfowl to poultry is the first step in a chain of events that can ultimately lead to exposure and infection of humans. Herein, we study the outcome of infection with eight different mallard-origin IAV subtypes in two different avian hosts: tufted ducks and chickens. We found that infection and shedding patterns as well as innate immune responses were highly dependent on viral subtypes, host species, and inoculation routes. For example, intraoesophageal inoculation, commonly used in mallard infection experiments, resulted in no infections in contrast to oculonasal inoculation, suggesting a difference in transmission routes. Despite H9N2 being endemic in chickens, inoculation of mallard-origin H9N2 failed to cause viable infection beyond 1 day postinfection in our study design. The innate immune responses were markedly different in chickens and tufted ducks, and despite the presence of retinoic acid-inducible gene-I (RIG-I) in tufted duck transcriptomes, it was neither up nor downregulated in response to infection. Overall, we have revealed the heterogeneity of infection patterns and responses in two markedly different avian hosts following a challenge with mallard-origin IAV. These virus-host interactions provide new insights into important aspects of interspecies transmission of IAV.IMPORTANCE Our current findings highlight important aspects of IAV infection in birds that have implications for our understanding of its zoonotic ecology. In contrast to mallards where the intestinal tract is the main site of IAV replication, chickens and tufted ducks show limited or no signs of intestinal infection suggesting that the fecal-oral transmission route might not apply to all bird IAV host species. Our results indicate that mallard-origin IAVs undergo genetic changes upon introduction into new hosts, suggesting rapid adaptation to a new environment. However, similar to the mallard, chickens and tufted ducks show a limited immune response to infection with low pathogenic avian influenza viruses. These findings and future studies in different IAV hosts are important for our understanding of barriers to IAV transmission between species and ultimately from the wild reservoir to humans. Our current findings highlight important aspects of IAV infection in birds that have implications for our understanding of its zoonotic ecology. In contrast to mallards where the intestinal tract is the main site of IAV replication, chickens and tufted ducks show limited or no signs of intestinal infection suggesting that the fecal-oral transmission route might not apply to all bird IAV host species.
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41.
  • Nilsson, M., et al. (författare)
  • Privacy Enhancements in the Mobile Internet
  • 2001
  • Konferensbidrag (refereegranskat)abstract
    • While the mobile Internet makes available location-based as well as other useful services to the mobile users, risks to the users privacy have to be taken into consideration as well. Personal user data, such as traffic data, location data, device and user specific capability and preference information, and content data is exposed at different sites, such as the WAP Gateway/Proxy or the Origin Servers sites. In this paper, we first define privacy and basic privacy requirements and analyze privacy risks in the mobile Internet environment. We especially investigate those generated by the use of device and user specific profiles. Furthermore, we discuss technical means for enhancing privacy. Particularly, we show how the Platform for Privacy Preferences Project (P3P) protocol can be used to enforce the users control over the release of location data and capability and preference information, and how it can be enhanced.
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42.
  • Omenn, Gilbert S., et al. (författare)
  • Progress Identifying and Analyzing the Human Proteome : 2021 Metrics from the HUPO Human Proteome Project
  • 2021
  • Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 20:12, s. 5227-5240
  • Tidskriftsartikel (refereegranskat)abstract
    • The 2021 Metrics of the HUPO Human Proteome Project (HPP) show that protein expression has now been credibly detected (neXtProt PE1 level) for 18 357 (92.8%) of the 19 778 predicted proteins coded in the human genome, a gain of 483 since 2020 from reports throughout the world reanalyzed by the HPP. Conversely, the number of neXtProt PE2, PE3, and PE4 missing proteins has been reduced by 478 to 1421. This represents remarkable progress on the proteome parts list. The utilization of proteomics in a broad array of biological and clinical studies likewise continues to expand with many important findings and effective integration with other omics platforms. We present highlights from the Immunopeptidomics, Glycoproteomics, Infectious Disease, Cardiovascular, MusculoSkeletal, Liver, and Cancers B/D-HPP teams and from the Knowledge-base, Mass Spectrometry, Antibody Profiling, and Pathology resource pillars, as well as ethical considerations important to the clinical utilization of proteomics and protein biomarkers.
