De novo lipogenesis alters the phospholipidome of esophageal adenocarcinoma

The incidence of esophageal adenocarcinoma is rising, survival remains poor, and new tools to improve early diagnosis and precise treatment are needed. Cancer phospholipidomes quantified with mass spectrometry imaging can support objective diagnosis in minutes using a routine frozen tissue section. However, whether mass spectrometry imaging can objectively identify primary esophageal adenocarcinoma is currently unknown and represents a significant challenge, as this microenvironment is complex with phenotypically similar tissue-types. Here we used desorption electrospray ionisation mass spectrometry imaging (DESI-MSI) and bespoke chemometrics to assess the phospholipidomes of esophageal adenocarcinoma and relevant control tissues. Multivariable models derived from phospholipid profiles of 117 patients were highly discriminant for esophageal adenocarcinoma both in discovery (area-under-curve = 0.97) and validation cohorts (AUC = 1). Among many other changes, esophageal adenocarcinoma samples were markedly enriched for polyunsaturated phosphatidylglycerols with longer acyl chains, with stepwise enrichment in pre-malignant tissues. Expression of fatty acid and glycerophospholipid synthesis genes was significantly upregulated, and characteristics of fatty acid acyls matched glycerophospholipid acyls. Mechanistically, silencing the carbon switch ACLY in esophageal adenocarcinoma cells shortened GPL chains, linking de novo lipogenesis to the phospholipidome. Thus, DESI-MSI can objectively identify invasive esophageal adenocarcinoma from a number of pre-malignant tissues and unveils mechanisms of phospholipidomic reprogramming. These results call for accelerated diagnosis studies using DESI-MSI in the upper gastrointestinal endoscopy suite as well as functional studies to determine how polyunsaturated phosphatidylglycerols contribute to esophageal carcinogenesis

A New Multistage Encryption Scheme Using Linear Feedback Register and Chaos-Based Quantum Map

With the increasing volume of data transmission through insecure communication channels, big data security has become one of the important concerns in the cybersecurity domain. To address these concerns and keep data safe, a robust privacy-preserving cryptosystem is necessary. Such a solution relies on chaos encryption algorithms over standard cryptographic methods that possess multistage encryption levels, including high speed, high security, low compute overheads, and procedural power, among other characteristics. In this work, a secure image encryption scheme is proposed using linear feedback shift register (LFSR) and chaos-based quantum chaotic map. e focus of the scheme is mainly dependent on the secret keys from the input of the algorithm. e threat landscape, the statistical test analysis, along critical comparisons with other schemes indicate that the presented algorithm is significantly secure and is resistant to a wide range of different attacks such as differential and statistical attacks. e proposed method has sufficiently higher sensitivity and security when compared to existing encryption algorithms. Several security parameters validated the security of proposed work such as correlation coefficient analyses among the neighboring pixels, entropy, the number of pixels change rate (NPCR), unified average change intensity (UACI), mean square error (MSE), brute force, key sensitivity, and peak signal to noise ratio (PSNR) analyses. e randomness of the ciphers produced by the proposed technique is also passed through NIST-800-22. e results of NIST indicate that the ciphers are highly random and do not produce any type of periodicity or pattern

Review on unidirectional non-isolated high gain DC-DC converters for EV sustainable DC fast charging applications

Modern electrical transportation systems require eco-friendly refueling stations worldwide. This has attracted the interest of researchers toward a feasible optimal solution for electric vehicle (EV) charging stations. EV charging can be simply classified as Slow charging (domestic use), Fast charging and Ultrafast charging (commercial use). This study highlights recent advancements in commercial DC charging. The battery voltage varies widely from 36V to 900V according to the EVs. This study focuses on non-isolated unidirectional converters for off-board charging. Various standards and references for fast off-board charging have been proposed. Complete transportation is changed to EVs, which are charged by the grid supply obtained by burning natural fuels, contributing to environmental concerns. Sustainable charging from sustainable energy sources will make future EV completely eco-friendly transportation. The research gap in complete eco-friendly transit is located in interfacing sustainable energy sources and fast DC EV charging. The first step towards clean, eco-friendly transportation is identifying a suitable converter for bridging the research gap in this locality. A simple approach has been made to identify the suitable DC-DC converter for DC fast-charging EVs. This article carefully selected suitable topologies derived from Boost, SEPIC, Cuk, Luo, and Zeta converters for clean EV charging applications. A detailed study on the components count, voltage stress on the controlled and uncontrolled switches, voltage gain obtained, output voltage, power rating of the converters, switching frequency, efficiency obtained, and issues associated with the selected topologies are presented. The outcome of this study is presented as the research challenges or expectations of future converter topologies for charging

