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Sökning: WFRF:(Andersson Harry)

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1.
  • Abrahamsson, Sara, et al. (författare)
  • Inheritance of height growth and autumn cold hardiness based on two generations of full-sib and half-sib families of Pinus sylvestris
  • 2012
  • Ingår i: Scandinavian Journal of Forest Research. - : Informa UK Limited. - 0282-7581 .- 1651-1891. ; 27, s. 405-413
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetic variability in height growth and autumn cold hardiness were evaluated in a full-sib family of Scots pine (Pinus sylvestris (L.)) in a field trial in northern Sweden and 358 open pollinated families generated from the progeny of the full-sib cross. Height and autumn cold hardiness were assessed in the progeny of the full-sib cross at 9-19 years of age and on 3995 open pollinated progenies at three years of age. The autumn cold hardiness [critical temperature (CT)] of trees and progenies was tested by artificial freeze testing of detached needles at various temperatures. Significant genetic variation was found among progenies in both height growth and cold hardiness with a narrow sense heritability of 0.16 and 0.37, respectively. There was also a significant positive genetic correlation (r(a) = 0.39) between height growth and CT with taller trees showing later autumn cold acclimation. It was concluded that there is significant additive genetic variance for height and CT which warrants a potential for mapping quantitative trait loci. Furthermore, the low heritability for height growth shows the importance of removing the environmental influence by using additive genetic predictions instead of phenotypic measurements thereby improving the accuracy of genetic associations.
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3.
  • Andersson, Tommy D, et al. (författare)
  • Leisure events and regional economic impact
  • 1999
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • I dag är det alltid en tuff tävlan om att få arrangera ett stort idrottsevenmang. Regioner och städer är villiga att spendera stora pengar för att utses som arrangör för ett OS, VM och andra mega-event.   Den här rapporten tar upp flera aspekter till vad ett stort arrangemang kostar och vad det ger för effekter för respektive region.   De stora inkomstkällorna för ett stort arrangemang kan delas in fyra delar: - besökarnas konsumtion. - sponsorpengar. - bidrag från olika myndigheter. - inkomster från medias aktiviteter/rättigheter.   I den här rapporten redogörs för utfallet av VM-tävlingarna på skidor i Trondheim 1997.  
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5.
  • Berg, Katarina, et al. (författare)
  • Elevated CD14++CD16− Monocytes Predict Cardiovascular Events
  • 2012
  • Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 1942-325X .- 1942-3268. ; 5:1, s. 122-131
  • Tidskriftsartikel (refereegranskat)abstract
    • Background—Although monocytes in peripheral blood are no longer considered to be a homogeneous population, associations between distinct monocyte subsets and cardiovascular disease have not been highlighted in large epidemiological studies. Methods and Results—The study included 700 randomly selected subjects from the cardiovascular arm of the Malmö Diet and Cancer study. Among these, 123 subjects experienced ischemic cardiovascular events during the follow-up until December 2008. Mononuclear leukocytes frozen at the baseline investigation in 1991 to 1994 were thawed and analyzed with flow cytometry to enumerate monocyte subsets, based on CD14 and CD16 expression. The percentage and number of classical CD14++CD16− monocytes were increased in the cardiovascular-event group compared with the event-free subjects (median, 69% [interquartile range, 62% to 76%] versus 67% [59% to 72%], P=0.017; 344 [251 to 419] cells/μL versus 297 [212 to 384] cells/μL, P=0.003). The hazard ratio was 1.66 for suffering a cardiovascular event in the highest tertile of the number of CD14++CD16− monocytes compared with the lowest tertile, even after adjustment for common risk factors (HR, 1.66; 95% CI: 1.02 to 2.72). CD14++CD16− monocytes did not, however, associate with the extent of atherosclerosis at baseline. In contrast, the percentage of monocytes expressing CD16 was negatively associated to the extent of carotid atherosclerosis measured as intima-media thickness at baseline. The chemokine receptors CCR2, CX3CR1, and CCR5 were not differentially expressed between cases and controls on any of the monocyte subsets, but CCR5 expression on CD14+CD16++ monocytes was negatively associated to carotid intima-media thickness. Conclusions—This study shows that classical CD14++CD16− monocytes can predict future cardiovascular risk independently of other risk factors in a randomly selected population.
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  • Chen, Zhiqiang, et al. (författare)
  • Accuracy of genomic selection for growth and wood quality traits in two control-pollinated progeny trials using exome capture as the genotyping platform in Norway spruce
  • 2018
  • Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 19
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundGenomic selection (GS) can increase genetic gain by reducing the length of breeding cycle in forest trees. Here we genotyped 1370 control-pollinated progeny trees from 128 full-sib families in Norway spruce (Picea abies (L.) Karst.), using exome capture as genotyping platform. We used 116,765 high-quality SNPs to develop genomic prediction models for tree height and wood quality traits. We assessed the impact of different genomic prediction methods, genotype-by-environment interaction (GxE), genetic composition, size of the training and validation set, relatedness, and number of SNPs on accuracy and predictive ability (PA) of GS.ResultsUsing G matrix slightly altered heritability estimates relative to pedigree-based method. GS accuracies were about 11-14% lower than those based on pedigree-based selection. The efficiency of GS per year varied from 1.71 to 1.78, compared to that of the pedigree-based model if breeding cycle length was halved using GS. Height GS accuracy decreased to more than 30% while using one site as training for GS prediction and using this model to predict the second site, indicating that GxE for tree height should be accommodated in model fitting. Using a half-sib family structure instead of full-sib structure led to a significant reduction in GS accuracy and PA. The full-sib family structure needed only 750 markers to reach similar accuracy and PA, as compared to 100,000 markers required for the half-sib family, indicating that maintaining the high relatedness in the model improves accuracy and PA. Using 4000-8000 markers in full-sib family structure was sufficient to obtain GS model accuracy and PA for tree height and wood quality traits, almost equivalent to that obtained with all markers.ConclusionsThe study indicates that GS would be efficient in reducing generation time of breeding cycle in conifer tree breeding program that requires long-term progeny testing. The sufficient number of trees within-family (16 for growth and 12 for wood quality traits) and number of SNPs (8000) are required for GS with full-sib family relationship. GS methods had little impact on GS efficiency for growth and wood quality traits. GS model should incorporate GxE effect when a strong GxE is detected.
