| 1. |
- Arnoldt, Sina, et al.
(författare)
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Mass spectroscopy reveals compositional differences in copepodamides from limnic and marine copepods
- 2024
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Ingår i: Scientific reports. - 2045-2322. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Marine copepods, the most abundant animals in the global ocean, imprint their surrounding waters with chemical cues, called copepodamides. Copepodamides induce defensive traits such as toxin production, bioluminescence, and colony size plasticity in a variety of marine phytoplankton. The role of copepodamides in freshwater ecosystems is, however, unknown. Here we report the consistent presence of copepodamides in copepods from six Swedish freshwater lakes. Copepodamide concentrations in freshwater copepods are similar to those of marine copepods, around 0.1ppt of dry mass in millimetre sized individuals. The composition substantially overlaps with marine copepodamides but is also distinctly different. Marine copepods commonly contain both subgroups of copepodamides, the copepodamides (CA) and the dihydro-copepodamides (dhCA), whereas freshwater copepods are dominated by the dhCAs. Taxonomic groups had consistent copepodamide profiles across sampling sites and timepoints, supporting the presence of species-specific copepodamide signatures. We describe 10 new copepodamide structures, four of which were found exclusively in freshwater copepods. The presence of copepodamides in limnic copepods also warrants studies into their potential function as predator alarm cues in freshwater systems.
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| 2. |
- Dahlblom, Victor, et al.
(författare)
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Artificial intelligence detection of missed cancers at digital mammography that were detected at digital breast tomosynthesis
- 2021
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Ingår i: Radiology: Artificial Intelligence. - : Radiological Society of North America (RSNA). - 2638-6100. ; 3:6
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate how an artificial intelligence (AI) system performs at digital mammography (DM) from a screening population with ground truth defined by digital breast tomosynthesis (DBT), and whether AI could detect breast cancers at DM that had originally only been detected at DBT. Materials and Methods: In this secondary analysis of data from a prospective study, DM examinations from 14 768 women (mean age, 57 years), examined with both DM and DBT with independent double reading in the Malmӧ Breast Tomosynthesis Screening Trial (MBTST) (ClinicalTrials.gov: NCT01091545; data collection, 2010–2015), were analyzed with an AI system. Of 136 screening-detected cancers, 95 cancers were detected at DM and 41 cancers were detected only at DBT. The system identifies suspicious areas in the image, scored 1–100, and provides a risk score of 1 to 10 for the whole examination. A cancer was defined as AI detected if the cancer lesion was correctly localized and scored at least 62 (threshold determined by the AI system developers), therefore resulting in the highest examination risk score of 10. Data were analyzed with descriptive statistics, and detection performance was analyzed with receiver operating characteristics. Results: The highest examination risk score was assigned to 10% (1493 of 14 786) of the examinations. With 90.8% specificity, the AI system detected 75% (71 of 95) of the DM-detected cancers and 44% (18 of 41) of cancers at DM that had originally been detected only at DBT. The majority were invasive cancers (17 of 18). Conclusion: Almost half of the additional DBT-only screening-detected cancers in the MBTST were detected at DM with AI. AI did not reach double reading performance; however, if combined with double reading, AI has the potential to achieve a substantial portion of the benefit of DBT screening.
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| 3. |
- Hober, Andreas, et al.
(författare)
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Rapid and sensitive detection of SARS-CoV-2 infection using quantitative peptide enrichment LC-MS analysis
- 2021
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Ingår i: eLIFE. - : eLIFE SCIENCES PUBL LTD. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Reliable, robust, large-scale molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for monitoring the ongoing coronavirus disease 2019 (COVID-19) pandemic. We have developed a scalable analytical approach to detect viral proteins based on peptide immuno-affinity enrichment combined with liquid chromatography-mass spectrometry (LC-MS). This is a multiplexed strategy, based on targeted proteomics analysis and read-out by LC-MS, capable of precisely quantifying and confirming the presence of SARS-CoV-2 in phosphate-buffered saline (PBS) swab media from combined throat/nasopharynx/saliva samples. The results reveal that the levels of SARS-CoV-2 measured by LC-MS correlate well with their correspondingreal-time polymerase chain reaction (RT-PCR) read-out (r = 0.79). The analytical workflow shows similar turnaround times as regular RT-PCR instrumentation with a quantitative read-out of viral proteins corresponding to cycle thresholds (Ct) equivalents ranging from 21 to 34. Using RT-PCR as a reference, we demonstrate that the LC-MS-based method has 100% negative percent agreement (estimated specificity) and 95% positive percent agreement (estimated sensitivity) when analyzing clinical samples collected from asymptomatic individuals with a Ct within the limit of detection of the mass spectrometer (Ct <= 30). These results suggest that a scalable analytical method based on LC-MS has a place in future pandemic preparedness centers to complement current virus detection technologies.
