DSpace Collection:https://hdl.handle.net/2440/836962024-03-29T00:59:58Z2024-03-29T00:59:58ZAssessing the risk of bias of quantitative analytical studies: introducing the vision for critical appraisal within JBI systematic reviewsMunn, Z.Stone, J.Aromataris, E.Klugar, M.Sears, K.Leonardi-Bee, J.Barker, T.H.https://hdl.handle.net/2440/1401022023-12-06T02:42:50Z2023-01-01T00:00:00ZTitle: Assessing the risk of bias of quantitative analytical studies: introducing the vision for critical appraisal within JBI systematic reviews
Author: Munn, Z.; Stone, J.; Aromataris, E.; Klugar, M.; Sears, K.; Leonardi-Bee, J.; Barker, T.H.
Abstract: A key step in the systematic review process is the assessment of the methodological quality (or risk of bias) of the included studies. At JBI, we have developed several tools to assist with this evaluation. As evidence synthesis methods continue to evolve, it has been necessary to revise and reflect on JBI's current approach to critical appraisal and to plan a strategy for the future. In this first paper of a series focusing on risk of bias assessment, we introduce our vision for risk of bias assessment for JBI. In future papers in this series, the methodological approach taken for this revision process will be discussed, along with the revised tools and guidance for using these tools.2023-01-01T00:00:00ZA Transgenic Line That Reports CSF1R Protein Expression Provides a Definitive Marker for the Mouse Mononuclear Phagocyte SystemGrabert, K.Sehgal, A.Irvine, K.M.Wollscheid-Lengeling, E.Ozdemir, D.D.Stables, J.Luke, G.A.Ryan, M.D.Adamson, A.Humphreys, N.E.Sandrock, C.J.Rojo, R.Verkasalo, V.A.Mueller, W.Hohenstein, P.Pettit, A.R.Pridans, C.Hume, D.A.https://hdl.handle.net/2440/1399702023-11-28T00:11:18Z2020-01-01T00:00:00ZTitle: A Transgenic Line That Reports CSF1R Protein Expression Provides a Definitive Marker for the Mouse Mononuclear Phagocyte System
Author: Grabert, K.; Sehgal, A.; Irvine, K.M.; Wollscheid-Lengeling, E.; Ozdemir, D.D.; Stables, J.; Luke, G.A.; Ryan, M.D.; Adamson, A.; Humphreys, N.E.; Sandrock, C.J.; Rojo, R.; Verkasalo, V.A.; Mueller, W.; Hohenstein, P.; Pettit, A.R.; Pridans, C.; Hume, D.A.
Abstract: The proliferation, differentiation, and survival of cells of the mononuclear phagocyte system (MPS; progenitors, monocytes, macrophages, and classical dendritic cells) are controlled by signals from the M-CSF receptor (CSF1R). Cells of the MPS lineage have been identified using numerous surface markers and transgenic reporters, but none is both universal and lineage restricted. In this article, we report the development and characterization of a CSF1R reporter mouse. A FusionRed (FRed) cassette was inserted in-frame with the C terminus of CSF1R, separated by a T2A-cleavable linker. The insertion had no effect of CSF1R expression or function. CSF1R-FRed was expressed in monocytes and macrophages and absent from granulocytes and lymphocytes. In bone marrow, CSF1R-FRed was absent in lineage-negative hematopoietic stem cells, arguing against a direct role for CSF1R in myeloid lineage commitment. It was highly expressed in marrow monocytes and common myeloid progenitors but significantly lower in granulocyte-macrophage progenitors. In sections of bone marrow, CSF1R-FRed was also detected in osteoclasts, CD169+ resident macrophages, and, consistent with previous mRNA analysis, in megakaryocytes. In lymphoid tissues, CSF1R-FRed highlighted diverse MPS populations, including classical dendritic cells. Whole mount imaging of nonlymphoid tissues in mice with combined CSF1R-FRed/Csf1r-EGFP confirmed the restriction of CSF1R expression to MPS cells. The two markers highlight the remarkable abundance and regular distribution of tissue MPS cells, including novel macrophage populations within tendon and skeletal muscle and underlying the mesothelial/serosal/capsular surfaces of every major organ. The CSF1R-FRed mouse provides a novel reporter with exquisite specificity for cells of the MPS.2020-01-01T00:00:00ZA kinase-dead Csf1r mutation associated with adult-onset leukoencephalopathy has a dominant inhibitory impact on CSF1R signallingStables, J.Green, E.K.Sehgal, A.Patkar, O.L.Keshvari, S.Taylor, I.Ashcroft, M.E.Grabert, K.Wollscheid-Lengeling, E.Szymkowiak, S.McColl, B.W.Adamson, A.Humphreys, N.E.Mueller, W.Starobova, H.Vetter, I.Shabestari, S.K.Blurton-Jones, M.M.Summers, K.M.Irvine, K.M.et al.https://hdl.handle.net/2440/1399482023-11-27T02:26:43Z2022-01-01T00:00:00ZTitle: A kinase-dead Csf1r mutation associated with adult-onset leukoencephalopathy has a dominant inhibitory impact on CSF1R signalling
Author: Stables, J.; Green, E.K.; Sehgal, A.; Patkar, O.L.; Keshvari, S.; Taylor, I.; Ashcroft, M.E.; Grabert, K.; Wollscheid-Lengeling, E.; Szymkowiak, S.; McColl, B.W.; Adamson, A.; Humphreys, N.E.; Mueller, W.; Starobova, H.; Vetter, I.; Shabestari, S.K.; Blurton-Jones, M.M.; Summers, K.M.; Irvine, K.M.; et al.
