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2. |
- Bergman, Per, 1960, et al.
(author)
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Emission from HCN and CH3OH in comets Onsala 20-m observations and radiative transfer modelling
- 2022
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 660
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Journal article (peer-reviewed)abstract
- Aims. The aim of this work is to characterise HCN and CH3OH emission from recent comets. Methods. We used the Onsala 20-m telescope to search for millimetre transitions of HCN towards a sample of 11 recent and mostly bright comets in the period from December 2016 to November 2019. Also, CH3OH was searched for in two comets. The HCN sample includes the interstellar comet 2I/Borisov. For the short-period comet 46P/Wirtanen, we were able to monitor the variation of HCN emission over a time-span of about one month. We performed radiative transfer modelling for the observed molecular emission by also including time-dependent effects due to the outgassing of molecules. Results. HCN was detected in six comets. Two of these are short-period comets and four are long-period. Six methanol transitions were detected in 46P/Wirtanen, enabling us to determine the gas kinetic temperature. From the observations, we determined the molecular production rates using time-dependent radiative transfer modelling. For five comets, we were able to determine that the HCN mixing ratios lie near 0.1% using contemporary water production rates, Q(H2O), taken from other studies. This HCN mixing ratio was also found to be typical in our monitoring observations of 46P/Wirtanen but here we notice deviations of up to 0.2% on a daily timescale which could indicate short-time changes in outgassing activity. From our radiative transfer modelling of cometary comae, we find that time-dependent effects on the HCN level populations are of the order of 5-15% when Q(H2O) is around 2 x 10(28) mol s(-1). The effects may be stronger for comets with lower Q(H2O). The exact details of the time-dependent effects depend on the amount of neutral and electron collisions, radiative pumping, and molecular parameters such as the spontaneous rate coefficient.
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3. |
- Wallin, Johan, et al.
(author)
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Laborationer i naturvetenskapsundervisningen
- 2020
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Reports (other academic/artistic)abstract
- I denna systematiska översikt sammanställs forskning om laborationer i naturvetenskapsundervisningen. De frågor som översikten besvarar är:• Vad kännetecknar laborationer i naturvetenskapsundervisningen som utförs i syfte att utveckla elevers ämneskunskaper och förmåga att genomföra systematiska undersökningar?• Vilka metoder och arbetssätt som kan bidra till att utveckla elevers ämneskunskaper och förmåga att genomföra systematiska undersökningar lyfts fram i forskningen om laborationer och laborationsundervisning?I översikten definierar vi laborationer som praktiska undersökningar där elever observerar reella objekt, det vill säga själva samlar in data om naturvetenskapliga fenomen. Översikten fokuserar på undervisning i biologi, fysik och kemi i grundskolans högstadium och i gymnasieskolan.Översiktens resultat beskriver både möjligheter och utmaningar med elevers laborationer och laborationsundervisningen. Resultaten delas upp i relation till tre övergripande målområden för undervisningen i de naturvetenskapliga ämnena:• att lära sig naturvetenskap• att lära sig utföra naturvetenskap• att lära sig om naturvetenskap.Att elever ska lära sig naturvetenskap innebär att de ska utveckla kunskaper om naturvetenskapliga begrepp, teorier och förklaringsmodeller. Att elever ska lära sig utföra naturvetenskap innebär att de ska utveckla en förmåga att genomföra systematiska naturvetenskapliga undersökningar. Att elever ska lära sig om naturvetenskap betyder att de ska utveckla en förståelse av naturvetenskapens karaktär. Undervisningen kan inte adressera alla målområden samtidigt utan lärare behöver göra väl motiverade val och prioriteringar.
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4. |
- Adill, Anders, et al.
(author)
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Biologisk recipientkontroll vid Forsmarks kärnkraftverk : årsrapport för 2022
- 2023
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Reports (other academic/artistic)abstract
- Forsmarks kärnkraftverk är Sveriges största elproducent. På grund av intag och utsläpp av kylvatten från havet som kyler processen i verket sker en påverkan på den omgivande kustvattenmiljön. Denna påverkan övervakas och analyseras i det pågående biologiska recipientkontrollprogrammet. Föreliggande årsrapport presenterar resultat i undersökningarna inom kontrollprogrammet för 2022 med fokus på samhällena av fisk, bentisk fauna (bottenlevande djur) och sjöfågel. Under 2022 producerade Forsmarks kärnkraftverk 25,5 terawattimmar (TWh) el i sina anläggningar, vilket var samma som föregående års produktionsrekord av elektricitet. Den rekordstora produktionen kan härledas till de senaste åren moderniseringar och livstidsförlängande åtgärder i anläggningarna, vilket resultaterat i effekthöjningar i kraftverket. Den höga produktionen under 2022 medförde därmed en hög omsättning på kylvatten. Utsläppsområdet för kylvatten, Biotestsjön, hade vattentemperaturer över 25ºC i 29 dagar under sommarperioden. På grund av revisionsarbeten på F2 under juli månad förekom inga extrema temperaturer över 29ºC i Biotestsjön, något som vanligtvis brukar förekomma under högsommaren. I utsläppsområdet för F3 noterades vattentemperaturer över 30°C under endast ett dygn och med högsta notering 30,1°C i mitten av augusti. Förlusterna av fisk i silstationerna vid kylvattenintaget utgjordes som tidigare år av främst småväxta fiskarter och årsyngel. Totalt fastnade cirka 37,5 miljoner individer i silstationerna under provtagningsperioderna under 2022, närmare 20 miljoner färre jämfört med 57 miljoner individer som fastnade 2021. Det lägre antalet beror på att det fastnade färre årsyngel under hösten, som kan vara ett tecken på att det har varit sämre fiskreproduktion i närområdet under 2022, vilket också återspeglades i yngelundersökningarna i Forsmarksskärgård. Likt föregående år var storspigg den dominerande arten i provtagningarna och omfattade cirka 85 % av förlusterna under året. Resultatet för storspigg speglar sannolikt artens stora förekomst i omgivande kust- och havsområden. Antalet ålar som fastnade i silstationen var relativt litet. Till skillnad från tidigare år var förlusterna av ål högre under våren än på hösten, med fler småväxta individer. Genom framtagen metodik kunde totalt fem ålar tas hand om och återutsättas till havet levande. Under de senaste åren har varmvattenarterna mört, björkna och sutare blivit allt vanligare i silstationerna, sannolikt en effekt av de gynnsamma förhållandena i Biotestsjön för lek hos dessa arter. Undersökningarna i Biotestsjön under våren visade att tätheterna av fisk var de absolut största som någonsin observerats. De arter som förekommer i störst omfattning var likt föregående år mört, björkna, abborre och sarv. Likt tidigare fanns tydliga tecken på att stora mängder fisk lockas till Biotestsjöns varma vatten för lek. Förutom stora mängder lekmogen mört och abborre förekom höga tätheter av björkna under våren. Under senare år förefaller även tätheterna av gädda och sutare ha ökat i området. För ålen däremot är utvecklingen den motsatta och förekomsten av arten är låg i jämförelse med tidigare år. Till skillnad från nätprovfiskena i Forsmarks skärgård påträffas inga så kallade kallvattenarter i Biotestsjön, såsom strömming, nors, sik och tånglake. För varmvattenarter som mört och abborre visade resultaten att förhållandena i Biotestsjön var goda under 2022, då både tillväxt och kondition låg på goda nivåer. Under hösten 2022 noterades flera äldre individer av abborre vid provfiskena i Biotestsjön; 7 % av undersökta abborrar var fyra år eller äldre. Tidigare år har nästintill samtliga abborrar varit tre år eller yngre. I Forsmarks skärgård visade undersökningarna att tätheterna av fisk var höga om än något lägre jämfört med rekordfångsterna 2021. Fångsterna för de flesta arterna var något lägre än föregående år, men de mindre totala fångsterna var till stor del ett resultat av de förhållandevis låga antalet fångade mörtar i Forsmark. Förekomsten av mört i undersökningsområdet har under nästintill hela provfiskeperioden uppvisat en negativ utveckling, men har med de stora fångsterna under de senaste tre åren visat på en möjlig återhämtning. Det Sammanfattning låga antalet mörtar i årets provfisken i kombination med den förhållandevis låga förekomsten i silstationen skulle kunna tyda på en generell minskning av mört i Forsmarks skärgård. Ett fåtal individer registrerades av sutare och vimma, två karpfiskar (Cyprinidae) som vanligtvis inte förekommer i provfisket, men som de senaste åren blivit alltmer vanliga i fisket. Under 2022 års undersökningar av mjukbottenfauna registrerades totalt tio arter i Forsmark och femton arter i referensområdet Finbofjärden. Likt tidigare år var arttätheten högre i referensområdet än i Forsmark på både djupa och medeldjupa bottnar. Förekomsten av nyckelarten vitmärla var lägre än föregående år på samtliga stationer både i Finbofjärden och Forsmarks skärgård. Alla hårdbottenstationer frånsett Borgarna hade ett högre artantal än föregående år, men på alla stationer utom Plymen var individtätheten lägre. I Biotestsjön hade individtätheten mer än halverats jämfört med senaste året. Förändringen beror främst på den ovanligt låga förekomsten av tångmärla. Den låga förekomsten kan troligtvis kopplas till de stora mängderna röd pungräka som tillkommit på lokalen. Den röda pungräkan hittades för första gången under 2021 då en enda individ registrerades, medan under 2022 hittades nästan 280 individer per artificiellt substrat. Antalet sjöfåglar i inventeringsområdet var fortsatt hög under 2022. De höga förekomsterna kan förklaras med att antalet mellanskarv i undersökningsområdet dubblerades jämfört med 2021. Den största mängden mellanskarv observerades i Biotestsjön och likt tidigare år noterades misslyckade häckningsförsök. Biotestsjön är det enskilt viktigaste området för sjöfågel i Forsmarks skärgård följt av Asphällafjärden utanför intagskanalen. Utsläppet av varmt kylvatten från kärnkraftverket in i Biotestsjön ger bra förutsättningar till hög produktion av vegetation, bottenlevande djur och fisk samt en isfri yta under vintern. Detta ger gynnsamma förhållanden för sjöfågel under hela året men särskilt under häckningstiden och vinter. Antalet viggar i Forsmarks skärgård var lägre under 2022 jämfört med föregående år, trots detta var viggen tillsammans med mellanskarven de mest vanliga förekommande arterna. Förekomsterna av knölsvan var fortsatt hög i Forsmarks skärgård, trots att antalet var något lägre än föregående år. Det finns skillnader för vilka funktionella grupper som nyttjar de olika områdena i inventeringsområdet. Fisk- och växtätande fåglar föredrar Biotestsjön året om medan bottendjursätande fåglar visar skillnader säsongsvis med en täthetstopp i Biotestsjön under hösten och i Asphällafjärden under vintern.
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6. |
- Andersson, Maria L.E. 1968-, et al.
(author)
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Baseline levels of circulating galectin-1 associated with radiographic hand but not radiographic knee osteoarthritis at a two-year follow-up
- 2024
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In: OSTEOARTHRITIS AND CARTILAGE OPEN. - Oxford : Elsevier. - 2665-9131. ; 6:2
-
Journal article (peer-reviewed)abstract
- Objective: We tested the potential of circulating galectin-1, interleukin (IL)-1 beta, IL-6, and tumour necrosis factor alpha (TNF alpha) levels at baseline in individuals with knee pain as biomarkers for development of radiographic knee and/or hand osteoarthritis (OA). Design:This study comprised 212 individuals with knee pain from the Halland osteoarthritis cohort (HALLOA). Clinical characteristics and serum/plasma levels of galectin-1, IL-1 beta, IL-6, and TNF alpha were measured at baseline, and knee and hand radiographs were obtained at a two-year follow-up. The predictive value of circulating inflammatory markers and clinical variables at baseline was assessed using multinominal logistic regression for those who developed radiographic OA in knees only (n = 25), in hands only (n = 40), and in both knees and hands (n = 43); the group who did not develop OA (n = 104) was used as reference. Correlations were assessed using Spearman's correlation coefficients. Results: As expected, age was identified as a risk factor for having radiographic knee and/or hand OA at the twoyear follow-up. Baseline circulating galectin-1 levels did not associate with developing radiographic knee OA but associated with developing radiographic hand OA (odds ratio (OR) for a 20% increased risk: 1.14, 95% confidence interval (CI) 1.01-1.29) and both radiographic knee and hand OA (OR for a 20% increased risk: 1.18, 95% CI 1.05-1.30). However, baseline IL-1 beta, IL-6, and TNF alpha did not associate with developing radiographic knee and/or hand OA. Conclusion: Non-age adjusted circulating galectin-1 is superior to IL-6, IL-1 beta, and TNF alpha in predicting radiographic hand but not knee OA.
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8. |
- Bergman, Joakim, et al.
(author)
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Location matters : highly divergent protein levels in samples from diferent CNS compartments in a clinical trial of rituximab for progressive MS
- 2020
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In: Fluids and Barriers of the CNS. - : BioMed Central. - 2045-8118. ; :1
-
Journal article (peer-reviewed)abstract
- Background: The relationship between proteins in different CNS extracellular compartments is unknown. In this study the levels of selected proteins in three compartments in people with progressive multiple sclerosis (PMS) were compared.Methods: During an open label, phase 1b study on intraventricular administration of rituximab for PMS, samples were collected from the interstitial space (ISS) of the brain through microdialysis. Samples were also obtained from ventricular and lumbar cerebrospinal fluid (CSF). These samples were analyzed with a multiplexed proximity extension assay, measuring the levels of 180 proteins split equally between two panels, detecting proteins associated with immunology and neurology, respectively.Results: Considerable differences in concentrations were observed between the three analyzed compartments. Compared to ventricular CSF, ISS fluid contained statistically significant higher levels of 25 proteins (84% immunology panel and 16% neurology panel). Ventricular CSF contained significantly higher levels of 54 proteins (31% immunology panel and 69% neurology panel) compared to ISS fluid, and 17 proteins (76% immunology panel and 24% neurology panel) compared to lumbar CSF. Lumbar CSF showed significantly higher levels of 115 proteins (32% immunology panel and 68% neurology panel) compared to ventricular CSF. The three compartments displayed poor correlation with a median Spearman’s rho of -0.1 (IQR 0.4) between ISS and ventricular CSF and 0.3 (IQR 0.4) between ventricular and lumbar CSF.Conclusion: A substantial heterogeneity in the protein levels of samples obtained from different CNS compartments was seen. Therefore, data obtained from analysis of lumbar CSF should be interpreted with caution when making conclusions about pathophysiological processes in brain tissue.
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9. |
- Bergman, Karl-Olof, et al.
(author)
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Clear-cuts are temporary habitats, not matrix, for endangered grassland burnet moths (Zygaena spp.)
- 2020
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In: Journal of Insect Conservation. - : Springer Science and Business Media LLC. - 1366-638X .- 1572-9753. ; 24:2, s. 269-277
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Journal article (peer-reviewed)abstract
- Burnet moths (Zygaena spp.) are day-flying Lepidoptera considered indicative of species-rich grasslands. In the present study, our aim was to clarify whether clear-cuts are habitat, supporting habitat or matrix for three species of Zygaena. We did so by sampling these species with sex pheromones on 48 clear-cuts, varying in amount of host and nectar plants, in southern Sweden. To compare the efficiency of such sampling, we also conducted transect walks on these clearcuts. Overall, host-plants on clear-cuts best explained the abundance of Zygaena spp. recorded, better than nectar-plants or connectivity with nearby grasslands. These results indicate that clear-cuts with an abundance of host plants are used as a fully functional habitat, and not a supporting habitat in the sense of only providing nectar. There is no support in these results for considering clear-cuts as an inert matrix. With about half the work-effort, pheromone traps recorded 100 times more Zygaena spp. as transect walks. The poor correspondence between observations during transects walks and pheromone trap catches suggest Zygaena spp. being difficult to monitor by transect walks. In contrast to grasslands, clear-cuts are short-term in nature requiring repeated recolonization, indicating the importance of permanent grasslands. However, clear-cuts are important temporary insect habitats due to their great acreage, and suitable management can increase the time they remain a habitat.
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- Bergman-Larsson, Julia, et al.
(author)
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Combined expression of HOXA11 and CD10 identifies endometriosis versus normal tissue and tumors
- 2022
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In: Annals of Diagnostic Pathology. - : Elsevier. - 1092-9134 .- 1532-8198. ; 56
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Journal article (peer-reviewed)abstract
- The gold standard for diagnosing endometriosis is by laparoscopic visual demonstration of ectopic endometrial lesions outside the uterus, preferably verified by biopsy and microscopical examination. Molecular markers to facilitate the microscopical diagnosis of endometriosis and for distinguishing endometriosis from other benign and malignant lesions are lacking. Our aim was to test and validate an immunohistochemical antibody panel for improved diagnostic accuracy of endometriosis. Both CD10 and HOXA11 have been implicated in regulation of endometrial homeostasis. Here we have analyzed the expression pattern of these two proteins using immunohistochemistry on human tissues in a tissue microarray format. CD10 and HOXA11 expression in endometriosis lesions were compared to expression patterns in a range of normal tissues and in primary- and metastatic lesions of endometrial-, cervical- and ovarian cancer. HOXA11 and CD10 were expressed in 98% and 91% of endometriosis lesions and the combined double-positive expression profile of both HOXA11 and CD10 was highly sensitive for ectopic endometrial tissue (90%). The specificity and sensitivity for this double-positive signature in endometriosis was significantly different from all investigated tissues, cancers and metastases except normal, eutopic endometrial- and cervical mucosa. The combination of HOXA11 and CD10 expression profiles provides a useful tool to identify ectopic endometrial tissue and for distinguishing endometriosis from various types of gynecological malignancies and metastases.
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11. |
- Bergman, Peter, et al.
(author)
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Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial
- 2021
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In: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 74
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Journal article (peer-reviewed)abstract
- Background: Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls.Methods: 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection.Findings: Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively.Interpretation: The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity.
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12. |
- Bergman, Per, 1960, et al.
(author)
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Submillimetre water masers at 437, 439, 471, and 474 GHz towards evolved stars: APEX observations and radiative transfer modelling*
- 2020
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 638
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Journal article (peer-reviewed)abstract
- Aims. Here we aim to characterise submillimetre water masers at 437, 439, 471, and 474 GHz towards a sample of evolved stars. Methods. We used the Atacama Pathfinder Experiment (APEX(1)) to observe submillimetre water transitions and the CO (4-3) line towards 11 evolved stars. The sample included semi-regular and Mira variables, plus a red supergiant star. We performed radiative transfer modelling for the water masers. We also used the CO observations to determine mass loss rates for the stars. Results. From the sample of 11 evolved stars, 7 display one or more of the masers at 437, 439, 471, and 474 GHz. We therefore find that these masers are common in evolved star circumstellar envelopes. The fact that the maser lines are detected near the stellar velocity indicates that they are likely to originate from the inner circumstellar envelopes of our targets. We tentatively link the presence of masers to the degree of variability of the target star, that is, masers are more likely to be present in Mira variables than in semi-regular variables. We suggest that this indicates the importance of strong shocks in creating the necessary conditions for the masers. Typically, the 437 GHz line is the strongest maser line observed among those studied here. We cannot reproduce the above finding in our radiative transfer models. In general, we find that maser emission is very sensitive to dust temperature in the lines studied here. To produce strong maser emission, the dust temperature must be significantly lower than the gas kinetic temperature. In addition to running grids of models in order to determine the optimum physical conditions for strong masers in these lines, we performed smooth wind modelling for which we cannot reproduce the observed line shapes. This also suggests that the masers must originate predominantly from the inner envelopes.
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13. |
- Bratulic, Sinisa, 1981, et al.
(author)
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Noninvasive detection of any-stage cancer using free glycosaminoglycans.
- 2022
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:50
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Journal article (peer-reviewed)abstract
- Cancer mortality is exacerbated by late-stage diagnosis. Liquid biopsies based on genomic biomarkers can noninvasively diagnose cancers. However, validation studies have reported ~10% sensitivity to detect stage I cancer in a screening population and specific types, such as brain or genitourinary tumors, remain undetectable. We investigated urine and plasma free glycosaminoglycan profiles (GAGomes) as tumor metabolism biomarkers for multi-cancer early detection (MCED) of 14 cancer types using 2,064 samples from 1,260 cancer or healthy subjects. We observed widespread cancer-specific changes in biofluidic GAGomes recapitulated in an in vivo cancer progression model. We developed three machine learning models based on urine (Nurine = 220 cancer vs. 360 healthy) and plasma (Nplasma = 517 vs. 425) GAGomes that can detect any cancer with an area under the receiver operating characteristic curve of 0.83-0.93 with up to 62% sensitivity to stage I disease at 95% specificity. Undetected patients had a 39 to 50% lower risk of death. GAGomes predicted the putative cancer location with 89% accuracy. In a validation study on a screening-like population requiring ≥ 99% specificity, combined GAGomes predicted any cancer type with poor prognosis within 18 months with 43% sensitivity (21% in stage I; N = 121 and 49 cases). Overall, GAGomes appeared to be powerful MCED metabolic biomarkers, potentially doubling the number of stage I cancers detectable using genomic biomarkers.
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14. |
- Carl, Tadeus, 1992, et al.
(author)
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Deep search for glycine conformers in Barnard 5
- 2023
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In: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 524:4, s. 5993-6003
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Journal article (peer-reviewed)abstract
- One of the most fundamental hypotheses in astrochemistry and astrobiology states that crucial biotic molecules like glycine (NH2CH2COOH) found in meteorites and comets are inherited from early phases of star formation. Most observational searches for glycine in the interstellar medium have focused on warm high-mass molecular cloud sources. However, recent studies suggest that it might be appropriate to shift the observational focus to cold low-mass sources. We aim to detect glycine towards the so-called methanol hotspot in the Barnard 5 dark cloud. The hotspot is a cold source (Tgas ≈ 7.5 K) with yet high abundances of complex organic molecules (COMs) and water in the gas phase. We carried out deep pointed observations with the Onsala 20 m telescope, targeting several transitions of glycine conformers I and II (Gly-I and Gly-II) in the frequency range 70.2-77.9 GHz. No glycine lines are detected towards the targeted position, but we use a line stacking procedure to derive sensitive abundance upper limits w.r.t. H2 for Gly-I and Gly-II, i.e. ≤(2-5) × 10-10 and ≤(0.7-3) × 10-11, respectively. The obtained Gly-II upper limits are the most stringent for a cold source, while the Gly-I upper limits are mostly on the same order as previously measured limits. The measured abundances w.r.t. H2 of other COMs at the B5 methanol hotspot range from 2 × 10-10 (acetaldehyde) to 2 × 10-8 (methanol). Hence, based on a total glycine upper limit of (2-5) × 10-10, we cannot rule out that glycine is present but undetected.
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15. |
- Chen, Puran, et al.
(author)
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Real-world assessment of immunogenicity in immunocompromised individuals following SARS-CoV-2 mRNA vaccination : a one-year follow-up of the prospective clinical trial COVAXID
- 2023
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In: EBioMedicine. - : Elsevier. - 2352-3964. ; 94
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Journal article (peer-reviewed)abstract
- Background: Immunocompromised patients have varying responses to SARS-CoV-2 mRNA vaccination. However, there is limited information available from prospective clinical trial cohorts with respect to long-term immunogenicity-related responses in these patient groups following three or four vaccine doses, and in applicable cases infection.Methods: In a real-world setting, we assessed the long-term immunogenicity-related responses in patients with primary and secondary immunodeficiencies from the prospective open-label clinical trial COVAXID. The original clinical trial protocol included two vaccine doses given on days 0 and 21, with antibody titres measured at six different timepoints over six months. The study cohort has subsequently been followed for one year with antibody responses evaluated in relation to the third and fourth vaccine dose, and in applicable cases SARS-CoV-2 infection. In total 356/539 patients were included in the extended cohort. Blood samples were analysed for binding antibody titres and neutralisation against the Spike protein for all SARS-CoV-2 variants prevailing during the study period, including Omicron subvariants. SARS-CoV-2 infections that did not require hospital care were recorded through quarterly in-person, or phone-, interviews and assessment of IgG antibody titres against SARSCoV-2 Nucleocapsid. The original clinical trial was registered in EudraCT (2021-000175-37) and clinicaltrials.gov (NCT04780659).Findings: The third vaccine dose significantly increased Spike IgG titres against all the SARS-CoV-2 variants analysed in all immunocompromised patient groups. Similarly, neutralisation also increased against all variants studied, except for Omicron. Omicron-specific neutralisation, however, increased after a fourth dose as well as after three doses and infection in many of the patient subgroups. Noteworthy, however, while many patient groups mounted strong serological responses after three and four vaccine doses, comparably weak responders were found among patient subgroups with specific primary immunodeficiencies and subgroups with immunosuppressive medication.Interpretation: The study identifies particularly affected patient groups in terms of development of long-term immunity among a larger group of immunocompromised patients. In particular, the results highlight poor vaccine-elicited neutralising responses towards Omicron subvariants in specific subgroups. The results provide additional knowledge of relevance for future vaccination strategies.
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16. |
- Chen, Qiao Sen, et al.
(author)
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A machine learning based approach to identify carotid subclinical atherosclerosis endotypes
- 2023
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In: Cardiovascular Research. - : OXFORD UNIV PRESS. - 0008-6363 .- 1755-3245. ; 119:16, s. 2594-2606
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Journal article (peer-reviewed)abstract
- Aims To define endotypes of carotid subclinical atherosclerosis. Methods and results We integrated demographic, clinical, and molecular data (n = 124) with ultrasonographic carotid measurements from study participants in the IMPROVE cohort (n = 3340). We applied a neural network algorithm and hierarchical clustering to identify carotid atherosclerosis endotypes. A measure of carotid subclinical atherosclerosis, the c-IMTmean-max, was used to extract atherosclerosis-related features and SHapley Additive exPlanations (SHAP) to reveal endotypes. The association of endotypes with carotid ultrasonographic measurements at baseline, after 30 months, and with the 3-year atherosclerotic cardiovascular disease (ASCVD) risk was estimated by linear (& beta;, SE) and Cox [hazard ratio (HR), 95% confidence interval (CI)] regression models. Crude estimates were adjusted by common cardiovascular risk factors, and baseline ultrasonographic measures. Improvement in ASCVD risk prediction was evaluated by C-statistic and by net reclassification improvement with reference to SCORE2, c-IMTmean-max, and presence of carotid plaques. An ensemble stacking model was used to predict endotypes in an independent validation cohort, the PIVUS (n = 1061). We identified four endotypes able to differentiate carotid atherosclerosis risk profiles from mild (endotype 1) to severe (endotype 4). SHAP identified endotype-shared variables (age, biological sex, and systolic blood pressure) and endotype-specific biomarkers. In the IMPROVE, as compared to endotype 1, endotype 4 associated with the thickest c-IMT at baseline (& beta;, SE) 0.36 (0.014), the highest number of plaques 1.65 (0.075), the fastest c-IMT progression 0.06 (0.013), and the highest ASCVD risk (HR, 95% CI) (1.95, 1.18-3.23). Baseline and progression measures of carotid subclinical atherosclerosis and ASCVD risk were associated with the predicted endotypes in the PIVUS. Endotypes consistently improved measures of ASCVD risk discrimination and reclassification in both study populations. Conclusions We report four replicable subclinical carotid atherosclerosis-endotypes associated with progression of atherosclerosis and ASCVD risk in two independent populations. Our approach based on endotypes can be applied for precision medicine in ASCVD prevention.
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17. |
- Cuapio, Angelica, et al.
(author)
-
NK cell frequencies, function and correlates to vaccine outcome in BNT162b2 mRNA anti-SARS-CoV-2 vaccinated healthy and immunocompromised individuals
- 2022
-
In: Molecular Medicine. - : BioMed Central (BMC). - 1076-1551 .- 1528-3658. ; 28:1
-
Journal article (peer-reviewed)abstract
- Adaptive immune responses have been studied extensively in the course of mRNA vaccination against COVID-19. Considerably fewer studies have assessed the effects on innate immune cells. Here, we characterized NK cells in healthy individuals and immunocompromised patients in the course of an anti-SARS-CoV-2 BNT162b2 mRNA prospective, open-label clinical vaccine trial. See trial registration description in notes. Results revealed preserved NK cell numbers, frequencies, subsets, phenotypes, and function as assessed through consecutive peripheral blood samplings at 0, 10, 21, and 35 days following vaccination. A positive correlation was observed between the frequency of NKG2C+ NK cells at baseline (Day 0) and anti-SARS-CoV-2 Ab titers following BNT162b2 mRNA vaccination at Day 35. The present results provide basic insights in regards to NK cells in the context of mRNA vaccination, and have relevance for future mRNA-based vaccinations against COVID-19, other viral infections, and cancer.Trial registration: The current study is based on clinical material from the COVAXID open-label, non-randomized prospective clinical trial registered at EudraCT and clinicaltrials.gov (no. 2021–000175-37). Description: https://clinicaltrials.gov/ct2/show/NCT04780659?term=2021-000175-37&draw=2&rank=1.