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8.
  • Dahlin, Mats, et al. (författare)
  • Worry-specific versus self-tailored internet-based treatments for generalized anxiety disorder, with scheduled support or support on demand : A pilot factorial design trial
  • 2022
  • Ingår i: Internet Interventions. - : Elsevier BV. - 2214-7829. ; 28
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies suggest that internet-delivered cognitive behaviour therapy (ICBT) can be effective when treating generalized anxiety disorder (GAD). This pilot factorial design study examined the effects of two types of ICBT (worry-specific and self-tailored treatment), and two support types (scheduled weekly support and support on demand), on measures of worry, anxiety, and depressive symptoms. Participants (N = 85) were randomized into four treatment groups. Post-treatment measures were completed by 76.5% after eight weeks (n = 65). Intention to treat analysis showed significant improvements, with moderate to large within-group effects on the primary outcome measure, Penn State Worry Questionnaire (Cohen's d = 0.77–1.43). Minor to large effects on the secondary measures were found in all groups (Cohen's d = 0.13–1.66). No significant differences in outcome measures were found between the groups. Receiving scheduled support and self-tailored treatment was rated as more positive than receiving support on demand and the worry-specific program. A limitation is the low number of participants. The pilot results suggest that GAD can be treated with both worry-specific and self-tailored treatments, and that ICBT can be supported both with scheduled and support on demand.
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9.
  • de Las Heras Gala, Hugo, et al. (författare)
  • Quality control in cone-beam computed tomography (CBCT): EFOMP-ESTRO-IAEA protocol
  • 2017
  • Rapport (refereegranskat)abstract
    • Quality control of cone-beam computed tomography (CBCT) systems is an essential part of quality assurance to periodically check that quality requirements are met, reduce uncertainties and errors and reduce the likelihood of accidents and incidents. Radiation exposure levels must be measured to ensure that patient doses associated with CBCT examinations are kept as low as reasonably achievable consistent with the required diagnostic information. The main purpose of this document is to present procedures for quality control of CBCT systems used for dental, radiotherapy, interventional radiology and guided surgery applications.
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10.
  • de Las Heras Gala, Hugo, et al. (författare)
  • Quality control in cone-beam computed tomography (CBCT) EFOMP-ESTRO-IAEA protocol (summary report)
  • 2017
  • Ingår i: Physica medica (Testo stampato). - : Elsevier BV. - 1120-1797 .- 1724-191X. ; 39, s. 67-72
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the guideline presented in this article is to unify the test parameters for image quality evaluation and radiation output in all types of cone-beam computed tomography (CBCT) systems. The applications of CBCT spread over dental and interventional radiology, guided surgery and radiotherapy. The chosen tests provide the means to objectively evaluate the performance and monitor the constancy of the imaging chain. Experience from all involved associations has been collected to achieve a consensus that is rigorous and helpful for the practice. The guideline recommends to assess image quality in terms of uniformity, geometrical precision, voxel density values (or Hounsfield units where available), noise, low contrast resolution and spatial resolution measurements. These tests usually require the use of a phantom and evaluation software. Radiation output can be determined with a kerma-area product meter attached to the tube case. Alternatively, a solid state dosimeter attached to the flat panel and a simple geometric relationship can be used to calculate the dose to the isocentre. Summary tables including action levels and recommended frequencies for each test, as well as relevant references, are provided. If the radiation output or image quality deviates from expected values, or exceeds documented action levels for a given system, a more in depth system analysis (using conventional tests) and corrective maintenance work may be required.
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11.
  • Di Saverio, Salomone, et al. (författare)
  • Diagnosis and treatment of acute appendicitis: 2020 update of the WSES Jerusalem guidelines
  • 2020
  • Ingår i: World Journal of Emergency Surgery. - : BMC. - 1749-7922. ; 15:1
  • Forskningsöversikt (refereegranskat)abstract
    • Background and aims Acute appendicitis (AA) is among the most common causes of acute abdominal pain. Diagnosis of AA is still challenging and some controversies on its management are still present among different settings and practice patterns worldwide. In July 2015, the World Society of Emergency Surgery (WSES) organized in Jerusalem the first consensus conference on the diagnosis and treatment of AA in adult patients with the intention of producing evidence-based guidelines. An updated consensus conference took place in Nijemegen in June 2019 and the guidelines have now been updated in order to provide evidence-based statements and recommendations in keeping with varying clinical practice: use of clinical scores and imaging in diagnosing AA, indications and timing for surgery, use of non-operative management and antibiotics, laparoscopy and surgical techniques, intra-operative scoring, and peri-operative antibiotic therapy. Methods This executive manuscript summarizes the WSES guidelines for the diagnosis and treatment of AA. Literature search has been updated up to 2019 and statements and recommendations have been developed according to the GRADE methodology. The statements were voted, eventually modified, and finally approved by the participants to the consensus conference and by the board of co-authors, using a Delphi methodology for voting whenever there was controversy on a statement or a recommendation. Several tables highlighting the research topics and questions, search syntaxes, and the statements and the WSES evidence-based recommendations are provided. Finally, two different practical clinical algorithms are provided in the form of a flow chart for both adults and pediatric (< 16 years old) patients. Conclusions The 2020 WSES guidelines on AA aim to provide updated evidence-based statements and recommendations on each of the following topics: (1) diagnosis, (2) non-operative management for uncomplicated AA, (3) timing of appendectomy and in-hospital delay, (4) surgical treatment, (5) intra-operative grading of AA, (6) ,management of perforated AA with phlegmon or abscess, and (7) peri-operative antibiotic therapy.
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  • Engelbertsen, Daniel, et al. (författare)
  • T-Helper 2 Immunity Is Associated With Reduced Risk of Myocardial Infarction and Stroke.
  • 2013
  • Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636.
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Experimental studies in mice have attributed T-helper (Th) 1 and Th2 cells important roles in atherosclerosis, but the clinical importance of these cells in cardiovascular disease (CVD) remains to be clarified. Here, we investigated associations between Th1 and Th2 cells, carotid intima-media thickness, and cardiovascular risk. METHODS AND RESULTS: Blood drawn at baseline and incident cardiovascular events during 15-year follow-up were assessed in 700 participants. Baseline Th1 (CD3(+)CD4(+)interferon-γ(+)) and Th2 (CD3(+)CD4(+)IL-4(+)) cells were analyzed by flow cytometry, and cytokine-release from activated mononuclear leukocytes was measured by multiplex technology. High numbers of Th2 cells were independently associated with decreased mean common carotid intima-media thickness. High numbers of Th2 cells were also independently associated with a reduced risk of acute myocardial infarction in women (hazard ratio, 0.19; 95% confidence interval, 0.06-0.56; P=0.002 for the highest versus the lowest tertile of Th2 cells). Moreover, release of the Th2 cytokine IL-4 from activated mononuclear leukocytes was independently associated with a reduced risk of CVD. No independent associations between Th1 cells and carotid intima-media thickness or CVD risk were found. CONCLUSIONS: Our observations provide the first clinical evidence for a protective role of Th2 immunity in CVD. They also suggest this protection is more prominent in women than in men. In spite of convincing evidence from experimental studies, we found no support for a role of Th1 immunity in CVD.
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  • Eriksson, Kimmo, et al. (författare)
  • Perceptions of the appropriate response to norm violation in 57 societies
  • 2021
  • Ingår i: Nature Communications. - : Nature Research. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Norm enforcement may be important for resolving conflicts and promoting cooperation. However, little is known about how preferred responses to norm violations vary across cultures and across domains. In a preregistered study of 57 countries (using convenience samples of 22,863 students and non-students), we measured perceptions of the appropriateness of various responses to a violation of a cooperative norm and to atypical social behaviors. Our findings highlight both cultural universals and cultural variation. We find a universal negative relation between appropriateness ratings of norm violations and appropriateness ratings of responses in the form of confrontation, social ostracism and gossip. Moreover, we find the country variation in the appropriateness of sanctions to be consistent across different norm violations but not across different sanctions. Specifically, in those countries where use of physical confrontation and social ostracism is rated as less appropriate, gossip is rated as more appropriate. Little is known about peoples preferred responses to norm violations across countries. Here, in a study of 57 countries, the authors highlight cultural similarities and differences in peoples perception of the appropriateness of norm violations.
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14.
  • Faymonville, Louise, 1979- (författare)
  • Hövisk litteratur och förändringar i det fornsvenska textlandskapet
  • 2023
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis aims to shed light on the presence of the Old Swedish courtly literature in the changing profane textual landscape of medieval Sweden to better understand the function and significance of this literature. The point of departure for this study are the three verse romances collectively known as the Eufemiavisor and their properties in their capacity as courtly literature. The material consists of 31 profane literary works and 26 manuscripts produced between 1300 and 1529. The study draws on polysystem theory (Even-Zohar 1990) and makes use of notions and approaches from various fields of textual scholarship such as philology and the history of literature.The study is divided into three main parts. The first part focuses on the work perspective and structures the development of the Old Swedish profane textual landscape into four stages: introduction and establishment; diversification and expansion; politicizing and centralisation; and further development and administration of literary traditions. The second part, which analyses the use of a courtly repertoire in the corpus, uses these stages to interpret the results. The courtly repertoire is defined as a set of properties manifested in the Eufemiavisor. The properties included in the analysis are a courtly vocabulary, certain expressions, the form Knittelvers, adventure as a theme, and the intratextual temporal and spatial settings. The analysis shows that certain parts of the repertoire quickly become obsolete while others (such as a core vocabulary and the Knittelvers) remain productive until the end of the Middle Ages but gradually transform into stereotypes or evolve to become useful outside of a courtly literary context. The third part focuses on the manuscript perspective. A network analysis of the texts’ appearances in manuscripts shows that even though the Eufemiavisor had a central position, the rhyme chronicle Erikskrönikan could be considered the central node connecting various interests and textual orientations, keeping the chronicle relevant throughout the Middle Ages. The analysis of the transmission of the Eufemiavisor reveals their dynamic and multifunctional nature. Of the three romances, Hertig Fredrik av Normandie is perhaps the most nuanced, a factor that may have contributed to it being the most copied as well as the longest-lasting of the Eufemiavisor.The results suggest a gradual move of the courtly repertoire from a central position towards a peripheral position in the literary system as a consequence of a growing system, new interests, and new groups governing the system. By the end of the Middle Ages, the function of the courtly repertoire appears to have become one of preservation of traditional literary taste.
