| 1. |
- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 2. |
- MacLeod, Dominic, et al.
(författare)
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A clinico-pathological study of 79 bronchoscopies in HIV-positive patients
- 1993
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Ingår i: Irish Medical Journal. - Dublin. - 0332-3102. ; 86:5, s. 167-169
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Tidskriftsartikel (refereegranskat)abstract
- We investigated lung pathology in 61 HIV-positive patients who underwent 79 bronchoscopies. There were 27 cases of pneumo cystis carinii pneumonia (PCP), 22 cases of pyogenic pulmonary infection and six cases of mycobacterial infection. Eleven cases of non-specific interstitial pneumonitis were found and 10 intravenous drug abusers had birefringent pulmonary talc granulomata in biopsy specimens. Women and intravenous drug abusers had higher rates of pyogenic pulmonary infection than men and other risk groups respectively. When compared with a previous survey from the same hospital using the same methodology the present study showed a change in the risk groups with 50 % more intravenous drug abusers, 42% more haemophiliacs and 45% fewer patients with sexually transmitted infection. However, apparent changes in the spectrum of diseases encountered were not significant.
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| 3. |
- Walsh, Darragh R., et al.
(författare)
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Mechanical characterisation of the human dura mater, falx cerebri and superior sagittal sinus
- 2021
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 134, s. 388-400
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Tidskriftsartikel (refereegranskat)abstract
- The cranial meninges have been shown to play a pivotal role in traumatic brain injury mechanopathology. However, while the mechanical response of the brain and its many subregions have been studied extensively, the meninges have conventionally been overlooked. This paper presents the first comparative mechanical analysis of human dura mater, falx cerebri and superior sagittal sinus tissues. Biaxial tensile analysis identified that these tissues are mechanically heterogeneous, in contrast to the assumption that the tissues are mechanically homogeneous which is typically employed in FE model design. A thickness of 0.91 +/- 0.05 (standard error) mm for the falx cerebri was also identified. This data can aid in improving the biofidelity of the influential falx structure in FE models. Additionally, the use of a collagen hybridizing peptide on the superior sagittal sinus suggests this structure is particularly susceptible to the effects of circumf erential stretch, which may have important implications for clinical treatment of dural venous sinus pathologies. Collectively, this research progresses understanding of meningeal mechanical and structural characteristics and may aid in elucidating the behaviour of these tissues in healthy and diseased conditions.
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