Establishing key research questions for the implementation of artificial intelligence in colonoscopy - a modified Delphi method

Background and Aims Artificial intelligence (AI) research in colonoscopy is progressing rapidly but widespread clinical implementation is not yet a reality. We aimed to identify the top implementation research priorities. Methods An established modified Delphi approach for research priority setting was used. Fifteen international experts, including endoscopists and translational computer scientists/engineers from 9 countries participated in an online survey over 9 months. Questions related to AI implementation in colonoscopy were generated as a long-list in the first round, and then scored in two subsequent rounds to identify the top 10 research questions. Results The top 10 ranked questions were categorised into 5 themes. Theme 1: Clinical trial design/end points (4 questions), related to optimum trial designs for polyp detection and characterisation, determining the optimal end-points for evaluation of AI and demonstrating impact on interval cancer rates. Theme 2: Technological Developments (3 questions), including improving detection of more challenging and advanced lesions, reduction of false positive rates and minimising latency. Theme 3: Clinical adoption/Integration (1 question) concerning effective combination of detection and characterisation into one workflow. Theme 4: Data access/annotation (1 question) concerning more efficient or automated data annotation methods to reduce the burden on human experts. Theme 5: Regulatory Approval (1 question) related to making regulatory approval processes more efficient. Conclusions This is the first reported international research priority setting exercise for AI in colonoscopy. The study findings should be used as a framework to guide future research with key stakeholders to accelerate the clinical implementation of AI in endoscopy

Bio-nanotechnology application in wastewater treatment

The nanoparticles have received high interest in the field of medicine and water purification, however, the nanomaterials produced by chemical and physical methods are considered hazardous, expensive, and leave behind harmful substances to the environment. This chapter aimed to focus on green-synthesized nanoparticles and their medical applications. Moreover, the chapter highlighted the applicability of the metallic nanoparticles (MNPs) in the inactivation of microbial cells due to their high surface and small particle size. Modifying nanomaterials produced by green-methods is safe, inexpensive, and easy. Therefore, the control and modification of nanoparticles and their properties were also discussed

Altered expression of topoisomerase IIα contributes to cross-resistant to etoposide K562/MX2 cell line by aberrant methylation

KRN 8602 (MX2) is a novel morpholino anthracycline derivative having the chemical structure 3′-deamino-3′-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride. To investigate the mechanisms of resistance to MX2, we established an MX2-resistant phenotype (K562/MX2) of the human myelogeneous leukaemia cell line (K562/P), by continuously exposing a suspension culture to increasing concentrations of MX2. K562/MX2 cells were more resistant to MX2 than the parent cells, and also showed cross-resistance to etoposide and doxorubicin. Topoisomerase (Topo) IIα protein levels in K562/MX2 cells were lower of those in K562/P cells on immunoblot analysis and decreased expression of Topo IIα mRNA was seen in K562/MX2 cells. Topoisomerase II catalytic activity was also reduced in the nuclear extracts from K562/MX2 cells when compared with K562/P cells. Aberrant methylated CpG of Topo IIα gene was observed in K562/MX2 cells when compared with the parent line on methylation-specific restriction enzyme analysis. To overcome the drug resistance to MX2 and etoposide, we investigated treatment with 5-Aza-2′-deoxycytidine (5AZ), which is a demethylating agent, in K562/MX2 cells. 5-Aza-2′-deoxycytidine treatment increased Topo IIα mRNA expression in K562/MX2 cells, but not in K562/P cells, and increased the cytotoxicity of MX2 and etoposide. Methylated CpG was decreased in K562/MX2 cells after 5AZ treatment. We concluded that the mechanism of drug resistance to MX2 and etoposide in K562/MX2 cells might be the combination of decreased expression of Topo IIα gene and increased methylation, and that 5AZ could prove to be a novel treatment for etoposide-resistant cell lines, such as K562/MX2

Quality assurance in pathology in colorectal cancer screening and diagnosis—European recommendations

