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1.	Gongora, M., et al. (författare) Characteristics of Patients in SPCG-15-A Randomized Trial Comparing Radical Prostatectomy with Primary Radiotherapy plus Androgen Deprivation Therapy in Men with Locally Advanced Prostate Cancer 2022 Ingår i: European Urology Open Science. - : Elsevier BV. - 2666-1691 .- 2666-1683. ; 41, s. 63-73 Tidskriftsartikel (refereegranskat)abstract Background: There is no high-grade evidence for surgery as primary treatment for locally advanced prostate cancer. The SPCG-15 study is the first randomized trial comparing surgical treatment with radiotherapy. Objective: To describe the baseline characteristics of the first 600 randomized men in the SPCG-15 study. The study will compare mortality and functional outcomes. Design, setting, and participants: This study is a Scandinavian prospective, open, multicenter phase III randomized clinical trial aiming to randomize 1200 men. Intervention: Radical prostatectomy with or without consecutive radiotherapy (experimental) and radiotherapy with neoadjuvant androgen deprivation therapy (standard of care). Outcome measurements and statistical analysis: Cause-specific survival, metastasis-free survival, overall survival, and patient-reported bowel function, sexual health, and lower urinary tract symptoms were measured. Results and limitations: The distribution of characteristics was similar in the two study arms. The median age was 67 yr (range 45-75 yr). Among the operated men, 36% had pT3a stage of disease and 39% had pT3b stage. International Society of Urological Pathology grades 2, 3, 4, and 5 were prevalent in 21%, 35%, 7%, and 27%, respectively. Half of the men (51%) in the surgery arm had no positive lymph nodes. The main limitation is the pragmatic design comparing the best available practice at each study site leading to heterogeneity of treatment regimens within the study arms. Conclusions: We have proved that randomization between surgery and radiotherapy for locally advanced prostate cancer is feasible. The characteristics of the study population demonstrate a high prevalence of advanced disease, well-balanced comparison groups, and a demography mirroring the Scandinavian population of men with prostate cancer at large. Patient summary: This study, which has recruited >600 men, compares radiotherapy with surgery for prostate cancer, and an analysis at the time of randomization indicates that the study will be informative and generalizable to most men with locally advanced but not metastasized prostate cancer. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.
2.	Prakash, A, et al. (författare) Deliverable D6.3 : Trials and experimentation (cycle 3) 2022 Rapport (refereegranskat)abstract This deliverable presents the third and final cycle of trials and experimentation activities executed over 5GENESIS facilities. The document is the continuation of deliverables D6.1 and D6.2, in the sense that it captures tests carried out over the evolved infrastructures hosting 5GENESIS facilities following the methodology defined in the previous editions of this deliverable. The tests reported in this document focus on i) the final 5G infrastructure deployments that includes radio and core elements mostly in Stand-Alone (SA) deployment configurations based on commercial and open implementations, and ii) the various use cases/applications, some of them also involving field trials. Most of the tests described herein, especially the generic/lab ones are performed using the Open5GENESIS experimentation suite.
3.	Boonen, Annelies, et al. (författare) EULAR Points to Consider (PtC) for designing, analysing and reporting of studies with work participation as an outcome domain in patients with inflammatory arthritis 2021 Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 80:9, s. 1116-1123 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Clinical studies with work participation (WP) as an outcome domain pose particular methodological challenges that hamper interpretation, comparison between studies and meta-analyses.OBJECTIVES: To develop Points to Consider (PtC) for design, analysis and reporting of studies of patients with inflammatory arthritis that include WP as a primary or secondary outcome domain.METHODS: The EULAR Standardised Operating Procedures were followed. A multidisciplinary taskforce with 22 experts including patients with rheumatic diseases, from 10 EULAR countries and Canada, identified methodologic areas of concern. Two systematic literature reviews (SLR) appraised the methodology across these areas. In parallel, two surveys among professional societies and experts outside the taskforce sought for additional methodological areas or existing conducting/reporting recommendations. The taskforce formulated the PtC after presentation of the SLRs and survey results, and discussion. Consensus was obtained through informal voting, with levels of agreement obtained anonymously.RESULTS: Two overarching principles and nine PtC were formulated. The taskforce recommends to align the work-related study objective to the design, duration, and outcome domains/measurement instruments of the study (PtC: 1-3); to identify contextual factors upfront and account for them in analyses (PtC: 4); to account for interdependence of different work outcome domains and for changes in work status over time (PtC: 5-7); to present results as means as well as proportions of patients reaching predefined meaningful categories (PtC: 8) and to explicitly report volumes of productivity loss when costs are an outcome (PtC:9).CONCLUSION: Adherence to these EULAR PtC will improve the methodological quality of studies evaluating WP.
4.	Lehtiö, Janne, et al. (författare) Proteogenomics of non-small cell lung cancer reveals molecular subtypes associated with specific therapeutic targets and immune-evasion mechanisms 2021 Ingår i: Nature Cancer. - : Springer Science and Business Media LLC. - 2662-1347. ; 2:11, s. 1224-1242 Tidskriftsartikel (refereegranskat)abstract Despite major advancements in lung cancer treatment, long-term survival is still rare and a deeper understanding of molecular phenotypes would allow the identification of specific cancer dependencies and immune-evasion mechanisms. Here we performed in-depth mass-spectrometry-based proteogenomic analysis of 141 tumors representing all major histologies of non-small cell lung cancer (NSCLC). We identified six distinct proteome subtypes with striking differences in immune cell composition and subtype-specific expression of immune checkpoints. Unexpectedly, high neoantigen burden was linked to global hypomethylation and complex neoantigens mapped to genomic regions, such as endogenous retroviral elements and introns, in immune-cold subtypes. Further, we linked immune evasion with LAG-3 via STK11 mutation-dependent HNF1A activation and FGL1 expression. Finally, we develop a data-independent acquisition mass-spectrometry-based NSCLC subtype classification method, validate it in an independent cohort of 208 NSCLC cases and demonstrate its clinical utility by analyzing an additional cohort of 84 late-stage NSCLC biopsy samples.
5.	Hero, Johan S., et al. (författare) Endo-xylanases from Cohnella sp. AR92 aimed at xylan and arabinoxylan conversion into value-added products 2021 Ingår i: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 1432-0614 .- 0175-7598. ; 105:18, s. 6759-6778 Tidskriftsartikel (refereegranskat)abstract The genus Cohnella belongs to a group of Gram-positive endospore-forming bacteria within the Paenibacillaceae family. Although most species were described as xylanolytic bacteria, the literature still lacks some key information regarding their repertoire of xylan-degrading enzymes. The whole genome sequence of an isolated xylan-degrading bacterium Cohnella sp. strain AR92 was found to contain five genes encoding putative endo-1,4-β-xylanases, of which four were cloned, expressed, and characterized to better understand the contribution of the individual endo-xylanases to the overall xylanolytic properties of strain AR92. Three of the enzymes, CoXyn10A, CoXyn10C, and CoXyn11A, were shown to be effective at hydrolyzing xylans-derived from agro-industrial, producing oligosaccharides with substrate conversion values of 32.5%, 24.7%, and 10.6%, respectively, using sugarcane bagasse glucuronoarabinoxylan and of 29.9%, 19.1%, and 8.0%, respectively, using wheat bran-derived arabinoxylan. The main reaction products from GH10 enzymes were xylobiose and xylotriose, whereas CoXyn11A produced mostly xylooligosaccharides (XOS) with 2 to 5 units of xylose, often substituted, resulting in potentially prebiotic arabinoxylooligosaccharides (AXOS). The endo-xylanases assay displayed operational features (temperature optima from 49.9 to 50.4 °C and pH optima from 6.01 to 6.31) fitting simultaneous xylan utilization. Homology modeling confirmed the typical folds of the GH10 and GH11 enzymes, substrate docking studies allowed the prediction of subsites (- 2 to + 1 in GH10 and - 3 to + 1 in GH11) and identification of residues involved in ligand interactions, supporting the experimental data. Overall, the Cohnella sp. AR92 endo-xylanases presented significant potential for enzymatic conversion of agro-industrial by-products into high-value products.Key points• Cohnella sp. AR92 genome encoded five potential endo-xylanases.• Cohnella sp. AR92 enzymes produced xylooligosaccharides from xylan, with high yields.• GH10 enzymes from Cohnella sp. AR92 are responsible for the production of X2 and X3 oligosaccharides.• GH11 from Cohnella sp. AR92 contributes to the overall xylan degradation by producing substituted oligosaccharides.
