Mode Bifurcation and Fold Points of Complex Dispersion Curves for the Metamaterial Goubau Line

In this paper the complex dispersion curves of the four lowest-order transverse magnetic modes of a dielectric Goubau line ($\epsilon>0, \mu>0$) are compared with those of a dispersive metamaterial Goubau line. The vastly different dispersion curve structure for the metamaterial Goubau line is characterized by unusual features such as mode bifurcation, complex fold points, both proper and improper complex modes, and merging of complex and real modes

The combined immunohistochemical expression of AMBRA1 and SQSTM1 identifies patients with poorly differentiated cutaneous squamous cell carcinoma at risk of metastasis: A proof of concept study

\ua9 2024 AMLo Biosciences Ltd. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.Background: Cutaneous squamous cell carcinoma (cSCC) incidence continues to increase globally with, as of yet, an unmet need for reliable prognostic biomarkers to identify patients at increased risk of metastasis. The aim of the present study was to test the prognostic potential of the combined immunohistochemical expression of the autophagy regulatory biomarkers, AMBRA1 and SQSTM1, to identify high-risk patient subsets. Methods: A retrospective cohort of 68 formalin-fixed paraffin-embedded primary cSCCs with known 5-year metastatic outcomes were subjected to automated immunohistochemical staining for AMBRA1 and SQSTM1. Digital images of stained slides were annotated to define four regions of interest: the normal and peritumoral epidermis, the tumor mass, and the tumor growth front. H-score analysis was used to semi-quantify AMBRA1 or SQSTM1 expression in each region of interest using Aperio ImageScope software, with receiver operator characteristics and Kaplan–Meier analysis used to assess prognostic potential. Results: The combined loss of expression of AMBRA1 in the tumor growth front and SQSTM1 in the peritumoral epidermis identified patients with poorly differentiated cSCCs at risk of metastasis (*p < 0.05). Conclusions: Collectively, these proof of concept data suggest loss of the combined expression of AMBRA1 in the cSCC growth front and SQSTM1 in the peritumoral epidermis as a putative prognostic biomarker for poorly differentiated cSCC

Behavioral Impact of the Regulation of the Brain 2-Oxoglutarate Dehydrogenase Complex by Synthetic Phosphonate Analog of 2-Oxoglutarate: Implications into the Role of the Complex in Neurodegenerative Diseases

Decreased activity of the mitochondrial 2-oxoglutarate dehydrogenase complex (OGDHC) in brain accompanies neurodegenerative diseases. To reveal molecular mechanisms of this association, we treated rats with a specific inhibitor of OGDHC, succinyl phosphonate, or exposed them to hypoxic stress. In males treated with succinyl phosphonate and in pregnancy-sensitized females experiencing acute hypobaric hypoxia, we revealed upregulation of brain OGDHC (within 24 hours), with the activity increase presumably representing the compensatory response of brain to the OGDHC inhibition. This up-regulation of brain OGDHC was accompanied by an increase in exploratory activity and a decrease in anxiety of the experimental animals. Remarkably, the hypoxia-induced elevation of brain OGDHC and most of the associated behavioral changes were abrogated by succinyl phosphonate. The antagonistic action of hypoxia and succinyl phosphonate demonstrates potential therapeutic significance of the OGDHC regulation by the phosphonate analogs of 2-oxoglutarate

Interobserver Variability in the Assessment of Fluorescence Angiography in the Colon

BACKGROUND: Fluorescence angiography in colorectal surgery is a technique that may lead to lower anastomotic leak rates. However, the interpretation of the fluorescent signal is not standardised and there is a paucity of data regarding interobserver agreement. The aim of this study is to assess interobserver variability in selection of the transection point during fluorescence angiography before anastomosis. METHODS: An online survey with still images of fluorescence angiography was distributed through colorectal surgery channels containing images from 13 patients where several areas for transection were displayed to be chosen by raters. Agreement was assessed overall and between pre-planned rater cohorts (experts vs non-experts; trainees vs consultants; colorectal specialists vs non colorectal specialists), using Fleiss' kappa statistic. RESULTS: 101 raters had complete image ratings. No significant difference was found between raters when choosing a point of optimal bowel transection based on fluorescence angiography still images. There was no difference between pre-planned cohorts analysed (experts vs non-experts; trainees vs consultants; colorectal specialists vs non colorectal specialists). Agreement between these cohorts was poor (<.26). CONCLUSION: Whilst there is no learning curve for the technical adoption of FA, understanding the fluorescent signal characteristics is key to successful use. We found significant variation exists in interpretation of static fluorescence angiography data. Further efforts should be employed to standardise fluorescence angiography assessment

Unpacking the complexity of the UK plastic packaging value chain: A stakeholder perspective

The pace to achieving a sustainable plastics economy remains noticeably slow. This could be due to a lack of understanding of the role and importance of stakeholder dynamics in the plastic packaging system. Therefore, this study aims to unpack and assess the role of stakeholders in improving the plastics recycling rate and circularity in the UK, using polyethylene terephthalate (PET) drinks bottles value chain as a case study. Via the theoretical lens of stakeholder theory the study identifies and groups the stakeholders in the PET drinks bottles value chain, and tries to make sense of, and analyse, their complex interactions via the use of the Complex Value Optimisation for Resource Recovery (CVORR) systems thinking approach. This integrated approach reveals, that even though external stakeholders (e.g. NGOs, trade associations) engage with internal stakeholders (e.g. suppliers, consumers, investors), and vice versa, at different levels and scales in promoting the circularity in the PET drink bottles value chain, there is a strong drive in incentivising the production and consumption processes. This is driven by the significant lobbying power of internal stakeholders operating upstream of the PET bottles value chain (i.e. producers and brand owners), that is supported by financial institutions, and which, strongly influences national and local government policies and decision-making processes. Meanwhile, the waste management processes are short-sighted, being unable to gain improved momentum and increase the PET bottles recycling rates. This dynamic conceals, and somewhat retains, the prevailing resistance in removing the infrastructural, regulatory and technological lock-ins. A collaboration between internal and external stakeholders is paramount to sustainably managing PET drinks bottles in the UK and achieving a transition to a sustainable circular plastics economy. Creating a level playing field and fostering a closer collaboration between all stakeholders involved in the system can aid the development of new value networks, and support new policy interventions that can improve circularity in the plastic packaging sector

Unpacking the complexity of the UK plastic packaging value chain: A stakeholder perspective

Copyright © 2021 The Author(s). The pace to achieving a sustainable plastics economy remains noticeably slow due to a lack of understanding on the role and importance of stakeholder dynamics in the plastic packaging system. This study aims to unpack and assess the role of stakeholders in improving plastics recycling rates and circularity in the UK, using polyethylene terephthalate (PET) drinks bottles value chain as a case study. Via the theoretical lens of stakeholder theory we identify and group the stakeholders involved in the PET drinks bottles value chain, and integrate this in the Complex Value Optimisation for Resource Recovery (CVORR) systems thinking approach to make sense of, and analyse, stakeholders complex interactions. Results highlight that even though, external stakeholders (e.g. NGOs, trade associations) engage on different levels and scales in promoting circularity in the PET bottles value chain, there is strong drive in incentivising production and consumption processes driven by the significant lobbying power of internal stakeholders operating upstream of the PET bottles value chain (i.e. producers and brand owners). This lobbying power, which arises from the well-established market of PET bottles in the UK, and its support by financial institutions, it strongly influences national and local government policies and decision-making processes. Meanwhile, the waste management processes are short-sighted, being unable to gain improved momentum and increasing the PET bottles recycling rates. This dynamic conceals, and somewhat retains, the prevailing resistance in removing the infrastructural, regulatory and technological lock-ins. The development of an interdisciplinary collaboration between internal and external stakeholders is paramount to sustainably managing PET drinks bottles in the UK and achieving a transition to a sustainable circular plastics economy. Fostering closer collaboration between all stakeholders involved in the system, can aid the development of new value networks and support new policy interventions that can improve circularity in the plastic packaging sector.Brunel University London as part of the Brunel Research Initiative & Enterprise Fund (BRIEF) award No.11683100, in the context of ‘Closing the Plastic Food Packaging Loop’ project, and generously supported by the Oxford Martin School, University of Oxford

An optimised saliva collection method to produce high-yield, high-quality RNA for translational research