In Europe, colorectal cancer is the most common newly diagnosed cancer and the second most common cause of cancer deaths, accounting for approximately 436,000 incident cases and 212,000 deaths in 2008. The potential of high-quality screening to improve control of the disease has been recognized by the Council of the European Union who issued a recommendation on cancer screening in 2003. Multidisciplinary, evidence-based European Guidelines for quality assurance in colorectal cancer screening and diagnosis have recently been developed by experts in a pan-European project coordinated by the International Agency for Research on Cancer. The full guideline document consists of ten chapters and an extensive evidence base. The content of the chapter dealing with pathology in colorectal cancer screening and diagnosis is presented here in order to promote international discussion and collaboration leading to improvements in colorectal cancer screening and diagnosis by making the principles and standards recommended in the new EU Guidelines known to a wider scientific community

Helicobacter pylori Infection of Gastrointestinal Epithelial Cells in vitro Induces Mesenchymal Stem Cell Migration through an NF-κB-Dependent Pathway

The role of bone marrow-derived mesenchymal stem cells (MSC) in the physiology of the gastrointestinal tract epithelium is currently not well established. These cells can be recruited in response to inflammation due to epithelial damage, home, and participate in tissue repair. In addition, in the case of tissue repair failure, these cells could transform and be at the origin of carcinomas. However, the chemoattractant molecules responsible for MSC recruitment and migration in response to epithelial damage, and particularly to Helicobacter pylori infection, remain unknown although the role of some chemokines has been suggested. This work aimed to get insight into the mechanisms of mouse MSC migration during in vitro infection of mouse gastrointestinal epithelial cells by H. pylori. Using a cell culture insert system, we showed that infection of gastrointestinal epithelial cells by different H. pylori strains is able to stimulate the migration of MSC. This mechanism involves the secretion by infected epithelial cells of multiple cytokines, with a major role of TNFα, mainly via a Nuclear Factor-kappa B-dependent pathway. This study provides the first evidence of the role of H. pylori infection in MSC migration and paves the way to a better understanding of the role of bone marrow-derived stem cells in gastric pathophysiology and carcinogenesis

Three new chondrosarcoma cell lines: one grade III conventional central chondrosarcoma and two dedifferentiated chondrosarcomas of bone

BackgroundChondrosarcoma is the second most common primary sarcoma of bone. High-grade conventional chondrosarcoma and dedifferentiated chondrosarcoma have a poor outcome. In pre-clinical research aiming at the identification of novel treatment targets, the need for representative cell lines and model systems is high, but availability is scarce.MethodsWe developed and characterized three cell lines, derived from conventional grade III chondrosarcoma (L835), and dedifferentiated chondrosarcoma (L2975 and L3252) of bone. Proliferation and migration were studied and we used COBRA-FISH and array-CGH for karyotyping and genotyping. Immunohistochemistry for p16 and p53 was performed as well as TP53 and IDH mutation analysis. Cells were injected into nude mice to establish their tumorigenic potential.ResultsWe show that the three cell lines have distinct migrative properties, L2975 had the highest migration rate and showed tumorigenic potential in mice. All cell lines showed chromosomal rearrangements with complex karyotypes and genotypic aberrations were conserved throughout late passaging of the cell lines. All cell lines showed loss of CDKN2A, while TP53 was wild type for exons 5–8. L835 has an IDH1 R132C mutation, L2975 an IDH2 R172W mutation and L3252 is IDH wild type.ConclusionsBased on the stable culturing properties of these cell lines and their genotypic profile resembling the original tumors, these cell lines should provide useful functional models to further characterize chondrosarcoma and to evaluate new treatment strategies

Glucose-Insulin Therapy, Plasma Substrate Levels and Cardiac Recovery After Cardiac Ischemic Events