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  • Sinclair, Georges, et al. (författare)
  • Adaptive radiosurgery based on two simultaneous dose prescriptions in the management of large renal cell carcinoma brain metastases in critical areas: Towards customization
  • 2020
  • Ingår i: Surgical Neurology International. - : Scientific Scholar. - 2229-5097 .- 2152-7806. ; 11, s. 21-21
  • Forskningsöversikt (refereegranskat)abstract
    • The long-term benefits of local therapy in metastatic renal cell carcinoma (mRCC) have been widely documented. In this context, single fraction gamma knife radiosurgery (SF-GKRS) is routinely used in the management of brain metastases. However, SF-GKRS is not always feasible due to volumetric and regional constraints. We intend to illustrate how a dose-volume adaptive hypofractionated GKRS technique based on two concurrent dose prescriptions termed rapid rescue radiosurgery (RRR) can be utilized in this particular scenario.Case Description:A 56-year-old man presented with left-sided hemiparesis; the imaging showed a 13.1 cc brain metastasis in the right central sulcus (Met 1). Further investigation confirmed the histology to be a metastatic clear cell RCC. Met 1 was treated with upfront RRR. Follow-up magnetic resonance imaging (MRI) at 10 months showed further volume regression of Met 1; however, concurrently, a new 17.3 cc lesion was reported in the boundaries of the left frontotemporal region (Met 2) as well as a small metastasis (<1 cc) in the left temporal lobe (Met 3). Met 2 and Met 3 underwent RRR and SF-GKRS, respectively.Results:Gradual and sustained tumor ablation of Met 1 and Met 2 was demonstrated on a 20 months long follow- up. The patient succumbed to extracranial disease 21 months after the treatment of Met 1 without evidence of neurological impairment post-RRR.Conclusion:Despite poor prognosis and precluding clinical factors (failing systemic treatment, eloquent location, and radioresistant histology), RRR provided optimal tumor ablation and salvage of neurofunction with limited toxicity throughout follow-up.
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44.
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45.
  • Staf, H., et al. (författare)
  • Numerical implementation of an advanced powder-die frictional model
  • 2019
  • Ingår i: Euro PM 2019 Congress and Exhibition. - : European Powder Metallurgy Association (EPMA).
  • Konferensbidrag (refereegranskat)abstract
    • It is known that the shape of a cutting insert blank, after pressing and sintering, can be predicted with FE-simulations. It is also known that such simulations have the potential to save costs and time when used for press tool compensation. In such simulations, the frictional behaviour has a great impact. Here, two frictional models are discussed and implemented into FEM. The results from the different frictional descriptions, when for instance analysing density after compaction, shows a clear difference. It can be concluded that friction also at low forces must be modelled in detail.
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46.
  • Stenman, Maria, M.D. 1987-, et al. (författare)
  • Metastatic renal cell carcinoma to the brain : optimizing patient selection for gamma knife radiosurgery
  • 2021
  • Ingår i: Acta Neurochirurgica. - : Springer Nature. - 0001-6268 .- 0942-0940. ; 163:2, s. 333-342
  • Tidskriftsartikel (refereegranskat)abstract
    • IntroductionThe effects of single-fraction gamma knife radiosurgery (sf-GKRS) on patients with renal cell carcinoma (RCC) brain metastases (BM) in the era of targeted agents (TA) and immune checkpoint inhibitors (ICI) are insufficiently studied.Methods and materialsClear cell metastatic RCC patients treated with sf-GKRS due to BM in 2005–2014 at three European centres were retrospectively analysed (n = 43). Median follow-up was 56 months. Ninety-five percent had prior nephrectomy, 53% synchronous metastasis and 86% extracranial disease at first sf-GKRS. Karnofsky performance status (KPS) ranged from 60 to 100%. Outcome measures were overall survival (OS), local control (LC) and adverse radiation effects (ARE).ResultsOne hundred and ninety-four targets were irradiated. The median number of targets at first sf-GKRS was two. The median prescription dose was 22.0 Gy. Thirty-seven percent had repeated sf-GKRS. Eighty-eight percent received TA. LC rates at 12 and 18 months were 97% and 90%. Median OS from the first sf-GKRS was 15.7 months. Low serum albumin (HR for death 5.3), corticosteroid use pre-sf-GKRS (HR for death 5.8) and KPS < 80 (HR for death 9.1) were independently associated with worse OS. No further prognostic information was gleaned from MSKCC risk group, synchronous metastasis, age, number of BM or extracranial metastases. Other prognostic scores for BM radiosurgery, including DS-GPA, renal-GPA, LLV-SIR and CITV-SIR, again, did not add further prognostic value. ARE were seldom symptomatic and were associated with tumour volume, 10-Gy volume and pre-treatment perifocal oedema. ARE were less common among patients treated with TA within 1 month of sf-GKRS.ConclusionsWe identified albumin, corticosteroid use and KPS as independent prognostic factors for sf-GKRS of clear cell RCC BM. Studies focusing on the prognostic significance of albumin in sf-GKRS are rare. Further studies with a larger number of patients are warranted to confirm the above analytical outcome. Also, in keeping with previous studies, our data showed optimal rates of local tumour control and limited toxicity post radiosurgery, rendering GKRS the tool of choice in the management of RCC BM.
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47.
