| 41. |
- Buus, Terkild Brink, et al.
(författare)
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Single-cell heterogeneity in Sézary syndrome
- 2018
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 2:16, s. 2115-2126
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Tidskriftsartikel (refereegranskat)abstract
- Sezary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL) with a median life expectancy of less than 4 years. Although initial treatment responses are often good, the vast majority of patients with SS fail to respond to ongoing therapy. We hypothesize that malignant T cells are highly heterogeneous and harbor subpopulations of SS cells that are both sensitive and resistant to treatment. Here, we investigate the presence of single-cell heterogeneity and resistance to histone deacetylase inhibitors (HDACi) within primary malignant T cells from patients with SS. Using single-cell RNA sequencing and flow cytometry, we find that malignant T cells from all investigated patients with SS display a high degree of single-cell heterogeneity at both the mRNA and protein levels. We show that this heterogeneity divides the malignant cells into distinct subpopulations that can be isolated by their expression of different surface antigens. Finally, we show that treatment with HDACi (suberanilohydroxamic acid and romidepsin) selectively eliminates some subpopulations while leaving other subpopulations largely unaffected. In conclusion, we show that patients with SS display a high degree of single-cell heterogeneity within the malignant T-cell population, and that distinct subpopulations of malignant T cells carry HDACi resistance. Our data point to the importance of understanding the heterogeneous nature of malignant SS cells in each individual patient to design combinational and new therapies to counter drug resistance and treatment failure.
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| 42. |
- Edwin, Aaron, et al.
(författare)
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Structure of the N-terminal domain of the metalloprotease PrtV from Vibrio cholerae
- 2015
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Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 24:12, s. 2076-2080
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Tidskriftsartikel (refereegranskat)abstract
- The metalloprotease PrtV from Vibrio cholerae serves an important function for the ability of bacteria to invade the mammalian host cell. The protein belongs to the family of M6 proteases, with a characteristic zinc ion in the catalytic active site. PrtV constitutes a 918 amino acids (102 kDa) multidomain pre-pro-protein that undergoes several N- and C-terminal modifications to form a catalytically active protease. We report here the NMR structure of the PrtV N- terminal domain (residues 23-103) that contains two short alpha-helices in a coiled coil motif. The helices are held together by a cluster of hydrophobic residues. Approximately 30 residues at the C-terminal end, which were predicted to form a third helical structure, are disordered. These residues are highly conserved within the genus Vibrio, which suggests that they might be functionally important.
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| 43. |
- Ekblom Bak, Elin, 1981-, et al.
(författare)
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Accelerometer derived physical activity patterns in 27.890 middle‐aged adults : The SCAPIS cohort study
- 2022
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 32:5, s. 866-880
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Tidskriftsartikel (refereegranskat)abstract
- The present study aims to describe accelerometer-assessed physical activity (PA) patterns and fulfillment of PA recommendations in a large sample of middle-aged men and women, and to study differences between subgroups of socio-demographic, socio-economic, and lifestyle-related variables. A total of 27 890 (92.5% of total participants, 52% women, aged 50–64 years) middle-aged men and women with at least four days of valid hip-worn accelerometer data (Actigraph GT3X+, wGT3X+ and wGT3X-BT) from the Swedish CArdioPulmonary bioImage Study, SCAPIS, were included. In total, 54.5% of daily wear time was spent sedentary, 39.1% in low, 5.4% in moderate, and only 0.1% in vigorous PA. Male sex, higher education, low financial strain, born in Sweden, and sedentary/light working situation were related to higher sedentary time, but also higher levels of vigorous PA. High BMI and having multiple chronic diseases associated strongly with higher sedentary time and less time in all three PA intensities. All-year physically active commuters had an overall more active PA pattern. The proportion fulfilling current PA recommendations varied substantially (1.4% to 92.2%) depending on data handling procedures and definition used. Twenty-eight percent was defined as having an “at-risk” behavior, which included both high sedentary time and low vigorous PA. In this large population-based sample, a majority of time was spent sedentary and only a fraction in vigorous PA, with clinically important variations between subgroups. This study provides important reference material and emphasizes the importance of a comprehensive assessment of all aspects of the individual PA pattern in future research and clinical practice.
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| 44. |
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| 45. |
- Ekström, Magnus Pär, et al.
(författare)
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The association of body mass index, weight gain and central obesity with activity-related breathlessness : the Swedish Cardiopulmonary Bioimage Study
- 2019
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Ingår i: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 74:10, s. 958-964
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) >30 kg/m(2)) is rapidly increasing globally and its impact on breathlessness is unclear.Methods: This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score >= 1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex.Results: We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m(2); and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; p<0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness.Conclusion: Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.
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| 46. |
- Enochsson, Lars, et al.
(författare)
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Kvalitetsregister för gallstenskirurgi har förbättrat vården
- 2015
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 112
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish Registry for cholecystectomy and endoscopic retrograde cholangiopancreatography (ERCP) (GallRiks) is a validated register with high coverage. The registry started on May 1, 2005 and serves as a base for audit on gallstone disease treatment and also provides a database for clinical research. The aim of this study is to present an overview of the clinical consequences and implementations in patient care that GallRiks research may have contributed to during a 10-year period. Results from studies on GallRiks data have reduced the use of antibiotic and thromboembolic prophylaxis as well as showed the importance of intraoperative cholangiography. Furthermore, the studies on GallRiks data have most probably changed the treatment strategies in ERCP. Studies on GallRiks data have changed and improved the management of patients in Sweden who undergo gallstone surgery or ERCP.