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15.
  • Grönberg, Caitriona, et al. (författare)
  • Human Carotid Plaques With High Levels of Interleukin-16 Are Associated With Reduced Risk for Cardiovascular Events.
  • 2015
  • Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 46:10, s. 2748-2754
  • Tidskriftsartikel (refereegranskat)abstract
    • Interleukin-16 (IL-16) functions as a regulator of T-cell growth and acts as an inducer of cell migration. The aim of this study was to determine whether IL-16 measured in human carotid plaques was associated with symptoms (eg, stroke, transient ischemic attack, or amaurosis fugax), markers of plaque stability, and postoperative cardiovascular events.
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16.
  • Hong, Zhou, et al. (författare)
  • Measuring stiffness using acoustic tool for Scots pine breeding selection
  • 2015
  • Ingår i: Scandinavian Journal of Forest Research. - : Informa UK Limited. - 0282-7581 .- 1651-1891. ; 30:4, s. 363-372
  • Tidskriftsartikel (refereegranskat)abstract
    • Stiffness (modulus of elasticity, MOE) of conifer trees is the most important trait for structural wood products. Finding a fast, reliable and non-destructive way to measure MOE is a priority for screening large progeny trials in tree breeding programmes. For Scots pine, time-of-flight (TOF) velocity measured on standing trees accounted for 47% of the variation to the benchmark SilviScan-based clearwood MOE (MOEs), under the assumption of constant wood density. If wood density was included, 59% of the variation was accounted for. The TOF stiffness measurements on standing trees were, however, more related to the clearwood MOEs in the outerwood, and the prediction was the most reliable at breast height compared to the stem base and the top section. Microfibril angle (MFA) had higher correlation with acoustic velocity (VEL) of standing trees than wood density, and among the early, transition and latewood density, the latewood density had the highest correlation with stiffness measurements on standing trees. VEL measured at breast height in combination with wood density was the most reliable predictor of MOE of standing trees for selection and breeding in Scots pine.
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17.
  • Jakobsson, Gabriel, et al. (författare)
  • Therapeutic S100A8/A9 blockade inhibits myocardial and systemic inflammation and mitigates sepsis-induced myocardial dysfunction
  • 2023
  • Ingår i: Critical Care. - : BMC. - 1364-8535 .- 1466-609X. ; 27, s. 1-16
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims: The triggering factors of sepsis-induced myocardial dysfunction (SIMD) are poorly understood and are not addressed by current treatments. S100A8/A9 is a pro-inflammatory alarmin abundantly secreted by activated neutrophils during infection and inflammation. We investigated the efficacy of S100A8/A9 blockade as a potential new treatment in SIMD. Methods: The relationship between plasma S100A8/A9 and cardiac dysfunction was assessed in a cohort of 62 patients with severe sepsis admitted to the intensive care unit of Linköping University Hospital, Sweden. We used S100A8/A9 blockade with the small-molecule inhibitor ABR-238901 and S100A9−/− mice for therapeutic and mechanistic studies on endotoxemia-induced cardiac dysfunction in mice. Results: In sepsis patients, elevated plasma S100A8/A9 was associated with left-ventricular (LV) systolic dysfunction and increased SOFA score. In wild-type mice, 5 mg/kg of bacterial lipopolysaccharide (LPS) induced rapid plasma S100A8/A9 increase and acute LV dysfunction. Two ABR-238901 doses (30 mg/kg) administered intraperitoneally with a 6 h interval, starting directly after LPS or at a later time-point when LV dysfunction is fully established, efficiently prevented and reversed the phenotype, respectively. In contrast, dexamethasone did not improve cardiac function compared to PBS-treated endotoxemic controls. S100A8/A9 inhibition potently reduced systemic levels of inflammatory mediators, prevented upregulation of inflammatory genes and restored mitochondrial function in the myocardium. The S100A9−/− mice were protected against LPS-induced LV dysfunction to an extent comparable with pharmacologic S100A8/A9 blockade. The ABR-238901 treatment did not induce an additional improvement of LV function in the S100A9−/− mice, confirming target specificity. Conclusion: Elevated S100A8/A9 is associated with the development of LV dysfunction in severe sepsis patients and in a mouse model of endotoxemia. Pharmacological blockade of S100A8/A9 with ABR-238901 has potent anti-inflammatory effects, mitigates myocardial dysfunction and might represent a novel therapeutic strategy for patients with severe sepsis. Graphical Abstract: [Figure not available: see fulltext.].
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18.
  • Kolbus, Daniel, et al. (författare)
  • Association between CD8+ T-cell subsets and cardiovascular disease
  • 2013
  • Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 274:1, s. 41-51
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The findings of experimental studies suggest that the immune system plays a key role in atherosclerosis, but the clinical importance of different immune cells in cardiovascular disease remains poorly characterized. In this study we investigated the association between CD8+ T cells and carotid disease as well as development of cardiovascular disease events. Methods The study cohort comprised 700 subjects from the cardiovascular arm of the Malmö Diet and Cancer Study. Peripheral blood mononuclear cells, obtained at the 1991–1994 baseline investigation and stored at −140 °C, were thawed and the different CD8+ T-cell populations analysed by flow cytometry. Baseline carotid intima–media thickness and stenosis were assessed by ultrasonography and clinical events were monitored through validated national registers. Results Subjects with a high fraction of CD8+ T cells were characterized by decreased cytokine release from activated leucocytes, metabolic signs of insulin resistance and increased incidence of coronary events; hazard ratios (95% confidence intervals) for the second and third tertiles of CD8+ T cells were 2.57 (1.16, 5.67) and 2.61 (1.19, 5,71), respectively, in a Cox proportional hazards regression model. Correlations were found between the fraction of CD8+CD25+ T cells and the degree of carotid stenosis (r = 0.11, P < 0.01), and between the CD8+CD56−IFN-γ+ T-cell fraction and the degree of stenosis (r = −0.18, P < 0.005). The association between CD8+CD56−IFN-γ+ T cells and carotid stenosis remained significant after controlling for major cardiovascular disease risk factors. Conclusion This study provides prospective clinical evidence for a role of CD8+ T cells in cardiovascular disease and suggests the existence of CD8+ T-cell subsets with different pathological functions.