6.	Ran, Ylva, et al. (författare) Environmental assessment of diets: overview and guidance on indicator choice 2024 Ingår i: The Lancet Planetary Health. - : Elsevier BV. - 2542-5196. ; 8:3, s. e172-e187 Forskningsöversikt (refereegranskat)abstract Comprehensive but interpretable assessment of the environmental performance of diets involves choosing a set of appropriate indicators. Current knowledge and data gaps on the origin of dietary foodstuffs restrict use of indicators relying on site-specific information. This Personal View summarises commonly used indicators for assessing the environmental performance of diets, briefly outlines their benefits and drawbacks, and provides recommendations on indicator choices for actors across multiple fields involved in activities that include the environmental assessment of diets. We then provide recommendations on indicator choices for actors across multiple fields involved in activities that use environmental assessments, such as health and nutrition experts, policy makers, decision makers, and private-sector and public-sector sustainability officers. We recommend that environmental assessment of diets should include indicators for at least the five following areas: climate change, biosphere integrity, blue water consumption, novel entities, and impacts on natural resources (especially wild fish stocks), to capture important environmental trade-offs. If more indicators can be handled in the assessment, indicators to capture impacts related to land use quantity and quality and green water consumption should be used. For ambitious assessments, indicators related to biogeochemical flows, stratospheric ozone depletion, and energy use can be added.
7.	Ran, Ylva, et al. (författare) Environmental assessment of diets: overview and guidance on indicator choice 2024 Ingår i: The Lancet Planetary Health. - : ELSEVIER SCI LTD. - 2542-5196. ; 8:3, s. e172-e187 Forskningsöversikt (refereegranskat)abstract Comprehensive but interpretable assessment of the environmental performance of diets involves choosing a set of appropriate indicators. Current knowledge and data gaps on the origin of dietary foodstuffs restrict use of indicators relying on site-specific information. This Personal View summarises commonly used indicators for assessing the environmental performance of diets, briefly outlines their benefits and drawbacks, and provides recommendations on indicator choices for actors across multiple fields involved in activities that include the environmental assessment of diets. We then provide recommendations on indicator choices for actors across multiple fields involved in activities that use environmental assessments, such as health and nutrition experts, policy makers, decision makers, and private-sector and public-sector sustainability officers. We recommend that environmental assessment of diets should include indicators for at least the five following areas: climate change, biosphere integrity, blue water consumption, novel entities, and impacts on natural resources (especially wild fish stocks), to capture important environmental trade-offs. If more indicators can be handled in the assessment, indicators to capture impacts related to land use quantity and quality and green water consumption should be used. For ambitious assessments, indicators related to biogeochemical flows, stratospheric ozone depletion, and energy use can be added.
8.	Ran, Ylva, et al. (författare) Environmental assessment of diets: overview and guidance on indicator choice 2024 Ingår i: The Lancet Planetary Health. - 2542-5196. ; 8:3, s. e172-e187 Tidskriftsartikel (refereegranskat)abstract Comprehensive but interpretable assessment of the environmental performance of diets involves choosing a set of appropriate indicators. Current knowledge and data gaps on the origin of dietary foodstuffs restrict use of indicators relying on site-specific information.This Personal View summarises commonly used indicators for assessing the environmental performance of diets, briefly outlines their benefits and drawbacks, and provides recommendations on indicator choices for actors across multiple fields involved in activities that include the environmental assessment of diets.We then provide recommendations on indicator choices for actors across multiple fields involved in activities that use environmental assessments, such as health and nutrition experts, policy makers, decision makers, and private-sector and public-sector sustainability officers. We recommend that environmental assessment of diets should include indicators for at least the five following areas: climate change, biosphere integrity, blue water consumption, novel entities, and impacts on natural resources (especially wild fish stocks), to capture important environmental trade-offs.If more indicators can be handled in the assessment, indicators to capture impacts related to land use quantity and quality and green water consumption should be used. For ambitious assessments, indicators related to biogeochemical flows, stratospheric ozone depletion, and energy use can be added.
9.	Ran, Ylva, et al. (författare) Environmental assessment of diets: overview and guidance on indicator choice 2024 Ingår i: The Lancet Planetary Health. - : ELSEVIER SCI LTD. - 2542-5196. ; 8:3, s. e172-e187 Tidskriftsartikel (refereegranskat)abstract Comprehensive but interpretable assessment of the environmental performance of diets involves choosing a set of appropriate indicators. Current knowledge and data gaps on the origin of dietary foodstuffs restrict use of indicators relying on site-specific information. This Personal View summarises commonly used indicators for assessing the environmental performance of diets, briefly outlines their benefits and drawbacks, and provides recommendations on indicator choices for actors across multiple fields involved in activities that include the environmental assessment of diets. We then provide recommendations on indicator choices for actors across multiple fields involved in activities that use environmental assessments, such as health and nutrition experts, policy makers, decision makers, and privatesector and public-sector sustainability officers. We recommend that environmental assessment of diets should include indicators for at least the five following areas: climate change, biosphere integrity, blue water consump tion, novel entities, and impacts on natural resources (especially wild fish stocks), to capture important environ mental trade-offs. If more indicators can be handled in the assessment, indicators to capture impacts related to land use quantity and quality and green water consumption should be used. For ambitious assessments, indicators related to biogeochemical flows, stratospheric ozone depletion, and energy use can be added.
10.	Ranta, S., et al. (författare) High need for intensive care in paediatric acute myeloid leukaemia: A population-based study 2022 Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 111:11, s. 2235-2241 Tidskriftsartikel (refereegranskat)abstract Aim Risk of treatment-related life-threatening toxicity is high in childhood acute myeloid leukaemia (AML), and access to intensive care units (ICU) is crucial. We explored the ICU admission rate and outcome after intensive care in childhood AML in Sweden. Methods Patients diagnosed between 2008 and 2016 were identified from the Swedish Childhood Cancer Registry (SCCR), a national quality registry. Data from SCCR was cross-referenced with clinical questionnaire data from paediatric oncology centers and the Swedish Intensive Care Registry (SIR), another national quality registry. Results According to combined data, 46% of the children (58/126) were admitted to ICU, 17% (21/126) within 1 month from diagnosis. Overall, ICU mortality per admission was 12% and 6% during first-line treatment. There was a discrepancy between admission rate from the clinical questionnaires and SCCR (29%; 36/126 children) and SIR (44%; 55/126) All deaths during first-line treatment occurred at or after ICU care. Conclusion Although admission rate under AML treatment was high, the treatment-related mortality under first-line treatment was low. No child died under first-line treatment without admission to ICU, suggesting good availability. The discrepancy between the two registries, SCCR and SIR, highlights the need for future validation of registry data.