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| 47. |
- Enochsson, Lars, et al.
(författare)
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The Swedish Registry of Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks) : A nationwide registry for quality assurance of gallstone surgery.
- 2013
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Ingår i: JAMA Surgery. - : American Medical Association (AMA). - 2168-6254 .- 2168-6262. ; 148:5, s. 471-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To describe the process of initiating and organizing a nationwide validated web-based quality registry of gallstone surgery and endoscopic retrograde cholangiopancreatography (ERCP) and to present some clinical data and the impact the registry has had on the clinical treatment of gallstones.DESIGN: Observational, population-based registry study.SETTING: Data from the nationwide Swedish Registry of Gallstone Surgery and ERCP (GallRiks).PATIENTS: From May 1, 2005, to December 31, 2011, 63 685 cholecystectomies (laparoscopic and open) and 37 860 ERCPs have been prospectively registered in GallRiks.INTERVENTIONS: Cholecystectomies, laparoscopic or conventional, as well as ERCP in a population-based setting.MAIN OUTCOME MEASURES: Registrations of all cholecystectomies and ERCPs are performed online by the surgeon or endoscopist. Thirty-day follow-up of both gallstone surgery and ERCP is mandatory, as is an additional 6-month follow-up of the cholecystectomies. Scores on the 36-Item Short Form Health Survey are registered preoperatively and 6 months postoperatively in elective cholecystectomies at selected units.RESULTS: The 30-day overall complication rate is 6.1% in elective cholecystectomy, 11.2% in urgent cholecystectomy, and 12.0% following ERCP. The use of antibiotic and thromboembolic prophylaxis in elective laparoscopic cholecystectomy in Sweden has decreased by 8.7% and 17.8% (2006-2011), respectively, mainly owing to presentation of GallRiks data both at meetings and published in peer-reviewed publications. The large database has also enabled several research projects, including one demonstrating that the intention to perform intraoperative cholangiography reduced the risk of death after cholecystectomy. The database has reached greater than 90% national coverage and is continuously validated.CONCLUSIONS: GallRiks is a validated national quality registry for gallstone surgery and ERCP, serving as a base for audit of gallstone disease treatment. It also provides a database for clinical research.
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| 48. |
- Eriksson, Anders, et al.
(författare)
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Postmortem imaging : a systematic review
- 2015
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Ingår i: Scandinavian Journal of Forensic Science. - : Walter de Gruyter. - 1503-9552. ; 21:1, s. 47-47
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 49. |
- Esberg, Anders, et al.
(författare)
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Streptococcus Mutans Adhesin Biotypes that Match and Predict Individual Caries Development
- 2017
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 24, s. 205-215
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Tidskriftsartikel (refereegranskat)abstract
- Dental caries, which affects billions of people, is a chronic infectious disease that involves Streptococcus mutans, which is nevertheless a poor predictor of individual caries development. We therefore investigated if adhesin types of S.mutans with sucrose-independent adhesion to host DMBT1 (i.e. SpaP A, B or C) and collagen (i.e. Cnm, Cbm) match and predict individual differences in caries development. The adhesin types were measured in whole saliva by qPCR in 452 12-year-old Swedish children and related to caries at baseline and prospectively at a 5-year follow-up. Strains isolated from the children were explored for genetic and phenotypic properties. The presence of SpaP B and Cnm subtypes coincided with increased 5-year caries increment, and their binding to DMBT1 and saliva correlated with individual caries scores. The SpaP B subtypes are enriched in amino acid substitutions that coincided with caries and binding and specify biotypes of S. mutans with increased acid tolerance. The findings reveal adhesin subtypes of S. mutans that match and predict individual differences in caries development and provide a rationale for individualized oral care.
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| 50. |
- Fowler, Christopher J, et al.
(författare)
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Targeting the endocannabinoid system for the treatment of cancer : a practical view
- 2010
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Ingår i: Current Topics in Medicinal Chemistry. - : Bentham Science Publishers. - 1568-0266 .- 1873-4294. ; 10:8, s. 814-827
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Forskningsöversikt (refereegranskat)abstract
- In recent years, considerable interest has been generated by findings that cannabinoids not only have useful palliative effects, but also can affect the viability and invasivity of a variety of different cancer cells. In the present review, the potential of targeting the cannabinoid system for the treatment of cancer is considered from a practical, rather than a mechanistic viewpoint, addressing questions such as whether human tumour cells express CB receptors; whether the potencies of action of cannabinoids in vitro match the potencies expected on the base of receptor theory; what is known about the in vivo effects of cannabinoids and cancer, and how relevant the experiments undertaken are to the clinical situation; and finally, what approaches can be taken to minimise unwanted effects of cannabinoid treatment. It is concluded that cannabinoids (or agents modulating the endogenous cannabinoid system) are an attractive target for drug development in the cancer area, but that more in vivo studies, particularly those investigating the potential of cannabinoids as an addition to current treatment strategies, are needed.
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