| 1. |
- Luttens, Andreas, et al.
(författare)
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Ultralarge Virtual Screening Identifies SARS-CoV-2 Main Protease Inhibitors with Broad-Spectrum Activity against Coronaviruses
- 2022
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 144:7, s. 2905-2920
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Tidskriftsartikel (refereegranskat)abstract
- Drugs targeting SARS-CoV-2 could have saved millions of lives during the COVID-19 pandemic, and it is now crucial to develop inhibitors of coronavirus replication in preparation for future outbreaks. We explored two virtual screening strategies to find inhibitors of the SARS-CoV-2 main protease in ultralarge chemical libraries. First, structure-based docking was used to screen a diverse library of 235 million virtual compounds against the active site. One hundred top-ranked compounds were tested in binding and enzymatic assays. Second, a fragment discovered by crystallographic screening was optimized guided by docking of millions of elaborated molecules and experimental testing of 93 compounds. Three inhibitors were identified in the first library screen, and five of the selected fragment elaborations showed inhibitory effects. Crystal structures of target-inhibitor complexes confirmed docking predictions and guided hit-to-lead optimization, resulting in a noncovalent main protease inhibitor with nanomolar affinity, a promising in vitro pharmacokinetic profile, and broad-spectrum antiviral effect in infected cells.
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| 2. |
- Nord, Anette, et al.
(författare)
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HLR och rätten till en värdig död
- 2016
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Ingår i: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; :20
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 3. |
- Sengpiel, Verena, 1977, et al.
(författare)
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Confirmed reinfection with SARS-CoV-2 during a pregnancy: A case report.
- 2022
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Ingår i: Clinical case reports. - : Wiley. - 2050-0904. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Pregnancy might impact immunity after SARS-CoV-2 infection and/or vaccination. We describe the first case of reinfection with SARS-CoV-2 during a pregnancy. While the mother lacked detectable antibodies 2 months after the first infection, both mother and baby had IgG antibodies at delivery. Infection did not cause any adverse pregnancy outcome.
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| 4. |
- Franco, Irene, et al.
(författare)
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Whole genome DNA sequencing provides an atlas of somatic mutagenesis in healthy human cells and identifies a tumor-prone cell type
- 2019
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The lifelong accumulation of somatic mutations underlies age-related phenotypes and cancer. Mutagenic forces are thought to shape the genome of aging cells in a tissue-specific way. Whole genome analyses of somatic mutation patterns, based on both types and genomic distribution of variants, can shed light on specific processes active in different human tissues and their effect on the transition to cancer. Results: To analyze somatic mutation patterns, we compile a comprehensive genetic atlas of somatic mutations in healthy human cells. High-confidence variants are obtained from newly generated and publicly available whole genome DNA sequencing data from single non-cancer cells, clonally expanded in vitro. To enable a well-controlled comparison of different cell types, we obtain single genome data (92% mean coverage) from multi-organ biopsies from the same donors. These data show multiple cell types that are protected from mutagens and display a stereotyped mutation profile, despite their origin from different tissues. Conversely, the same tissue harbors cells with distinct mutation profiles associated to different differentiation states. Analyses of mutation rate in the coding and non-coding portions of the genome identify a cell type bearing a unique mutation pattern characterized by mutation enrichment in active chromatin, regulatory, and transcribed regions. Conclusions: Our analysis of normal cells from healthy donors identifies a somatic mutation landscape that enhances the risk of tumor transformation in a specific cell population from the kidney proximal tubule. This unique pattern is characterized by high rate of mutation accumulation during adult life and specific targeting of expressed genes and regulatory regions.
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| 5. |
- Furukawa, Toshi A., et al.
(författare)
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Dismantling, optimising, and personalising internet cognitive behavioural therapy for depression : a systematic review and component network meta-analysis using individual data
- 2021
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Ingår i: Lancet psychiatry. - London, United Kingdom : Elsevier. - 2215-0374 .- 2215-0366. ; 8:6, s. 500-511
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Forskningsöversikt (refereegranskat)abstract
- Findings We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42.0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD -1.83 [95% credible interval (CrI) -2.90 to -0.80]) and that relaxation might be harmful (1.20 [95% CrI 0.17 to 2.27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0.32 [95% CrI 0.13 to 0.93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components. 511
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| 6. |
- Johansson, Peter, 1962-, et al.