11.	Robba, Chiara, et al. (författare) Oxygen targets and 6-month outcome after out of hospital cardiac arrest : a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial 2022 Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 26, s. 1-13 Tidskriftsartikel (refereegranskat)abstract Background: Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients’ outcome. Methods: Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 < 60 mmHg and severe hyperoxemia as PaO2 > 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. Results: 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93–1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95–1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). Conclusions: In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. Trial registration: clinicaltrials.gov NCT02908308, Registered September 20, 2016.
12.	Venkatakrishnan, Vignesh, 1987, et al. (författare) Glycan analysis of human neutrophil granules implicates a maturation-dependent glycosylation machinery 2020 Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 295:36, s. 12648-12660 Tidskriftsartikel (refereegranskat)abstract Protein glycosylation is essential to trafficking and immune functions of human neutrophils. During granulopoiesis in the bone marrow, distinct neutrophil granules are successively formed. Distinct receptors and effector proteins, many of which are glycosylated, are targeted to each type of granule according to their time of expression, a process called "targeting by timing." Therefore, these granules are time capsules reflecting different times of maturation that can be used to understand the glycosylation process during granulopoiesis. Herein, neutrophil subcellular granules were fractionated by Percoll density gradient centrifugation, andN- andO-glycans present in each compartment were analyzed by LC-MS. We found abundant paucimannosidicN-glycans and lack ofO-glycans in the early-formed azurophil granules, whereas the later-formed specific and gelatinase granules and secretory vesicles contained complexN-andO-glycans with remarkably elongatedN-acetyllactosamine repeats with Lewis epitopes. Immunoblotting and histochemical analysis confirmed the expression of Lewis X and sialyl-Lewis X in the intracellular granules and on the cell surface, respectively. Many glycans identified are unique to neutrophils, and their complexity increased progressively from azurophil granules to specific granules and then to gelatinase granules, suggesting temporal changes in the glycosylation machinery indicative of "glycosylation by timing" during granulopoiesis. In summary, this comprehensive neutrophil granule glycome map, the first of its kind, highlights novel granule-specific glycosylation features and is a crucial first step toward a better understanding of the mechanisms regulating protein glycosylation during neutrophil granulopoiesis and a more detailed understanding of neutrophil biology and function.
13.	Altena, Renske, et al. (författare) Human Epidermal Growth Factor Receptor 2 (HER2) PET Imaging of HER2-Low Breast Cancer with [ 68 Ga]Ga-ABY-025 : Results from a Pilot Study 2024 Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine and Molecular Imaging. - 0161-5505 .- 1535-5667. ; 65:5, s. 700-707 Tidskriftsartikel (refereegranskat)abstract Patients with HER2-low metastatic breast cancer (mBC), defined as an immunohistochemistry (IHC) score of 1+ or 2+ without HER2 gene amplification, may benefit from HER2 antibody-drug conjugates. Identifying suitable candidates is a clinical challenge because of spatial and temporal heterogeneity in HER2 expression and discrepancies in pathologic reporting. We aimed to investigate the feasibility and safety of HER2-specific PET imaging with [ 68 Ga]Ga-ABY-025 for visualization of HER2-low mBC.Methods: A prospective pilot study was done with 10 patients who had HER2-low mBC, as part of a phase 2 basket imaging study with [ 68 Ga]Ga-ABY-025 in HER2-expressing solid tumors. Patients were recruited at the Breast Clinic at the Karolinska University Hospital, Stockholm, Sweden. PET/CT images were acquired 3 h after injection of 200 MBq of [ 68 Ga]Ga-ABY-025. The SUV max was used to quantify tracer uptake. Ultrasound-guided tumor biopsies were guided by results from the HER2 PET. The main outcome-the safety and feasibility of HER2 PET in patients with HER2low mBC, measured the occurrence of possible procedure -related adverse events.Results: Ten patients with HER2-low mBC underwent [ 68 Ga]Ga-ABY-025 PET/CT with paired tumor biopsies. No adverse events occurred. In all patients, [ 68 Ga]Ga-ABY-025-avid lesions with substantial intra- and interindividual heterogeneity in tracer uptake were noted. In 8 of 10 patients with ABY-025-avid lesions, the HER2low status of the corresponding lesions was confirmed by IHC or in situ hybridization. Two patients had an IHC score of 0 in the tumor biopsies:1 in a cutaneous lesion with a low SUV max and 1 in a liver metastasis with a high SUV max but a "cold" core.Conclusion: The visualization of HER2-low mBC with [ 68 Ga]Ga-ABY-025 PET/CT was feasible and safe. Areas of tracer uptake showed varying levels of HER2 expression on IHC. The observed intra- and interindividual heterogeneity in [ 68 Ga]Ga-ABY-025 uptake suggested that HER2 PET might be used as a tool for the noninvasive assessment of disease heterogeneity and has the potential to identify patients in whom HER2-targeted drugs can have a clinical benefit.
14.	Ben-Akiva, Elana, et al. (författare) Biodegradable lipophilic polymeric mRNA nanoparticles for ligand-free targeting of splenic dendritic cells for cancer vaccination 2023 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:26 Tidskriftsartikel (refereegranskat)abstract Nanoparticle (NP) -based mRNA cancer vaccines hold great promise to realize person-alized cancer treatments. To advance this technology requires delivery formulations for efficient intracellular delivery to antigen-presenting cells. We developed a class of bioreducible lipophilic poly(beta- amino ester) nanocarriers with quadpolymer architec-ture. The platform is agnostic to the mRNA sequence, with one -step self-assembly allow-ing for delivery of multiple antigen-encoding mRNAs as well as codelivery of nucleic acid-based adjuvants. We examined structure-function relationships for NP-mediated mRNA delivery to dendritic cells (DCs) and identified that a lipid subunit of the pol-ymer structure was critical. Following intravenous administration, the engineered NP design facilitated targeted delivery to the spleen and preferential transfection of DCs without the need for surface functionalization with targeting ligands. Treatment with engineered NPs codelivering antigen-encoding mRNA and toll -like receptor agonist adjuvants led to robust antigen-specific CD8+ T cell responses, resulting in efficient antitumor therapy in in vivo models of murine melanoma and colon adenocarcinoma.
