| 1. |
- Adnan, Ali, et al.
(författare)
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Health-related quality of life among tonsillar carcinoma patients in Sweden in relation to treatment and comparison with quality of life among the population
- 2020
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Ingår i: Head and Neck-Journal for the Sciences and Specialties of the Head and Neck. - : Wiley. - 1043-3074 .- 1097-0347. ; 42:5, s. 860-872
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Tidskriftsartikel (refereegranskat)abstract
- Background The health-related quality of life (HRQOL) of tonsillar carcinoma survivors was explored to investigate any HRQOL differences associated with tumor stage and treatment. The survivors' HRQOL was also compared to reference scores from the population. Methods In this exploratory cross-sectional study patients were invited 15 months after their diagnosis and asked to answer two quality of life questionnaires (EORTC QLQ- C30, EORTC QLQ- HN35), 405 participated. Results HRQOL was associated with gender, with males scoring better than females on a few scales. Patients' HRQOL was more associated with treatment than tumor stage. Patients' HRQOL was worse than that in an age- and sex-matched reference group from the normal population, the largest differences were found for problems with dry mouth followed by problems with sticky saliva, senses, swallowing and appetite loss. Conclusions The tonsillar carcinoma patients had a worse HRQOL compared to the general population one year after treatment.
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| 2. |
- Danielsson, Henrik, et al.
(författare)
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A Systematic Review of Longitudinal Trajectories of Mental Health Problems in Children with Neurodevelopmental Disabilities
- 2024
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Ingår i: Journal of Developmental and Physical Disabilities. - : Springer. - 1056-263X .- 1573-3580. ; 36, s. 203-242
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Forskningsöversikt (refereegranskat)abstract
- To review the longitudinal trajectories - and the factors influencing their development - of mental health problems in children with neurodevelopmental disabilities. Systematic review methods were employed. Searches of six databases used keywords and MeSH terms related to children with neurodevelopmental disabilities, mental health problems, and longitudinal research. After the removal of duplicates, reviewers independently screened records for inclusion, extracted data (outcomes and influencing factors), and evaluated the risk of bias. Findings were tabulated and synthesized using graphs and a narrative. Searches identified 94,662 unique records, from which 49 publications were included. The median publication year was 2015. Children with attention deficit hyperactivity disorder were the most commonly included population in retrieved studies. In almost 50% of studies, trajectories of mental health problems changed by < 10% between the first and last time point. Despite multiple studies reporting longitudinal trajectories of mental health problems, greater conceptual clarity and consideration of the measures included in research is needed, along with the inclusion of a more diverse range of populations of children with neurodevelopmental disabilities.
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| 3. |
- Gebre-Medhin, Maria, et al.
(författare)
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ARTSCAN III : A randomized phase III study comparing chemoradiotherapy with cisplatin versus cetuximab in patients with locoregionally advanced head and neck squamous cell cancer
- 2021
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 39:1, s. 38-47
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE We performed an open-label randomized controlled phase III study comparing treatment outcome and toxicity between radiotherapy (RT) with concomitant cisplatin versus concomitant cetuximab in patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC; stage III-IV according to the Union for International Cancer Control TNM classification, 7th edition). MATERIALS AND METHODS Eligible patients were randomly assigned 1:1 to receive either intravenous cetuximab 400 mg/m2 1 week before start of RT followed by 250 mg/m2/wk, or weekly intravenous cisplatin 40 mg/m2, during RT. RT was conventionally fractionated. Patients with T3-T4 tumors underwent a second random assignment 1:1 between standard RT dose 68.0 Gy to the primary tumor or dose escalation to 73.1 Gy. Primary end point was overall survival (OS) evaluated using adjusted Cox regression analysis. Secondary end points were locoregional control, local control with dose-escalated RT, pattern of failure, and adverse effects. RESULTS Study inclusion was prematurely closed after an unplanned interim analysis when 298 patients had been randomly assigned. At 3 years, OS was 88% (95% CI, 83% to 94%) and 78% (95% CI, 71% to 85%) in the cisplatin and cetuximab groups, respectively (adjusted hazard ratio, 1.63; 95% CI, 0.93 to 2.86; P 5 .086). The cumulative incidence of locoregional failures at 3 years was 23% (95% CI, 16% to 31%) compared with 9% (95% CI, 4% to 14%) in the cetuximab versus the cisplatin group (Gray’s test P 5 .0036). The cumulative incidence of distant failures did not differ between the treatment groups. Dose escalation in T3-T4 tumors did not increase local control. CONCLUSION Cetuximab is inferior to cisplatin regarding locoregional control for concomitant treatment with RT in patients with locoregionally advanced HNSCC. Additional studies are needed to identify possible subgroups that still may benefit from concomitant cetuximab treatment.
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| 4. |
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| 5. |
- Högmo, Anders, et al.
(författare)
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Base of tongue squamous cell carcinomas, outcome depending on treatment strategy and p16 status. A population-based study from the Swedish Head and Neck Cancer Register
- 2022
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 61:4, s. 433-440
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Tidskriftsartikel (refereegranskat)abstract
- Background: The base of tongue squamous cell carcinoma (BOTSCC) is mainly an HPV-related tumor. Radiotherapy (EBRT) ± concomitant chemotherapy (CT) is the backbone of the curatively intended treatment, with brachytherapy (BT) boost as an option. With four different treatment strategies in Sweden, a retrospective study based on the population-based Swedish Head and Neck Cancer Register (SweHNCR) was initiated.Material and methods: Data on tumors, treatment and outcomes in patients with BOTSCC treated between 2008 and 2014 were validated through medical records and updated as needed. Data on p16 status were updated or completed with immunohistochemical analysis of archived tumor material. Tumors were reclassified according to the UICC 8th edition.Results: Treatment was EBRT, EBRT + CT, EBRT + BT or EBRT + CT + BT in 151, 145, 82 and 167 patients respectively (n = 545). A p16 analysis was available in 414 cases; 338 were p16+ and 76 p16−. 5-year overall survival (OS) was 68% (95% CI: 64–72%), with76% and 37% for p16+ patients and p16− patients, respectively. An increase in OS was found with the addition of CT to EBRT for patients with p16+ tumors, stages II–III, but for patients with tumor stage I, p16+ (UICC 8) none of the treatment strategies was superior to EBRT alone.Conclusion: In the present retrospective population-based study of BOTSCC brachytherapy was found to be of no beneficial value in curatively intended treatment. An increase in survival was found for EBRT + CT compared to EBRT alone in patients with advanced cases, stages II and III (UICC 8), but none of the regimes was significantly superior to EBRT as a single treatment modality for stage I (UICC 8), provided there was p16 positivity in the tumor. In the small group of patients with p16− tumors, a poorer prognosis was found, but the small sample size did not allow any comparisons between different treatment strategies.
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| 6. |
- Larena, Maximilian, et al.
(författare)
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Multiple migrations to the Philippines during the last 50,000 years
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 118:13
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Tidskriftsartikel (refereegranskat)abstract
- Island Southeast Asia has recently produced several surprises regarding human history, but the region's complex demography remains poorly understood. Here, we report similar to 2.3 million genotypes from 1,028 individuals representing 115 indigenous Philippine populations and genome-sequence data from two similar to 8,000-y-old individuals from Liangdao in the Taiwan Strait. We show that the Philippine islands were populated by at least five waves of human migration: initially by Northern and Southern Negritos (distantly related to Australian and Papuan groups), followed by Manobo, Sama, Papuan, and Cordilleran-related populations. The ancestors of Cordillerans diverged from indigenous peoples of Taiwan at least similar to 8,000 y ago, prior to the arrival of paddy field rice agriculture in the Philippines similar to 2,500 y ago, where some of their descendants remain to be the least admixed East Asian groups carrying an ancestry shared by all Austronesian-speaking populations. These observations contradict an exclusive "out-of-Taiwan" model of farming-language-people dispersal within the last four millennia for the Philippines and Island Southeast Asia. Sama-related ethnic groups of southwestern Philippines additionally experienced some minimal South Asian gene flow starting similar to 1,000 y ago. Lastly, only a few lowlanders, accounting for <1% of all individuals, presented a low level of West Eurasian admixture, indicating a limited genetic legacy of Spanish colonization in the Philippines. Altogether, our findings reveal a multilayered history of the Philippines, which served as a crucial gateway for the movement of people that ultimately changed the genetic landscape of the Asia-Pacific region.
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| 7. |
- Mannervik, Bengt, et al.
(författare)
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Glutathione Transferases as Efficient Ketosteroid Isomerases
- 2021
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Ingår i: Frontiers in Molecular Biosciences. - : Frontiers Media SA. - 2296-889X. ; 8
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Forskningsöversikt (refereegranskat)abstract
- In addition to their well-established role in detoxication, glutathione transferases (GSTs) have other biological functions. We are focusing on the ketosteroid isomerase activity, which appears to contribute to steroid hormone biosynthesis in mammalian tissues. A highly efficient GST A3-3 is present in some, but not all, mammals. The alpha class enzyme GST A3-3 in humans and the horse shows the highest catalytic efficiency with kcat/Km values of approximately 107 M−1s−1, ranking close to the most active enzymes known. The expression of GST A3-3 in steroidogenic tissues suggests that the enzyme has evolved to support the activity of 3β-hydroxysteroid dehydrogenase, which catalyzes the formation of 5-androsten-3,17-dione and 5-pregnen-3,20-dione that are substrates for the double-bond isomerization catalyzed by GST A3-3. The dehydrogenase also catalyzes the isomerization, but its kcat of approximately 1 s−1 is 200-fold lower than the kcat values of human and equine GST A3-3. Inhibition of GST A3-3 in progesterone-producing human cells suppress the formation of the hormone. Glutathione serves as a coenzyme contributing a thiolate as a base in the isomerase mechanism, which also involves the active-site Tyr9 and Arg15. These conserved residues are necessary but not sufficient for the ketosteroid isomerase activity. A proper assortment of H-site residues is crucial to efficient catalysis by forming the cavity binding the hydrophobic substrate. It remains to elucidate why some mammals, such as rats and mice, lack GSTs with the prominent ketosteroid isomerase activity found in certain other species. Remarkably, the fruit fly Drosophila melanogaster, expresses a GSTE14 with notable steroid isomerase activity, even though Ser14 has evolved as the active-site residue corresponding to Tyr9 in the mammalian alpha class.
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| 8. |
- Ranlund, Åsa, et al.
(författare)
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Metodbeskrivning : 2020 års inventeringar av gräsmarker och lövskogar
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- En generell stickprovsdesign, inom vilken det går att inventera både vanliga och ovanliga fenomen på såväl nationell som regional nivå, utvecklades under 2019 och 2020. Under 2020 har den nya stickprovsdesignen använts för inventeringar av gräsmarker och lövskogar med syfte att förbättra nationella data på naturtyper med höga naturvärden, dvs. naturtyper som uppfyller kriterierna för EU:s art- och habitatdirektivs annex 1, samtidigt som vanligare naturtyper följdes där behov funnits för att komplettera befintliga data. I den här rapporten redovisar vi metodiken vi utvecklat för flygbilds- och fältinventeringarna samt hur urval av trakter till stickprov och provytor för fältbesök gått till.För gräsmarks- och lövskogsinventeringarna gjordes först ett gemensamt så kallat balanserat urval för att slumpmässigt välja ut trakter ur urvalsramen till stickprov. Sedan klassades alla provytor inom de utvalda trakterna i en flygbildsinventering till både lövskogs- och gräsmarksklasser. Utifrån de flygbildsinventerade klasserna skapades urvalsklasser separat för gräsmarks- respektive lövskogsinventeringen. Urvalsklasserna användes sedan för att välja ut provytor för fältbesök, ett urval som gjordes för gräsmarks- respektive lövskogsinventeringen oberoende av varandra.Metodiken för flygbildsinventering utvecklades för att gräsmarks- och lövskogsinventeringarna skulle kunna använda stora stickprov, i linje med den nya stickprovsdesignen. En viktig princip vid flygbildsinveteringen var överklassning, dvs att provytor inkluderades där klassningen var osäker. Detta för att säkerställa att alla gräsmarker och lövskogar inom inventeringarnas respektive ramverk hade möjlighet att ingå så att det statistiska kravet för stickprovsdesignen var uppfyllda. Provytor som utifrån flygbildsinventeringen helt säkert inte innehöll eftersökta naturtyper behövde inte besökas i fält vilket gjorde att fältbesöken fokuserades till provytor av intresse för gräsmarks- eller lövskogsinventeringarna. Det minskade kostnaden för fältbesök och vi kunde använda större stickprov. Sammantaget flygbildsinventerades över 137 000 provytor fördelat på 701 trakter inför fältinventeringen 2020.För fältinventeringen inom gräsmarks- och lövskogsinventeringarna introducerades flera nyheter jämfört med tidigare inventeringar för att samla in mer data på bl.a. naturtypers kvalitet. Varje delyta klassades t.ex. till en naturtyp oavsett om den uppfyller kravet för att bli klassad som en annex 1-naturtyp. Utöver det registrerades ett antal kvalitetsvariabler som visar vilka kriterier för annex 1 som är uppfyllda eller inte. Det gör att det går att jämföra areal och statusvariabler för en annex 1-naturtyp) med areal och statusvariabler av motsvarande naturtyp med låga naturvärden (dvs. där annex 1-kriterierna inte är uppfyllda). 