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Since its emergence into the human population at the end of 2019, SARS-CoV-2 has caused significant morbidity and mortality worldwide. Efforts to develop a protective vaccine against COVID-19 have yielded several vaccine platforms currently in distribution targeting the original SARS-CoV-2 spike protein sequence from the first cases of infection. In recent months, variants of SARS-CoV-2 have raised concerns that viral mutation may undermine vaccination efforts through viral escape of host immune memory acquired from infection or vaccination. We therefore used a computational approach to predict changes in spike protein antigenicity with respect to host B cell and CD8+ T cell immunity across six SARS-CoV-2 variants (D614G, B.1.1.7, B.1.351, P.1, B.1.429, and mink-related). Our epitope analysis using DiscoTope suggests possible changes in B cell epitopes in the S1 region of the spike protein across variants, in particular the B.1.1.7 and B.1.351 lineages, which may influence immunodominance. Additionally, we show that high-affinity MHC-I-binding peptides and glycosylation sites on the spike protein appear consistent between variants with the exception of an extra glycosylation site in the P.1 variant. Together, these analyses suggests T cell vaccine strategies have the most longevity before reformulation.

Background Studies have shown that abnormal changes of specific-gene DNA methylation in leukocytes may be associated with elevated risk of cancer. However, associations between the methylation of zinc-related genes, WT1 and CA10, and breast cancer risk, and interactions between WT1, CA10 methylation and dietary zinc intake on breast cancer risk remain unknown. Methods The methylation of WT1, CA10 was analyzed by methylation-sensitive high-resolution-melting (MS-HRM) in a case-control study with female subjects (N = 959). Logistic regression was used to analyze the associations and propensity score (PS) method was used to adjust confounders. Results The results showed that WT1 hypermethylation was associated with an increased risk of breast cancer with an odds ratio (OR) of 3.069 [95% confidence interval (CI): 1.669–5.643, P < 0.001]. Subgroup analyses showed that WT1 hypermethylation was specifically associated with an elevated risk of Luminal A subtype (OR = 2.620, 95%CI: 1.107-6.200, P = 0.029) and Luminal B subtype (OR = 3.231, 95%CI: 1.339–7.796, P = 0.009). CA10 hypermethylation was associated with an increased risk of Luminal B subtype (OR = 1.798, 95%CI: 1.085–2.982, P = 0.023). Furthermore, the joint effects of methylation of WT1, CA10 and lower dietary zinc intake were associated a strongly elevated risk of breast cancer with ORs of 11.220 (95%CI: 4.057–31.032, P < 0.001) and 4.145 (95%CI: 2.717–6.324, P < 0.001), respectively. Conclusion The study suggested the hypermethylation of WT1 methylation in leukocytes was significantly associated with an increased risk of breast cancer. Notably, the joint effects of WT1, CA10 methylation and lower dietary zinc intake might significantly associate with breast cancer risk.

Aims This study aimed to use intraoperative free electromyography to examine how the placement of a retractor at different positions along the anterior acetabular wall may affect the femoral nerve during total hip arthroplasty (THA) when undertaken using the direct anterior approach (THA-DAA). Methods Intraoperative free electromyography was performed during primary THA-DAA in 82 patients (94 hips). The highest position of the anterior acetabular wall was defined as the “12 o’clock” position (middle position) when the patient was in supine position. After exposure of the acetabulum, a retractor was sequentially placed at the ten, 11, 12, one, and two o’clock positions (right hip; from superior to inferior positions). Action potentials in the femoral nerve were monitored with each placement, and the incidence of positive reactions (defined as explosive, frequent, or continuous action potentials, indicating that the nerve was being compressed) were recorded as the primary outcome. Secondary outcomes included the incidence of positive reactions caused by removing the femoral head, and by placing a retractor during femoral exposure; and the incidence of femoral nerve palsy, as detected using manual testing of the strength of the quadriceps muscle. Results Positive reactions were significantly less frequent when the retractor was placed at the ten (15/94; 16.0%), 11 (12/94; 12.8%), or 12 o’clock positions (19/94; 20.2%), than at the one (37/94; 39.4%) or two o’clock positions (39/94; 41.5%) (p < 0.050). Positive reactions also occurred when the femoral head was removed (28/94; 29.8%), and when a retractor was placed around the proximal femur (34/94; 36.2%) or medial femur (27/94; 28.7%) during femoral exposure. After surgery, no patient had reduced strength in the quadriceps muscle. Conclusion Placing the anterior acetabular retractor at the one or two o’clock positions (right hip; inferior positions) during THA-DAA can increase the rate of electromyographic signal changes in the femoral nerve. Thus, placing a retractor in these positions may increased the risk of the development of a femoral nerve palsy. Cite this article: Bone Joint J 2022;104-B(2):193–199.