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18. |
- Darnerud, Per Ola, et al.
(author)
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Critical review on disposition of chlorinated paraffins in animals and humans
- 2022
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In: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 163
-
Research review (peer-reviewed)abstract
- Even though the chlorinated paraffins (CPs) have been on the environmental pollution agenda throughout the last 50 years it is a class of chemicals that only now is discussed in terms of an emerging issue with extensive annual publication rates. Major reviews on CPs have been produced, but a deeper understanding of the chemical fate of CPs, including formation of metabolites in animals and humans, is still missing. Thus, the present review aims to critically compile our present knowledge on the disposition, i.e. Adsorption, Disposition, Metabolism, and Excretion (ADME) of CPs in biota and to identify research needs. We conclude that CPs could be effectively absorbed from the gastro-intestinal tract (GI) tract, and probably also from the lungs, and transported to various organs. A biphasic elimination is suggested, with a rapid initial phase followed by a terminal phase, the latter (e.g., fat tissues) covering half-lives of weeks and months. CPs are metabolized in the liver and excreted mainly via the bile and faeces, and the metabolic rate and type of metabolites are dependent on chlorine content and chain length. Results that strengthen CP metabolism are in vivo findings of phase II metabolites in bile, and CP degradation to carbon fragments in experimental animals. Still the metabolic transformations of CPs are poorly studied, and no metabolic scheme has yet been presented. Further, toxicokinetic mass balance calculations suggest that a large part of a given dose (not found as parent compound) is transformation products of CPs, and in vitro metabolism studies present numerous CP metabolites (e.g., chloroalkenes, chlorinated ketones, aldehydes, and carboxylic acids).
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19. |
- Freiholtz, David, et al.
(author)
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SPP1/osteopontin : a driver of fibrosis and inflammation in degenerative ascending aortic aneurysm?
- 2023
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In: Journal of Molecular Medicine. - : Springer Nature. - 0946-2716 .- 1432-1440. ; 101:10, s. 1323-1333
-
Journal article (peer-reviewed)abstract
- Abstract: Degenerative ascending aortic aneurysm (AscAA) is a silent and potentially fatal disease characterized by excessive vascular inflammation and fibrosis. We aimed to characterize the cellular and molecular signature for the fibrotic type of endothelial mesenchymal transition (EndMT) that has previously been described in degenerative AscAA. Patients undergoing elective open-heart surgery for AscAA and/or aortic valve repair were recruited. Gene expression in the intima-media of the ascending aorta was measured in 22 patients with non-dilated and 24 with dilated aortas, and candidate genes were identified. Protein expression was assessed using immunohistochemistry. Interacting distal gene enhancer regions were identified using targeted chromosome conformation capture (HiCap) in untreated and LPS-treated THP1 cells, and the associated transcription factors were analyzed. Differential expression analysis identified SPP1 (osteopontin) as a key gene in the signature of fibrotic EndMT in patients with degenerative AscAA. The aortic intima-media expression of SPP1 correlated with the expression of inflammatory markers, the level of macrophage infiltration, and the aortic diameter. HiCap analysis, followed by transcription factor binding analysis, identified ETS1 as a potential regulator of SPP1 expression under inflammatory conditions. In conclusion, the present findings suggest that SPP1 may be involved in the development of the degenerative type of AscAA. Key messages: In the original manuscript titled “SPP1/osteopontin, a driver of fibrosis and inflammation in degenerative ascending aortic aneurysm?” by David Freiholtz, Otto Bergman, Saliendra Pradhananga, Karin Lång, Flore-Anne Poujade, Carl Granath, Christian Olsson, Anders Franco-Cereceda, Pelin Sahlén, Per Eriksson, and Hanna M Björck, we present novel findings on regulatory factors on osteopontin (SPP1) expression in immune cells involved in degenerative ascending aortic aneurysms (AscAA). The central findings convey: SPP1 is a potential driver of the fibrotic endothelial-to-mesenchymal transition in AscAA.SPP1/osteopontin expression in AscAA is predominately by immune cells.ETS1 is a regulatory transcription factor of SPP1 expression in AscAA immune cells.
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20. |
- Gao, Yu, et al.
(author)
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Immunodeficiency syndromes differentially impact the functional profile of SARS-CoV-2-specific T cells elicited by mRNA vaccination
- 2022
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In: Immunity. - : Elsevier. - 1074-7613 .- 1097-4180. ; 55:9, s. 1732-1746.e5
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Journal article (peer-reviewed)abstract
- Many immunocompromised patients mount suboptimal humoral immunity after SARS-CoV-2 mRNA vaccination. Here, we assessed the single-cell profile of SARS-CoV-2-specific T cells post-mRNA vaccination in healthy individuals and patients with various forms of immunodeficiencies. Impaired vaccine-induced cell-mediated immunity was observed in many immunocompromised patients, particularly in solid-organ transplant and chronic lymphocytic leukemia patients. Notably, individuals with an inherited lack of mature B cells, i.e., X-linked agammaglobulinemia (XLA) displayed highly functional spike-specific T cell responses. Single-cell RNA-sequencing further revealed that mRNA vaccination induced a broad functional spectrum of spike-specific CD4+ and CD8+ T cells in healthy individuals and patients with XLA. These responses were founded on polyclonal repertoires of CD4+ T cells and robust expansions of oligoclonal effector-memory CD45RA+ CD8+ T cells with stem-like characteristics. Collectively, our data provide the functional continuum of SARS-CoV-2-specific T cell responses post-mRNA vaccination, highlighting that cell-mediated immunity is of variable functional quality across immunodeficiency syndromes.
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21. |
- Ghorbani, Mahin, et al.
(author)
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Persistence of salivary antibody responses after COVID-19 vaccination is associated with oral microbiome variation in both healthy and people living with HIV
- 2023
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In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 13
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Journal article (peer-reviewed)abstract
- Coevolution of microbiome and immunity at mucosal sites is essential for our health. Whether the oral microbiome, the second largest community after the gut, contributes to the immunogenicity of COVID-19 vaccines is not known. We investigated the baseline oral microbiome in individuals in the COVAXID clinical trial receiving the BNT162b2 mRNA vaccine. Participants (n=115) included healthy controls (HC; n=57) and people living with HIV (PLHIV; n=58) who met the study selection criteria. Vaccine-induced Spike antibodies in saliva and serum from 0 to 6 months were assessed and comparative analyses were performed against the individual salivary 16S ASV microbiome diversity. High- versus low vaccine responders were assessed on general, immunological, and oral microbiome features. Our analyses identified oral microbiome features enriched in high- vs. low-responders among healthy and PLHIV participants. In low-responders, an enrichment of Gram-negative, anaerobic species with proteolytic activity were found including Campylobacter, Butyrivibrio, Selenomonas, Lachnoanaerobaculum, Leptotrichia, Megasphaera, Prevotella and Stomatobaculum. In high-responders, enriched species were mainly Gram-positive and saccharolytic facultative anaerobes: Abiotrophia, Corynebacterium, Gemella, Granulicatella, Rothia, and Haemophilus. Combining identified microbial features in a classifier using the area under the receiver operating characteristic curve (ROC AUC) yielded scores of 0.879 (healthy controls) to 0.82 (PLHIV), supporting the oral microbiome contribution in the long-term vaccination outcome. The present study is the first to suggest that the oral microbiome has an impact on the durability of mucosal immunity after Covid-19 vaccination. Microbiome-targeted interventions to enhance long-term duration of mucosal vaccine immunity may be exploited.
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22. |
- Grimfjärd, Per, et al.
(author)
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Outcome of PCI with Xience versus other commonly used modern drug eluting stents : a SCAAR report
- 2021
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In: Catheterization and cardiovascular interventions. - : Wiley. - 1522-1946 .- 1522-726X. ; 98:2, s. E197-E204
-
Journal article (peer-reviewed)abstract
- Objectives To analyze the clinical outcome of percutaneous coronary intervention (PCI) using the Xience drug eluting stent (DES) versus other modern DES.Methods This retrospective study based on the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) analyzed the outcome of PCI using Xience versus other commonly used modern DES, 2007 to 2017. The primary outcome measure was a combination of all-cause death, myocardial infarction (MI) and revascularisation with PCI. Angiographical outcome measures were in-stent restenosis (ISR) and stent thrombosis (ST).Results Rates of the primary outcome measure for Xience and other DES were 31.9% and 28.2% respectively, adjusted hazard ratio (HR) 0.99 (95% CI 0.95-1.03). Crude rates of ISR were 2.9% versus 2.1% over 4.3 and 2.9 years respectively, adjusted HR 0.93 (95% CI 0.81-1.06). Crude rates of ST were 0.9% versus 0.7%, adjusted HR 1.07 (95% CI 0.82-1.39). Results were consistent in all sensitivity analyses.Conclusions This nationally complete, real-world study confirms that Xience is a safe and effective DES with low-event rates of ISR and ST. Compared with a control group containing a large proportion of thinner strut stents and absorbable polymers, Xience exhibits similar results in all important clinical endpoint
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23. |
- Gustafsson, Åsa, 1975-, et al.
(author)
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Bioavailability of inhaled or ingested PFOA adsorbed to house dust
- 2022
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In: Environmental Science and Pollution Research. - : Springer. - 0944-1344 .- 1614-7499. ; 29:52, s. 78698-78710
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Journal article (peer-reviewed)abstract
- Indoor environments may impact human health due to chemical pollutants in the indoor air and house dust. This study aimed at comparing the bioavailability and distribution of PFOA following both an inhalation and an oral exposure to PFOA coated house dust in rats. In addition, extractable organofluorine (EOF) was measured in different tissue samples to assess any potential influence of other organofluorine compounds in the experimental house dust. Blood samples were collected at sequential time points after exposure and at the time of termination; the lungs, liver, and kidney were collected for quantification of PFOA and EOF. The concentration of PFOA in plasma increased rapidly in both exposure groups attaining a Cmax at 3 h post exposure. The Cmax following inhalation was four times higher compared to oral exposures. At 48 h post exposure, the levels of PFOA in the plasma, liver, and kidney were twice as high from inhalation exposures. This shows that PFOA is readily bioavailable and has a rapid systemic distribution following an inhalation or oral exposure to house dust coated with PFOA. The proportion of PFOA to EOF corresponded to 65-71% and 74-87% in plasma and tissues, respectively. The mass balance between EOF and target PFOA indicates that there might be other unknown PFAS precursor and/or fluorinated compounds that co-existed in the house dust sample that can have accumulated in rats.