1763 provytor fördelat på 187 trakter slumpades ut för att inventeras i fält 2020. Av dem inventerades 64 provytor 2021 eftersom de inte hanns med säsongen 2020.Eftersom antalet trakter är den viktigaste faktorn i att bestämma precisionen i skattningarna så vill vi inte minska antalet trakter eftersom det ökar osäkerheten i skattningarna. För att effektivisera inventeringarna arbetar vi därför med två olika angreppssätt för en viss stickprovstäthet. Dels vill vi förbättra möjligheten att korrekt kunna utesluta provytor, och ibland hela trakter, från fältbesök genom att förbättra flygbildsinventeringen. Det kan t.ex. handla om att minska överklassningen, genom att göra kriterierna för klasserna snävare . Under det första inventeringsåret 2020 tog det lite längre tid att inventera en trakt i fält än vad som var önskvärt. För att minska fälttiden kan vi därför behöva minska antalet provytor som vi inventerar per trakt alternativt förenkla fältmetodiken per provyta. Fältinsatsen kan också bli effektivare genom att inventering av smala linjära objekt, som åker- och vägrenar, görs genom en linjekorsningsinventering istället för via gräsmarks- och lövskogsinventeringarnas provytor. För lövskogsinventeringen 2020 var ålderskriteriet >30 år . Ett sätt att fokusera denna inventering mot naturtyper av större intresse är att höja ålderskriteriet så att inventeringen riktas mer mot äldre lövskogar. Utöver färre provytor skulle det antagligen också leda till att vi behöver besöka färre trakter inom lövskogsinventeringen. Nackdelen blir förstås att inventeringen inte inkluderar yngre skogar, så det är ett beslut som bör tas utifrån vilka frågeställningar som ska besvaras och hur prioriteringen ser ut för vilka data som ska samlas in.För att kunna ta tillvara de möjligheter som den nya stickprovsdesignen ger har vi utvecklat ny metodik för flygbildsinventering av stora stickprov inom gräsmarks- och lövskogsinventeringarna. Det förbättrar våra möjligheter att möta kraven på tillfredställande data även för mer ovanliga naturtyper. För att möta de ökade kraven på data till artikel 17-rapporteringen har vi också utvecklat och omprioriterat fältinventeringen. 2020 var det första året för gräsmarks- och lövskogsinventeringarna. Redan då fanns allt på plats men många delar behöver utvecklas vidare för att ytterligare effektivisera dem.
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| 9. |
- Schlebusch, Carina, 1977-, et al.
(författare)
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Khoe-San Genomes Reveal Unique Variation and Confirm the Deepest Population Divergence in Homo sapiens
- 2020
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 37:10, s. 2944-2954
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Tidskriftsartikel (refereegranskat)abstract
- The southern African indigenous Khoe-San populations harbor the most divergent lineages of all living peoples. Exploring their genomes is key to understanding deep human history. We sequenced 25 full genomes from five Khoe-San populations, revealing many novel variants, that 25% of variants are unique to the Khoe-San, and that the Khoe-San group harbors the greatest level of diversity across the globe. In line with previous studies, we found several gene regions with extreme values in genome-wide scans for selection, potentially caused by natural selection in the lineage leading to Homo sapiens and more recent in time. These gene regions included immunity-, sperm-, brain-, diet-, and muscle-related genes. When accounting for recent admixture, all Khoe-San groups display genetic diversity approaching the levels in other African groups and a reduction in effective population size starting around 100,000 years ago. Hence, all human groups show a reduction in effective population size commencing around the time of the Out-of-Africa migrations, which coincides with changes in the paleoclimate records, changes that potentially impacted all humans at the time.
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| 10. |
- Škerlová, Jana, et al.
(författare)
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Structural and functional analysis of the inhibition of equine glutathione transferase A3-3 by organotin endocrine disrupting pollutants
- 2021
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Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491 .- 1873-6424. ; 268
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Tidskriftsartikel (refereegranskat)abstract
- Organotin compounds are highly toxic environmental pollutants with neurotoxic and endocrinedisrupting effects. They are potent inhibitors of glutathione transferases (GSTs), thus impeding their detoxication and antioxidant functions. Several GSTs, including equine GST A3-3 (EcaGST A3-3), exhibit steroid double-bond isomerase activity and are involved in the biosynthesis of testosterone and progesterone. We have performed enzyme kinetics analyses of the inhibition of EcaGST A3-3 by organotin compounds. We have also solved crystal structures of EcaGST A3-3 in complexes with glutathione, and with glutathione together with covalently bound triethyltin. Our structural data indicate that the tin atom forms strong bonds with a covalent character not only with the glutathione, but also with a tyrosyl residue of the enzyme itself, thereby preventing the release of the glutathione-organotin adduct and completely blocking the enzyme function. This work presents a structural basis for the general mechanism of GST inhibition by organotin compounds and contributes to the understanding of their neurotoxic and endocrine disrupting effects.
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