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19.
  • Liu, Ka‐Cheuk, et al. (författare)
  • Inhibition of Cdk5 Promotes β-Cell Differentiation From Ductal Progenitors
  • 2017
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 67:1, s. 58-70
  • Tidskriftsartikel (refereegranskat)abstract
    • Inhibition of notch signaling is known to induce differentiation of endocrine cells in zebrafish and mouse. After performing an unbiased in vivo screen of ∼2,200 small molecules in zebrafish, we identified an inhibitor of Cdk5 (roscovitine), which potentiated the formation of β-cells along the intrapancreatic duct during concurrent inhibition of notch signaling. We confirmed and characterized the effect with a more selective Cdk5 inhibitor, (R)-DRF053, which specifically increased the number of duct-derived β-cells without affecting their proliferation. By duct-specific overexpression of the endogenous Cdk5 inhibitors Cdk5rap1 or Cdkal1 (which previously have been linked to diabetes in genome-wide association studies), as well as deleting cdk5, we validated the role of chemical Cdk5 inhibition in β-cell differentiation by genetic means. Moreover, the cdk5 mutant zebrafish displayed an increased number of β-cells independently of inhibition of notch signaling, in both the basal state and during β-cell regeneration. Importantly, the effect of Cdk5 inhibition to promote β-cell formation was conserved in mouse embryonic pancreatic explants, adult mice with pancreatic ductal ligation injury, and human induced pluripotent stem (iPS) cells. Thus, we have revealed a previously unknown role of Cdk5 as an endogenous suppressor of β-cell differentiation and thereby further highlighted its importance in diabetes.
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20.
  • Lluis, Nuria, et al. (författare)
  • Intraductal papillary neoplasms of the bile duct: a European retrospective multicenter observational study (EUR-IPNB study)
  • 2023
  • Ingår i: International Journal of Surgery. - : LIPPINCOTT WILLIAMS & WILKINS. - 1743-9191 .- 1743-9159. ; 109:4, s. 760-771
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Purpose:Intraductal papillary neoplasm of the bile duct (IPNB) is a rare disease in Western countries. The main aim of this study was to characterize current surgical strategies and outcomes in the mainly European participating centers. Methods:A multi-institutional retrospective series of patients with a diagnosis of IPNB undergoing surgery between 1 January 2010 and 31 December 2020 was gathered under the auspices of the European-African Hepato-Pancreato-Biliary Association. The textbook outcome (TO) was defined as a non-prolonged length of hospital stay plus the absence of any Clavien-Dindo grade at least III complications, readmission, or mortality within 90 postoperative days. Results:A total of 28 centers contributed 85 patients who underwent surgery for IPNB. The median age was 66 years (55-72), 49.4% were women, and 87.1% were Caucasian. Open surgery was performed in 72 patients (84.7%) and laparoscopic in 13 (15.3%). TO was achieved in 54.1% of patients, reaching 63.8% after liver resection and 32.0% after pancreas resection. Median overall survival was 5.72 years, with 5-year overall survival of 63% (95% CI: 50-82). Overall survival was better in patients with Charlson comorbidity score 4 or less versus more than 4 (P=0.016), intrahepatic versus extrahepatic tumor (P=0.027), single versus multiple tumors (P=0.007), those who underwent hepatic versus pancreatic resection (P=0.017), or achieved versus failed TO (P=0.029). Multivariable Cox regression analysis showed that not achieving TO (HR: 4.20; 95% CI: 1.11-15.94; P=0.03) was an independent prognostic factor of poor overall survival. Conclusions:Patients undergoing liver resection for IPNB were more likely to achieve a TO outcome than those requiring a pancreatic resection. Comorbidity, tumor location, and tumor multiplicity influenced overall survival. TO was an independent prognostic factor of overall survival.
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21.
  • Lluís, Núria, et al. (författare)
  • Intraductal papillary neoplasms of the bile ducts : a comparative study of a rare disease in Europe and Nagoya, Japan
  • 2024
  • Ingår i: HPB. - : ELSEVIER SCI LTD. - 1365-182X .- 1477-2574. ; 26:4, s. 565-575
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Intraductal papillary neoplasm of the bile ducts (IPNB) is a rare disease in Western countries. The aim of this study was to compare tumor characteristics, management strategies, and outcomes between Western and Eastern patients who underwent surgical resection for IPNB. Methods: A multi-institutional retrospective series of patients with IPNB undergoing surgery between January 2010 and December 2020 was gathered under the auspices of the European-African Hepato-Pancreato-Biliary Association (E-AHPBA), and at Nagoya University Hospital, Japan. Results: A total of 85 patients (51% male; median age 66 years) from 28 E-AHPBA centers were compared to 91 patients (64% male; median age 71 years) from Nagoya. Patients in Europe had more multiple lesions (23% vs 2%, P < .001), less invasive carcinoma (42% vs 85%, P < .001), and more intrahepatic tumors (52% vs 24%, P < .001) than in Nagoya. Patients in Europe experienced less 90-day grade >3 Clavien-Dindo complications (33% vs 68%, P < .001), but higher 90-day mortality rate (7.0% vs 0%, P = .03). R0 resections (81% vs 82%) were similar. Overall survival, excluding 90-day postoperative deaths, was similar in both regions. Discussion: Despite performing more extensive resections, the low perioperative mortality rate observed in Nagoya was probably influenced by a combination of patient-, tumor-, and surgery-related factors.
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23.
  • Mantani, Polyxeni, et al. (författare)
  • Circulating CD40(+) and CD86(+) B Cell Subsets Demonstrate Opposing Associations With Risk of Stroke
  • 2014
  • Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : Lippincott Williams & Wilkins. - 1079-5642 .- 1524-4636. ; 34:1, s. 211-218
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective-Accumulating evidence shows that immune cells play an important role in atherosclerosis. Most attention has focused on the role of different T cell subsets, whereas the possible involvement of B cells has been less studied. In this study, we assessed the association of 2 different B cell subsets, CD19(+)CD40(+) and CD19(+)CD86(+) B cells, with risk for development of acute cardiovascular events. Approach and Results-The prospective study included 700 subjects randomly selected from the cardiovascular cohort of the Malmo Diet and Cancer study. Mononuclear leukocytes, stored at -140 degrees C at the baseline investigation in 1991-1994, were thawed and B cell subsets analyzed by flow cytometry. Cytokine release from CD3/CD28-stimulated mononuclear leukocytes was measured with multiplex ELISA. Baseline carotid intima-media thickness and stenosis were assessed by ultrasonography, and clinical events were monitored through validated national registers during a median/mean follow-up time of 15 years. The subjects in the highest tertile of CD19(+)CD40(+) B cells had a significantly lower risk of incident stroke after adjustment for other risk factors. In contrast, CD19(+)CD86(+) B cells were associated with higher risk for development of a stroke event and increased release of proinflammatory cytokines from mononuclear leukocytes. Conclusions-These observations provide evidence for an involvement of B cells in the incidence of stroke and suggest that both pathogenic and protective B cell subsets exist.
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24.
  • Miller, Paul S. J., et al. (författare)
  • Nocturia Work Productivity and Activity Impairment Compared with Other Common Chronic Diseases
  • 2016
  • Ingår i: PharmacoEconomics (Auckland). - : ADIS INT LTD. - 1170-7690 .- 1179-2027. ; 34:12, s. 1277-1297
  • Tidskriftsartikel (refereegranskat)abstract
    • The International Continence Society defines nocturia as the need to void one or more times during the night, with each of the voids preceded and followed by sleep. The chronic sleep disturbance and sleep deprivation experienced by patients with nocturia affects quality of life, compromising both mental and physical well-being. This paper aims to characterise the burden of nocturia by comparing published data from patients with nocturia with data from patients with any of 12 other common chronic conditions, specifically focusing on its impact on work productivity and activity impairment, as measured by the instrument of the same name (WPAI). A systematic literature review of multiple data sources identified evaluable studies for inclusion in the analysis. Study eligibility criteria included use of the WPAI instrument in patients with one of a predefined list of chronic conditions. We assessed the quality of each included study using the Newcastle-Ottawa scale and extracted basic study information, work and activity impairment data. To assess how work and activity impairment from nocturia compares with impairment from other common chronic diseases, we conducted two data syntheses (pooled and unpooled). The number of evaluable studies and the range of overall work productivity impairment reported, respectively, were as follows: nocturia (3; 14-39 %), overactive bladder (5; 11-41 %), irritable bowel syndrome/constipation (14; 21-51 %), gastroesophageal reflux disease (GERD) (13; 6-42 %), asthma/allergies (11; 6-40 %), chronic obstructive pulmonary disease (COPD) (7; 19-42 %), sleep problems (3; 12-37 %), arthritis (13; 21-69 %), pain (9; 29-64 %), depression (4; 15-43 %) and gout (2; 20-37 %). The overall work productivity impairment as a result of nocturia is substantial and was found to be similar to impairment observed as a result of several other more frequently researched common chronic diseases. Greater awareness of the burden of nocturia, a highly bothersome and prevalent condition, will help policy makers and healthcare decision makers provide appropriate management of nocturia.
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25.
  • Olofsson, Katarina E, et al. (författare)
  • Nanomolar concentrations of lysophosphatidylcholine recruit monocytes and induce pro-inflammatory cytokine production in macrophages
  • 2008
  • Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 370:2, s. 348-352
  • Tidskriftsartikel (refereegranskat)abstract
    • Lysophosphatidylcholine (LPC) has been attributed a pro-inflammatory role in atherosclerosis. Cell culture studies have identified stimulation of cytokine expression and chemotaxis by micromolar (muM) concentrations of LPC. In the present study we have investigated if LPC, in similarity with many other lipid mediators, has pro-inflammatory effects also at nanomolar (nM) concentrations. Cultured mouse bone marrow derived and RAW264.7 macrophages exposed to LPC demonstrated two peaks of increased MIP-2 release and mRNA expression; one at 0.1-10nM and another at muM concentrations. Both concentration ranges of LPC were also found to stimulate THP-1 monocyte chemotaxis. However, stimulation of the cells with muM concentrations of LPC may cause cell injury as increased release of lactate dehydrogenase was observed. Our findings demonstrate two peaks of LPC-induced pro-inflammatory activity, one in the nM and one in the muM range, and indicate that the latter may involve a stress response to lipid cytotoxicity.