15.	Bjällmark, Anna, et al. (författare) Radiology departmental policy compliance with Swedish guidelines regarding post-contrast acute kidney injury for examinations with iodinated contrast media 2021 Ingår i: Radiography. - : Elsevier. - 1078-8174 .- 1532-2831. ; 27:4, s. 1058-1063 Tidskriftsartikel (refereegranskat)abstract INTRODUCTION: Guidelines concerning intravenous iodinated contrast media (CM) during computed tomography (CT) examinations are important to follow to minimize the risk for post-contrast acute kidney injury (PC-AKI). The purpose of this study was to investigate the radiology departmental policy compliance with Swedish guidelines concerning PC-AKI.METHODS: In February 2020, an electronic survey was distributed to the responsible radiographer at 41 radiology departments in all university hospitals and medium-sized hospitals in Sweden. The questions focused on routines around renal functional tests, individualized contrast administration and handling of patients with diabetes mellitus taking metformin.RESULTS: The response rate was 83%. Seventy-six percent (n = 26) of radiology departments calculated estimated glomerular filtration rate (eGFR) from serum creatinine prior to CM administration, but only 24% (n = 8) followed the recommendation to calculate eGFR from both serum creatinine and cystatin C. For acute/inpatients, 55% (n = 18) followed the recommendation that renal functional tests should be performed within 12 h before CM administration. For elective patients, 97% (n = 33) followed the recommendation to have eGFR newer than three months which is acceptable for patients with no history of disease that may have affected renal function. Approximately 80% of the radiology departments followed the recommendation that CM dose always should be individually adjusted to patient eGFR. Seventy-six percent (n = 26) followed the recommendation to continue with metformin at eGFR ≥ 45 ml/min.CONCLUSION: Compliance with the national guidelines was high regarding routines around renal functional tests, dose adjustment of CM and metformin discontinuation. Improvements can be made in using both cystatin C and serum creatinine for eGFR calculations as well as ensuring renal function tests within 12 h for acute/inpatients with acute disease that may affect renal function.IMPLICATIONS FOR PRACTICE: This study raises awareness of the importance of adhering to guidelines in healthcare. To have knowledge about the current level of compliance regarding PCI-AKI is important to maintain and develop effective clinical implementation of guidelines. The variation in practice seen in this study emphasizes the need of more effective implementation strategies to ensure adherence with best practice.
16.	Correnty, Siobhán (författare) Numerical methods for parameterized linear systems 2024 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Solving linear systems of equations is a fundamental problem in engineering. Moreover, applications involving the solution to linear systems arise in the social sciences, business, and economics. Specifically, the research conducted in this dissertation explores solutions to linear systems where the system matrix depends nonlinearly on a parameter. The parameter can be a scalar or a vector, and a change in the parameter results in a change in the solution. Such a setting arises in the study of partial differential equations and time-delay systems, and we are interested in obtaining solutions corresponding to many values of the parameter simultaneously. The methods developed in this thesis can also be used to solve parameter estimation problems. Furthermore, software has been developed and is available online. This thesis consists of four papers and presents both algorithms and theoretical analysis. In Paper A, a linearization based on an infinite Taylor series expansion is considered. Specifically, the linearized system is a shifted parameterized system, and the parameter is a scalar. The GMRES method is used to solve the systems corresponding to many values of the parameter, and only one Krylov subspace basis matrix is required. Convergence analysis is based on solutions to a nonlinear eigenvalue problem and the magnitude of the parameter. Notably, the algorithm is carried out in a finite number of computations. The approach in Paper B is based on a preconditioned linearized system solved using the inexact GMRES method. In this setting, the linearization incorporates all terms in an infinite Taylor series expansion, and the preconditioner is applied approximately using iterative methods. Solutions corresponding to many values of the scalar parameter are generated from one subspace, and this is done in a finite number of linear algebra operations. Theoretical analysis, based on the error in the application of the preconditioner and the magnitude of the parameter, leads to a bound on the residual. Paper C proposes a short recurrence Krylov subspace method for solving linear systems that depend on a scalar parameter. In particular, a Chebyshev approximation is used to construct a linearization, and the linearized system is solved in a Bi-CG setting. Additionally, shift-and-invert preconditioning leads to fast convergence of the Krylov method for many different values of the parameter. An inexact variant of the method is also derived and analyzed. In Paper D, a reduced order model is constructed from snapshots to solve parameterized linear systems. Specifically, the parameter is a vector of dimension 2, and the sampling is performed on a sparse grid using the method proposed in Paper C. A tensor decomposition is utilized to build the model. Approaches of this kind are not always successful, and it is not known a priori if a decomposition will converge on a given set of snapshots. This work offers a novel way to generate a new set of snapshots in the same parameter space, to be used if the decomposition does not converge, with little extra computation.
17.	Fisher, Jane, et al. (författare) Proteome profiling of recombinant DNase therapy in reducing NETs and aiding recovery in COVID-19 patients 2021 Ingår i: Molecular and Cellular Proteomics. - : Elsevier BV. - 1535-9484 .- 1535-9476. ; 20 Tidskriftsartikel (refereegranskat)abstract Severe COVID-19 can result in pneumonia and acute respiratory failure. Accumulation of mucus in the airways is a hall mark of the disease and can result in hypoxemia. Here, we show that quantitative proteome analysis of the sputum from severe COVID-19 patients reveal high levels of neutrophil extracellular trap(s) (NETs) components, which was confirmed by microscopy. Extracellular DNA from excessive NET formation can increase sputum viscosity and can lead to acute respiratory distress syndrome (ARDS). Recombinant human DNase (rhDNase/Pulmozyme) has been shown to be beneficial in reducing sputum viscosity and improve lung function. We treated 5 COVID-19 patients presenting acute symptoms with clinically approved aerosolized Pulmozyme. No adverse reactions to the drug were seen, and improved oxygen saturation and recovery in all severely ill COVID-19 patients was observed after therapy. Immunofluorescence and proteome analysis of sputum and blood plasma samples after treatment revealed a marked reduction of NETs and a set of statistically significant proteome changes that indicate reduction of haemorrhage, plasma leakage and inflammation in the airways, and reduced systemic inflammatory state in the blood plasma of patients. Taken together, the results indicate that NETs contribute to acute respiratory failure in COVID-19 and that degrading NETs may reduce dependency on external high flow oxygen therapy in patients. Targeting NETs using rhDNase may have significant therapeutic implications in COVID-19 disease and warrants further studies.
18.	Garza, Raquel, et al. (författare) LINE-1 retrotransposons drive human neuronal transcriptome complexity and functional diversification 2023 Ingår i: Science Advances. - 2375-2548. ; 9:44 Tidskriftsartikel (refereegranskat)abstract The genetic mechanisms underlying the expansion in size and complexity of the human brain remain poorly understood. Long interspersed nuclear element-1 (L1) retrotransposons are a source of divergent genetic information in hominoid genomes, but their importance in physiological functions and their contribution to human brain evolution are largely unknown. Using multiomics profiling, we here demonstrate that L1 promoters are dynamically active in the developing and the adult human brain. L1s generate hundreds of developmentally regulated and cell type-specific transcripts, many that are co-opted as chimeric transcripts or regulatory RNAs. One L1-derived long noncoding RNA, LINC01876, is a human-specific transcript expressed exclusively during brain development. CRISPR interference silencing of LINC01876 results in reduced size of cerebral organoids and premature differentiation of neural progenitors, implicating L1s in human-specific developmental processes. In summary, our results demonstrate that L1-derived transcripts provide a previously undescribed layer of primate- and human-specific transcriptome complexity that contributes to the functional diversification of the human brain.
