Optimality in DNA repair

Peer reviewedPublisher PD

Development of a bespoke 3D-printed spinal brace for lumbar support

Low back pain (LBP) is a significant contributor to disabilities in the United Kingdom. This article presents the user-centred design approach undertaken by a multidisciplinary design team to develop a bespoke 3D-printed spinal brace using a digital design workflow.</p

Encapsulated Silicon Nitride Nanobeam Cavity for Hybrid Nanophotonics

Most existing implementations of silicon nitride photonic crystal cavities rely on suspended membranes due to their low refractive index. Such floating membranes are not mechanically robust, making them suboptimal for developing a hybrid optoelectronic platform where new materials, such as layered 2D materials, are transferred onto prefabricated optical cavities. To address this issue, we design and fabricate a silicon nitride nanobeam resonator where the silicon nitride membrane is encapsulated by material with a refractive index of ∼1.5, such as silicon dioxide or PMMA. The theoretically calculated quality factor of the cavities can be as large as 10⁵, with a mode-volume of ∼2.5­(λ/<i>n</i>)³. We fabricated the cavity and measured the transmission spectrum with the highest quality factor reaching 7000. We also successfully transferred monolayer tungsten diselenide on the encapsulated silicon nitride nanobeam and demonstrated coupling of the cavity with both the monolayer exciton and the defect emissions

Corrigendum to ‘An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs’ [J Hepatol 2021;75(3):572–581] (Journal of Hepatology (2021) 75(3) (572–581), (S0168827821003342), (10.1016/j.jhep.2021.04.055))

It has come to our attention that the name of one of the authors in our manuscript was incorrectly spelled ‘Jinyoung Byan’; the correct spelling is ‘Jinyoung Byun’ as in the author list above. In addition, the excel files of the supplementary tables were not included during the online publication of our article. These have now been made available online. We apologize for any inconvenience caused

Corrigendum to \u2018An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs\u2019 [J Hepatol 2021;75(3):572\u2013581] (Journal of Hepatology (2021) 75(3) (572\u2013581), (S0168827821003342), (10.1016/j.jhep.2021.04.055))

It has come to our attention that the name of one of the authors in our manuscript was incorrectly spelled \u2018Jinyoung Byan\u2019; the correct spelling is \u2018Jinyoung Byun\u2019 as in the author list above. In addition, the excel files of the supplementary tables were not included during the online publication of our article. These have now been made available online. We apologize for any inconvenience caused

An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs.

BACKGROUNDS & AIMS Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. METHODS We combined new and existing genotype data for 10,516 cases and 20,772 controls from 5 European and 2 East Asian cohorts. RESULTS We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57 genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, which each play key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, JAK-STAT signalling, and differentiation of T helper (T)1 and T17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some of which are well-established in the treatment of other autoimmune disorders. CONCLUSIONS This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. LAY SUMMARY Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10,516 people with PBC and 20,772 healthy individuals recruited in Canada, China, Italy, Japan, the UK, or the USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these 'candidate genes' to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC