A deep-learning approach to aid in diagnosing Barrett’s oesophagus related dysplasia

Barrett's oesophagus is the only known precursor to oesophagus carcinoma. Histologically, it is defined as a condition of columnar cells replacing the standard squamous lining. Those altered cells are prone to cytological and architectural abnormalities, known as dysplasia. The dysplastic degree varies from low to high grade and can evolve into invasive carcinoma or adenocarcinoma. Thus, detecting high-grade and intramucosal carcinoma during the surveillance of Barrett's oesophagus patients is vital so they can be treated by surgical resection. Unfortunately, the achieved interobserver agreement for grading dysplasia among pathologists is only fair to moderate. Nowadays, grading Barrett's dysplasia is limited to visual examination by pathologists for glass or virtual slides. This work aims to diagnose different grades of dysplasia in Barrett’s oesophagus, particularly high-grade dysplasia, from virtual histopathological slides of oesophagus tissue. In the first approach, virtual slides were analysed at a low magnification to detect regions of interest and predict the grade of dysplasia based on the analysis of the virtual slides at 10X magnification. Transfer learning was employed to partially fine-tune two deep-learning networks using healthy and Barrett’s oesophagus tissue. Then, the two networks were connected. The proposed model achieved 0.57 sensitivity, 0.79 specificity and moderate agreement with a pathologist. On the contrary, the second approach processed the slides at a higher magnification (40X magnification). It adapted novelty detection and local outlier factor alongside transfer learning to solve the multiple instances learning problem. It increased the performance of the diagnosis to 0.84 sensitivity and 0.92 specificity, and the interobserver agreement reached a substantial level. Finally, the last approach mimics the pathologists’ procedure to diagnose dysplasia, relying on both magnifications. Thus, their behaviours during the assessment were analysed. As a result, it was found that employing a multi-scale approach to detect dysplastic tissue using a low magnification level (10X magnification) and grade dysplasia at a higher level (40X magnification). The proposed computer-aided diagnosis system was built using networks from the first two approaches. It scored 0.90 sensitivity, 0.94 specificity and a substantial agreement with the pathologist and a moderate agreement with the other expert

The effect of animal venom in the treatment of pancreatic and colorectal cancer

Pancreatic and colorectal cancer are aggressive, difficult to target cancers with new therapeutic options desperately required to improve prognosis. Animal venoms are useful in drug discovery due to huge variety of bioactive components evolved over millions of years. Venom has already been utilised in drug discovery with several venom derived drugs currently on the market. A plate-based resazurin assay was used to determine cytotoxicity of a panel of cobra venoms against BxPC-3 pancreatic and SW620 colorectal cancer cell lines in-vitro. African spitting cobra (Afronaja) venoms displayed selective toxicity against SW620 cells compared to non-spitting and Asian cobra venoms. Five Afronaja venoms were fractionated using HPLC then the venom components were rescreened in a miniaturised resazurin assay. Dose response curves for both lines were performed using selected fractions, giving IC50 values between 17-225 μg/ml. Four venom fractions were analysed using Mass Spectrometry (MS) and identified as cytotoxins. MS outputs plus bioinformatic techniques predicted likely sequences for each fraction. A structure activity relationship was performed and AA residue 7 and AAs 26-29 were identified as conferring the most significant selective toxicity. Finally, a preliminarily qPCR study assessed the effect of each fraction on the tested cell lines. This study investigated 20 genes commonly mis-regulated in pancreatic and colorectal cancer. The cell lines were exposed to three venom fractions and regulation of each gene assessed compared to untreated controls. SMAD4, Tp53, WNT1 and EGFR genes were significantly upregulated following addition of venom and MMP9 and Bcl-2 were significantly downregulated in this preliminary study. A larger scale qPCR study should be performed to confirm these findings and assess other potential genetic alterations caused by the venom fraction to assess the potential for development into an anti-cancer treatment option

Abstracts from the 50th European Society of Human Genetics Conference: Posters

International audienc

XXIV congreso anual de la sociedad española de ingeniería biomédica (CASEIB2016)

En la presente edición, más de 150 trabajos de alto nivel científico van a ser presentados en 18 sesiones paralelas y 3 sesiones de póster, que se centrarán en áreas relevantes de la Ingeniería Biomédica. Entre las sesiones paralelas se pueden destacar la sesión plenaria Premio José María Ferrero Corral y la sesión de Competición de alumnos de Grado en Ingeniería Biomédica, con la participación de 16 alumnos de los Grados en Ingeniería Biomédica a nivel nacional. El programa científico se complementa con dos ponencias invitadas de científicos reconocidos internacionalmente, dos mesas redondas con una importante participación de sociedades científicas médicas y de profesionales de la industria de tecnología médica, y dos actos sociales que permitirán a los participantes acercarse a la historia y cultura valenciana. Por primera vez, en colaboración con FENIN, seJane Campos, R. (2017). XXIV congreso anual de la sociedad española de ingeniería biomédica (CASEIB2016). Editorial Universitat Politècnica de València. http://hdl.handle.net/10251/79277EDITORIA