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24. |
- Healy, Katie, et al.
(author)
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Salivary IgG to SARS-CoV-2 indicates seroconversion and correlates to serum neutralization in mRNA-vaccinated immunocompromised individuals
- 2022
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In: Med. - : Cell Press. - 2666-6359 .- 2666-6340. ; 3:2, s. 137-153.e3
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Journal article (peer-reviewed)abstract
- Background: Immunocompromised individuals are highly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Whether vaccine-induced immunity in these individuals involves oral cavity, a primary site of infection, is presently unknown.Methods: Immunocompromised patients (n = 404) and healthy controls (n = 82) participated in a prospective clinical trial (NCT04780659) encompassing two doses of the mRNA BNT162b2 vaccine. Primary immunodeficiency (PID), secondary immunodeficiencies caused by human immunodeficiency virus (HIV) infection, allogeneic hematopoietic stem cell transplantation (HSCT)/chimeric antigen receptor T cell therapy (CAR-T), solid organ transplantation (SOT), and chronic lymphocytic leukemia (CLL) patients were included. Salivary and serum immunoglobulin G (IgG) reactivities to SARS-CoV-2 spike were measured by multiplex bead-based assays and Elecsys anti-SARS-CoV-2 S assay.Findings: IgG responses to SARS-CoV-2 spike antigens in saliva in HIV and HSCT/CAR-T groups were comparable to those of healthy controls after vaccination. The PID, SOT, and CLL patients had weaker responses, influenced mainly by disease parameters or immunosuppressants. Salivary responses correlated remarkably well with specific IgG titers and the neutralizing capacity in serum. Receiver operating characteristic curve analysis for the predictive power of salivary IgG yielded area under the curve (AUC) = 0.95 and positive predictive value (PPV) = 90.7% for the entire cohort after vaccination.Conclusions: Saliva conveys vaccine responses induced by mRNA BNT162b2. The predictive power of salivary spike IgG makes it highly suitable for screening vulnerable groups for revaccination.
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25. |
- Humphreys, E., et al.
(author)
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(Sub)mm Observations of Evolved Stars
- 2022
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In: Proceedings of the International Astronomical Union. - 1743-9213 .- 1743-9221. ; 18, s. 309-313
-
Conference paper (peer-reviewed)abstract
- Evolved stars on the asymptotic giant branch and red supergiants have multiple processes that can be studied in the (sub)mm, including stellar surfaces, circumstellar thermal gas and dust, and masers. Telescopes such as APEX and ALMA have opened the possibility to perform studies that are revealing new information on these, as well as on the role of binaries in shaping stellar winds and the evolution to planetary nebulae. Here, we discuss some recent results for (sub)mm observations towards evolved stars focusing particularly on masers. This includes SiO and water masers, as well as ALMA high angular resolution observations of HCN masers towards a carbon-rich star.
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26. |
- Israelsson Larsen, Hanna, et al.
(author)
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Implementing primary care behavioral health in Swedish primary care : study protocol for a pragmatic stepped wedge cluster trial
- 2024
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In: BMC Primary Care. - : BioMed Central (BMC). - 2731-4553. ; 25
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Journal article (peer-reviewed)abstract
- BACKGROUND: Mental health problems represent a large and growing public health concern. Primary care handles most of the patients with mental health problems, but there are many barriers to detection and treatment in this setting, causing under-recognition and under-treatment of patients. The service delivery model Primary Care Behavioral Health (PCBH) shows promise to manage mental health problems in primary care, but more research is needed regarding its effects on multiple levels.METHODS: This project investigates the effectiveness and implementation of a large-scale implementation of PCBH in Region Östergötland, Sweden. The aim is to generate new knowledge concerning the impact of a real-world implementation and use of PCBH in routine primary care. A Pragmatic Stepped-Wedge Cluster Trial will be used: 24 PCBH primary care centres in one region will be compared with 48 standard care centres in three other regions. The model will be implemented sequentially at the PCBH centres according to a staggered timetable. Results will be investigated at patient, staff and organization levels and various forms of data will be collected: (1) local and national registry data; (2) questionnaire data; (3) interview data; and (4) document data.DISCUSSION: This project investigates the effectiveness and implementation of PCBH in routine primary care. The project could result in improved mental health care for the included patients and contribute to the general good for a wider population who have mental health problems. The project's study design will make it possible to assess many important effects of the PCBH service delivery model at different levels, providing evidence of the effectiveness (or not) of the PCBH model under routine conditions in primary care. The project has the potential to generate clinically meaningful results that can provide a basis for decisions concerning further implementation and use of the model and thus for future development of mental health care provision in primary care.TRIAL REGISTRATION: NCT05633940, date of registration: 2021-04-21.
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27. |
- Kalenskii, Sergei. V., et al.
(author)
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Spectral-line Survey of the Region of Massive Star Formation W51e1/e2 in the 4 mm Wavelength Range
- 2022
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In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 932:1
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Journal article (peer-reviewed)abstract
- We present the results of a spectral-line survey of the W51e1/e2 star-forming region at 68-88 GHz. 79 molecules and their isotopologues were detected, from simple diatomic or triatomic molecules, such as SO, SiO, and CCH, to complex organic compounds, such as CH3OCH3 or CH3COCH3. A number of lines that are absent from the Lovas list of molecular lines observed in space were detected, and most of these were identified. A significant number of the detected molecules are typical for hot cores. These include the neutral molecules HCOOCH3, CH3CH2OH, and CH3COCH3, which are currently believed to exist in the gas phase only in hot cores and shock-heated gas. In addition, vibrationally excited C4H and HC3N lines with upper-level energies of several hundred Kelvins were found. Such lines can arise only in hot gas with temperatures on the order of 100 K or higher. Apart from neutral molecules, various molecular ions were also detected. Some of these ((HCO+)-O-18, (HCO+)-C-13, and HCS+) usually exist in molecular clouds with high visual extinctions. Potential formation pathways of complex organic molecules and hydrocarbons, along with nitriles, are considered. These formation routes are first discussed in the context of laboratory experiments elucidating the synthesis of organic molecules in interstellar ices in cold molecular clouds, followed by sublimation into the gas phase in the hot core stage. Thereafter, we discuss the predominant formation of hydrocarbons and their nitriles in the gas phase through bimolecular neutral-neutral reactions.
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28. |
- Koopen, A., et al.
(author)
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Duodenal Anaerobutyricum soehngenii infusion stimulates GLP-1 production, ameliorates glycaemic control and beneficially shapes the duodenal transcriptome in metabolic syndrome subjects: a randomised double-blind placebo-controlled cross-over study
- 2022
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In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 71:8, s. 1577-1587
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Journal article (peer-reviewed)abstract
- Objective Although gut dysbiosis is increasingly recognised as a pathophysiological component of metabolic syndrome (MetS), the role and mode of action of specific gut microbes in metabolic health remain elusive. Previously, we identified the commensal butyrogenic Anaerobutyricum soehngenii to be associated with improved insulin sensitivity in subjects with MetS. In this proof-of-concept study, we investigated the potential therapeutic effects of A. soehngenii L2-7 on systemic metabolic responses and duodenal transcriptome profiles in individuals with MetS. Design In this randomised double-blind placebo-controlled cross-over study, 12 male subjects with MetS received duodenal infusions of A. soehngenii/ placebo and underwent duodenal biopsies, mixed meal tests (6 hours postinfusion) and 24-hour continuous glucose monitoring. Results A. soehngenii treatment provoked a markedly increased postprandial excursion of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) and an elevation of plasma secondary bile acids, which were positively associated with GLP-1 levels. Moreover, A. soehngenii treatment robustly shaped the duodenal expression of 73 genes, with the highest fold induction in the expression of regenerating islet-protein 1B (REG1B)-encoding gene. Strikingly, duodenal REG1B expression positively correlated with GLP-1 levels and negatively correlated with peripheral glucose variability, which was significantly diminished in the 24 hours following A. soehngenii intake. Mechanistically, Reg1B expression is induced upon sensing butyrate or bacterial peptidoglycan. Importantly, A. soehngenii duodenal administration was safe and well tolerated. Conclusions A single dose of A. soehngenii improves peripheral glycaemic control within 24 hours; it specifically stimulates intestinal GLP-1 production and REG1B expression. Further studies are needed to delineate the specific pathways involved in REG1B induction and function in insulin sensitivity.
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29. |
- Lagou, Vasiliki, et al.
