Identification of Tissue Types and Gene Mutations From Histopathology Images for Advancing Colorectal Cancer Biology.

Objective: Colorectal cancer (CRC) patients respond differently to treatments and are sub-classified by different approaches. We evaluated a deep learning model, which adopted endoscopic knowledge learnt from AI-doscopist, to characterise CRC patients by histopathological features. Results: Data of 461 patients were collected from TCGA-COAD database. The proposed framework was able to 1) differentiate tumour from normal tissues with an Area Under Receiver Operating Characteristic curve (AUROC) of 0.97; 2) identify certain gene mutations (MYH9, TP53) with an AUROC > 0.75; 3) classify CMS2 and CMS4 better than the other subtypes; and 4) demonstrate the generalizability of predicting KRAS mutants in an external cohort. Conclusions: Artificial intelligent can be used for on-site patient classification. Although KRAS mutants were commonly associated with therapeutic resistance and poor prognosis, subjects with predicted KRAS mutants in this study have a higher survival rate in 30 months after diagnoses.

Promoting the Delivery of Nanoparticles to Atherosclerotic Plaques by DNA Coating.

Many nanoparticle-based carriers to atherosclerotic plaques contain peptides, lipoproteins, and sugars, yet the application of DNA-based nanostructures for targeting plaques remains infrequent. In this work, we demonstrate that DNA-coated superparamagnetic iron oxide nanoparticles (DNA-SPIONs), prepared by attaching DNA oligonucleotides to poly(ethylene glycol)-coated SPIONs (PEG-SPIONs), effectively accumulate in the macrophages of atherosclerotic plaques following an intravenous injection into apolipoprotein E knockout (ApoE-/-) mice. DNA-SPIONs enter RAW 264.7 macrophages faster and more abundantly than PEG-SPIONs. DNA-SPIONs mostly enter RAW 264.7 cells by engaging Class A scavenger receptors (SR-A) and lipid rafts and traffic inside the cell along the endolysosomal pathway. ABS-SPIONs, nanoparticles with a similarly polyanionic surface charge as DNA-SPIONs but bearing abasic oligonucleotides also effectively bind to SR-A and enter RAW 264.7 cells. Near-infrared fluorescence imaging reveals evident localization of DNA-SPIONs in the heart and aorta 30 min post-injection. Aortic iron content for DNA-SPIONs climbs to the peak (∼60% ID/g) 2 h post-injection (accompanied by profuse accumulation in the aortic root), but it takes 8 h for PEG-SPIONs to reach the peak aortic amount (∼44% ID/g). ABS-SPIONs do not appreciably accumulate in the aorta or aortic root, suggesting that the DNA coating (not the surface charge) dictates in vivo plaque accumulation. Flow cytometry analysis reveals more pronounced uptake of DNA-SPIONs by hepatic endothelial cells, splenic macrophages and dendritic cells, and aortic M2 macrophages (the cell type with the highest uptake in the aorta) than PEG-SPIONs. In summary, coating nanoparticles with DNA is an effective strategy of promoting their systemic delivery to atherosclerotic plaques.

A Therapeutic Wireless Capsule for Treatment of Gastrointestinal Haemorrhage by Balloon Tamponade Effect.

OBJECTIVE: Wireless capsule endoscope (WCE) is a revolutionary approach to diagnose small bowel pathologies. Currently available WCEs are mostly passive devices with image capturing function only, while on-going efforts have been placed on robotizing WCEs or to enhance them with therapeutic functions. In this paper, the authors present a novel inflatable WCE for haemostasis in the gastrointestinal (GI) tracts by balloon tamponade effect. METHODS: The proposed wireless capsule consists of a balloon that can be inflated using the endothermic reaction of acid and base. When the balloon reached a precalculated pressure level, it is able to stop at a bleeding site in the bowel, and achieve haemostasis by tamponade effect. The prototype is 14 mm in diameter, with three sections of 13, 35, and 12 mm in length, respectively. The three sections are linked together with flexible joints and enclosed in a silicone balloon. The prototypes were tested in ex vivo porcine intestine models. RESULTS: In the ten ex vivo trials conducted, the inflatable wireless capsule achieved average balloon pressure of 46.0 mmHg and withstood average maximum longitudinal pulling force at 1.46 N. An in vivo study was carried out as a proof-of-concept for treating bleeding in a porcine model. The proposed inflatable WCE succeeded in the animal test by controlling haemostasis within 5 min. No rebleeding was observed in the next 20 min. CONCLUSION: The results suggested that the inflatable capsule with a real-time bleeding detection algorithm can be implemented. Moreover, the proposed inflatable WCE prototype can achieve haemorrhage control in the lower GI. SIGNIFICANCE: To our best knowledge, this is the first study that demonstrated the potential to treat GI haemorrhage by an inflatable WCE. The proposed capsule enables the development of a closed-loop system based on a body sensor network to provide early treatment of GI bleeding for p-medicine.