Saliva represents an ideal matrix for diagnostic biomarker development as it is readily available and requires no invasive collection procedures. However, salivary RNA is labile and rapidly degrades. Previous attempts to isolate RNA from saliva have yielded poor quality and low concentrations. Here we compare collection and processing methods and propose an approach for future studies. The effects of RNA stabilisers, storage temperatures, length of storage and fasting windows were investigated on pooled saliva samples from healthy volunteers. Isolated RNA was assessed for concentration and quality. Bacterial growth was investigated through RT-PCR using bacterial and human primers. Optimal conditions were implemented and quality controlled in a clinical setting. The addition of RNAlater increased mean RNA yield from 4912 ng/μl to 15,473 ng and RNA Integrity Number (RIN) from 4.5 to 7.0. No significant changes to RNA yield were observed for storage at room temperature beyond 1 day or at -80 °C. Bacterial growth did not occur in samples stored at ambient temperature for up to a week. There was a trend towards higher RNA concentration when saliva was collected after overnight fasting but no effect on RIN. In the clinic, RNA yields of 6307 ng and RINs of 3.9 were achieved, improving on previous reports. The method we describe here is a robust, clinically feasible saliva collection method using preservative that gives high concentrations and improved RINs compared to saliva collected without preservative

HPV sensitizes OPSCC cells to cisplatin-induced apoptosis by inhibiting autophagy through E7-mediated degradation of AMBRA1

Oropharyngeal squamous cell carcinoma (OPSCC) is an increasing world health problem with a more favorable prognosis for patients with human papillomavirus (HPV)-positive tumors compared to those with HPV-negative OPSCC. How HPV confers a less aggressive phenotype, however, remains undefined. We demonstrated that HPV-positive OPSCC cells display reduced macroautophagy/autophagy activity, mediated by the ability of HPV-E7 to interact with AMBRA1, to compete with its binding to BECN1 and to trigger its calpain-dependent degradation. Moreover, we have shown that AMBRA1 downregulation and pharmacological inhibition of autophagy sensitized HPV-negative OPSCC cells to the cytotoxic effects of cisplatin. Importantly, semi-quantitative immunohistochemical analysis in primary OPSCCs confirmed that AMBRA1 expression is reduced in HPV-positive compared to HPV-negative tumors. Collectively, these data identify AMBRA1 as a key target of HPV to impair autophagy and propose the targeting of autophagy as a viable therapeutic strategy to improve treatment response of HPV-negative OPSCC. Abbreviations: AMBRA1: autophagy and beclin 1 regulator 1; CDDP: cisplatin (CDDP); FFPE: formalin-fixed paraffin-embedded (FFPE); HNC: head and neck cancers (HNC); HPV: human papillomavirus (HPV); hrHPV: high risk human papillomavirus (hrHPV); OCSCC: oral cavity squamous carcinomas (OCSSC); OPSCC: oropharyngeal squamous cell carcinoma (OPSCC); OS: overall survival (OS); qPCR: quantitative polymerase chain reaction; RB1: RB transcriptional corepressor 1; ROC: receiver operating characteristic curve (ROC)

A clinically interpretable convolutional neural network for the real time prediction of early squamous cell cancer of the esophagus; comparing diagnostic performance with a panel of expert European and Asian endoscopists

BACKGROUND AND AIMS: Intrapapillary capillary loops (IPCLs) are microvascular structures that correlate with invasion depth of early squamous cell neoplasia (ESCN) and allow accurate prediction of histology. Artificial intelligence may improve human recognition of IPCL patterns and prediction of histology to allow prompt access to endoscopic therapy of ESCN where appropriate METHODS: One hundred fifteen patients were recruited at 2 academic Taiwanese hospitals. ME-NBI videos of squamous mucosa were labeled as dysplastic or normal according to their histology and IPCL patterns classified by consensus of 3 experienced clinicians. A convolutional neural network (CNN) was trained to classify IPCLs, using 67742 high quality ME-NBI by 5-fold cross validation. Performance measures were calculated to give an average F1 score, accuracy, sensitivity, and specificity. A panel of 5 Asian and 4 European experts predicted the histology of a random selection of 158 images using the JES IPCL classification; accuracy, sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: Expert European Union (EU) and Asian endoscopists attained F1 scores (a measure of binary classification accuracy) of 97.0% and 98%, respectively. Sensitivity and accuracy of the EU and Asian clinicians were 97%, 98% and 96.9%, 97.1% respectively. The CNN average F1 score was 94%, sensitivity 93.7% and accuracy 91.7%. Our CNN operates at video rate and generates class activation maps that can be used to visually validate CNN predictions. CONCLUSIONS: We report a clinically interpretable CNN developed to predict histology based on IPCL patterns, in real-time, using the largest reported dataset of images for this purpose. Our CNN achieved diagnostic performance comparable to an expert panel of endoscopists

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