INTRODUCTION: The potential usefulness of glucose-insulin therapy relies to a large extent on the premise that it prevents hyperglycemia and hyperlipidemia following cardiac ischemic events. METHODS: In this review we evaluate the literature concerning plasma glucose and free fatty acids levels during and following cardiac ischemic events. RESULTS: The data indicate that hyperlipidemia and hyperglycemia most likely occur during acute coronary ischemic syndromes in the conscious state (e.g. acute myocardial infarction) and less so during reperfusion following CABG reperfusion. This is in accordance with observations that glucose-insulin therapy during early reperfusion post CABG may actually cause hypolipidemia, because substantial hyperlipidemia does not appear to occur during that stage of cardiac surgery. DISCUSSION: Considering recent data indicating that hypolipidemia may be detrimental for cardiac function, we propose that free fatty acid levels during reperfusion post CABG with the adjunct glucose-insulin therapy need to be closely monitored. CONCLUSION: From a clinical point of view, a strategy directed at monitoring and thereafter maintaining plasma substrate levels in the normal range for both glucose (4-6 mM) and FFA (0.2-0.6 mM) as well as stimulation of glucose oxidation, promises to be the most optimal metabolic reperfusion treatment following cardiac ischemic episodes. Future (preclinical and subsequently clinical) investigations are required to investigate whether the combination of glucose-insulin therapy with concomitant lipid administration may be beneficial in the setting of reperfusion post CAB

Separase Phosphosite Mutation Leads to Genome Instability and Primordial Germ Cell Depletion during Oogenesis

To ensure equal chromosome segregation and the stability of the genome during cell division, Separase is strictly regulated primarily by Securin binding and inhibitory phosphorylation. By generating a mouse model that contained a mutation to the inhibitory phosphosite of Separase, we demonstrated that mice of both sexes are infertile. We showed that Separase deregulation leads to chromosome mis-segregation, genome instability, and eventually apoptosis of primordial germ cells (PGCs) during embryonic oogenesis. Although the PGCs of mutant male mice were completely depleted, a population of PGCs from mutant females survived Separase deregulation. The surviving PGCs completed oogenesis but produced deficient initial follicles. These results indicate a sexual dimorphism effect on PGCs from Separase deregulation, which may be correlated with a gender-specific discrepancy of Securin. Our results reveal that Separase phospho-regulation is critical for genome stability in oogenesis. Furthermore, we provided the first evidence of a pre-zygotic mitotic chromosome segregation error resulting from Separase deregulation, whose sex-specific differences may be a reason for the sexual dimorphism of aneuploidy in gametogenesis

Elastofibroma dorsi – differential diagnosis in chest wall tumours

BACKGROUND: Elastofibromas are benign soft tissue tumours mostly of the infrascapular region between the thoracic wall, the serratus anterior and the latissimus dorsi muscle with a prevalence of up to 24% in the elderly. The pathogenesis of the lesion is still unclear, but repetitive microtrauma by friction between the scapula and the thoracic wall may cause the reactive hyperproliferation of fibroelastic tissue. METHODS: We present a series of seven cases with elastofibroma dorsi with reference to clinical findings, further clinical course and functional results after resection, as well as recurrence. Data were obtained retrospectively by clinical examination, phone calls to the patients' general practitioners and charts review. Follow-up time ranged from four months to nine years and averaged 53 months. RESULTS: The patients presented with swelling of the infrascapular region or snapping scapula. In three cases, the lesion was painful. The ratio men/women was 2/5 with a mean age of 64 years. The tumor sizes ranged from 3 to 13 cm. The typical macroscopic aspect was characterized as poorly defined fibroelastic soft tissue lesion with a white and yellow cut surface caused by intermingled remnants of fatty tissue. Microscopically, the lesions consisted of broad collagenous strands and densely packed enlarged and fragmented elastic fibres with mostly round shapes. In all patients but one, postoperative seroma (which had to be punctuated) occurred after resection; however, at follow-up time, no patient reported any decrease of function or sensation at the shoulder or the arm of the operated side. None of the patients experienced a relapse. CONCLUSION: In differential diagnosis of soft tissue tumors located at this specific site, elastofibroma should be considered as likely diagnosis. Due to its benign behaviour, the tumor should be resected only in symptomatic patients