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26.
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27.
  • Saxena, Amit, et al. (författare)
  • The Vascular Repair Process after Injury of the Carotid Artery is regulated by IL-1RI and MyD88 Signalling.
  • 2011
  • Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 1755-3245 .- 0008-6363. ; 91, s. 350-357
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: The aim of this study was to determine if innate immune signalling influences the vascular repair process in response to mechanical injury of arteries in mice. Methods and Results: A non-obstructive collar was introduced around the carotid artery of MyD88-deficient mice and neointima formation was compared to that observed in MyD88-competent mice. MyD88-deficient mice are characterized by impaired signal transduction from interleukin (IL)-1/IL-18 receptors and most Toll-like receptors. The vascular response to injury was severely impaired in MyD88-deficient mice as neointima formation was not different from sham operated mice, whereas MyD88-competent mice displayed robust neointima formation. Furthermore, infiltration of CD68 positive leukocytes was dependent on MyD88. During the early response to injury, 3 days after collar placement, a transient increase in the expression of Toll-like receptor (TLR) 4 on vascular smooth muscle cells was observed. To determine the relative importance of IL-1 receptor and TLR4 activation in the vascular response to injury mice were injected with blocking antibodies to these receptors prior to the collar placement. Neointima formation was reduced by 80% in mice administered IL-1RI blocking antibodies compared to mice given a control antibody, whereas administration of TLR4 blocking antibodies was without effect. Conclusion: These results show that inhibition of MyD88- or IL-1 receptor signalling reduces neointima formation in response to vascular injury and could offer therapeutic options for reducing clinical complications of excessive smooth muscle cell proliferation, such as that observed in in-stent restenosis.
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28.
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29.
  • Svensson, Harry R:son, 1976- (författare)
  • Fabian Philip, familjen Ruben och örlogsstaden : Entreprenörsfamiljen som grundade Mosaiska församlingen i Karlskrona 1780–1945
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The purpose of the dissertation is to investigate Jewish integration in the naval city of Karlskrona in the period 1780–1945. This was done by the investigation of the economic, social and cultural strategies that the Jewish Philip/Ruben family used in their family business in Karlskrona during the 19th century. This has made it possible to understand how a Jewish family and congregation interacted with and became integrated in a Swedish naval-city environment. The study gives also new information about and a better understanding of the Swedish naval environment and naval production capacity. The study provides new knowledge on different fields of studies as Swedish Jewish history, urban history, naval history (the history of the Swedish Royal Navy), history of migration and integration, and the history of Karlskrona. The dissertation studies the history of the Philip/Ruben family in three distinct perspectives: economic, social and cultural. Moreover, the study pays attention to the process of the family’s integration and adaptation of different Jewish groups in Karlskrona.Fabian Philip obtained an exception from the Swedish legislation forbidding Jews to live in other towns than Stockholm, Göteborg and Norrköping, and settled in the naval city of Karlskrona. His family came to constitute the Jewish congregation in Karlskrona in the period 1782–1862. Karlskrona therefore became the fourth city in Sweden where Jews were allowed to settle. Fabian Philip and his family originated from Bützow in northern Germany. Fabian Philip’s establishment in Karlskrona depended upon his role as contractor, supplying sailcloth to the Swedish Royal Navy. After the Vienna Congress of 1815 Sweden adopted a Doctrine of Central defense and The Swedish Royal Navy lost its importance for the defense of Sweden. With a minimum of funding the Swedish Royal Navy went into a state of despair and so did Karlskrona’s local economy.By 1830 agriculture was the only viable economic niche in the economically neglected Karlskrona but Jews were prohibited to own landed property until 1860. Fabian Philip was able, with the help of Karlskrona’s officer staff, to circumnavigate the legislation and became a landowner of big Afvelsgärde estate. Of all the Jewish-owned estates in Sweden in the mid-century 10 percent were to be owned by the Philip/Ruben family. When Sweden was industrialized in 1870–1890, the local economy of Karlskrona managed to compensate for the decline in activities of the Swedish Royal Navy. The family succeeded to take part in the program of local modernization that was launched from the 1880s. The Philip/Ruben family contributed to the economic modernization of Karlskrona as bankers and factory owners. The family thrived in the city’s surprisingly open and cosmopolitan environment. Until now, no research has been undertaken about the Jewish congregation or the Jewish life in Karlskrona. The results of this dissertation contribute to the understanding of Jewish life in Sweden.
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30.
  • Tomas, Lukas, et al. (författare)
  • Invariant natural killer T cells and incidence of first-time coronary events: a nested case-control study
  • 2023
  • Ingår i: European Heart Journal Open. - : Oxford University Press. - 2752-4191. ; 3:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Invariant natural killer T (iNKT) cells, a T cell subset that is CD1d-restricted and expresses a semi-invariant T cell receptor, have been proposed to contribute to dyslipidaemia-driven cardiovascular disease due to their ability to specifically recognize lipid antigens. Studies in mice have attributed pro-atherogenic properties to iNKT cells, but studies in humans investigating associations of iNKT cells with incident coronary events (CE) are lacking.Methods and results: Here, we used flow cytometry to enumerate circulating iNKT cells (CD3+ CD1d-PBS57-Tetramer+) in a case-control cohort nested within the prospective population-based Malmö Diet and Cancer Study (n = 416) to explore associations with incident first-time CE during a median follow-up of 14 years. We found a significant inverse association between CD4- and CD8- double negative (DN) iNKT cells and incident CE, with an odds ratio of 0.62 [95% confidence interval (CI) 0.38-0.99; P = 0.046] comparing the highest vs. the lowest tertile of DN iNKT cells. The association remained significant after adjustment for cardiovascular risk factors with an odds ratio of 0.57 (95% CI 0.33-0.99; P = 0.046). In contrast, total iNKT cells were not significantly associated with incident CE after adjustment, with an odds ratio of 0.74 (95% CI 0.43-1.27; P = 0.276).Conclusion: Our findings indicate that animal studies suggesting an atherosclerosis-promoting role for iNKT cells may not translate to human cardiovascular disease as our data show an association between high circulating numbers of DN iNKT cells and decreased risk of incident CE.
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31.
  • Tomas, Lukas, et al. (författare)
  • Low Levels of CD4+CD28null T Cells at Baseline Are Associated With First-Time Coronary Events in a Prospective Population-Based Case-Control Cohort
  • 2020
  • Ingår i: Arteriosclerosis, Thrombosis, and Vascular Biology. - 1524-4636. ; 40:2, s. 426-436
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: CD4+CD28null T cells have been shown to be associated with recurrent coronary events and suggested as potential biomarker and therapeutic target. It is unknown whether CD4+CD28null T cells associate with first-time cardiovascular events. We examined CD4+CD28null T cells in a prospective population-based cohort and in patients with advanced atherosclerosis. Approach and Results: CD4+CD28null T cells were quantified in 272 individuals experiencing a first-time coronary event during up to 17 years of follow-up and 272 age- and sex-matched controls in a case-control study, nested within the population-based Malmö Diet and Cancer study. The highest tertile of CD4+CD28null T cells was associated with a lower incidence of first-time coronary events compared with the lowest tertile (odds ratio, 0.48 [95% CI, 0.29-0.79], P=0.004) when adjusting for Framingham risk factors. This association remained significant for events recorded after >9 years of follow-up, when most coronary events occurred, but not during the first 9 years of follow-up, despite similar odds ratio. Additionally, we analyzed CD4+CD28null T cells in 201 patients with advanced atherosclerosis undergoing carotid endarterectomy. The adjusted hazard ratio for cardiovascular events in patients with advanced atherosclerosis was 2.11 (95% CI, 1.10-4.05, P=0.024), comparing the highest with the lowest CD4+CD28null T-cell tertile.CONCLUSIONS: Our findings reveal complex associations between CD4+CD28null T cells and cardiovascular disease. Although we confirm the reported positive associations with an adverse prognosis in patients with already established disease, the opposite associations with first-time coronary events in the population-based cohort may limit the clinical use of CD4+CD28null T cells.
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32.
  • Uhlén, Mathias, et al. (författare)
  • A human protein atlas for normal and cancer tissues based on antibody proteomics
  • 2005
  • Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 4:12, s. 1920-1932
  • Tidskriftsartikel (refereegranskat)abstract
    • Antibody-based proteomics provides a powerful approach for the functional study of the human proteome involving the systematic generation of protein-specific affinity reagents. We used this strategy to construct a comprehensive, antibody-based protein atlas for expression and localization profiles in 48 normal human tissues and 20 different cancers. Here we report a new publicly available database containing, in the first version, similar to 400,000 high resolution images corresponding to more than 700 antibodies toward human proteins. Each image has been annotated by a certified pathologist to provide a knowledge base for functional studies and to allow queries about protein profiles in normal and disease tissues. Our results suggest it should be possible to extend this analysis to the majority of all human proteins thus providing a valuable tool for medical and biological research.
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33.
  • Wigren, Maria, et al. (författare)
  • Low Levels of Circulating CD4+FoxP3+ T Cells Are Associated With an Increased Risk for Development of Myocardial Infarction But Not for Stroke.
  • 2012
  • Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : Lippincott Williams & Wilkins. - 1524-4636 .- 1079-5642. ; 32:8, s. 2000-2007
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Regulatory T cells (Tregs) protect against atherosclerosis in experimental models, but their association with cardiovascular disease in humans remains to be elucidated. The aim of the present study was to determine whether circulating Tregs predict the development of acute cardiovascular events in humans. METHODS AND RESULTS: The study cohort consisted of a random sample of participants (n=700), aged 68 to 73 years, from the Malmo Diet and Cancer Study. Mononuclear leukocytes, stored at -140°C at the baseline investigation in 1991.1994, were thawed and Tregs, defined by the expression of FoxP3 in CD4+ T cells, were analyzed by flow cytometry. There was no detectable loss of cells during storage, and the viability of thawed leukocytes was 95%. A low fraction of both CD4+FoxP3+ and CD4+CD25+FoxP3+ T cells was associated with a higher release of proinflammatory cytokines from activated mononuclear leukocytes, and this association was strongest for CD4+FoxP3+ cells. Eighty-four coronary events and 66 strokes were registered during follow-up until December 31, 2008. In a Cox proportional hazard regression model adjusting for major risk factors, low levels of baseline CD4+FoxP3+ T cells were associated with an increased risk for the development of acute coronary events but not stroke. There were no associations between CD4+CD25+FoxP3+ T cells and development of an acute coronary event or stroke. CONCLUSIONS: This study provides prospective evidence for the role of Tregs in the development of myocardial infarction. The findings are in accordance with previous experimental studies and provide clinical support for a protective role of Tregs in atherosclerosis. The lack of association between Tregs and stroke may reflect the more heterogeneous cause of this disease.
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34.
  • Zamora, Juan Carlos, et al. (författare)
  • Considerations and consequences of allowing DNA sequence data as types of fungal taxa
  • 2018
  • Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
  • Tidskriftsartikel (refereegranskat)abstract
    • Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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