(author)
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Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
- 2021
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In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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30. |
- Lewerentz, Jacob, 1992-
(author)
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Genomic adaptation and gene-dosage regulation of Drosophila melanogaster cells, and long-read software developments
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Cells are the vehicles that allows genetic code to proliferate in the world, taking on various forms – as illustrated by the tree of life. The cell features are determined by the manufacturing of proteins, a process that has its blueprints encoded as genes in the genome. It is crucial for all cells to have the right amount of protein, regardless of context (part of a multicellular organism or self-sustained). The protein landscape (amount and type) vary depending on the environment. Cells of the multicellular organism should maintain the protein balance to provide its’ intended function in the organism tissue. The cells of multicellular organisms are faced with an imbalance due to sex-related chromosomal imbalances and other genome effects that change the number of gene copies. Restoration from the imbalance is done by dosage compensation systems. Cells that are isolated from the organism and grown inside the lab are common in research, known as cell lines. Cancer cells are similar to cell lines and have lost their original function in the organism in favor of a self-sustained lifestyle. The new environment (context) for these isolated cells impose a challenge; the cells must reorganize their genomes (holding the blueprints for proteins) to obtain autonomy.In this thesis, the genome evolution of isolated cells, cell lines, has been studied using Drosophila melanogaster (the fruit fly). Compared to normal cells of the host organism, cell line genomes are highly mutated and rearranged. With the emergence of novel sequencing technologies that can read long fragments of the genome, this complexity of cell line genomes can be captured. On the topic of novel sequencing technologies, new software implementations are presented and the future of software for long reads and complex genomes is discussed. The main focus of this thesis is to describe how an established and commonly used cell line has reorganized its’ genome to sustain a culture environment. Important information about the genome structure is provided to the research community. The thesis also describes the genome reorganization in new cell lines, covering the early adaptations to cell autonomy. Together, these investigations are of high relevance to human cancer research. This thesis has also studied the fundamentals for regulation of protein balance in organismal cells. Specifically, a recognition sequence to the X chromosome of the protein Painting of Fourth. This protein is related to dosage compensation and primarily enhance transcription from the 4 thchromosome in Drosophila melanogaster, but has been observed tooccasionally bind to the X chromosome.
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31. |
- Lindner, Philip, et al.
(author)
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Gamified, Automated Virtual Reality Exposure Therapy for Fear of Spiders : A Single-Subject Trial Under Simulated Real-World Conditions
- 2020
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In: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 11
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Journal article (peer-reviewed)abstract
- Background: Virtual Reality exposure therapy (VRET) is an evidence-based treatment of phobias and recent research suggests that this applies also to self-contained, automated interventions requiring no therapist guidance. With the advent and growing adoption of consumer VR technology, automated VR intervention have the potential to close the considerable treatment gap for specific phobias through dissemination as consumer applications, self-help at clinics, or as blended treatment. There is however a lack of translational effectiveness studies on VRET treatment effects under real-world conditions.Methods: We conducted a single-arm (n = 25), single-subject study of automated, gamified VRET for fear of spiders, under simulated real-world conditions. After setup and reading instructions, participants completed the automated, single-session treatment by themselves. Self-rated fear of spiders and quality of life served as outcome measures, measured twice before, and one and two weeks after treatment, and at a six-month follow-up. Session characteristics and user experience measures were collected at the end of the session.Results: Mixed-effects modeling revealed a significant and large (d = 1.26) effect of treatment-onset on phobia symptoms (p < .001), and a small (d = 0.49) effect on quality of life (p = .025). Results were maintained at a six-month follow-up (p > .053). The intervention was tolerable and practical. There were no significant correlations between any user experience measure and decrease in phobia symptoms (p > .209).Conclusions: An automated VRET intervention for fear of spiders showed equivalent effects on phobia symptoms under effectiveness conditions as previously reported under efficacy conditions. These results suggest that automated VRET applications are promising self-help treatments also when provided under real-world conditions.
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32. |
- Meledin, Denis, 1974, et al.
(author)
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SEPIA345: A 345 GHz dual polarization heterodyne receiver channel for SEPIA at the APEX telescope
- 2022
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 668
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Journal article (peer-reviewed)abstract
- Context. We describe the new SEPIA345 heterodyne receiver channel installed at the Atacama Pathfinder EXperiment (APEX) telescope, including details of its configuration, characteristics, and test results on sky. SEPIA345 is designed and built to be a part of the Swedish ESO PI Instrument for the APEX telescope (SEPIA). This new receiver channel is suitable for very high-resolution spectroscopy and covers the frequency range 272- 376 GHz. It utilizes a dual polarization sideband separating (2SB) receiver architecture, employing superconductor-isolator-superconductor mixers (SIS), and provides an intermediate frequency (IF) band of 4- 12 GHz for each sideband and polarization, thus covering a total instantaneous IF bandwidth of 4 ÃÂ - 8 = 32 GHz. Aims. This paper provides a description of the new receiver in terms of its hardware design, performance, and commissioning results. Methods. The methods of design, construction, and testing of the new receiver are presented. Results. The achieved receiver performance in terms of noise temperature, sideband rejection, stability, and other parameters are described. Conclusions. SEPIA345 is a commissioned APEX facility instrument with state-of-the-art wideband IF performance. It has been available on the APEX telescope for science observations since July 2021.
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33. |
- Meledin, Denis, 1974, et al.
(author)
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SEPIA345: a dual polarization 2SB cartridge receiver for APEX telescope: Design and Performance
- 2023
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In: Proceedings of the 32nd IEEE International Symposium on Space THz Technology.
-
Conference paper (peer-reviewed)abstract
- A new receiver channel covering the 271-377 GHz frequency band has been installed into the SEPIA receiver at the APEX telescope. The receiver channel was designed and built in an ALMA-compatible cartridge layout. The receiver has a dual polarization layout with OMT and employs 2SB SIS mixers featuring an extended 4-12 GHz IF band, providing 32 GHz instantaneous IF bandwidth for two polarizations and two sidebands.
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34. |
- Meledin, Denis, 1974, et al.
(author)
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SEPIA345: a dual polarization 2SB cartridge receiver for APEX telescope: Design and Performance
- 2022
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In: 32nd International Symposium of Space Terahertz Technology, ISSTT 2022.
-
Conference paper (peer-reviewed)abstract
- A new receiver channel covering the 271-377 GHz frequency band has been installed into the SEPIA receiver at the APEX telescope. The receiver channel was designed and built in an ALMA-compatible cartridge layout. The receiver has a dual polarization layout with OMT and employs 2SB SIS mixers featuring an extended 4-12 GHz IF band, providing 32 GHz instantaneous IF bandwidth for two polarizations and two sidebands.
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35. |
- Milberg, Per, et al.
(author)
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Assemblages of flower-visiting insects in clear-cuts are rich and dynamic
- 2021
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In: European Journal of Entomology. - : Akademie Ved Ceske Republiky Entomologicky Ustav,Czech Academy of Sciences, Institute of Entomology. - 1210-5759 .- 1802-8829. ; 118, s. 182-191
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Journal article (peer-reviewed)abstract
- Clear-cuts in production forests provide an open, sunny environment, with an abundance of nectar, as well as exposed soil and woody debris. This makes them a potential habitat for several groups of insects that typically use open habitats like grassland, including those species that visit flowers. In the current study, we used colour pan traps to catch flower-visiting species. Study sites were selected according to age (2-8 yrs since clear-cut) and land-use history (forest or meadow 150 yrs ago). We caught and identified solitary bees (395 specimens belonging to 59 species), social bees (831/16), other Hymenoptera (367/66), Syrphidae (256/31), and beetles (Lepturinae & Cetoniinae; 11,409/12). Age of the clear-cut strongly affected species composition as well as several groups and species, with most species caught mainly in the younger clear-cuts. Flower abundance statistically affected several groups and species, but inferring causation is difficult due to the flower-richness bias in pan trap catches. Bare soil and woody debris were important for the insect assemblage sampled, while bare rock was not. Although the majority of the insects caught were forest species, about one third of the species were associated with open, agricultural sites and hence seem to be able to locate and exploit resources in clear-cuts.
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36. |
- Milberg, Per, 1959-, et al.
(author)
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Assemblages of flower-visiting insects in clear-cuts are rich and dynamic
- 2021
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Other publicationabstract
- Clear-cuts in production forests provide an open, sunny environment, with an abundance of nectar, as well as exposed soil and woody debris. This makes them a potential habitat for several groups of insects that typically use open habitats like grassland, including those species that visit flowers. In the current study, we used colour pan traps to catch flower-visiting species. Study sites were selected according to age (2-8 yrs since clear-cut) and land-use history (forest or meadow 150 yrs ago). We caught and identified solitary bees (395 specimens belonging to 59 species), social bees (831/16), other Hymenoptera (367/66), Syrphidae (256/31), and beetles (Lepturinae & Cetoniinae; 11,409/12). Age of the clear-cut strongly affected species composition as well as several of the groups and species, with most species caught mainly in the younger clear-cuts. Flower abundance statistically affected several groups and species, but such effects are potentially suspect due to the flower-richness bias in pan trap catches. Bare soil and woody debris seemed irrelevant were important for the insect assemblage sampled, while bare rock sometimes positively affected flower-visiting insectswas not. Although the majority of the insects caught were forest species, about one third of the species were associated with open, agricultural sites and hence seem to be able to locate and exploit resources in clear-cuts.
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37. |
- Milberg, Per, et al.
(author)
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Site factors are more important than management for indicator species in semi-natural grasslands in southern Sweden
- 2020
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In: Plant Ecology. - : SPRINGER. - 1385-0237 .- 1573-5052. ; 221:7, s. 577-594
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Journal article (peer-reviewed)abstract
- Management of semi-natural grasslands is essential to retain the characteristic diversity of flora and fauna found in these habitats. To maintain, restore or recreate favourable conditions for grassland species, knowledge regarding how they occur in relation to grazing intensity and soil nutrient availability is crucial. We focused on grassland plant species, i.e., species selected to indicate high natural values in semi-natural grasslands. Environmental monitoring data collected at 366 grassland sites in southern Sweden between 2006 and 2010 were used to relate the occurrence of indicator species to factors describing geographic location, local site conditions related to nutrients and moisture, and management. Site productivity, soil moisture and cover of trees and shrubs were the main structuring factors, while other factors related to management had a lesser effect (grass sward height, amount of litter, type of grazer). Not surprisingly, these patterns were also reflected in species-wise analyses of the 25 most commonly occurring indicator species, with almost all species negatively related to site productivity and most also to soil moisture. Furthermore, many species were negatively affected by increasing sward height and litter. In contrast, species-wise responses varied among species in relation to increasing cover of trees and shrubs. In comparison to cattle grazing, sheep grazing was detrimental to six species and beneficial to none, while horse grazing was detrimental to no species and beneficial to four species. When evaluating species traits, taller plant species were favoured when site productivity, grass sward height and the amount of grass litter were high. There were no strong patterns related to the flowering time, leaf arrangement, or nutrient and light requirements of species. These results highlight the importance of nutrient-poor and dry sites, e.g., when selecting sites for conservation, and the importance of the type of management executed.
