| 1. |
- Backman, Max, et al.
(författare)
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Infiltration of NK and plasma cells is associated with a distinct immune subset in non‐small cell lung cancer
- 2021
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Ingår i: Journal of Pathology. - : John Wiley & Sons. - 0022-3417 .- 1096-9896. ; 255:3, s. 243-256
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Tidskriftsartikel (refereegranskat)abstract
- Immune cells of the tumor microenvironment are central but erratic targets for immunotherapy. The aim of this study was to characterize novel patterns of immune cell infiltration in non-small cell lung cancer (NSCLC) in relation to its molecular and clinicopathologic characteristics. Lymphocytes (CD3+, CD4+, CD8+, CD20+, FOXP3+, CD45RO+), macrophages (CD163+), plasma cells (CD138+), NK cells (NKp46+), PD1+, and PD-L1+ were annotated on a tissue microarray including 357 NSCLC cases. Somatic mutations were analyzed by targeted sequencing for 82 genes and a tumor mutational load score was estimated. Transcriptomic immune patterns were established in 197 patients based on RNA sequencing data. The immune cell infiltration was variable and showed only poor association with specific mutations. The previously defined immune phenotypic patterns, desert, inflamed, and immune excluded, comprised 30, 13, and 57% of cases, respectively. Notably, mRNA immune activation and high estimated tumor mutational load were unique only for the inflamed pattern. However, in the unsupervised cluster analysis, including all immune cell markers, these conceptual patterns were only weakly reproduced. Instead, four immune classes were identified: (1) high immune cell infiltration, (2) high immune cell infiltration with abundance of CD20+ B cells, (3) low immune cell infiltration, and (4) a phenotype with an imprint of plasma cells and NK cells. This latter class was linked to better survival despite exhibiting low expression of immune response-related genes (e.g. CXCL9, GZMB, INFG, CTLA4). This compartment-specific immune cell analysis in the context of the molecular and clinical background of NSCLC reveals two previously unrecognized immune classes. A refined immune classification, including traits of the humoral and innate immune response, is important to define the immunogenic potency of NSCLC in the era of immunotherapy. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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| 2. |
- Backman, Max, 1987-, et al.
(författare)
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Spatial immunophenotyping of the tumour microenvironment in non-small cell lung cancer
- 2023
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 185, s. 40-52
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Immune cells in the tumour microenvironment are associated with prognosis and response to therapy. We aimed to comprehensively characterise the spatial im-mune phenotypes in the mutational and clinicopathological background of non-small cell lung cancer (NSCLC).Methods: We established a multiplexed fluorescence imaging pipeline to spatially quantify 13 immune cell subsets in 359 NSCLC cases: CD4 effector cells (CD4-Eff), CD4 regulatory cells (CD4-Treg), CD8 effector cells (CD8-Eff), CD8 regulatory cells (CD8-Treg), B-cells, natural killer cells, natural killer T-cells, M1 macrophages (M1), CD163 thorn myeloid cells (CD163), M2 macrophages (M2), immature dendritic cells (iDCs), mature dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs).Results: CD4-Eff cells, CD8-Eff cells and M1 macrophages were the most abundant immune cells invading the tumour cell compartment and indicated a patient group with a favourable prognosis in the cluster analysis. Likewise, single densities of lymphocytic subsets (CD4-Eff, CD4-Treg, CD8-Treg, B-cells and pDCs) were independently associated with longer survival. However, when these immune cells were located close to CD8-Treg cells, the favourable impact was attenuated. In the multivariable Cox regression model, including cell densities and distances, the densities of M1 and CD163 cells and distances between cells (CD8-Treg-B-cells, CD8-Eff-cancer cells and B-cells-CD4-Treg) demonstrated positive prognostic impact, whereas short M2-M1 distances were prognostically unfavourable.Conclusion: We present a unique spatial profile of the in situ immune cell landscape in NSCLC as a publicly available data set. Cell densities and cell distances contribute independently to prognostic information on clinical outcomes, suggesting that spatial information is crucial for diagnostic use.
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| 3. |
- Barucca, G., et al.
