The fibroblast growth factor receptors (FGFR) are tyrosine kinases that are present in many types of endothelial and tumor cells and play an important role in tumor cell growth, survival, and migration as well as in maintaining tumor angiogenesis. Overexpression of FGFRs or aberrant regulation of their activities has been implicated in many forms of human malignancies. Therefore, targeting FGFRs represents an attractive strategy for development of cancer treatment options by simultaneously inhibiting tumor cell growth, survival, and migration as well as tumor angiogenesis. Here, we describe a potent, selective, small-molecule FGFR inhibitor, (R)-(E)-2-(4-(2-(5-(1-(3,5-Dichloropyridin-4-yl)ethoxy)-1H-indazol-3yl)vinyl)-1H-pyrazol-1-yl)ethanol, designated as LY2874455. This molecule is active against all 4 FGFRs, with a similar potency in biochemical assays. It exhibits a potent activity against FGF/FGFR-mediated signaling in several cancer cell lines and shows an excellent broad spectrum of antitumor activity in several tumor xenograft models representing the major FGF/FGFR relevant tumor histologies including lung, gastric, and bladder cancers and multiple myeloma, and with a well-defined pharmacokinetic/pharmacodynamic relationship. LY2874455 also exhibits a 6-to 9-fold in vitro and in vivo selectivity on inhibition of FGF-over VEGF-mediated target signaling in mice. Furthermore, LY2874455 did not show VEGF receptor 2-mediated toxicities such as hypertension at efficacious doses. Currently, this molecule is being evaluated for its potential use in the clinic.
Sarcopenia, with risk factors such as poor nutrition and physical inactivity, is becoming prevalent among the older population. The aims of this study were (i) to systematically review the existing data on sarcopenia prevalence in the older Chinese population, (ii) to generate pooled estimates of the sex-specific prevalence among different populations, and (iii) to identify the factors associated with the heterogeneity in the estimates across studies. A search was conducted in seven databases for studies that reported the prevalence of sarcopenia in Chinese older adults, aged 60 years and over, published through April 2020. We then performed a meta-analysis to estimate the pooled prevalence, and investigated the factors associated with the variation in the prevalence across the studies using meta-regression. A total of 58 studies were included in this review. Compared with community-dwelling Chinese older adults (men: 12.9%, 95% CI: 10.7–15.1%; women: 11.2%, 95% CI: 8.9–13.4%), the pooled prevalence of sarcopenia in older adults from hospitals (men: 29.7%, 95% CI:18.4–41.1%; women: 23.0%, 95% CI:17.1–28.8%) and nursing homes (men: 26.3%, 95% CI: 19.1 to 33.4%; women: 33.7%, 95% CI: 27.2 to 40.1%) was higher. The multivariable meta-regression quantified the difference of the prevalence estimates in different populations, muscle mass assessments, and areas. This study yielded pooled estimates of sarcopenia prevalence in Chinese older adults not only from communities, but also from clinical settings and nursing homes. This study added knowledge to the current epidemiology literature about sarcopenia in older Chinese populations, and could provide background information for future preventive strategies, such as nutrition and physical activity interventions, tailored to the growing older population.
This study aimed to estimate the infection curve of local cases of the coronavirus disease (COVID-19) in Hong Kong and identify major events and preventive measures associated with the trajectory of the infection curve in the first two waves. The daily number of onset local cases was used to estimate the daily number of infections based on back-projection. The estimated infection curve was examined to identify the preventive measures or major events associated with its trajectory. Until 30 April 2020, there were 422 confirmed local cases. The infection curve of the local cases in Hong Kong was constructed and used for evaluating the impacts of various policies and events in a narrative manner. Social gatherings and some pre-implementation announcements on inbound traveler policies coincided with peaks on the infection curve.
Background
Since December 2019, coronavirus disease (COVID-19) has affected over 50 000 people in Wuhan, China. However, the number of daily infection cases, hospitalization rate, lag time from onset to diagnosis date and their associations with measures introduced to slow down the spread of COVID-19 have not been fully explored.
Methods
This study recruited 6872 COVID-19 patients in the Wuchang district, Wuhan. All of the patients had an onset date from 21 December 2019 to 23 February 2020. The overall and weekly hospitalization rate and lag time from onset to diagnosis date were calculated. The number of daily infections was estimated by the back-projection method based on the number of daily onset cases. Their association with major government reactions and measures was analyzed narratively.
Results
The overall hospitalization rate was 45.9% (95% CI 44.7 to 47.1%) and the mean lag time from onset to diagnosis was 11.1±7.4 d. The estimated infection curve was constructed for the period from 14 December 2019 to 23 February 2020. Raising public awareness regarding self-protecting and social distancing, as well as the provision of timely testing and inpatient services, were coincident with the decline in the daily number of infections.
Conclusion
Early public awareness, early identification and early quarantine, supported by appropriate infrastructure, are important elements for containing the spread of COVID-19 in the community.
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