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- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 4. |
- Archambault, Alexi N., et al.
(författare)
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Cumulative Burden of Colorectal Cancer Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 158:5, s. 1274-1286.e12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants.RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 x 10(-5)). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings.CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
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| 5. |
- Bahnan, Wael, et al.
(författare)
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Spike-Dependent Opsonization Indicates Both Dose-Dependent Inhibition of Phagocytosis and That Non-Neutralizing Antibodies Can Confer Protection to SARS-CoV-2
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Spike-specific antibodies are central to effective COVID19 immunity. Research efforts have focused on antibodies that neutralize the ACE2-Spike interaction but not on non-neutralizing antibodies. Antibody-dependent phagocytosis is an immune mechanism enhanced by opsonization, where typically, more bound antibodies trigger a stronger phagocyte response. Here, we show that Spike-specific antibodies, dependent on concentration, can either enhance or reduce Spike-bead phagocytosis by monocytes independently of the antibody neutralization potential. Surprisingly, we find that both convalescent patient plasma and patient-derived monoclonal antibodies lead to maximum opsonization already at low levels of bound antibodies and is reduced as antibody binding to Spike protein increases. Moreover, we show that this Spike-dependent modulation of opsonization correlate with the outcome in an experimental SARS-CoV-2 infection model. These results suggest that the levels of anti-Spike antibodies could influence monocyte-mediated immune functions and propose that non-neutralizing antibodies could confer protection to SARS-CoV-2 infection by mediating phagocytosis.
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| 6. |
- Bergenfelz, Caroline, et al.
(författare)
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Clinical relevance of systemic monocytic-MDSCs in patients with metastatic breast cancer
- 2020
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Ingår i: Cancer Immunology, Immunotherapy. - : Springer Science and Business Media LLC. - 0340-7004 .- 1432-0851. ; 69:3, s. 435-448
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Tidskriftsartikel (refereegranskat)abstract
- The overall aim of this prospective study was to delineate the role of monocytic myeloid-derived suppressor cells (Mo-MDSCs) in patients with metastatic breast cancer (MBC). MDSCs are a heterogeneous group of immunosuppressive cells often enriched in different malignancies which hold prognostic and predictive value for clinical outcomes. Here, we assessed the clinical significance of Mo-MDSCs in 54 patients with de novo or distant recurrent MBC. We show that high levels of Mo-MDSCs significantly correlated with de novo MBC (metastatic disease at initial diagnosis), estrogen receptor (ER) negativity, and liver- and bone metastasis. A trend towards an association between high levels of Mo-MDSCs and survival (P = 0.053) was also found in patients with distant recurrent ER-positive MBC. We therefore propose that an increased population of Mo-MDSCs may be related to the metastatic or immunoregulatory switch associated with transition to a more systemic disease. Our data imply that high levels of systemic Mo-MDSCs represent patients with more aggressive disease and worse outcome.
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| 7. |
- Bernhardsson, Susanne, 1958, et al.
(författare)
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Digital physiotherapy assessment vs conventional face-to-face physiotherapy assessment of patients with musculoskeletal disorders: A systematic review.
- 2023
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Ingår i: PloS One. - : Public Library of Science (PLoS). - 1932-6203. ; 18:3
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Forskningsöversikt (refereegranskat)abstract
- This systematic review aimed to assess the certainty of evidence for digital versus conventional, face-to-face physiotherapy assessment of musculoskeletal disorders, concerning validity, reliability, feasibility, patient satisfaction, physiotherapist satisfaction, adverse events, clinical management, and cost-effectiveness.Eligibility criteria: Original studies comparing digital physiotherapy assessment with face-to-face physiotherapy assessment of musculoskeletal disorders. Systematic database searches were performed in May 2021, and updated in May 2022, in Medline, Cochrane Library, Cinahl, AMED, and PEDro. Risk of bias and applicability of the included studies were appraised using the Quality Assessment of Diagnostic Accuracy Studies-2 tool and the Quality Appraisal of Reliability Studies tool. Included studies were synthesised narratively. Certainty of evidence was evaluated for each assessment component using GRADE.Ten repeated-measures studies were included, involving 193 participants aged 23-62 years. Reported validity of digital physiotherapy assessment ranged from moderate/acceptable to almost perfect/excellent for clinical tests, range of motion, patient-reported outcome measures (PROMs), pain, neck posture, and management decisions. Reported validity for assessing spinal posture varied and was for clinical observations unacceptably low. Reported validity and reliability for digital diagnosis ranged from moderate to almost perfect for exact+similar agreement, but was considerably lower when constrained to exact agreement. Reported reliability was excellent for digital assessment of clinical tests, range of motion, pain, neck posture, and PROMs. Certainty of evidence varied from very low to high, with PROMs and pain assessment obtaining the highest certainty. Patients were satisfied with their digital assessment, but did not perceive it as good as face-to-face assessment.Evidence ranging from very low to high certainty suggests that validity and reliability of digital physiotherapy assessments are acceptable to excellent for several assessment components. Digital physiotherapy assessment may be a viable alternative to face-to-face assessment for patients who are likely to benefit from the accessibility and convenience of remote access.The review was registered in the PROSPERO database, CRD42021277624.
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| 9. |
- Bornhoft, Lena, et al.
(författare)
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Monitoring handgrip strength to motivate lifestyle choices for patients with diabetes type 2-a pragmatic randomised controlled trial
- 2024
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Ingår i: SCANDINAVIAN JOURNAL OF PRIMARY HEALTH CARE. - 0281-3432 .- 1502-7724.
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Tidskriftsartikel (refereegranskat)abstract
- Physical strength can be an important parameter to monitor for patients with diabetes mellitus type 2 (T2DM) to promote healthy lifestyle choices. Functional measurements can contribute to healthcare advice and possibly motivate more active lifestyles. The aim of the study was to investigate whether adding measurement and feedback concerning handgrip strength (HGS) to the parameters measured for patients with T2DM at annual check-ups leads to change in physical activity (PA) level, HGS, HbA1c or waist circumference.MethodsMeasurement of HGS with Jamar dynamometers was added to annual check-ups for patients with T2DM by diabetes nurses in primary care with feedback about normal values for age and sex in the intervention group. The control group had standard check-ups. Change in self-reported PA level was measured with questionnaires.ResultsSeven clinics and 334 patients participated. The intervention led to similar effects on PA in both groups. Patients with T2DM had comparable HGS to the general public. Regression analyses showed statistically significantly higher HGS in the intervention group than in the control group at follow-up and no improvement in PA, HbA1c, or waist circumference. Increased HGS was found for older people, men, and people with normal-to-high inclusion HGS, while patients with low inclusion HGS reduced their strength levels.ConclusionsMeasuring HGS and giving feedback to patients with T2DM can lead to increased HGS but does not seem to affect general PA level, HbA1c, or waist circumference. People over 65 years, men, and people with normal-to-high HGS were influenced positively by the intervention. Patients with low HGS may need personalised support to increase physical activity and improve function.ClinicalTrials registration: NCT03693521ConclusionsMeasuring HGS and giving feedback to patients with T2DM can lead to increased HGS but does not seem to affect general PA level, HbA1c, or waist circumference. People over 65 years, men, and people with normal-to-high HGS were influenced positively by the intervention. Patients with low HGS may need personalised support to increase physical activity and improve function.
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| 10. |
- Chen, Zhishan, et al.
(författare)
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Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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