RESUMO
Prostate cancer is frequently treated with radiotherapy. Unfortunately, aggressive radioresistant relapses can arise, and the molecular underpinnings of radioresistance are unknown. Modern clinical radiotherapy is evolving to deliver higher doses of radiation in fewer fractions (hypofractionation). We therefore analyzed genomic, transcriptomic and proteomic data to characterize prostate cancer radioresistance in cells treated with both conventionally fractionated and hypofractionated radiotherapy. Independent of fractionation schedule, resistance to radiotherapy involved massive genomic instability and abrogation of DNA mismatch repair. Specific prostate cancer driver genes were modulated at the RNA and protein levels, with distinct protein subcellular responses to radiotherapy. Conventional fractionation led to a far more aggressive biomolecular response than hypofractionation. Testing pre-clinical candidates identified in cell lines, we revealed POLQ (DNA Polymerase Theta) as a radiosensitizer. POLQ-modulated radioresistance in model systems and was predictive of it in large patient cohorts. The molecular response to radiation is highly multi-modal, and sheds light on prostate cancer lethality.
RESUMO
Traditionally, dengue is controlled by fogging, and the prime location for the control measure is at the patient's residence. However, when Malaysia was hit by the first wave of the Coronavirus disease (COVID-19), and the government-imposed movement control order, dengue cases have decreased by more than 30% from the previous year. This implies that residential areas may not be the prime locations for dengue-infected mosquitoes. The existing early warning system was focused on temporal prediction wherein the lack of consideration for spatial component at the microlevel and human mobility were not considered. Thus, we developed MozzHub, which is a web-based application system based on the bipartite network-based dengue model that is focused on identifying the source of dengue infection at a small spatial level (400 m) by integrating human mobility and environmental predictors. The model was earlier developed and validated; therefore, this study presents the design and implementation of the MozzHub system and the results of a preliminary pilot test and user acceptance of MozzHub in six district health offices in Malaysia. It was found that the MozzHub system is well received by the sample of end-users as it was demonstrated as a useful (77.4%), easy-to-operate system (80.6%), and has achieved adequate client satisfaction for its use (74.2%).
RESUMO
Malaysia is currently facing an outbreak of COVID-19. We aim to present the first study in Malaysia to report the reproduction numbers and develop a mathematical model forecasting COVID-19 transmission by including isolation, quarantine, and movement control measures. We utilized a susceptible, exposed, infectious, and recovered (SEIR) model by incorporating isolation, quarantine, and movement control order (MCO) taken in Malaysia. The simulations were fitted into the Malaysian COVID-19 active case numbers, allowing approximation of parameters consisting of probability of transmission per contact (ß), average number of contacts per day per case (ζ), and proportion of close-contact traced per day (q). The effective reproduction number (Rt) was also determined through this model. Our model calibration estimated that (ß), (ζ), and (q) were 0.052, 25 persons, and 0.23, respectively. The (Rt) was estimated to be 1.68. MCO measures reduce the peak number of active COVID-19 cases by 99.1% and reduce (ζ) from 25 (pre-MCO) to 7 (during MCO). The flattening of the epidemic curve was also observed with the implementation of these control measures. We conclude that isolation, quarantine, and MCO measures are essential to break the transmission of COVID-19 in Malaysia.