  • Strom, Peter, et al. (författare)
  • Artificial intelligence for diagnosis and grading of prostate cancer in biopsies : a population-based, diagnostic study
  • 2020
  • Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 21:2, s. 222-232
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundAn increasing volume of prostate biopsies and a worldwide shortage of urological pathologists puts a strain on pathology departments. Additionally, the high intra-observer and inter-observer variability in grading can result in overtreatment and undertreatment of prostate cancer. To alleviate these problems, we aimed to develop an artificial intelligence (AI) system with clinically acceptable accuracy for prostate cancer detection, localisation, and Gleason grading.MethodsWe digitised 6682 slides from needle core biopsies from 976 randomly selected participants aged 50–69 in the Swedish prospective and population-based STHLM3 diagnostic study done between May 28, 2012, and Dec 30, 2014 (ISRCTN84445406), and another 271 from 93 men from outside the study. The resulting images were used to train deep neural networks for assessment of prostate biopsies. The networks were evaluated by predicting the presence, extent, and Gleason grade of malignant tissue for an independent test dataset comprising 1631 biopsies from 246 men from STHLM3 and an external validation dataset of 330 biopsies from 73 men. We also evaluated grading performance on 87 biopsies individually graded by 23 experienced urological pathologists from the International Society of Urological Pathology. We assessed discriminatory performance by receiver operating characteristics and tumour extent predictions by correlating predicted cancer length against measurements by the reporting pathologist. We quantified the concordance between grades assigned by the AI system and the expert urological pathologists using Cohen's kappa.FindingsThe AI achieved an area under the receiver operating characteristics curve of 0·997 (95% CI 0·994–0·999) for distinguishing between benign (n=910) and malignant (n=721) biopsy cores on the independent test dataset and 0·986 (0·972–0·996) on the external validation dataset (benign n=108, malignant n=222). The correlation between cancer length predicted by the AI and assigned by the reporting pathologist was 0·96 (95% CI 0·95–0·97) for the independent test dataset and 0·87 (0·84–0·90) for the external validation dataset. For assigning Gleason grades, the AI achieved a mean pairwise kappa of 0·62, which was within the range of the corresponding values for the expert pathologists (0·60–0·73).InterpretationAn AI system can be trained to detect and grade cancer in prostate needle biopsy samples at a ranking comparable to that of international experts in prostate pathology. Clinical application could reduce pathology workload by reducing the assessment of benign biopsies and by automating the task of measuring cancer length in positive biopsy cores. An AI system with expert-level grading performance might contribute a second opinion, aid in standardising grading, and provide pathology expertise in parts of the world where it does not exist.
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48.
  • Voronkov, Artem, 1990-, et al. (författare)
  • Systematic Literature Review on Usability of Firewall Configuration
  • 2018
  • Ingår i: ACM Computing Surveys. - New York, NY, USA : Association for Computing Machinery (ACM). - 0360-0300 .- 1557-7341. ; 50:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Firewalls are network security components that handle incoming and outgoing network traffic based on a set of rules. The process of correctly configuring a firewall is complicated and prone to error, and it worsens as the network complexity grows. A poorly configured firewall may result in major security threats; in the case of a network firewall, an organization’s security could be endangered, and in the case of a personal firewall, an individual computer’s security is threatened. A major reason for poorly configured firewalls, as pointed out in the literature, is usability issues. Our aim is to identify existing solutions that help professional and non-professional users to create and manage firewall configuration files, and to analyze the proposals in respect of usability. A systematic literature review with a focus on the usability of firewall configuration is presented in the article. Its main goal is to explore what has already been done in this field. In the primary selection procedure, 1,202 articles were retrieved and then screened. The secondary selection led us to 35 articles carefully chosen for further investigation, of which 14 articles were selected and summarized. As main contributions, we propose a taxonomy of existing solutions as well as a synthesis and in-depth discussion about the state of the art in firewall usability. Among the main findings, we perceived that there is a lack (or even an absence) of usability evaluation or user studies to validate the proposed models. Although all articles are related to the topic of usability, none of them clearly defines it, and only a few actually employ usability design principles and/or guidelines.
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49.
  • Wairimu, Samuel, 1988-, et al. (författare)
  • On the Evaluation of Privacy Impact Assessment and Privacy Risk Assessment Methodologies : A Systematic Literature Review
  • 2024
  • Ingår i: IEEE Access. - : IEEE. - 2169-3536. ; 12, s. 19625-19650
  • Forskningsöversikt (refereegranskat)abstract
    • Assessing privacy risks and incorporating privacy measures from the onset requires a comprehensive understanding of potential impacts on data subjects. Privacy Impact Assessments (PIAs) offer a systematic methodology for such purposes, which are closely related to Data Protection Impact Assessments (DPIAs), particularly outlined in Article 35 of the General Data Protection Regulation (GDPR). The core of a PIA is a Privacy Risk Assessment (PRA). PRAs can be integrated as part of full-fledged PIAs or independently developed to support PIA processes. Although these methodologies have been identified as essential enablers of privacy by design, their effectiveness has been criticized because of the lack of evidence of their rigorous and systematic evaluation. Hence, we conducted a Systematic Literature Review (SLR) to identify published PIA and PRA methodologies and assess how and to what extent they have been scientifically validated or evaluated. We found that these methodologies are rarely evaluated for their performance in practice, and most of them have only been validated in limited studies. Most validation evidence is found with PRA methodologies. Of the evaluated methodologies, PIAs were the most evaluated, where case studies were the predominant evaluation method. These evaluated methodologies can be easily transferred to an industrial setting or used by practitioners, as they provide evidence of their use in practice. In addition, the findings in this study can be used to inform researchers of the current state-of-the-art, and practitioners can understand the benefits and current limitations of the methodologies and adopt evidence-based practices. 
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