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38. |
- Müller, Thomas R., et al.
(author)
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Additive effects of booster mRNA vaccination and SARS-CoV-2 Omicron infection on T cell immunity across immunocompromised states
- 2023
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In: Science Translational Medicine. - 1946-6234 .- 1946-6242. ; 15:704, s. eadg9452-
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Journal article (peer-reviewed)abstract
- Suboptimal immunity to SARS-CoV-2 mRNA vaccination has frequently been observed in individuals with various immunodeficiencies. Given the increased antibody evasion properties of emerging SARS-CoV-2 subvariants, it is necessary to assess whether other components of adaptive immunity generate resilient and protective responses against infection. We assessed T cell responses in 279 individuals, covering five different immunodeficiencies and healthy controls, before and after booster mRNA vaccination, as well as after Omicron infection in a subset of patients. We observed robust and persistent Omicron-reactive T cell responses that increased markedly upon booster vaccination and correlated directly with antibody titers across all patient groups. Poor vaccination responsiveness in immunocompromised or elderly individuals was effectively counteracted by the administration of additional vaccine doses. Functionally, Omicron-reactive T cell responses exhibited a pronounced cytotoxic profile and signs of longevity, characterized by CD45RA+ effector memory subpopulations with stem cell-like properties and increased proliferative capacity. Regardless of underlying immunodeficiency, booster-vaccinated and Omicron-infected individuals appeared protected against severe disease and exhibited enhanced and diversified T cell responses against conserved and Omicron-specific epitopes. Our findings indicate that T cells retain the ability to generate highly functional responses against newly emerging variants, even after repeated antigen exposure and a robust immunological imprint from ancestral SARS-CoV-2 mRNA vaccination.
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39. |
- Müller, Thomas R., et al.
(author)
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Memory T cells effectively recognize the SARS-CoV-2 hypermutated BA.2.86 variant
- 2024
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In: Cell Host and Microbe. - : Elsevier. - 1931-3128 .- 1934-6069. ; 32:2, s. 156-161.e3
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Journal article (peer-reviewed)abstract
- T cells are critical in mediating the early control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection. However, it remains unknown whether memory T cells can effectively cross-recognize new SARS-CoV-2 variants with a broad array of mutations, such as the emergent hypermutated BA.2.86 variant. Here, we report in two separate cohorts, including healthy controls and individuals with chronic lymphocytic leukemia, that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection or vaccination demonstrate resilient immune recognition of BA.2.86. In both cohorts, we found largely preserved SARS-CoV-2 spike-specific CD4+ and CD8+ T cell magnitudes against mutated spike epitopes of BA.2.86. Functional analysis confirmed that both cytokine expression and proliferative capacity of SARS-CoV-2 spike-specific T cells to BA.2.86-mutated spike epitopes are similarly sustained. In summary, our findings indicate that memory CD4+ and CD8+ T cells continue to provide cell-mediated immune recognition to highly mutated emerging variants such as BA.2.86.
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40. |
- Olsson, Per-Ola, et al.
(author)
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Exploring the potential to use in-between pixel variability for early detection of bark beetle attacked trees
- 2023. - 35
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In: 26th AGILE Conference on Geographic Information Science “Spatial data for design”. ; 4:1
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Conference paper (peer-reviewed)abstract
- The European spruce bark beetle (Ips typographus L.) is a major disturbance agent in Norway spruce (Picea abies (L.) Karst) forests in Europe and it is estimated that a changing climate will result in more severe outbreaks in the future. To reduce the risk of large outbreaks it is important to have methods that enable early detection of bark beetle attacks to help forest managers to prevent population build-up, e.g by sanitary cutting. Several studies have been devoted to early detection of bark beetle attacks with Sentinel-2 data with a focus on spectral properties and vegetation indices for early detection with pixel-based methods. In this study we explore the potential to use changes in variability between pixels in windows of different sizes (3×3, 4×4 and 5×5 pixels). We compute the coefficient of variation for four vegetation indices (NDVI, NDWI, CCI and NDRS) in a time-series of Sentinel-2 data during a bark beetle outbreak in Sweden that was triggered by a drought in 2018. The results indicate that CCI is the most promising index for early detection and that the variability between pixels increase in windows with attacked trees from late July when the main swarming was the second week of May.
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41. |
- Röhl, Samuel, et al.
(author)
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Transcriptomic profiling of experimental arterial injury reveals new mechanisms and temporal dynamics in vascular healing response
- 2020
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In: JVS-Vascular Science. - : Elsevier BV. - 2666-3503. ; 315, s. E14-E14
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Journal article (peer-reviewed)abstract
- Objective: Endovascular interventions cause arterial injury and induce a healing response to restore vessel wall homeostasis. Complications of defective or excessive healing are common and result in increased morbidity and repeated interventions. Experimental models of intimal hyperplasia are vital for understanding the vascular healing mechanisms and resolving the clinical problems of restenosis, vein graft stenosis, and dialysis access failure. Our aim was to systematically investigate the transcriptional, histologic, and systemic reaction to vascular injury during a prolonged time. Methods: Balloon injury of the left common carotid artery was performed in male rats. Animals (n = 69) were euthanized before or after injury, either directly or after 2 hours, 20 hours, 2 days, 5 days, 2 weeks, 6 weeks, and 12 weeks. Both injured and contralateral arteries were subjected to microarray profiling, followed by bioinformatic exploration, histologic characterization of the biopsy specimens, and plasma lipid analyses. Results: Immune activation and coagulation were key mechanisms in the early response, followed by cytokine release, tissue remodeling, and smooth muscle cell modulation several days after injury, with reacquisition of contractile features in later phases. Novel pathways related to clonal expansion, inflammatory transformation, and chondro-osteogenic differentiation were identified and immunolocalized to neointimal smooth muscle cells. Analysis of uninjured arteries revealed a systemic component of the reaction after local injury, underlined by altered endothelial signaling, changes in overall tissue bioenergy metabolism, and plasma high-density lipoprotein levels. Conclusions: We demonstrate that vascular injury induces dynamic transcriptional landscape and metabolic changes identifiable as early, intermediate, and late response phases, reaching homeostasis after several weeks. This study provides a temporal “roadmap” of vascular healing as a publicly available resource for the research community.
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42. |
- Saldaño, H. P., et al.
(author)
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SuperCAM CO(3-2) APEX survey at a 6 pc resolution in the Small Magellanic Clouds
- 2024
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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 687
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Journal article (peer-reviewed)abstract
- Context. The Small Magellanic Cloud (SMC) is an ideal laboratory for studying the properties of star-forming regions thanks to its low metallicity, which has an impact on the molecular gas abundance. However, a small number of molecular gas surveys of the entire galaxy have been carried out in the last few years, limiting the measurements of interstellar medium (ISM) properties in a homogeneous manner. Aims. We present the CO(3-2) APEX survey at a 6 pc resolution of the bar of the SMC, observed with the SuperCAM receiver attached to the APEX telescope. This high-resolution survey has allowed us to study certain properties of the ISM and to identify CO clouds in the innermost parts of the H2 envelopes. Methods. We adopted the CO analysis in the SMC bar comparing the CO(3-2) survey with that of the CO(2-1) of a similar resolution. We studied the CO(3-2)-To-CO(2-1) ratio (R32), which is very sensitive to the environment properties (e.g., star-forming regions). We analyzed the correlation of this ratio with observational quantities that trace the star formation such as the local CO emission, the Spitzer color [70/160], and the total IR surface brightness measured from the Spitzer and Herschel bands. For the identification of the CO(3-2) clouds, we used the CPROPS algorithm, which allowed us to measure the physical properties of the clouds. We analyzed the scaling relationships of such physical properties. Results. We obtained R32 = 0.65 ± 0.02 for the SW bar and a slightly higher ratio, R32 = 0.7 ± 0.1, for N66 in the SMC. We found that R32 varies from region to region, depending on the star formation activity. In regions dominated by HII and photo-dissociated regions (e.g., N22, N66) R32 tends to be higher than the median values. Meanwhile, lower values were found toward quiescent clouds. We also found that R32 is correlated with the IR color [70/160] and the total IR surface brightness. This finding indicates that R32 increases with environmental properties, such as the dust temperature, total gas density, and radiation field. We identified 225 molecular clouds with sizes of R > 1.5 pc and signal-To-noise ratios (S/N) of >3, of which only 17 are well resolved CO(3-2) clouds with S/N 5. These 17 clouds follow consistent scaling relationships to the inner Milky Way clouds but with some departures. For instance, CO(3-2) tends to be less turbulent and less luminous than the inner Milky Way clouds of similar sizes. Finally, we estimated a median virial-based CO(3-2)-To-H2 conversion factor of 12.6-7+10 M-(K km s-1 pc2)-1 for the total sample.