Design of wormlike automated robotic endoscope: dynamic interaction between endoscopic balloon and surrounding tissues.

BACKGROUND: The current design of capsule endoscope is limited by the inability to control the motion within gastrointestinal tract. The rising incidence of gastrointestinal cancers urged improvement in the method of screening endoscopy. OBJECTIVES: This preclinical study aimed to design and develop a novel locomotive module for capsule endoscope. We investigated the feasibility and physical properties of this newly designed caterpillar-like capsule endoscope with a view to enhancing screening endoscopy. DESIGN: This study consisted of preclinical design and experimental testing on the feasibility of automated locomotion for a prototype caterpillar endoscope. The movement was examined first in the PVC tube and then in porcine intestine. The image captured was transmitted to handheld device to confirm the control of movement. The balloon pressure and volume as well as the contact force between the balloon and surroundings were measured when the balloon was inflated inside (1) a hard PVC tube, (2) a soft PVC tube, (3) muscular sites of porcine colons and (4) less muscular sites of porcine colons. RESULTS: The prototype caterpillar endoscope was able to move inward and backward within the PVC tubing and porcine intestine. Images were able to be captured from the capsule endoscope attached and being observed with a handheld device. Using the onset of a contact force as indication of the buildup of the gripping force between the balloon and the lumen walls, it is concluded from the results of this study that the rate of change in balloon pressure and volume is two good estimators to optimize the inflation of the balloon. CONCLUSION: The results of this study will facilitate further refinement in the design of caterpillar robotic endoscope to move inside the GI tract.

A mucoadhesive endoluminal wearable sensory system.

Bio- or muco-adhesive anchoring is a challenge for the development of advanced gastrointestinal (GI) surgical instruments, endoluminal monitoring devices and drug delivery systems. In this paper, we present a polymeric bio-adhesive film embedded with an optical sensor that can potentially be used to detect gastrointestinal bleeding. Four different formulas of mucoadhesive polymers were synthesized based on various chemical components and concentration combinations, and they were further layered with miniature photoplethymographic (PPG) sensors. The adhesive ability of the proposed mucoadhesive-sensor module was tested by attaching it to the lumen of a porcine stomach and compared amongst the four formulas. pH testing was also implemented to simulate the performance of the film in gastric cavity. To demonstrate the signal quality of this module, we also tested on the skin of five healthy subjects for hours. The observed shear detachment force between mucoadhesive film and porcine stomach tissue of all four formulations ranged from 0.09 to 1.38 N, and the performance of mucoadhesive film in pH 7 and pH 2 were similar. The module can attach firmly onto the skin for 3-10 hours with comparable PPG signal quality to traditional clip-based setup. With the advent of mucosal tissue anchoring by means of bioadhensive film, a wider extent of endoluminal procedures may become feasible. This emerging technology can also help shape the future of in-body wearable devices in the GI tract or other endoluminal cavities.

Molecular hyperdiversity defines populations of the nematode Caenorhabditis brenneri.

The biology of Sydney Brenner's eponymous species of nematode, Caenorhabditis brenneri, is little known to science, despite its famous sibling Caenorhabditis elegans. Here we demonstrate that C. brenneri harbors the most molecular diversity of any eukaryote, with its 14.1% of polymorphic synonymous sites between individuals being 150-fold greater than humans and most comparable to hyperdiverse bacteria. This diversity is not an artifact of cryptic species divergence but reflects an enormous pan-tropical population, confirmed by fully viable genetic crosses between continents, extensive intralocus recombination, selection on codon use, and only weak geographic genetic structure. These findings in an animal galvanize tests of theory about the evolution of complexity in genomes and phenotypes and enable molecular population genetics methods to finely resolve uncharacterized functional noncoding elements.