19.	Glintborg, B., et al. (författare) Uptake and effectiveness of newer biologic and targeted synthetic disease-modifying antirheumatic drugs in psoriatic arthritis: results from five Nordic biologics registries 2023 Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 82:6, s. 820-828 Tidskriftsartikel (refereegranskat)abstract BackgroundWe aimed to describe the uptake of newer biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in psoriatic arthritis (PsA) in the Nordic countries and to compare their retention and effectiveness. MethodsPatients with PsA starting a b/tsDMARD in 2012-2020 in five Nordic rheumatology registers were included. Uptake and patient characteristics were described, with comorbidities identified from linkages to national patient registries. One-year retention and 6-month effectiveness (proportions achieving low disease activity (LDA) on the Disease Activity Index for PSoriatic Arthritis based on 28-joint evaluation) for the newer b/tsDMARDs (abatacept/apremilast/ixekizumab/secukinumab/tofacitinib/ustekinumab) were compared with adalimumab through adjusted regression models stratified by treatment course (first, second/third, and fourth or more). ResultsIn total, 5659 treatment courses with adalimumab (56% biologic-naive) and 4767 courses with a newer b/tsDMARD (21% biologic-naive) were included. The uptake of newer b/tsDMARDs increased from 2014 and plateaued in 2018. Patient characteristics appeared similar across treatments at treatment start. Adalimumab was more often used as the first course and newer b/tsDMARDs more often in biologic-experienced patients. Used as a second/third b/tsDMARD, the retention rate and the proportion achieving LDA were significantly better for adalimumab (rate 65%, proportion 59%) compared with abatacept (45%, 37%), apremilast (43%, 35%), ixekizumab (LDA only, 40%) and ustekinumab (LDA only, 40%), but not significantly different from other b/tsDMARDs. ConclusionUptake of newer b/tsDMARDs occurred mainly in biologic-experienced patients. Regardless of mode of action, only a minority of patients starting a second or later b/tsDMARD course remained on drug and achieved LDA. Superior outcomes for adalimumab indicate that the positioning of newer b/tsDMARDs in the PsA treatment algorithm remains to be established.
20.	Gundlegård, David, et al. (författare) Integrated tracking and route classification for travel time estimation based on cellular network signalling data 2020 Ingår i: IET Intelligent Transport Systems. - : INST ENGINEERING TECHNOLOGY-IET. - 1751-956X .- 1751-9578. ; 14:9, s. 1087-1096 Tidskriftsartikel (refereegranskat)abstract This study evaluates the effectiveness of using detailed cellular network signalling data for travel time estimation and route classification. Here, the authors propose a processing pipeline for estimating travel times and route classification based on Cell ID and received signal strength (RSS) measurements from a cellular network. The pipeline combines cellular fingerprinting, particle filtering, integrity monitoring, and map matching based on a hidden Markov model (HMM). The method is evaluated using a dataset of 11,000 cellular RSS measurements with corresponding GPS locations for the city of Norrkoping, Sweden. The basic fingerprinting method has a CEP-67 location accuracy of 111 m and both particle filtering and integrity monitoring improved the results: 79 and 38 m for particle filtering and particle filtering with integrity monitoring, respectively. The route classification method resulted in a precision of 0.83 and a recall of 0.92, which are clear improvements compared to basic map matching of fingerprinting estimates. This new type of noise-adaptive travel time sampling in combination with an HMM-based route classification shows promising results and can potentially support large-scale estimates of both route choice and travel times using detailed cellular network signalling data in urban areas.
21.	Hartman, Erik, et al. (författare) Interpreting biologically informed neural networks for enhanced proteomic biomarker discovery and pathway analysis 2023 Ingår i: Nature Communications. - 2041-1723. ; 14, s. 1-13 Tidskriftsartikel (refereegranskat)abstract The incorporation of machine learning methods into proteomics workflows improves the identification of disease-relevant biomarkers and biological pathways. However, machine learning models, such as deep neural networks, typically suffer from lack of interpretability. Here, we present a deep learning approach to combine biological pathway analysis and biomarker identification to increase the interpretability of proteomics experiments. Our approach integrates a priori knowledge of the relationships between proteins and biological pathways and biological processes into sparse neural networks to create biologically informed neural networks. We employ these networks to differentiate between clinical subphenotypes of septic acute kidney injury and COVID-19, as well as acute respiratory distress syndrome of different aetiologies. To gain biological insight into the complex syndromes, we utilize feature attribution-methods to introspect the networks for the identification of proteins and pathways important for distinguishing between subtypes. The algorithms are implemented in a freely available open source Python-package ( https://github.com/InfectionMedicineProteomics/BINN ).
22.	Henriksson, I, et al. (författare) Utveckling av instrument för analys av benämningsförmåga i skrift för personer med afasi, resultat från en referensgrupp 2022 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
23.	Holmgren, Christina M, et al. (författare) Out-of-hospital cardiac arrest : Causes according to autopsy and electrocardiography - Analysis of 781 patients with neither hospital care nor prescribed medication during the preceding two years. 2020 Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 150, s. 65-71 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: There is a knowledge gap regarding aetiology of and potential for predicting out-of-hospital cardiac arrest (OHCA) among individuals who are healthy before the event.AIM: To describe causes of OHCA and the potential for predicting OHCA in apparently healthy patients.METHODS: Patients were recruited from the Swedish Register of Cardiopulmonary Resuscitation from November 2007 to January 2011. Inclusion criteria were: OHCA with attempted CPR but neither dispensed prescription medication nor hospital care two years before the event The register includes the majority of patients suffering OHCA in Sweden where cardiopulmonary resuscitation (CPR) was attempted. Medication status was defined by linkage to the Swedish Prescribed Drug Register. Cause of death was assessed based on autopsy and the Swedish Cause of Death Register. Prediction of OHCA was attempted based on available electrocardiograms (ECG) before the OHCA event.RESULTS: Altogether 781 individuals (16% women) fulfilled the inclusion criteria. Survival to 30 days was 16%. Autopsy rate was 72%. Based on autopsy, 70% had a cardiovascular aetiology and 59% a cardiac aetiology. An ECG recording before the event was found in 23% of cases. The ECG was abnormal in 22% of them.CONCLUSION: Among OHCA victims who appeared to be healthy prior to the event, the cause was cardiovascular in the great majority according to autopsy findings. A minority had a preceding abnormal ECG that could have been helpful in avoiding the event.
24.	Karlsson, A., et al. (författare) Total nasal airway resistance while sitting predicts airway collapse when lying down 2020 Ingår i: Journal of Laryngology and Otology. - 0022-2151. ; 134:10, s. 917-924 Tidskriftsartikel (refereegranskat)abstract Background Nasal obstruction when lying down is a common complaint in patients with chronic nasal obstruction, but rhinomanometry is typically performed in the sitting position. This study aimed to analyse whether adding rhinomanometry in a supine position is a useful examination. Method A total of 41 patients with chronic nasal obstruction underwent rhinomanometry and acoustic rhinometry, sitting and supine, before and after decongestion, as well as an over-night polygraphy. Results Total airway resistance was measurable in a supine position in 48 per cent (14 of 29) of the patients with total airway resistance of equal to or less than 0.3 Pa/cm3/second when sitting and in none (0 of 12) of the patients with total nasal airway resistance of more than 0.3 Pa/cm3/second when sitting. After decongestion, this increased to 83 per cent and 58 per cent, respectively. Conclusion Increased nasal resistance when sitting predicts nasal breathing problems when supine. Rhinomanometry in a supine position should be performed to diagnose upper airway collapse when supine. Copyright © JLO (1984) Limited, 2020.
25.	Karlsson, Johan, et al. (författare) Nanoparticle designs for delivery of nucleic acid therapeutics as brain cancer therapies. 2021 Ingår i: Advanced Drug Delivery Reviews. - : Elsevier BV. - 0169-409X .- 1872-8294. ; 179, s. 113999- Tidskriftsartikel (refereegranskat)abstract Glioblastoma (GBM) is an aggressive central nervous system cancer with a dismal prognosis. The standard of care involves surgical resection followed by radiotherapy and chemotherapy, but five-year survival is only 5.6% despite these measures. Novel therapeutic approaches, such as immunotherapies, targeted therapies, and gene therapies, have been explored to attempt to extend survival for patients. Nanoparticles have been receiving increasing attention as promising vehicles for non-viral nucleic acid delivery in the context of GBM, though delivery is often limited by low blood-brain barrier permeability, particle instability, and low trafficking to target brain structures and cells. In this review, nanoparticle design considerations and new advances to overcome nucleic acid delivery challenges to treat brain cancer are summarized and discussed.