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| 4. |
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| 6. |
- Johnson, Kristin, et al.
(författare)
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False-positive recalls in the prospective Malmö Breast Tomosynthesis Screening Trial
- 2023
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Ingår i: European Radiology. - 0938-7994. ; 33:11, s. 8089-8099
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate the total number of false-positive recalls, including radiographic appearances and false-positive biopsies, in the Malmö Breast Tomosynthesis Screening Trial (MBTST). Methods: The prospective, population-based MBTST, with 14,848 participating women, was designed to compare one-view digital breast tomosynthesis (DBT) to two-view digital mammography (DM) in breast cancer screening. False-positive recall rates, radiographic appearances, and biopsy rates were analyzed. Comparisons were made between DBT, DM, and DBT + DM, both in total and in trial year 1 compared to trial years 2 to 5, with numbers, percentages, and 95% confidence intervals (CI). Results: The false-positive recall rate was higher with DBT, 1.6% (95% CI 1.4; 1.8), compared to screening with DM, 0.8% (95% CI 0.7; 1.0). The proportion of the radiographic appearance of stellate distortion was 37.3% (91/244) with DBT, compared to 24.0% (29/121) with DM. The false-positive recall rate with DBT during trial year 1 was 2.6% (95% CI 1.8; 3.5), then stabilized at 1.5% (95% CI 1.3; 1.8) during trial years 2 to 5. The percentage of stellate distortion with DBT was 50% (19/38) trial year 1 compared to 35.0% (72/206) trial years 2 to 5. Conclusions: The higher false-positive recall rate with DBT compared to DM was mainly due to an increased detection of stellate findings. The proportion of these findings, as well as the DBT false-positive recall rate, was reduced after the first trial year. Clinical relevance statement: Assessment of false-positive recalls gives information on potential benefits and side effects in DBT screening. Key Points: • The false-positive recall rate in a prospective digital breast tomosynthesis screening trial was higher compared to digital mammography, but still low compared to other trials. • The higher false-positive recall rate with digital breast tomosynthesis was mainly due to an increased detection of stellate findings; the proportion of these findings was reduced after the first trial year.
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| 7. |
- Johnson, Kristin, et al.
(författare)
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Interval breast cancer rates and tumor characteristics in the prospective population-based Malmö breast tomosynthesis screening trial
- 2021
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Ingår i: Radiology. - : Radiological Society of North America (RSNA). - 0033-8419 .- 1527-1315. ; 299:3, s. 559-567
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interval cancer rates can be used to evaluate whether screening with digital breast tomosynthesis (DBT) contributes to a screening benefit. Purpose: To compare interval cancer rates and tumor characteristics in DBT screening to those in a contemporary population screened with digital mammography (DM). Materials and Methods: The prospective population-based Malmö Breast Tomosynthesis Screening Trial (MBTST) was designed to compare one-view DBT to two-view DM in breast cancer detection. The interval cancer rates and cancer characteristics in the MBTST were compared with an age-matched contemporary control group, screened with two-view DM at the same center. Conditional logistic regression was used for data analysis. Results: There were 14 848 women who were screened with DBT and DM in the MBTST between January 2010 and February 2015. The trial women were matched with two women of the same age and screening occasion at DM screening during the same period. Matches for 13 369 trial women (mean age, 56 years ± 10 [standard deviation]) were found with 26 738 women in the control group (mean age, 56 years ± 10). The interval cancer rate in the MBTST was 1.6 per 1000 screened women (21 of 13 369; 95% CI: 1.0, 2.4) compared with 2.8 per 1000 screened women in the control group (76 of 26 738 [95% CI: 2.2, 3.6]; conditional odds ratio, 0.6 [95% CI: 0.3, 0.9]; P = .02). The invasive interval cancers in the MBTST and in the control group showed in general high Ki-67 (63% [12 of 19] and 75% [54 of 72]), and low proportions of luminal A–like subtype (26% [five of 19] and 17% [12 of 72]), respectively. Conclusion: The reduced interval cancer rate after screening with digital breast tomosynthesis compared with a contemporary age-matched control group screened with digital mammography might translate into screening benefits. Interval cancers in the trial generally had nonfavorable characteristics.
