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Biology subjects

Gray, R. T.

Publications and source records attributed to Gray, R. T..

3 recordsLinked to original sources

Dengue transmission risk in a changing climate: Bangladesh could experience a longer dengue fever season in the future

Our changing climate is already affecting the transmission of vector borne diseases such as dengue fever. This issue presents a significant public health concern for some nations, such as Bangladesh, which already experience regular seasonal outbreaks of dengue fever under present day conditions. To provide guidance for proactive public health planning to potentially mitigate future infections, we explore the impact of climate change on dengue infections by calculating the change in vectorial capacity of Aedes aegypti mosquito at a seasonal level for all regions in Bangladesh under two scenarios for future atmospheric greenhouse gas concentrations. For each of the four climate models used, and for both scenarios, our analysis reveals that the annual vectorial capacity remains at a level that would enable potential dengue epidemic transmission in all regions in Bangladesh. We found a slight decline in vectorial capacity in half of the regions examined during the last two decades of the 21st Century for the lower-concentration scenario, with a pronounced decline in vectorial capacity in all geographic regions beginning in 2060 for the higher-concentration scenario. The likely reason is that in many regions, warming is leading to sub-optimal mosquito breeding temperatures. However, seasonal differences in vectorial capacity dissipates as the climate warms, to the point that there is almost no observable seasonality for the higher-concentration scenario during the last two decades of this century. This finding suggests there is the potential for the dengue season to extend all year, with outbreaks occurring at any time. Consequently, disease surveillance and control activities would need to be geographically and temporally adapted to mitigate dengue epidemic risk in response to climate change.

ecology↗

Bcl-xL as a poor prognostic biomarker and predictor of response to adjuvant chemotherapy specifically in BRAF-mutant stage II and III colon cancer

BackgroundBRAF mutation occurs in 8-15% of colon cancers (CC), and is associated with poor prognosis in metastatic disease. Compared to wild-type BRAF (BRAFWT) disease, stage II/III CC patients with BRAF mutant (BRAFMT) tumors have shorter overall survival after relapse; however, time-to-relapse is not significantly different. The aim of this investigation was to identify, and validate, novel predictors of relapse of stage II/III BRAFMT CC.\n\nPatients and methodsWe used gene expression data from a cohort of 460 patients (GSE39582) to perform a supervised classification analysis based on risk-of-relapse within BRAFMT stage II/III CC, to identify transcriptomic biomarkers associated with prognosis within this genotype. These findings were validated using immunohistochemistry in an independent population-based cohort of Stage II/III CC (n=691), applying Cox proportional hazards analysis to determine associations with survival.\n\nResultsHigh gene expression levels of Bcl-xL, a key regulator of apoptosis, were associated with increased risk of relapse, specifically in BRAFMT tumors (HR=8.3, 95% CI 1.7-41.7), but not KRASMT/BRAFWT or KRASWT/BRAFWT tumors. High Bcl-xL protein expression in BRAFMT, untreated, stage II/III CC was confirmed to be associated with an increased risk of death in an independent cohort (HR=12.13, 95% CI 2.49-59.13). Additionally, BRAFMT tumors with high levels of Bcl-xL protein expression appeared to benefit from adjuvant chemotherapy (P for interaction =0.006), indicating the potential predictive value of Bcl-xL expression in this setting.\n\nConclusionsThese findings provide evidence that Bcl-xL gene and/or protein expression identifies a poor prognostic subgroup of BRAFMT stage II/III CC patients, who may benefit from adjuvant chemotherapy.\n\nKey MessageO_LIUsing a combination of computational biology discovery and immunohistochemistry validation in independent patient cohorts, we show that high expression of the apoptosis regulator Bcl-xL is associated with disease relapse specifically within BRAF mutant stage II/III colon cancer.\nC_LIO_LIThis data could enable tailored disease management to reduce relapse rates in the most aggressive subtype.\nC_LI

cancer biology↗

QuPath: Open source software for digital pathology image analysis

QuPath is new bioimage analysis software designed to meet the growing need for a user-friendly, extensible, open-source solution for digital pathology and whole slide image analysis. In addition to offering a comprehensive panel of tumor identification and high-throughput biomarker evaluation tools, QuPath provides researchers with powerful batch-processing and scripting functionality, and an extensible platform with which to develop and share new algorithms to analyze complex tissue images. Furthermore, QuPaths flexible design make it suitable for a wide range of additional image analysis applications across biomedical research.

pathology↗