26.	Karlsson, Johan, 1979-, et al. (författare) Photocrosslinked Bioreducible Polymeric Nanoparticles for Enhanced Systemic siRNA Delivery as Cancer Therapy 2021 Ingår i: Advanced Functional Materials. - : John Wiley & Sons. - 1616-301X .- 1616-3028. ; 31:17 Tidskriftsartikel (refereegranskat)abstract Clinical translation of polymer-based nanocarriers for systemic delivery of RNA has been limited due to poor colloidal stability in the blood stream and intracellular delivery of the RNA to the cytosol. To address these limitations, this study reports a new strategy incorporating photocrosslinking of bioreducible nanoparticles for improved stability extracellularly and rapid release of RNA intracellularly. In this design, the polymeric nanocarriers contain ester bonds for hydrolytic degradation and disulfide bonds for environmentally triggered small interfering RNA (siRNA) release in the cytosol. These photocrosslinked bioreducible nanoparticles (XbNPs) have a shielded surface charge, reduced adsorption of serum proteins, and enable superior siRNA-mediated knockdown in both glioma and melanoma cells in high-serum conditions compared to non-crosslinked formulations. Mechanistically, XbNPs promote cellular uptake and the presence of secondary and tertiary amines enables efficient endosomal escape. Following systemic administration, XbNPs facilitate targeting of cancer cells and tissue-mediated siRNA delivery beyond the liver, unlike conventional nanoparticle-based delivery. These attributes of XbNPs facilitate robust siRNA-mediated knockdown in vivo in melanoma tumors colonized in the lungs following systemic administration. Thus, biodegradable polymeric nanoparticles, via photocrosslinking, demonstrate extended colloidal stability and efficient delivery of RNA therapeutics under physiological conditions, and thereby potentially advance systemic delivery technologies for nucleic acid-based therapeutics.
27.	Larsson, Simon B., et al. (författare) Epidemiology and clinical manifestations of different enterovirus and rhinovirus types show that EV-D68 may still have an impact on severity of respiratory infections 2022 Ingår i: Journal of Medical Virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 94:8, s. 3829-3839 Tidskriftsartikel (refereegranskat)abstract Respiratory infections are often caused by enteroviruses (EVs). The aim of this study was to identify whether certain types of EV were more likely to cause severe illness in 2016, when an increasing spread of upper respiratory infections was observed in Gothenburg, Sweden. The EV strain in 137 of 1341 nasopharyngeal samples reactive for EV by polymerase chain reaction could be typed by sequencing the viral 5 '-untranslated region and VP1 regions. Phylogenetic trees were constructed. Patient records were reviewed. Hospital care was needed for 46 of 74 patients with available medical records. The majority of the patients (83) were infected with the rhinovirus (RV). The remaining 54 were infected with EV A, B, C, and D strains of 13 different types, with EV-D68 and CV-A10 being the most common (17 vs. 14). Significantly more patients with EV-D68 presented with dyspnea, both when compared with other EV types (p = 0.003) and compared to all other EV and RV infections (p = 0.04). Phylogenetic analysis of the sequences revealed the spread of both Asian and European CV-A10 strains and 12 different RV C types. This study showed an abundance of different EV types spreading during a year with increased upper respiratory increased infections. EV-D68 infections were associated with more severe disease manifestation. Other EV and RV types were more evenly distributed between hospitalized and nonhospitalized patients. The EV type CV-A10 was also found in infected patients, which warrants further studies and surveillance, as this pathogen could cause more severe disease and outbreaks of hand, foot, and mouth disease.
28.	Leuchsenring, Anna Barslund, et al. (författare) Targeted mass spectrometry for Serum Amyloid A (SAA) isoform profiling in sequential blood samples from experimentally Staphylococcus aureus infected pigs 2020 Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919. Tidskriftsartikel (refereegranskat)abstract Serum amyloid A (SAA) is a well-described acute phase protein induced during the acute phase response (APR) to infection. Four isoform specific genes are found in most mammals. Depending on species, SAA3 and SAA4 are ge0nerally preferentially expressed extrahepatically whereas SAA1 and SAA2 are hepatic isoforms dominating the SAA serum pool. Little is known about how specific infections affect the serum SAA isoform profile, as SAA isoform discriminating antibodies are not generally available. An antibody independent, quantitative targeted MS method (Selected Reaction Monitoring, SRM) based on available information on porcine SAA isoform genes was developed and used to profile SAA in serum samples from pigs experimentally infected with Staphylococcus aureus (Sa). While results suggest SAA2 as the main circulating porcine SAA isoform, induced around 10 times compared to pre-infection, total SAA serum concentrations reached only around 3 μg/mL, much lower than established previously by immunoassays. This might suggest that SAA isoform variants not detected by the SRM method might be present in porcine serum. The assay allows monitoring host responses to experimental infections, infectious diseases and inflammation states in the pig at an unprecedented level of detail. It can also be used in a non-calibrated (relative quantification) format. SIGNIFICANCE: We developed an SRM MS method which for the first time allowed the specific quantification of each of the circulating porcine SAA isoforms (SAA2, SAA3, SAA4). It was found that SAA2 is the dominating circulating isoform of SAA in the pig and that, during the acute phase response SAA2, SAA3 and SAA4 are induced approx. 10, 15 and 2 times, respectively. Absolute levels of the isoforms as determined by SRM MS were much lower than reported previously for total SAA quantified by immunosassays, suggesting the existence of hitherto non-described SAA variants. SRM MS holds great promise for the study of the basic biology of SAA isoforms with the potential to study an even broader range of SAA variants.
29.	Li, Chen, et al. (författare) Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length 2020 Ingår i: American Journal of Human Genetics. - : CELL PRESS. - 0002-9297 .- 1537-6605. ; 106:3, s. 389-404 Tidskriftsartikel (refereegranskat)abstract Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
30.	Linares-Pastén, Javier A, et al. (författare) Novel xylan-degrading enzymes from polysaccharide utilizing loci of Prevotella copri DSM18205 2021 Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423. ; 31:10, s. 1330-1349 Tidskriftsartikel (refereegranskat)abstract Prevotella copri is a bacterium that can be found in the human gastrointestinal tract (GIT). The role of P. copri in the GIT is unclear, and elevated numbers of the microbe have been reported both in dietary fiber-induced improvement in glucose metabolism but also in conjunction with certain inflammatory conditions. These findings raised our interest in investigating the possibility of P. copri to grow on xylan, and identify the enzyme systems playing a role in digestion of xylan-based dietary fibers. Two xylan degrading polysaccharide utilizing loci (PUL10 and 15) were found in the genome, with three and eight glycoside hydrolase (GH) -encoding genes, respectively. Three of them were successfully produced in Escherichia coli: One extracellular enzyme from GH43 (subfamily 12, in PUL10, 60 kDa) and two enzymes from PUL15, one extracellular GH10 (41 kDa), and one intracellular GH43 (subfamily 137 kDa). Based on our results, we propose that in PUL15, GH10 (1) is an extracellular endo-1,4-β-xylanase, that hydrolazes mainly glucuronosylated xylan polymers to xylooligosaccharides (XOS); while, GH43-1 in the same PUL, is an intracellular β-xylosidase, catalyzing complete hydrolysis of the XOS to xylose. In PUL10, the characterized GH43-12 is an arabinofuranosidase, with a role in degradation of arabinoxylan, catalyzing removal of arabinose-residues on xylan.