Imaging of esophageal lymph node metastases by desorption electrospray ionization mass spectrometry

Histopathological assessment of lymph node metastases (LNM) depends on subjective analysis of cellular morphology with inter-/intra-observer variability. In this study, LNM from esophageal adenocarcinoma was objectively detected using desorption electrospray ionization-mass spectrometry imaging (DESI-MSI). Ninety lymph nodes and their primary tumor biopsies from 11 esophago-gastrectomy specimens were examined and analyzed by DESI-MSI. Images from mass spectrometry and corresponding histology were co-registered and analyzed using multivariate statistical tools. The MSIs revealed consistent lipidomic profiles of individual tissue types found within lymph nodes. Spatial mapping of the profiles showed identical distribution patterns as per the tissue types in matched immunohistochemistry images. Lipidomic profile comparisons of LNM versus the primary tumor revealed a close association in contrast to benign lymph node tissue types. This similarity was used for the objective prediction of LNM in mass spectrometry images utilizing the average lipidomic profile of esophageal adenocarcinoma. The multivariate statistical algorithm developed for LNM identification demonstrated a sensitivity, specificity, positive predictive value and negative predictive value of 89.5, 100, 100 and 97.2 per-cent, respectively, when compared to gold-standard immunohistochemistry. DESI-MSI has the potential to be a diagnostic tool for peri-operative identification of LNM and compares favorably with techniques currently used by histopathology experts

Characterisation of bioenergetic pathways and related regulators by multiple assays in human tumour cells

Background: Alterations in cellular metabolism are considered as hallmarks of cancers, however, to recognize these alterations and understand their mechanisms appropriate techniques are required. Our hypothesis was to determine whether dominant bioenergetic mechanism may be estimated by comparing the substrate utilisation with different methods to detect the labelled carbon incorporation and their application in tumour cells. Methods: To define the bioenergetic pathways different metabolic tests were applied: (a) measuring CO2 production from [1-14C]-glucose and [1-14C]-acetate; (b) studying the effect of glucose and acetate on adenylate energy charge; (c) analysing glycolytic and TCA cycle metabolites and the number of incorporated 13C atoms after [U-13C]-glucose/[2-13C]-acetate labelling. Based on [1-14C]-substrate oxidation two selected cell lines out of seven were analysed in details, in which the highest difference was detected at their substrate utilization. To elucidate the relevance of metabolic characterisation the expression of certain regulatory factors, bioenergetic enzymes, mammalian target of rapamycin (mTOR) complexes (C1/C2) and related targets as important elements at the crossroad of cellular signalling network were also investigated. Results: Both [U-13C]-glucose and [1-14C]-substrate labelling indicated high glycolytic capacity of tumour cells. However, the ratio of certain 13C-labelled metabolites showed detailed metabolic differences in the two selected cell lines in further characterisation. The detected differences of GAPDH, β-F1-ATP-ase expression and adenylate energy charge in HT-1080 and ZR-75.1 tumour cells also confirmed the altered metabolism. Moreover, the highly limited labelling of citrate by [2-13C]-acetate-representing a novel functional test in malignant cells-confirmed the defect of TCA cycle of HT-1080 in contrast to ZR-75.1 cells. Noteworthy, the impaired TCA cycle in HT-1080 cells were associated with high mTORC1 activity, negligible protein level and activity of mTORC2, high expression of interleukin-1β, interleukin-6 and heme oxygenase-1 which may contribute to the compensatory mechanism of TCA deficiency. Conclusions: The applied methods of energy substrate utilisation and other measurements represent simple assay system using 13C-acetate and glucose to recognize dominant bioenergetic pathways in tumour cells. These may offer a possibility to characterise metabolic subtypes of human tumours and provide guidelines to find biomarkers for prediction and development of new metabolism related targets in personalized therapy. © 2016 Jeney et al

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks