| 1. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 2. |
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| 3. |
- Svensson, Madeleine, 1983-, et al.
(författare)
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Strategies to Encourage E-health : The Effects of Using Different Reminders to Various Extents on Overall Response Patterns in a Large Randomized Internet-based Intervention Study
- 2011
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Konferensbidrag (refereegranskat)abstract
- BackgroundThe use of the Internet as a research tool has dramatically increased in the past several years. Yet, the current literature favors the response rate achieved from paper-based studies. Knowledge of successful methods to increase participation in Internet-based research is scarce. The objective of this study is to examine the effects of different reminders to encourage study participation on overall response patterns in an Internet-based intervention study.MethodsIn 2008, 3,876 employees at four companies in the railway sector in Sweden were randomly e-mailed an Internet-based lifestyle questionnaire consisting of: A) questions, B) questions + interactive personalized automated feedback, or C) questions + interactive personalized automated feedback + telephone counseling. The questionnaire assessed health aspects including diet, physical activity, sleep, stress, alcohol/tobacco consumption, and motivation to change health. Interactive feedback was provided for all health sections; telephone counseling was offered for diet, physical activity, alcohol and smoking habits. Nine months later, a follow-up questionnaire (C) was e-mailed to examine health improvements. 4-5 and 11 e-mail reminders were sent at baseline and follow-up, respectively. Additional reminders (flyers, texts in internal media/bulletin board, information talks, SMS, visit by the research group etc) were also administered at the four companies, to various extents. The number of additional reminders was summarized and analyses were based on the total number of received additional reminders (low, moderate or high). Response patterns were examined in relation to basic characteristics, company, work type (office/field worker), received e-mail reminders, and total number of received additional reminders. As a result of the study, the companies received recommendations for future health implementations.Results38% and 36% completed the baseline and follow-up questionnaire, respectively. The majority of the participants was male, non-smokers, employed as field workers, and had a BMI ≥25. The 4-5 e-mail reminders increased the total response rate by 15%; the 11 e-mail reminders by 21%. Additional reminders had a marginal effect on total response rate, yet generated a positive effective on the response rate among office workers (71%). Since the planning process of the study, the company involved had the highest overall response rate (61%: P<0.001), despite receiving a moderate number of additional reminders. The employees at this company were almost 1.80 (CI: 1.55-2.08) times more likely to participate in the baseline questionnaire, compared to the company which entered the study just prior to the start and had the lowest overall response rate. Participant characteristics including sex, age, BMI, smoking, motivation to change health habits, and version of the completed questionnaire (A, B or C) were not associated with time of response. The highest participation at follow-up, however, was found for those who completed baseline questionnaire A, consisting solely of questions.ConclusionsA well-established collaboration with the participants prior to study start and to send out e-mail reminders on a continuous basis are two effective strategies to increase the response rate in Internet-based studies. Additional reminders conducted in the work setting may only be effective among office workers participating in Internet-based studies.
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| 4. |
- Svensson, Madeleine, 1983-, et al.
(författare)
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The effect of reminders in a web-based intervention study
- 2012
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Ingår i: European Journal of Epidemiology. - Dordrecht : Springer Netherlands. - 0393-2990 .- 1573-7284. ; 27:5, s. 333-340
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge on effective strategies to encourage participation in epidemiological web-based research is scant. We studied the effects of reminders on overall participation. 3,876 employees were e-mailed a baseline web-based lifestyle questionnaire. Nine months later, a follow-up questionnaire was sent. To encourage study participation, 4–5 and 11 e-mail reminders were sent at baseline and follow-up, respectively. Additional reminders (media articles, flyers, SMS etc) were also administered. Reminders (e-mails + additional) were given in low (≤6 reminders), medium (7–9 reminders) or high amounts (>9 reminders). Participation was examined with respect to participant characteristics (i.e. age, sex, Body Mass Index, occupation), type/number of reminders, and time of participation. Most participants were males, 35–49 years, and field workers (non-office based). About 29 % responded before any e-mail reminder, following 26 and 45 % after 1 respective ≥ 2 e-mail reminders. Participant characteristics were not related to when the participants responded. The 4–5 e-mail reminders increased total response rate by 15 %, the eleven by 21 % (greatest increases in September). Those receiving medium amounts of reminders (reference) had the highest response rate (75 %), likewise office workers (54 %) compared to field workers (33 %). High amounts of reminders were particularly effective on office workers. The participants’ characteristics were not related to when they responded in this web-based study. Frequent reminders were effective on response rates, especially for those with high Internet availability. The highest increases in response rates were found in September. © The Author(s) 2012.
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| 5. |
- Svensson, Tobias, et al.