(författare)
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An internet-based cognitive behavioral therapy program adapted to patients with cardiovascular disease and depression : Randomized controlled trial
- 2019
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Ingår i: Journal of Medical Internet Research. - Toronto, Canada : Journal of Medical Internet Research. - 1438-8871. ; 21:10, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Depression is a common cause of reduced well-being and prognosis in patients with cardiovascular disease (CVD). However, there is a lack of effective intervention strategies targeting depression.Objective: The study aimed to evaluate the effects of a nurse-delivered and adapted internet-based cognitive behavioral therapy (iCBT) program aimed at reducing depression in patients with CVD.Methods: A randomized controlled trial was conducted. A total of 144 patients with CVD with at least mild depression (Patient Health Questionnaire–9 [PHQ-9] score ≥5) were randomized 1:1 to a 9-week program of iCBT (n=72) or an active control participating in a Web-based discussion forum (online discussion forum [ODF], n=72). The iCBT program, which included 7 modules, was adapted to fit patients with CVD. Nurses with an experience of CVD care provided feedback and a short introduction to cognitive behavioral therapy. The primary outcome, depression, was measured using PHQ-9. Secondary outcomes were depression measured using the Montgomery-Åsberg Depression Rating Scale–self-rating version (MADRS-S), health-related quality of life (HRQoL) measured using Short Form 12 (SF-12) survey and EuroQol Visual Analogue Scale (EQ-VAS), and the level of adherence. An intention-to-treat analysis with multiple imputations was used. Between-group differences in the primary and secondary outcomes were determined by the analysis of covariance, and a sensitivity analysis was performed using mixed models. Results: Compared with ODF, iCBT had a significant and moderate treatment effect on the primary outcome depression (ie, PHQ-9; mean group difference=−2.34 [95% CI −3.58 to −1.10], P<.001, Cohen d=0.62). In the secondary outcomes, compared with ODF, iCBT had a significant and large effect on depression (ie, MADRS-S; P<.001, Cohen d=0.86) and a significant and moderate effect on the mental component scale of the SF-12 (P<.001, Cohen d=0.66) and the EQ-VAS (P<.001, Cohen d=0.62). Overall, 60% (n=43) of the iCBT group completed all 7 modules, whereas 82% (n=59) completed at least half of the modules. No patients were discontinued from the study owing to a high risk of suicide or deterioration in depression.Conclusions: Nurse-delivered iCBT can reduce depression and improve HRQoL in patients with CVD, enabling treatment for depression in their own homes and at their preferred time.
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| 7. |
- Johansson, Peter, 1962-, et al.
(författare)
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Internet-Based Cognitive Behavioral Therapy and its Association With Self-efficacy, Depressive Symptoms, and Physical Activity : Secondary Analysis of a Randomized Controlled Trial in Patients With Cardiovascular Disease
- 2022
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Ingår i: JMIR Cardio. - Toronto, Canada : JMIR Publications, Inc.. - 2561-1011. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: In patients with cardiovascular disease (CVD), knowledge about the associations among changes in depressivesymptoms, self-efficacy, and self-care activities has been requested. This is because such knowledge can be helpful in the designof behavioral interventions aimed to improve self-efficacy, reduce depressive symptoms, and improve performance of self-careactivities in CVD patients.Objective: We aim to evaluate if internet-based cognitive behavioral therapy (iCBT) improves self-efficacy and explore therelationships among changes in depressive symptoms, self-efficacy, and physical activity, as well as the influence of iCBT onthese relationships.Methods: This study received funding in January 2015. Participant recruitment took place between January 2017 and February2018, and the main findings were published in 2019. This study is a secondary analysis of data collected in a randomized controlledstudy evaluating the effects of a 9-week iCBT program compared to an online discussion forum (ODF) on depressive symptomsin patients with CVD (N=144). Data were collected at baseline and at the 9-week follow-up. Analysis of covariance was used toevaluate the differences in self-efficacy between the iCBT and ODF groups. Structural equation modeling explored the relationshipsamong changes in depressive symptoms, self-efficacy, and physical activity, as well as the influence of iCBT on these relationships.Results: At follow-up, a significant difference in the increase in self-efficacy favoring iCBT was found (P=.04, Cohen d=0.27).We found an indirect association between changes in depressive symptoms and physical activity (ß=–.24, P<.01), with the changein self-efficacy acting as a mediator. iCBT had a direct effect on the changes in depressive symptoms, which in turn influencedthe changes in self-efficacy (ß=.23, P<.001) and physical activity (ß=.12, P<.001).Conclusions: Self-efficacy was improved by iCBT. However, the influence of iCBT on self-efficacy and physical activity wasmostly mediated by improvements in depressive symptoms.Trial Registration: ClinicalTrials.gov NCT02778074; https://clinicaltrials.gov/ct2/show/NCT02778074
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| 8. |
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| 9. |
- Johansson, Peter, 1962-, et al.
