Recovering Variations in Facial Albedo from Low Resolution Images

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Prospective, randomised, parallel-group, open-label study to evaluate the effectiveness and safety of IMU-838, in combination with oseltamivir, in adults with COVID-19 : the IONIC trial protocol

Background: Globally, there is a scarcity of effective treatments for SARS-CoV-2 infections (causing COVID-19). Repurposing existing medications may offer the best hope for treating patients with COVID-19 to curb the pandemic. IMU-838 is a dihydroorotate dehydrogenase inhibitor, which is an effective mechanism for antiviral effects against respiratory viruses. When used synergistically with oseltamivir, therapeutic effects have been observed against influenza and SARS-CoV-2 in rodents. The IMU-838 and Oseltamivir in the Treatment of COVID-19 (IONIC) trial is a randomised controlled trial that will investigate whether time to clinical improvement in patients with COVID-19 is improved following a 14-day course of IMU-838+oseltamivir versus oseltamivir alone. Methods: IONIC trial is an open-label study in which participants will be randomised 1:1 in two parallel arms: the intervention arm (IMU-838+oseltamivir) and the control arm (oseltamivir only). The primary outcome is time to clinical improvement; defined as the time from randomisation to a two-point improvement on WHO ordinal scale; discharge from hospital, or death (whichever occurs first). The study is sponsored by the University Hospitals Coventry and Warwickshire NHS Trust and funded by LifeArc. Discussion: The IONIC protocol describes an overarching trial design to provide reliable evidence on the effectiveness of IMU-838 (vidofludimus calcium) when delivered in combination with an antiviral therapy (oseltamivir) (IONIC intervention) for confirmed or suspected COVID-19 infection in adult patients receiving usual standard of care. Ethics and dissemination: This study has been independently reviewed and approved by Wales Research Ethics Committee. In addition, required regulatory approvals were received from Medicines and Healthcare products Regulatory Agency. Trial registration number: EudraCT 2020-001805-21, ISRCTN53038326, NCT04516915

Exploring relationships between micro-macroenvironment and colon cancer

Colorectal cancer (CRC) is a multifactorial disease characterized by complex interplay between genetic and epigenetic alterations occurring in epithelial cells, surrounding microenvironmental stroma and macroenvironmental factors, including obesity and metabolic syndrome. The bidirectional cross-talk between cancer cells and stromal cells within the tumour microenvironment has been proposed as active contributor to carcinogenesis, cancer progression and metastasis. The main aims of this study are: (1) to analyse the differential expression profile of peritumour adipose tissue and distal adipose tissue; (2) to evaluate cross-talk between cancer cells and adipocytes; (3) to investigate associations between BMI categories, metabolic syndrome and CRC molecular profile. Elucidating tumour micro-macroenvironment phenotype can lead to understanding molecular mechanisms underlying CRC and could lead to new therapies

The effect of the 2-week wait referral system on the detection of and mortality from colorectal cancer : protocol of a systematic review and meta-analysis

Background Colorectal cancer represents the fourth most common cancer in England and Wales; survival is high for early stage disease but declines sharply with advanced stage. UK figures suggest that cancer survival rates are lower than those of other Western European countries. Current 5-year survival is around 50 %. A rapid access strategy was introduced through the Department of Health in 2000. This 2-week wait (TWW) referral pathway was devised to streamline referral for suspected cancer, allow diagnosis at an earlier stage, reduce cancer survival inequality and reduce cancer-related mortality. However, only around half of patients with colorectal cancer have symptoms that fit the TWW criteria plus there is a fourfold difference in referral rates across England and Wales. High-quality evidence of TWW outcome measures for colorectal cancer is lacking. This systematic review will collate and evaluate the latest evidence on colorectal cancer detection rate, stage at diagnosis and mortality. Methods English-language publications from 2000 reporting outcomes on the TWW referral system for suspected colorectal cancer will be eligible for inclusion. Cochrane, EMBASE, MEDLINE via PubMed, NHS Evidence, Trip and the British Library Catalogue databases will be searched. Two paired reviewers will independently screen all titles/abstracts and full text for eligibility, then extract data and assess for bias using standardised formats. They will hand review reference lists of eligible articles. Disagreement will be resolved via third party adjudication. Summary effect measures for post-referral diagnosis and mortality rates will be calculated and expressed as relative risk, hazard rate ratio or risk difference with corresponding 95 % confidence intervals. Where possible summary effect measures will be pooled, heterogeneity and its extent for pooled estimates will be assessed via visual inspection of forest plots and explored via sub-group analysis. Discussion In this systematic review, we aim to summarise the relevant evidence on cancer detection rate, cancer stage at diagnosis and disease-related mortality rates for patients with suspected colorectal cancer investigated through the TWW referral system in England and Wales. We will highlight gaps in the evidence and provide a better understanding of whether it is meeting its desired effect