(författare)
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Conjugated Pneumococcal Vaccine Triggers a Better Immune Response than Polysaccharide Pneumococcal Vaccine in Patients with Chronic Lymphocytic Leukemia : A Randomized Study by the Swedish CLL group
- 2018
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 36:25, s. 3701-3707
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To determine if patients with untreated chronic lymphocytic leukemia (CLL) benefit from vaccination with a 13-valent conjugated pneumococcal vaccine (PCV13), Prevenar13®, compared with a 23-valent capsular polysaccharide vaccine (PPSV23), Pneumovax®, in terms of immune response. Background: Patients with CLL have an increased risk for infection and Streptococcus pneumoniae is one of the most common pathogens with high morbidity. Patients with CLL are known to respond poorly to the traditionally used polysaccharide vaccines. Conjugation of polysaccharide to protein carriers renders a thymus-dependent, memory-inducing and more immunogenic vaccine. In patients with CLL, there is no consensus on a recommendation for pneumococcal vaccination, due to a lack of comparative studies. Methods: 128 treatment naïve CLL patients from eight hematology clinics in Sweden were randomized to vaccination with PCV13 (n=63) or PPSV23 (n=65) after stratification by IgG levels and CLL clinical stage (Rai). Blood samples for evaluation of immune response were obtained at baseline, at one and at six months after vaccination. Analyses for each of the 12 pneumococcal serotypes common for PCV13 and PPSV23 were performed by opsonophagocytic assay (OPA) and enzyme-linked immunosorbent assay (ELISA). Results: PCV13 elicited a superior immune response than PPSV23 in 10/12 serotypes one month after vaccination and in 5/12 serotypes six months after vaccination, measured as OPA geometric mean titers (GMTs). Geometric mean concentrations of serotype-specific IgG antibodies elicited by PCV13 as measured by ELISA, were higher than those elicited by PPSV23 in half of the common serotypes, both after one and six months. The proportion of patients with good response (defined as response in 8 of 12 common serotypes according to predefined response criteria) was higher in PCV13 recipients than in PPSV23 recipients after one month (40% vs. 22%, p=0.034) as well as after six months (33% vs. 17%, p=0.041). Never did PPSV23 trigger a better immune response for any of the serotypes, than PCV13, regardless of analysis. For two of the serotypes, OPA GMTs were lower at the six months than at the one-month follow up. Negative predictive factors for vaccination response were hypogammaglobulinemia and long disease duration. Both vaccines were well tolerated. Conclusions: In patients with previously untreated CLL, the efficacy of PCV13 in terms of immune response is superior to PPSV23 for many serotypes common for the two vaccines. PCV13 should be considered as a part in vaccination programs against Streptococcus pneumoniae for these patients and administered as early as possible during the course of the disease.
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| 6. |
- Abarenkov, Kessy, et al.
(författare)
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Annotating public fungal ITS sequences from the built environment according to the MIxS-Built Environment standard – a report from a May 23-24, 2016 workshop (Gothenburg, Sweden)
- 2016
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Ingår i: MycoKeys. - : Pensoft Publishers. - 1314-4057 .- 1314-4049. ; 16, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Recent molecular studies have identified substantial fungal diversity in indoor environments. Fungi and fungal particles have been linked to a range of potentially unwanted effects in the built environment, including asthma, decay of building materials, and food spoilage. The study of the built mycobiome is hampered by a number of constraints, one of which is the poor state of the metadata annotation of fungal DNA sequences from the built environment in public databases. In order to enable precise interrogation of such data – for example, “retrieve all fungal sequences recovered from bathrooms” – a workshop was organized at the University of Gothenburg (May 23-24, 2016) to annotate public fungal barcode (ITS) sequences according to the MIxS-Built Environment annotation standard (http://gensc.org/mixs/). The 36 participants assembled a total of 45,488 data points from the published literature, including the addition of 8,430 instances of countries of collection from a total of 83 countries, 5,801 instances of building types, and 3,876 instances of surface-air contaminants. The results were implemented in the UNITE database for molecular identification of fungi (http://unite.ut.ee) and were shared with other online resources. Data obtained from human/animal pathogenic fungi will furthermore be verified on culture based metadata for subsequent inclusion in the ISHAM-ITS database (http://its.mycologylab.org).
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| 7. |
- Adolphi, Florian, et al.
(författare)
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Connecting the Greenland ice-core and U/Th timescales via cosmogenic radionuclides : Testing the synchroneity of Dansgaard-Oeschger events
- 2018
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 14:11, s. 1755-1781
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Tidskriftsartikel (refereegranskat)abstract
- During the last glacial period Northern Hemisphere climate was characterized by extreme and abrupt climate changes, so-called Dansgaard-Oeschger (DO) events. Most clearly observed as temperature changes in Greenland ice-core records, their climatic imprint was geographically widespread. However, the temporal relation between DO events in Greenland and other regions is uncertain due to the chronological uncertainties of each archive, limiting our ability to test hypotheses of synchronous change. In contrast, the assumption of direct synchrony of climate changes forms the basis of many timescales. Here, we use cosmogenic radionuclides (10Be, 36Cl, 14C) to link Greenland ice-core records to U=Th-dated speleothems, quantify offsets between the two timescales, and improve their absolute dating back to 45 000 years ago. This approach allows us to test the assumption that DO events occurred synchronously between Greenland ice-core and tropical speleothem records with unprecedented precision. We find that the onset of DO events occurs within synchronization uncertainties in all investigated records. Importantly, we demonstrate that local discrepancies remain in the temporal development of rapid climate change for specific events and speleothems. These may either be related to the location of proxy records relative to the shifting atmospheric fronts or to underestimated U=Th dating uncertainties. Our study thus highlights the potential for misleading interpretations of the Earth system when applying the common practice of climate wiggle matching.
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| 8. |
- Ahlberg, Erik, et al.
(författare)
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"Vi klimatforskare stödjer Greta och skolungdomarna"
- 2019
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Ingår i: Dagens nyheter (DN debatt). - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
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