A systematic review of resting state functional MRI connectivity changes and cognitive impairment in multiple sclerosis.
AuthorsJandric, Danka; email: email@example.com
Doshi, Anisha; email: firstname.lastname@example.org
Scott, Richelle; email: email@example.com
Paling, David; email: firstname.lastname@example.org
Rog, David; email: email@example.com
Chataway, Jeremy; email: firstname.lastname@example.org
Schoonheim, Menno; email: email@example.com
Parker, Geoff; email: firstname.lastname@example.org
Muhlert, Nils; email: email@example.com
MetadataShow full item record
AbstractCognitive impairment in multiple sclerosis (MS) is increasingly being investigated with resting state functional MRI (rs-fMRI) functional connectivity (FC) . However, results remain difficult to interpret, showing both high and low FC associated with cognitive impairment. We conducted a systematic review of rs-fMRI studies in MS to understand whether the direction of FC change relates to cognitive dysfunction, and how this may be influenced by the choice of methodology. Embase, Medline and PsycINFO were searched for studies assessing cognitive function and rs-fMRI FC in adults with MS. Fifty-seven studies were included in a narrative synthesis. Of these, 50 found an association between cognitive impairment and FC abnormalities. Worse cognition was linked to high FC in 18 studies, and to low FC in 17 studies. Nine studies found patterns of both high and low FC related to poor cognitive performance, in different regions or for different MR metrics. There was no clear link to increased FC during early stages of MS and reduced FC in later stages, as predicted by common models of MS pathology. Throughout, we found substantial heterogeneity in study methodology, and carefully consider how this may impact on the observed findings. These results indicate an urgent need for greater standardisation in the field - in terms of the choice of MRI analysis and the definition of cognitive impairment. This will allow us to use rs-fMRI FC as a biomarker in future clinical studies, and as a tool to understand mechanisms underpinning cognitive symptoms in MS.
DescriptionFrom PubMed via Jisc Publications Router
Publication status: aheadofprint
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Gene-Environment Interactions Relevant to Estrogen and Risk of Breast Cancer: Can Gene-Environment Interactions Be Detected Only among Candidate SNPs from Genome-Wide Association Studies?Park, JooYong; email: firstname.lastname@example.org; Choi, Ji-Yeob; email: email@example.com; Choi, Jaesung; email: firstname.lastname@example.org; Chung, Seokang; email: email@example.com; Song, Nan; orcid: 0000-0002-9182-1060; email: firstname.lastname@example.org; Park, Sue K.; orcid: 0000-0001-5002-9707; email: email@example.com; Han, Wonshik; email: firstname.lastname@example.org; Noh, Dong-Young; email: email@example.com; Ahn, Sei-Hyun; email: firstname.lastname@example.org; Lee, Jong Won; email: email@example.com; et al. (MDPI, 2021-05-14)In this study we aim to examine gene–environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10−3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10−4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.
No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database StudyDominguez-Valentin, Mev; orcid: 0000-0001-7856-0057; email: Mev.Dominguez.Valentin@rr-research.no; Plazzer, John-Paul; orcid: 0000-0001-5114-4301; email: firstname.lastname@example.org; Sampson, Julian R.; email: Sampson@cardiff.ac.uk; Engel, Christoph; orcid: 0000-0002-7247-282X; email: email@example.com; Aretz, Stefan; orcid: 0000-0002-5228-1890; email: firstname.lastname@example.org; Jenkins, Mark A.; email: email@example.com; Sunde, Lone; email: firstname.lastname@example.org; Bernstein, Inge; email: email@example.com; Capella, Gabriel; orcid: 0000-0002-4669-7320; email: firstname.lastname@example.org; Balaguer, Francesc; orcid: 0000-0002-0206-0539; email: email@example.com; et al. (MDPI, 2021-06-28)Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.
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