31.	Malmaeus, Mikael, et al. (författare) Färdplan Sysselsättning - Arbetsmarknadseffekter av en grön omställning i Sverige 2022 Rapport (övrigt vetenskapligt/konstnärligt)
32.	Nilsson, Lisa M, 1976, et al. (författare) Genetics and Therapeutic Responses to Tumor-Infiltrating Lymphocyte Therapy of Pancreatic Cancer Patient-Derived Xenograft Models 2022 Ingår i: Gastro Hep Advances. - : Elsevier BV. - 2772-5723. ; 1:6, s. 1037-1048 Tidskriftsartikel (refereegranskat)abstract Background and Aims Pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide. Checkpoint immunotherapy has not yet shown encouraging results in pancreatic cancer possibly because of a poor immunogenicity and/or an immune suppressive microenvironment. The aim of this study was to develop patient-derived xenograft (PDX) models, compare their genetics to the original biopsies, and assess if autologous tumor-infiltrating lymphocytes (TILs) would have antitumoral activity in pancreatic cancer. Methods We subcutaneously transplanted tumors from 29 patients into NOG mice to generate PDX models. We established TIL cultures and injected them into PDX mice. We analyzed histology and genetics of biopsies and PDX tumors. Results Tumor growths were confirmed in 11 of 29 transplantations. The PDX tumors histologically resembled their original biopsies, but because stromal cells in the PDX model tumors were from mouse, their gene expression differed from the original biopsies. Immune checkpoint ligands other than programmed death ligand-1 (PD-L1) were expressed in pancreatic cancers, but PD-L1 was rarely expressed. When it was expressed, it correlated with tumor take in PDX models. One of the 3 tumors that expressed PD-L1 was an adenosquamous cancer, and another had a mismatch repair deficiency. TILs were expanded from 6 tumors and were injected into NOG or human interleukin-2 transgenic-NOG mice carrying PDX tumors. Regression of tumors could be verified in human interleukin-2 transgenic-NOG mice in 3 of the 6 PDX models treated with autologous TILs, including the adenosquamous PDX model. Conclusion PDX models of pancreatic cancer can be used to learn more about tumor characteristics and biomarkers and to evaluate responses to adoptive cell therapy and combination therapies. The major benefit of the model is that modifications of T cells can be tested in an autologous humanized mouse model to gain preclinical data to support the initiation of a clinical trial.
33.	Olsson, H, et al. (författare) Predictors of short- and long-term mortality in critically ill, older adults admitted to the emergency department : an observational study 2022 Ingår i: BMC Emergency Medicine. - : Springer Nature. - 1471-227X. ; 22:1 Tidskriftsartikel (refereegranskat)abstract Background In the future, we can expect an increase in older patients in emergency departments (ED) and acute wards. The main purpose of this study was to identify predictors of short- and long-term mortality in the ED and at hospital discharge. Methods This is a retrospective, observational, single-center, cohort study, involving critically ill older adults, recruited consecutively in an ED. The primary outcome was mortality. All patients were followed for 6.5-7.5 years. The Cox proportional hazards model was used. Results Regarding all critically ill patients aged >= 70 years and identified in the ED (n = 402), there was a significant association between mortality at 30 days after ED admission and unconsciousness on admission (HR 3.14, 95% CI 2.09-4.74), hypoxia on admission (HR 2.51, 95% CI 1.69-3.74) and age (HR 1.06 per year, 95% CI 1.03-1.09), (all p < 0.001). Of 402 critically ill patients aged >= 70 years and identified in the ED, 303 were discharged alive from hospital. There was a significant association between long-term mortality and the Charlson Comorbidity Index (CCI) > 2 (HR 1.90, 95% CI 1.46-2.48), length of stay (LOS) > 7 days (HR 1.72, 95% CI 1.32-2.23), discharge diagnosis of pneumonia (HR 1.65, 95% CI 1.24-2.21) and age (HR 1.08 per year, 95% CI 1.05-1.10), (all p < 0.001). The only symptom or vital sign associated with long-term mortality was hypoxia on admission (HR 1.70, 05% CI 1.30-2.22). Conclusions Among critically ill older adults admitted to an ED and discharged alive the following factors were predictive of long-term mortality: CCI > 2, LOS > 7 days, hypoxia on admission, discharge diagnosis of pneumonia and age. The following factors were predictive of mortality at 30 days after ED admission: unconsciousness on admission, hypoxia and age. These data might be clinically relevant when it comes to individualized care planning, which should take account of risk prediction and estimated prognosis.
34.	Poetzelsberger, Elisabeth, et al. (författare) Mapping the patchy legislative landscape of non-native tree species in Europe 2020 Ingår i: Forestry (London). - : Oxford University Press. - 0015-752X .- 1464-3626. ; 93:4, s. 567-586 Tidskriftsartikel (refereegranskat)abstract Europe has a history rich in examples of successful and problematic introductions of trees with a native origin outside of Europe (non-native trees, NNT). Many international legal frameworks such as treaties and conventions and also the European Union have responded to the global concern about potential negative impacts of NNT that may become invasive in natural ecosystems. It is, however, national and regional legislation in particular that affects current and future management decisions in the forest sector and shapes the landscapes of Europe. We identified all relevant legal instruments regulating NNT, the different legal approaches and the regulatory intensity in 40 European countries (no microstates). Information on hard and effective soft law instruments were collected by means of a targeted questionnaire and consultation of international and national legislation information systems and databases. In total, 335 relevant legal instruments were in place in June/July 2019 to regulate the use of NNT in the investigated 116 geopolitical legal units (countries as well as sub-national regions with their own legislation). Countries and regions were empirically categorized according to ad hoc-defined legislation indicators. These indicators pay respect to the general bans on the introduction of non-native species, the generally allowed and prohibited NNT, approval mechanisms and specific areas or cases where NNT are restricted or prohibited. Our study revealed a very diverse landscape of legal frameworks across Europe, with a large variety of approaches to regulating NNT being pursued and the intensity of restriction ranging from very few restrictions on species choice and plantation surface area to the complete banning of NNT from forests. The main conclusion is that there is a clear need for more co-ordinated, science-based policies both at the local and international levels to enhance the advantages of NNT and mitigate potential negative effects.
35.	Ranta, Susanna, et al. (författare) Extracorporeal Membrane Oxygenation Support in Children With Hematologic Malignancies in Sweden 2021 Ingår i: Journal of Pediatric Hematology/Oncology. - : Wolters Kluwer. - 1077-4114 .- 1536-3678. ; 43:2, s. e272-e275 Tidskriftsartikel (refereegranskat)abstract Background: Extracorporeal membrane oxygenation (ECMO) is used in severe respiratory and/or circulatory failure when conventional critical care fails. Studies on patients with hematologic malignancies on ECMO have shown contradictory results; immunosuppression and coagulopathy are relative contraindications to ECMO.Observations: This nationwide Swedish retrospective chart review identified 958 children with hematologic malignancies of whom 12 (1.3%) required ECMO support. Eight patients survived ECMO, 7 the total intensive care period, and 6 survived the underlying malignancy.Conclusions: ECMO may be considered in children with hematologic malignancy. Short-term and long-term survival, in this limited group, was similar to that of children on ECMO at large.
36.	Sanne, Johan M., et al. (författare) Vart tog arbetslivet vägen? Kunskapsluckor i innovation och forskning kring cirkulär ekonomi 2022 Ingår i: Book of abstracts FALF 2022: Framtidens arbete-arbetets framtid. - : Luleå tekniska universitet. ; , s. 7-8 Konferensbidrag (refereegranskat)
37.	Scott, Aaron M, et al. (författare) Generalized precursor prediction boosts identification rates and accuracy in mass spectrometry based proteomics 2023 Ingår i: Communications Biology. - 2399-3642. ; 6, s. 1-13 Tidskriftsartikel (refereegranskat)abstract Data independent acquisition mass spectrometry (DIA-MS) has recently emerged as an important method for the identification of blood-based biomarkers. However, the large search space required to identify novel biomarkers from the plasma proteome can introduce a high rate of false positives that compromise the accuracy of false discovery rates (FDR) using existing validation methods. We developed a generalized precursor scoring (GPS) method trained on 2.75 million precursors that can confidently control FDR while increasing the number of identified proteins in DIA-MS independent of the search space. We demonstrate how GPS can generalize to new data, increase protein identification rates, and increase the overall quantitative accuracy. Finally, we apply GPS to the identification of blood-based biomarkers and identify a panel of proteins that are highly accurate in discriminating between subphenotypes of septic acute kidney injury from undepleted plasma to showcase the utility of GPS in discovery DIA-MS proteomics.
38.	Vala, Cecilie Hongslo, 1983, et al. (författare) Risk for hip fracture before and after total knee replacement in Sweden 2020 Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 31:5, s. 887-895 Tidskriftsartikel (refereegranskat)abstract We studied the risk for hip fracture before and after total knee replacement (TKR) in the entire population in Sweden. Women and men had a low risk for hip fracture before TKR but an increased risk the first year after TKR. Purpose It is known that osteoarthritis is associated with high bone mass. We therefore studied the risk of hip fracture before and after total knee replacement (TKR), risk of different hip fracture types, and risk subdivided in genders and age groups. Methods We followed the total Swedish population born between 1902 and 1952 (n = 4,258,934) during the period 1987-2002 and identified all patients with TKR due to primary OA (n = 39,291), and all patients with hip fracture (n = 195,860) in the Swedish National Inpatient Register. The risk time analyses were based on Poisson regression models. Results The hazard ratio (HR) for hip fracture the last year before TKR was 0.86 (95% CI 0.74 to 1.00) and the first year after 1.26 (95% CI 1.11 to 1.42) compared to individuals without TKR. The HR for femoral neck fracture 0-10 years after TKR was 0.95 (95% CI 0.89 to 1.01) and for trochanteric fracture was 1.13 (95% CI 1.06 to 1.21). The HR for hip fracture in the age group 50-74 was 1.28 (95% CI 1.14 to 1.43) and in the age group 75-90 years was 0.99 (95% CI 0.94 to 1.04) 0-10 years after TKR, compared to individuals without TKR. Conclusion Individuals had a low risk for hip fracture before TKR but an increased risk the first year after TKR. The risk in individuals below age 75 years and for trochanteric fractures was increased after TKR. Possible explanations include changed knee kinematics after a TKR, physical activity level, fall risk, and other unknown factors.
39.	Vilhav, Caroline, et al. (författare) Genetics and Therapeutic Responses to Tumor-infiltrating Lymphocyte Therapy of Pancreatic Cancer Patient-derived Xenograft Models 2023 Ingår i: HPB. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
40.	Villarroel, Beatriz, et al. (författare) The Vanishing and Appearing Sources during a Century of Observations Project. I. USNO Objects Missing in Modern Sky Surveys and Follow-up Observations of a "Missing Star" 2020 Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 159:1 Tidskriftsartikel (refereegranskat)abstract In this paper we report the current status of a new research program. The primary goal of the "Vanishing and Appearing Sources during a Century of Observations" project is to search for vanishing and appearing sources using existing survey data to find examples of exceptional astrophysical transients. The implications of finding such objects extend from traditional astrophysics fields to the more exotic searches for evidence of technologically advanced civilizations. In this first paper we present new, deeper observations of the tentative candidate discovered by Villarroel et al. in 2016. We then perform the first searches for vanishing objects throughout the sky by comparing 600 million objects from the US Naval Observatory Catalogue (USNO) B1.0 down to a limiting magnitude of similar to 20-21 with the recent Pan-STARRS Data Release-1 (DR1) with a limiting magnitude of similar to 23.4. We find about 150,000 preliminary candidates that do not have any Pan-STARRS counterpart within a 30 '' radius. We show that these objects are redder and have larger proper motions than typical USNO objects. We visually examine the images for a subset of about 24,000 candidates, superseding the 2016 study with a sample 10 times larger. We find about 100 point sources visible in only one epoch in the red band of the USNO, which may be of interest in searches for strong M-dwarf flares, high-redshift supernovae, or other categories of unidentified red transients.
41.	Walser, Marion, 1961, et al. (författare) Growth Hormone and Neuronal Hemoglobin in the Brain-Roles in Neuroprotection and Neurodegenerative Diseases 2021 Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 11 Tidskriftsartikel (refereegranskat)abstract In recent years, evidence for hemoglobin (Hb) synthesis in both animal and human brains has been accumulating. While circulating Hb originating from cerebral hemorrhage or other conditions is toxic, there is also substantial production of neuronal Hb, which is influenced by conditions such as ischemia and regulated by growth hormone (GH), insulin-like growth factor-I (IGF-I), and other growth factors. In this review, we discuss the possible functions of circulating and brain Hb, mainly the neuronal form, with respect to the neuroprotective activities of GH and IGF-I against ischemia and neurodegenerative diseases. The molecular pathways that link Hb to the GH/IGF-I system are also reviewed, although the limited number of reports on this topic suggests a need for further studies. In summary, GH and/or IGF-I appear to be significant determinants of systemic and local brain Hb concentrations through mediating responses to oxygen and metabolic demand, as part of the neuroprotective effects exerted by GH and IGF-I. The nature and quantity of the latter deserve further exploration in specific experiments.
42.	Wilhelmson, Anna S K, et al. (författare) Deficiency of mature B cells does not alter the atherogenic response to castration in male mice 2022 Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1 Tidskriftsartikel (refereegranskat)abstract Testosterone deficiency in men is associated with increased atherosclerosis burden and increased cardiovascular risk. In male mice, testosterone deficiency induced by castration increases atherosclerosis as well as mature B cell numbers in spleen. As B cells are potentially pro-atherogenic, we hypothesized that there may be a link between these effects. To address whether mature B cell deficiency alter the atherogenic response to castration, we studied B cell-deficient mu MT and genotype control male mice on an atherosclerosis-prone Apoe(-/-) background that were castrated or sham-operated pre-pubertally and fed a high-fat diet between 8 and 16 weeks of age to accelerate atherosclerosis development. Genotype did not affect the effects of castration on body weight or weights of fat depots and there were no differences in serum cholesterol levels across the four groups. Atherosclerosis assessed by quantification of lesion area in serial sections of the aortic root was significantly increased by castration and by the mu MT mutation, with no significant interaction between genotype and surgery. In conclusion, castration evokes a similar atherogenic response in B cell-deficient mu MT and control mice. These data suggest that atherogenesis following castration is unrelated to the effects of androgens on mature B cell numbers.

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