(författare)
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Feasibility studies for the measurement of time-like proton electromagnetic form factors from (p)over-barp -> mu(+)mu(-) at PANDA at FAIR
- 2021
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Ingår i: European Physical Journal A. - NEW YORK, USA : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:1
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Tidskriftsartikel (refereegranskat)abstract
- This paper reports on Monte Carlo simulation results for future measurements of the moduli of time-like proton electromagnetic form factors, vertical bar G(E)vertical bar and vertical bar G(M)vertical bar, using the (p) over barp -> mu(+)mu(-) reaction at PANDA (FAIR). The electromagnetic form factors are fundamental quantities parameterizing the electric and magnetic structure of hadrons. This work estimates the statistical and total accuracy with which the form factors can be measured at PANDA, using an analysis of simulated data within the PandaRoot software framework. The most crucial background channel is (p) over barp -> pi(+)pi(-), due to the very similar behavior of muons and pions in the detector. The suppression factors are evaluated for this and all other relevant background channels at different values of antiproton beam momentum. The signal/background separation is based on a multivariate analysis, using the Boosted Decision Trees method. An expected background subtraction is included in this study, based on realistic angular distributions of the background contribution. Systematic uncertainties are considered and the relative total uncertainties of the form factor measurements are presented.
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| 4. |
- Barucca, G., et al.
(författare)
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Study of excited Ξ baryons with the P¯ ANDA detector
- 2021
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Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
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Tidskriftsartikel (refereegranskat)abstract
- The study of baryon excitation spectra provides insight into the inner structure of baryons. So far, most of the world-wide efforts have been directed towards N∗ and Δ spectroscopy. Nevertheless, the study of the double and triple strange baryon spectrum provides independent information to the N∗ and Δ spectra. The future antiproton experiment P¯ANDA will provide direct access to final states containing a Ξ¯ Ξ pair, for which production cross sections up to μb are expected in p¯p reactions. With a luminosity of L= 10 31 cm- 2 s- 1 in the first phase of the experiment, the expected cross sections correspond to a production rate of ∼106events/day. With a nearly 4 π detector acceptance, P¯ANDA will thus be a hyperon factory. In this study, reactions of the type p¯p → Ξ¯ +Ξ∗ - as well as p¯p → Ξ¯ ∗ +Ξ- with various decay modes are investigated. For the exclusive reconstruction of the signal events a full decay tree fit is used, resulting in reconstruction efficiencies between 3 and 5%. This allows high statistics data to be collected within a few weeks of data taking.
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| 5. |
- Barucca, G., et al.
(författare)
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The potential of Λ and Ξ- studies with PANDA at FAIR
- 2021
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Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
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Tidskriftsartikel (refereegranskat)abstract
- The antiproton experiment PANDA at FAIR is designed to bring hadron physics to a new level in terms of scope, precision and accuracy. In this work, its unique capability for studies of hyperons is outlined. We discuss ground-state hyperons as diagnostic tools to study non-perturbative aspects of the strong interaction, and fundamental symmetries. New simulation studies have been carried out for two benchmark hyperon-antihyperon production channels: p¯ p→ Λ¯ Λ and p¯ p→ Ξ¯ +Ξ-. The results, presented in detail in this paper, show that hyperon-antihyperon pairs from these reactions can be exclusively reconstructed with high efficiency and very low background contamination. In addition, the polarisation and spin correlations have been studied, exploiting the weak, self-analysing decay of hyperons and antihyperons. Two independent approaches to the finite efficiency have been applied and evaluated: one standard multidimensional efficiency correction approach, and one efficiency independent approach. The applicability of the latter was thoroughly evaluated for all channels, beam momenta and observables. The standard method yields good results in all cases, and shows that spin observables can be studied with high precision and accuracy already in the first phase of data taking with PANDA.
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| 9. |
- Hansen, Violeta, 1979, et al.
(författare)
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Naturally occurring radionuclides assessment in the Arctic
- 2023
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Ingår i: The XIX conference of the Nordic Society for Radiation Protection, held at Malmö Live, Malmö, Sweden, June 5-9, 2023. - https://nsfs.org/?lang=en : The Nordic Society for Radiation Protection (NSFS).
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Naturally occurring radionuclides (NORs), primarily 210Po, accumulates in seafood, marine, and terrestrial mammals, which are an important part of the traditional Arctic diet. Arctic seafood plays an important role in the worldwide seafood industry. NORs were measured in glaciers from Svalbard, the Arctic Ocean, surface seawater and sediments from Norwegian marine areas, seabirds from Greenland, seafood and marine mammals from the Nordic region, Faroe Islands, Greenland, and Canada, terrestrial mammals from Greenland, and lake sediments in northernmost Finland. Outdoor 222Rn was measured in Finland, Canada, and Norway and atmospheric 210Pb, 212Pb, and 7Be were measured in Norway, Sweden, Finland, Iceland, and Canada. Deposited 210Pb and 7Be were measured in Sweden and Finland. Glaciers and marine sediment results show oil and gas, coal combustion, and ore mining as anthropogenic sources. NORs are long-range transported via atmospheric and oceanic currents in the Arctic. 210Pb has a long atmospheric residence time, especially in winter. 228Ra activities in the Transpolar Drift approximately doubled between 2007 and 2015, indicating that climate-driven changes may be increasing the release of shelf-derived elements to the open Arctic Ocean. Results showed no effect of climate change on 210Pb deposition in sediments in Lake Kevojarvi in northernmost Finland. 210Po is the major contributor to the annual effective dose via seafood and marine and terrestrial mammal consumption in the Arctic population, far exceeding dose contributions from 137Cs, 226Ra, 228Ra, and 210Pb. 210Po absorbed dose rates to studied biota are several orders of magnitude lower than the recommended dose rate screening value of 10 µGy h-1. NORs atmospheric results follow an annual cycle, which is mainly driven by seasonal weather and climate changes. Understanding the sources and associated doses from NORs is necessary to assess risks and public perception of risks, support science-based decision-making, and policy development engaging public and Indigenous peoples.
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| 10. |
- Indremo, Malin, et al.
(författare)
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Association of Media Coverage on Transgender Health With Referrals to Child and Adolescent Gender Identity Clinics in Sweden
- 2022
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Increasing numbers of transgender and gender diverse children and adolescents have been referred to gender identity clinics in Sweden in the past decade, and previous studies have found an association between media attention and referral counts. Whether the tone of media stories is associated with referrals is not yet known.OBJECTIVE To investigate whether positive or negative media coverage on transgender and gender diverse issues is associated with referral counts to child and adolescent gender identity clinics.DESIGN, SETTING, AND PARTICIPANTS In this cross-sectional study, referrals counts were collected from all 6 specialized gender identity clinics in Sweden, along with information on referral date, sex assigned at birth, and birth year. Participants were all individuals younger than 19 years, referred to a gender identity clinic between January 1, 2017, and December 31, 2019. Data were analyzed from May 2020 to September 2021.EXPOSURES Exposures included 3 major media events related to transgender health care in 2019; 1 event was categorized as positive and 2 events were categorized as negative press coverage.MAIN OUTCOMES AND MEASURES Referral counts before and after each of the 3 major media events were assessed, and the moderating association of sex assigned at birth and age was examined with stratified analyses. Weekly referral counts and trends were assessed with interrupted time series analysis.RESULTS Among 1784 referrals (359 referrals [21.4%] among individuals aged <13 years; 1034 referrals [72.1%] among individuals assigned female at birth and 401 referrals [27.9%] among individuals assigned male at birth), a negative association between media coverage and referral counts was found for the first of the negative media events. In the 3 months following the event, referrals decreased by 25.4% (95% CI, -31.9% to -18.9%) overall, by 32.2% (95 CI, -41.8% to -22.8%) for individuals assigned female at birth, and by 25.3% (95 CI, -32.4% to -18.3%) for individuals aged 13 to 18 years. In the interrupted time series analysis, a mean weekly decrease of 3% in the referrals was observed in the extended time interval of 39 weeks (incidence rate ratio, 0.97; 95 CI, 0.95 to 0.99). For the other 2 media events, no changes in referral counts or time trends were observed.CONCLUSIONS AND RELEVANCE These findings suggest that an event of negative media coverage on transgender-specific health care was negatively associated with access to health care for transgender children and adolescents; therefore, nuanced and accurate media coverage, as well as increased awareness of these mechanisms among key stakeholders, is essential.
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