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43. |
- Schlager, Angela
(author)
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Defining generalised joint hypermobility : Aspects of reliability, validity and the association to pregnancy induced pain
- 2024
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Doctoral thesis (other academic/artistic)abstract
- The aim of this thesis was to evaluate the definition of joint hypermobility and generalised joint hypermobility with aspects of reliability, validity and the association between generalised joint hypermobility and pregnancy-induced pain. Generalised joint hypermobility is used to reflect hereditary systematic connective tissue fragility. In study I, the inter-rater and intra-rater reliability, were evaluated in 49 women and men through 12 joint mobility tests included in three instruments for defining generalised joint hypermobility. In study II, the criterion validity was evaluated in 339 women in early pregnancy between the self-reported five-part questionnaire to identify generalised joint hypermobility, with the Beighton score. In study III, 255 women in early pregnancy were included to evaluate if a subset of joint mobility tests could define generalised joint hypermobility and establish limits for joint hypermobility. In study IV, 99 women pain-free before pregnancy were included to investigate the first onset of self-reported pain during pregnancy comparing women with and without generalised joint hypermobility, by parity and pain location. The reliability was good-to-excellent for both inter- and intra-rater reliability, for the majority of the joint mobility tests. The five-part questionnaire to identify generalised joint hypermobility with a cut-off level of ≥ 2 entailed the highest clinimetric values. However, the odds of having generalised joint hypermobility with a positive self-reported five-part questionnaire were low and yielding a false positive rate of 38%. No subset of joint mobility tests could define generalised joint hypermobility. Different combinations of joint mobility tests in upper- and lower limbs and the axial skeleton were compiled and evaluated for different standard deviation levels, where plus two standard deviations were most difficult to achieve. Women with generalised joint hypermobility and multiparous women experienced substantial earlier onset of self-reported pain during pregnancy, mainly in the lower back region. Thoroughly measured joint mobility and defining generalised joint hypermobility through different combinations of joint mobility tests, probably increased the precision of defining generalised joint hypermobility. Generalised joint hypermobility seems to be important for early development of pain during pregnancy. To identify women with generalised joint hypermobility in early pregnancy might be important in order to offer proper information, advice and rehabilitation.
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44. |
- Stanke, T., et al.
(author)
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The APEX Large CO Heterodyne Orion Legacy Survey (ALCOHOLS): I. Survey overview
- 2022
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 658
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Journal article (peer-reviewed)abstract
- Context. The Orion molecular cloud complex harbours the nearest Giant Molecular Clouds (GMCs) and the nearest site of high-mass star formation. Its young star and protostar populations are thoroughly characterized. The region is therefore a prime target for the study of star formation. Aims. Here, we verify the performance of the SuperCAM 64 pixel heterodyne array on the Atacama Pathfinder Experiment (APEX). We give a descriptive overview of a set of wide-field CO(32) spectral line cubes obtained towards the Orion GMC complex, aimed at characterizing the dynamics and structure of the extended molecular gas in diverse regions of the clouds, ranging from very active sites of clustered star formation in Orion B to comparatively quiet regions in southern Orion A. In a future publication, we will characterize the full population of protostellar outflows and their feedback over an entire GMC. Methods. We present a 2.7 square degree (130 pc2) mapping survey in the 12CO(32) transition, obtained using SuperCAM on APEX at an angular resolution of 19 (7600 AU or 0.037 pc at a distance of 400 pc), covering the main sites of star formation in the Orion B cloud (L 1622, NGC 2071, NGC 2068, Ori B9, NGC 2024, and NGC 2023), and a large patch in the southern part of the L 1641 cloud in Orion A. Results. We describe CO integrated line emission and line moment maps and position-velocity diagrams for all survey fields and discuss a few sub-regions in some detail. Evidence for expanding bubbles is seen with lines splitting into double components, often in areas of optical nebulosities, most prominently in the NGC 2024 H II region, where we argue that the bulk of the molecular gas is in the foreground of the H II region. High CO(32)/CO(10) line ratios reveal warm CO along the western edge of the Orion B cloud in the NGC 2023 & NGC 2024 region facing the IC 434 H II region. We see multiple, well separated radial velocity cloud components towards several fields and propose that L 1641-S consists of a sequence of clouds at increasingly larger distances. We find a small, seemingly spherical cloud, which we term Cow Nebula globule, north of NGC 2071. We confirm that we can trace high velocity line wings out to the extremely high velocity regime in protostellar molecular outflows for the NGC 2071-IR outflow and the NGC 2024 CO jet, and identify the protostellar dust core FIR4 (rather than FIR5) as the true driving source of the NGC 2024 monopolar outflow.
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45. |
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46. |
- Suur, Bianca E., et al.
(author)
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Therapeutic potential of the Proprotein Convertase Subtilisin/Kexin family in vascular disease
- 2022
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In: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 13
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Journal article (peer-reviewed)abstract
- Proprotein convertase subtilisin/kexins (PCSKs) constitute a family of nine related proteases: PCSK1-7, MBTPS1, and PCSK9. Apart from PCSK9, little is known about PCSKs in cardiovascular disease. Here, we aimed to investigate the expression landscape and druggability potential of the entire PCSK family for CVD. We applied an integrative approach, combining genetic, transcriptomic and proteomic data from three vascular biobanks comprising carotid atherosclerosis, thoracic and abdominal aneurysms, with patient clinical parameters and immunohistochemistry of vascular biopsies. Apart from PCSK4, all PCSK family members lie in genetic regions containing variants associated with human cardiovascular traits. Transcriptomic analyses revealed that FURIN, PCSK5, MBTPS1 were downregulated, while PCSK6/7 were upregulated in plaques vs. control arteries. In abdominal aneurysms, FURIN, PCSK5, PCSK7, MBTPS1 were downregulated, while PCSK6 was enriched in diseased media. In thoracic aneurysms, only FURIN was significantly upregulated. Network analyses of the upstream and downstream pathways related to PCSKs were performed on the omics data from vascular biopsies, revealing mechanistic relationships between this protein family and disease. Cell type correlation analyses and immunohistochemistry showed that PCSK transcripts and protein levels parallel each other, except for PCSK9 where transcript was not detected, while protein was abundant in vascular biopsies. Correlations to clinical parameters revealed a positive association between FURIN plaque levels and serum LDL, while PCSK6 was negatively associated with Hb. PCSK5/6/7 were all positively associated with adverse cardiovascular events. Our results show that PCSK6 is abundant in plaques and abdominal aneurysms, while FURIN upregulation is characteristic for thoracic aneurysms. PCSK9 protein, but not the transcript, was present in vascular lesions, suggesting its accumulation from circulation. Integrating our results lead to the development of a novel 'molecular' 5D framework. Here, we conducted the first integrative study of the proprotein convertase family in this context. Our results using this translational pipeline, revealed primarily PCSK6, followed by PCSK5, PCSK7 and FURIN, as proprotein convertases with the highest novel therapeutic potential.
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47. |
- Wallin, Johan, et al.
(author)
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Samhällsfrågor med naturvetenskapligt innehåll – en kartläggning av undervisningsmöjligheter
- 2022
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Reports (other academic/artistic)abstract
- Som individer och samhällsmedlemmar ställs vi inför samhällsfrågor som medför att vi behöver förhålla oss till olika valmöjligheter. För en del av dessa frågor har naturvetenskapliga kunskaper en central betydelse. En viktig uppgift för skolan är att göra eleverna väl rustade för att kunna resonera om och ta ställning i frågor som rör exempelvis hälsa, miljö, energiförsörjning och teknikutveckling. För att lyckas med detta uppdrag behöver lärare tillgång till en bred undervisningsrepertoar.I den här systematiska kartläggningen beskrivs undervisning i samhällsfrågor med naturvetenskapligt innehåll (SNI) som adresseras inom ramen för forskningsstudier. Syftet är att ge lärare kunskap om och inspiration till undervisningen. Genom att beskriva den palett av didaktiska val som har uppmärksammats i forskningen erbjuder kartläggningen en idébank av möjligheter som står till buds för lärare att använda. Forskningen som ingår har genomförts med elever i motsvarande grundskolan och gymnasieskolan. Den övergripande fråga som ställs i kartläggningen är: Vad kännetecknar undervisning i samhällsfrågor med naturvetenskapligt innehåll (SNI) där elever får möta och använda både kunskaper och värderingar?Den övergripande frågan besvaras utifrån de tre didaktiska frågorna:· Vad undervisar man om – vilka SNI adresseras?· Hur är undervisningen utformad – vilka metoder och arbetssätt används? · Vilka mål och syften framträder i den undervisning som har studerats? För att definiera SNI har vi använt fyra kriterier:· Frågan är relevant för samhällsutvecklingen.· Frågan är ämnesövergripande och komplex, det vill säga att olika aspekter och tänkbara ställningstaganden att resonera om hänger samman på ett svåröverskådligt sätt.· Naturvetenskapliga kunskaper har en central betydelse för de resonemang som kan föras om frågan.· Etiska perspektiv och värderingar är relevanta för frågan, hur man kan resonera om och göra ställningstaganden i relation till denna.
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48. |
- Zirakzadeh, A. Ali, et al.
(author)
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Tumour-associated B cells in urothelial urinary bladder cancer
- 2020
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In: Scandinavian Journal of Immunology. - : Wiley-Blackwell. - 0300-9475 .- 1365-3083. ; 91:2
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Journal article (peer-reviewed)abstract
- Tumour infiltrating B cells and CD38+ plasma cells have been correlated with survival in different malignancies but their role in urinary bladder cancer is unclear. IL-10 is a multifunctional cytokine with both anti-inflammatory and immunostimulatory properties, that can be released by regulatory B cells (Bregs). We have stained paraffin-embedded tumour sections from 31 patients with invasive urothelial urinary bladder cancer with respect to CD20+ B cells, CD38+ cells, IL-10-expressing cells, IgG, C1q and C3a and analysed the impact of these markers on survival. Interestingly, we observe tumour-associated CD20+ B cells forming follicle-like structures in tumours of some patients. We demonstrate that follicle-like structures, tumour-associated CD38+ cells, IL-10 produced by non-B cells, tumour infiltrating IgG and activation of the complement system, may associate to longer survival of urinary bladder cancer patients. IL-10 expression by tumour-associated Bregs may instead negatively affect prognosis. More research is needed to fully understand the role of B cells and IL-10 in urinary bladder cancer.
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