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Even as we near therapeutic translation, there remain many questions about the governance of muscle function in human health and disease. With this review, we provide a broad overview of contemporary understanding of myosin SRX, and explore the complexities of targeting this myosin state in human disease.This article has an associated Future Leaders to Watch interview with the authors of the paper.Human induced pluripotent stem cells (iPSCs) are important source for regenerative medicine. However, the links between pluripotency and oncogenic transformation raise safety issues. To understand the characteristics of iPSC-derived cells at single-cell resolution, we directly reprogrammed two human iPSC lines into cardiomyocytes and collected cells from four time points during cardiac differentiation for single-cell sequencing. We captured 32,365 cells and identified five molecularly distinct clusters that aligned well with our reconstructed differentiation trajectory. We discovered a set of dynamic expression events related to the upregulation of oncogenes and the decreasing expression of tumor suppressor genes during cardiac differentiation, which were similar to the gain-of-function and loss-of-function patterns during oncogenesis. In practice, we characterized the dynamic expression of the TP53 and Yamanaka factor genes (OCT4, SOX2, KLF4 and MYC), which were widely used for human iPSCs lines generation; and revealed the co-occurrence of MYC overexpression and TP53 silencing in some of human iPSC-derived TNNT2+ cardiomyocytes. Human cathelicidin cost In summary, our oncogenic expression atlas is valuable for human iPSCs application and the single-cell resolution highlights the clues potentially associated with the carcinogenic risk of human iPSC-derived cells.

To summarise the available information on efficacy and safety of immunomodulatory agents in SARS-CoV-2 infection.

As part of a European League Against Rheumatism (EULAR) taskforce, a systematic literature search was conducted from January 2019 to 11 December 2020. Two reviewers independently identified eligible studies according to the Population, Intervention, Comparator and Outcome framework and extracted data on efficacy and safety of immunomodulatory agents used therapeutically in SARS-CoV-2 infection at any stage. The risk of bias was assessed with validated tools.

Of the 60 372 records, 401 articles were eligible for inclusion. Studies were at variable risk of bias. Randomised controlled trials (RCTs) were available for the following drugs hydroxychloroquine (n=12), glucocorticoids (n=6), tocilizumab (n=4), convalescent plasma (n=4), interferon beta (n=2), intravenous immunoglobulins (IVIg) (n=2) and n=1 each for anakinra, baricitinib, colchicine, leflunomide, ruxolitinib, interferon kappa and vil of COVID-19, conclusive data are scarce with some conflicting data. Since glucocorticoids seem to improve survival in some subsets of patients, RCTs comparing glucocorticoids alone versus glucocorticoids plus anticytokine/immunomodulatory treatment are warranted. This systematic literature review informed the initiative to formulate EULAR ‘points to consider’ on COVID-19 pathophysiology and immunomodulatory treatment from the rheumatology perspective.

To evaluate the effect of signal strength (SS) on optical coherence tomography (OCT) parameters, and devise an algorithm to adjust the effect, when acceptable SS cannot be obtained.

5085 individuals (9582 eyes), aged ≥40 years from the Singapore Epidemiology of Eye Diseases population-based study were included. Everyone underwent a standardised ocular examination and imaging with Cirrus HD-OCT. Effect of SS was evaluated using multiple structural breaks linear mixed-effect models. Expected change for increment in SS between 4 and 10 for individual parameter was calculated. Subsequently we devised and evaluated an algorithm to adjust OCT parameters to higher SS.

Average retinal nerve fibre layer (RNFL) thickness showed shift of 4.11 µm from SS of 5 to 6. Above 6, it increased by 1.72 and 3.35 µm to 7 and 8; and by 1.09 µm (per unit increase) above 8 SS. Average ganglion cell-inner plexiform layer (GCIPL) thickness shifted 5.15 µm from SS of 5 to 6. Above 6, increased by 0.94 µm from 7 to 8; and by 0.16 µm (per unit increase) above 8 SS. When compared with reference in an independent test set, the algorithm produced less systemic bias. Algorithm-adjusted average RNFL was 0.549 µm thinner than the reference, while the unadjusted one was 2.841 µm thinner (p<0.001). Algorithm-adjusted and unadjusted average GCIPL was 1.102 µm and 2.228 µm thinner (p<0.001).

OCT parameters can be adjusted for poor SS using an algorithm. This can potentially assist in diagnosis and monitoring of glaucoma when scans with acceptable SS cannot be acquired from patients in clinics.

OCT parameters can be adjusted for poor SS using an algorithm. This can potentially assist in diagnosis and monitoring of glaucoma when scans with acceptable SS cannot be acquired from patients in clinics.

Largest basal diameter (LBD) appears to have independent prognostic value in uveal melanoma (UM).

All patients undergoing plaque brachytherapy or enucleation for UM involving the choroid and/or ciliary body between 2012 and 2019.

A total of 348 patients with a mean age of 60±14 years were included and followed for a mean of 40±26 months (3.3±2.2 years). On multivariate analysis, LBD >12 mm remained a significant independent predictor of metastasis for both class 1 (HR 21.90; 95% CI 2.69 to 178.02; p=0.004) and class 2 (HR 2.45; 95% CI, 1.03 to 5.83; p=0.04) tumours. Four prognostic groups were created group 1 (class 1, LBD <12 mm), group 2 (class 1, LBD ≥12 mm), group 3 (class 2, LBD <12 mm) and group 4 (class 2, LBD ≥12 mm). Life tables were used to calculate the 3-year and 5-year metastasis-free survival group 1 (98 and 98%), group 2 (86 and 86%), group 3 (81 and 62%) and group 4 (54 and 47%). Compared with the reference category (group 1), the Cox proportional hazard model demonstrated a significant worsening of survival for each progressive category (group 2 (HR 21.59; p=0.004), group 3 (HR 47.12, p<0.001), and group 4 (HR 114.24; p<0.001)). In our dataset, the four-category Cox model performed poorer compared with the American Joint Committee on Cancer (AJCC) and gene expression profile (AJCC+GEP) in the Akaike’s information criteria (AIC) (297 vs 291), fit better with the Bayesian information criteria (BIC) (309 vs 313) and performed similarly with the Harrel’s C (0.86 (95% CI 0.80 to 0.91) vs 0.89 (0.84 to 0.94), respectively).

Combination of GEP and LBD allows separation of patients into four easy-to-use prognostic groups and was similar to a model combining AJCC stage with GEP.

Combination of GEP and LBD allows separation of patients into four easy-to-use prognostic groups and was similar to a model combining AJCC stage with GEP.