(författare)
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The impact of internet-based cognitive behavioral therapy and depressive symptoms on self-care behavior in patients with heart failure : A secondary analysis of a randomised controlled trial
- 2021
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Ingår i: International Journal of Nursing Studies. - : Elsevier. - 0020-7489 .- 1873-491X. ; 116
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with chronic heart failure may require treatment of depressive symptoms to improve self-care behaviour.OBJECTIVES: To investigate the impact of internet-based cognitive behavioral therapy (CBT) on self-care behaviour in heart failure patients, and to study the association between changes in depressive symptoms and changes in self-care behaviour.DESIGN: A secondary analysis of data collected in a pilot randomized controlled study.SETTING: 50 heart failure patients with depressive symptoms were recruited from four hospitals in Sweden.METHODS: Patients were randomized to nine weeks of internet-based CBT (n = 25) or to an active control group participating in an online discussion forum (n = 25). In week two and three, those in the internet-based CBT group worked with psychoeducation about heart failure and depression, emphasizing heart failure self-care. During the same weeks those in the on-line discussion forum specifically discussed heart failure self-care. Patient Health Questionnaire-9 was used to measure depressive symptoms at baseline and at the nine-week follow-up. The European Heart Failure Self-care Behaviour Scale-9 was used to measure self-care behaviour (i.e., the summary score and the subscales autonomous based, provider based and consulting behaviour) at baseline, and at the three-week and nine-week follow-ups.RESULTS: No significant differences were found in self-care between the patients in the internet-based CBT and the patients in the online discussion group at the three- and nine-week follow-up. Within-group analysis of the changes in the European Heart Failure Self-care Behaviour Scale showed that from baseline to week three, the summary score increased significantly for the online discussion group (p = 0.04), but not for the internet-based CBT group (p = 0.15). At the nine-week follow-up, these scores had decreased. Similarly, consulting behaviour improved at week three for the online discussion group (p = 0.04), but not for the internet-based CBT group (p = 0.22). Provider-based adherence at the nine-week follow-up had increased from baseline in the internet-based CBT group (p = 0.05) whereas it had decreased in the on-line discussion group. Improvement in symptoms of depression was significantly associated with improvement in autonomy-based self-care (r = 0.34, p = 0.03).CONCLUSION: Improvement in depressive symptoms was associated with improved autonomous-based self-care. ICBT for depression in HF may benefit aspects of self-care that are vital to improve symptoms and prognosis.
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| 10. |
- Johansson, Peter, et al.
(författare)
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Time-course of depressive symptoms in patients with heart failure
- 2013
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Ingår i: Journal of Psychosomatic Research. - : Elsevier BV. - 0022-3999 .- 1879-1360. ; 74:3, s. 238-243
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Tidskriftsartikel (refereegranskat)abstract
- Background It is unclear how depressive symptoms in patients with heart failure developover time and whether this trajectory of depressive symptoms is associated with hospital admission and prognosis.Aim To describe the time-course of depressive symptoms and determine the relationship with hospital admission and mortality.Method Data was analysed using 611 patients with completed CES-D questionnaires at baseline and at 18 months. Data on hospital readmission was collected 18 months after discharge and data on mortality was collected 18 and 36 months post-discharge.Results The prevalence of depressive symptoms was 38% (n=229) at discharge and 26% (n=160) after 18 months. A total of 140 (61%) of the 229 patients with depressive symptoms at discharge had recovered from depressive symptoms after 18 months whereas 71 (18%) of the 382 non-depressed developed depressive symptoms and 89 (39%) of the 229 depressed remained depressed. Depressive symptoms at discharge were not associated with mortality after 18 months but patients with recently (i.e. during 18 months) developed depressive symptoms showed a significantly higher risk for cardiovascular readmissions (HR 1.7, p=0.016). After 36 months, patients with developed depressive symptoms after discharge were at a higher risk of all-cause mortality (HR 2.0, p=0.012) and there was a trend towards a higher risk of all-cause mortality in patients with ongoing depressive symptoms (HR 1.7, p=0.056).Conclusion A significant proportion of patients with HF, who were reported depressive symptoms at discharge recovered from depressive symptoms during the following 18 months. However, patients who remained having depressive symptoms or patients who developed depressive symptoms had a worse prognosis.
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