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| 8. |
- Krakowski, Isabelle, et al.
(författare)
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Association of metformin use and survival in patients with cutaneous melanoma and diabetes
- 2023
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Ingår i: The British journal of dermatology. - : Oxford University Press (OUP). - 1365-2133 .- 0007-0963. ; 188:1, s. 32-40
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Metformin use has been associated with improved survival in patients with different types of cancer, but research regarding the effect of metformin on cutaneous melanoma (CM) survival is sparse and inconclusive.OBJECTIVES: To investigate the association between metformin use and survival among patients with CM and diabetes.METHODS: All adult patients with a primary invasive CM between 2007 and 2014 were identified in the Swedish Melanoma Registry and followed until death, or end of follow-up on 31 December 2017 in this population-based cohort study. Patients with both CM and type 2 diabetes mellitus were assessed further. Overall survival (OS) and melanoma-specific survival (MSS) were the primary endpoints. Cox proportional hazard models estimating crude and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were used comparing peridiagnostic use vs. nonuse of metformin. Dose response was evaluated based on defined daily doses.RESULTS: Among a total of 23 507 patients, 1162 patients with CM and type 2 diabetes mellitus were included in the final cohort, with a median follow-up time of 4.1 years (interquartile range 2.4-6.1). Peridiagnostic metformin use was associated with a significantly decreased risk of death by any cause (HR 0.68, 95% CI 0.57-0.81). Cumulative pre- and postdiagnostic metformin use was also associated with improved OS: the HR for prediagnostic use was 0.90 (95% CI 0.86-0.95) for every 6 months of use and the HR for postdiagnostic use ranged from 0.98 (95% CI 0.97-0.98) for 0-6 months to 0.59 (0.49-0.70) for 24-30 months of use. No association was found for metformin use and MSS.CONCLUSIONS: Metformin use was associated with improved OS in patients with CM and diabetes regardless of timing (pre-, post- or peridiagnostic use) and followed a dose-response pattern. However, further research regarding the underlying mechanisms is warranted.
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| 9. |
- Livheim, Fredrik, et al.
(författare)
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A quasi-experimental, multicenter study of acceptance and commitment therapy for antisocial youth in residential care
- 2020
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Ingår i: Journal of Contextual Behavioral Science. - : Elsevier BV. - 2212-1447. ; 16, s. 119-127
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of youth in residential care may be a challenging task for most providers because comorbid problems are common and general psychosocial functioning is low. Cognitive behavioral therapy (CBT) is found to be the most effective treatment but results in only rather small improvements. Hence, there is potential to improve treatment approaches. Acceptance and Commitment Therapy (ACT) could be one such approach. The purpose of this study was to test the effectiveness and feasibility of a brief trans diagnostic ACT group intervention for youth with comorbid problems in residential care. We also wanted to see whether increased psychological flexibility (PF) mediated potential positive outcomes, and to test the intervention under real-world conditions in residential care when delivered by less-specialized staff. With a quasi-experimental design, 69 youth (mean age 17.3 years) received Treatment-As-Usual (TAU), and 91 youth received TAU with an additional 12 h of ACT in a group setting (TAU + ACT). Follow-ups were conducted two weeks, 1 month, 6 months and 18 months after baseline. Intention-to-Treat (ITT) analyses showed statistically significant improvements 18 months after baseline, measured by the interaction of treatment and time for the primary outcomes of, anxiety [ACT * Months = -0.885 (0.445), p < 0.05, d = 0.34], depression [ACT * Months = -1.058 (0.526), p < 0.05, d = 0.39] and psychological flexibility [ACT * Months = -0.970 (0.413), p < 0.05; ACT * Months(2) = 0.053 (0.023), p < 0.05; d = 0.44] in TAU + ACT youth compared to TAU alone. Regarding secondary outcomes 6 months after baseline, the TAU + ACT group showed a significant decrease in anger, disruptive behavior, and increased self-concept, with small to medium effect sizes. We also observed that psychological flexibility mediated the decrease in the primary outcome of decreased anxiety. ACT in group format may be of help in promoting various positive outcomes for youth in residential care when added to treatment as usual. Increasing PF is a promising process variable that can be targeted to increase the effectiveness of interventions for this population.
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| 10. |
- Lång, Kristina, et al.
(författare)
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Artificial intelligence-supported screen reading versus standard double reading in the Mammography Screening with Artificial Intelligence trial (MASAI) : a clinical safety analysis of a randomised, controlled, non-inferiority, single-blinded, screening accuracy study
- 2023
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Ingår i: The Lancet. Oncology. - 1474-5488. ; 24:8, s. 936-944
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Retrospective studies have shown promising results using artificial intelligence (AI) to improve mammography screening accuracy and reduce screen-reading workload; however, to our knowledge, a randomised trial has not yet been conducted. We aimed to assess the clinical safety of an AI-supported screen-reading protocol compared with standard screen reading by radiologists following mammography.METHODS: In this randomised, controlled, population-based trial, women aged 40-80 years eligible for mammography screening (including general screening with 1·5-2-year intervals and annual screening for those with moderate hereditary risk of breast cancer or a history of breast cancer) at four screening sites in Sweden were informed about the study as part of the screening invitation. Those who did not opt out were randomly allocated (1:1) to AI-supported screening (intervention group) or standard double reading without AI (control group). Screening examinations were automatically randomised by the Picture Archive and Communications System with a pseudo-random number generator after image acquisition. The participants and the radiographers acquiring the screening examinations, but not the radiologists reading the screening examinations, were masked to study group allocation. The AI system (Transpara version 1.7.0) provided an examination-based malignancy risk score on a 10-level scale that was used to triage screening examinations to single reading (score 1-9) or double reading (score 10), with AI risk scores (for all examinations) and computer-aided detection marks (for examinations with risk score 8-10) available to the radiologists doing the screen reading. Here we report the prespecified clinical safety analysis, to be done after 80 000 women were enrolled, to assess the secondary outcome measures of early screening performance (cancer detection rate, recall rate, false positive rate, positive predictive value [PPV] of recall, and type of cancer detected [invasive or in situ]) and screen-reading workload. Analyses were done in the modified intention-to-treat population (ie, all women randomly assigned to a group with one complete screening examination, excluding women recalled due to enlarged lymph nodes diagnosed with lymphoma). The lowest acceptable limit for safety in the intervention group was a cancer detection rate of more than 3 per 1000 participants screened. The trial is registered with ClinicalTrials.gov, NCT04838756, and is closed to accrual; follow-up is ongoing to assess the primary endpoint of the trial, interval cancer rate.FINDINGS: Between April 12, 2021, and July 28, 2022, 80 033 women were randomly assigned to AI-supported screening (n=40 003) or double reading without AI (n=40 030). 13 women were excluded from the analysis. The median age was 54·0 years (IQR 46·7-63·9). Race and ethnicity data were not collected. AI-supported screening among 39 996 participants resulted in 244 screen-detected cancers, 861 recalls, and a total of 46 345 screen readings. Standard screening among 40 024 participants resulted in 203 screen-detected cancers, 817 recalls, and a total of 83 231 screen readings. Cancer detection rates were 6·1 (95% CI 5·4-6·9) per 1000 screened participants in the intervention group, above the lowest acceptable limit for safety, and 5·1 (4·4-5·8) per 1000 in the control group-a ratio of 1·2 (95% CI 1·0-1·5; p=0·052). Recall rates were 2·2% (95% CI 2·0-2·3) in the intervention group and 2·0% (1·9-2·2) in the control group. The false positive rate was 1·5% (95% CI 1·4-1·7) in both groups. The PPV of recall was 28·3% (95% CI 25·3-31·5) in the intervention group and 24·8% (21·9-28·0) in the control group. In the intervention group, 184 (75%) of 244 cancers detected were invasive and 60 (25%) were in situ; in the control group, 165 (81%) of 203 cancers were invasive and 38 (19%) were in situ. The screen-reading workload was reduced by 44·3% using AI.INTERPRETATION: AI-supported mammography screening resulted in a similar cancer detection rate compared with standard double reading, with a substantially lower screen-reading workload, indicating that the use of AI in mammography screening is safe. The trial was thus not halted and the primary endpoint of interval cancer rate will be assessed in 100 000 enrolled participants after 2-years of follow up.FUNDING: Swedish Cancer Society, Confederation of Regional Cancer Centres, and the Swedish governmental funding for clinical research (ALF).
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