Role of tissue microenvironment resident adipocytes in colon cancer

Colorectal cancer (CRC) is a multifactorial disease characterized by several genetic and epigenetic alterations occurring in epithelial cells. It is increasingly recognized that tumour progression is also regulated by tumour microenvironment (TME). The bidirectional cross-talk between tumour resident adipocytes and cancer cells within TME has been proposed as active contributor to carcinogenesis. Tumour resident adipocytes exhibit an activated phenotype characterized by increased secretion of pro-tumorigenic factors (angiogenic/inflammatory/immune) which contribute to cancer cell proliferation, invasion, neoangiogenesis, evasion of immune surveillance and therapy resistance. Furthermore, adipocytes represent a fuel rich source for increasing energy demand of rapidly proliferating tumour cells. Interestingly, a relationship between obesity and molecular variants in CRC has recently been identified. Whether adipose tissue promotes cancer progression in subsets of molecular phenotypes or whether local tissue adipocytes are involved in inactivation of tumour suppressor genes and/or activation of oncogenes still needs to be explored. This editorial highlights the major findings related to cross-talk between adipocytes and colon cancer cells and how local paracrine interactions may promote cancer progression. Furthermore, we provide future strategies in studying colonic TME which could provide insights in bidirectional cross-talk mechanisms between adipocytes and colonic epithelial cells. This could enable to decipher critical signalling pathways of both early colonic carcinogenesis and cancer progression

The effect of application icon style design factors on the download intention of users

With the heavier reliance of the current generation to the digital world, mobile applications have become an integral part of smartphone users. The mobile application industry has been growing significantly and competition among applications and application developers have been fierce. All applications available in iOS App Store and Google Play Store are listed as icons. These icons serve as the initial visual representation of a mobile application and provide consumers a quick and intuitive representation of an application. It is the first and most powerful way to engage users in highly competitive app stores, thus, an effective mobile application icon design is essential for the success of an application to be downloaded. As icon style is identified as an element considered in the design of an icon, this study determines if the icon style design factors can help in the increased intention of users to download an application. By integrating a factor known to be affected by the use of an icon style, as well as affect the purchase (i.e. download) intention of users, this study was able to explore a reason for the effect of icon style design factors to download intention. This study also defined a set of icon style design guidelines that considered the significance of the icon style design factors. Emotion is the factor identified to have an effect on user download intention. It is also a factor that is determined by the use of icon style. Furthermore, emotion has been known to have an influence in the relationship of design and purchase/download intentions. With this thought, this study hypothesized emotion experienced by users to mediate the effect of the icon style design factors to their intention to download an application. Age has also been a common variable in icon style literatures wherein preferences, performances, etc. are said to be influenced by age of the user. Thus, this study hypothesized that age moderates the effect of the icon style design factors to the download intention of users. In order to prove the proposed hypotheses and suitably achieve the objectives of the study, the instrument of the main experiment was designed to simulate the scenario of browsing through an application store showing different redesigns of the same icon applying different levels of the icon style design factors. The respondents were surveyed regarding their chosen design, felt emotions, and download intention. After sufficient data was collected, it was analyzed using SEM analysis. From the results of the experimentation and analysis, the three icon style design factors considered were found to be significant in the download intention of users. Particularly, users are more inclined to download the icon design with subtle to no texture, subtle to no shadow, and bright or no highlights. Based on the post-interviews, the users would mainly base their response and selection from their perceived visual aesthetic of the icon. It was also determined from the analysis that emotion partially mediated the effect of the icon style design factors to download intention. With this, emotion can be used to explain the relationship between the icon style design factors to download intention. Based on the post-interview, the respondents said that the app icons with no texture and no shadow effects trigger their positive emotions more since they are more visually pleasing, thus, making them lean more to download the application with those icons. Lastly, no moderation effect was found from age. Increased exposure and familiarity of individuals of all ages in the digital world have led to potentially minimal difference in the effect of age in the relationship of the icon style design factors to emotion and download intention in this study

Acute Severe Colitis: Infliximab and/or Cyclosporine?

Acute severe ulcerative colitis is a serious condition that requires early hospitalization, with intensive monitoring and treatment. Despite the recent progress in the medical approach of Inflammatory Bowel Diseases acute severe ulcerative colitis remains a clinical challenge, with a mortality rate of nearly 1%. As of today, I.V. corticosteroids remain the 1st-line therapy for this complication. For non-responders (up to one-third of patients) possible options are surgery - whose timing is a critical point in the overall management of the disease - or rescue therapy with 2nd- line agents such as Cyclosporine and Infliximab. Here we will review the published studies dealing with the use of these medications in acute severe ulcerative colitis