Abstract: Amino acid substitutions in the kinase domain of the human CSF1R gene are associated with autosomal dominant adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). To model the human disease, we created a disease-associated mutation (pGlu631Lys; E631K) in the mouse Csf1r locus. Homozygous mutation (Csf1rE631K/E631K) phenocopied the Csf1r knockout, with prenatal mortality or severe postnatal growth retardation and hydrocephalus. Heterozygous mutation delayed the postnatal expansion of tissue macrophage populations in most organs. Bone marrow cells from Csf1rE631K/+mice were resistant to CSF1 stimulation in vitro, and Csf1rE631K/+ mice were unresponsive to administration of a CSF1-Fc fusion protein, which expanded tissue macrophage populations in controls. In the brain, microglial cell numbers and dendritic arborisation were reduced in Csf1rE631K/+ mice, as in patients with ALSP. The microglial phenotype is the opposite of microgliosis observed in Csf1r+/− mice. However, we found no evidence of brain pathology or impacts on motor function in aged Csf1rE631K/+ mice. We conclude that heterozygous disease-associated CSF1R mutations compromise CSF1R signalling. We speculate that leukoencephalopathy associated with dominant human CSF1R mutations requires an environmental trigger and/or epistatic interaction with common neurodegenerative disease-associated alleles.2022-01-01T00:00:00ZCognitive impairment, fatigue and depression in multiple sclerosis: Is there a difference between benign and non-benign MS?Bogaardt, H.Golan, D.Barrera, M.A.Attrill, S.Kaczmarek, O.Zarif, M.Bumstead, B.Buhse, M.Wilken, J.Doniger, G.M.Hancock, L.M.Penner, I.-K.Halper, J.Morrow, S.A.Covey, T.J.Gudesblatt, M.https://hdl.handle.net/2440/1378062023-11-19T21:20:42Z2023-01-01T00:00:00ZTitle: Cognitive impairment, fatigue and depression in multiple sclerosis: Is there a difference between benign and non-benign MS?
Author: Bogaardt, H.; Golan, D.; Barrera, M.A.; Attrill, S.; Kaczmarek, O.; Zarif, M.; Bumstead, B.; Buhse, M.; Wilken, J.; Doniger, G.M.; Hancock, L.M.; Penner, I.-K.; Halper, J.; Morrow, S.A.; Covey, T.J.; Gudesblatt, M.
Abstract: Introduction: Multiple Sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system (CNS). The severity of disability in people with MS (PwMS) is generally measured with the Expanded Disability Status Scale (EDSS). A variant of MS known as ‘benign MS’ (BMS) has been defined as an EDSS score of 3 or lower, combined with a disease duration of 10 years or longer; however, there is disagreement in the field about whether BMS really exists. Given that the EDSS does not capture cognitive issues, communication dysfunction, fatigue, depression, or anxiety properly, its ability to accurately represent disability in all PwMS, including BMS, remains questionable. Methods: In this study, 141 persons with BMS (PwBMS) were included, consisting of 115 females (82%) and 26 males (18%) with a mean age of 50.8 (±8.68). A computerized test battery (NeuroTrax®) was used to assess cognition, covering seven cognitive domains (memory, executive function, visual-spatial processing, verbal function, attention, information processing, and motor skills). Fatigue was measured using the Fatigue Severity Scale (FSS). The Beck Depression Inventory (BDI) was used to assess symptoms of depression. Cognitive impairment was defined for this study as when someone has a score lower than 85 in at least two subdomains of the cognitive test battery. Rates of impairment were compared to 158 persons with non-benign MS (PwNBMS; with a disease duration of 10 years and longer and an EDSS score higher than 3) and 487 PwMS with a disease duration of fewer than 10 years. Results: Cognitive impairment was found in 38% of PwBMS and in 66% of PwNBMS (p<0.001). In PwBMS, the lowest rate of impairment was found in the verbal function domain (18%) and the highest rate of impairment in the domain of information processing (32%). Fatigue and depression were found in 78% and 55% of all PwBMS, with no difference in these rates between PwBMS and PwNBMS (p = 0.787 and p = 0.316 resp.) Conclusion: Cognitive impairment, fatigue and depression are common among people with an EDSS-based definition of benign MS. These aspects should be incorporated into a new and better definition of truly benign MS
Description: Available online 21 March 20232023-01-01T00:00:00Z