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Coenzyme Q serves a number of important roles in cells, including as an electron shuttle and as an antioxidant, but the exact roles and specific details of these processes have been difficult to investigate. The discovery of a selective inhibitor for Coq2, a critical enzyme in the biosynthesis of coenzyme Q, now primes the field for new investigations. Coenzyme Q (Q) is an electron transporter in the respiratory chain and a lipid-soluble antioxidant that decreases in humans with age. Here we show that 4-nitrobenzoate inhibited 4-hydroxybenzoate:polyprenyl transferase (Coq2) in a competitive manner and dose-dependently decreased Q in mammalian cells without accumulation of Q intermediates. As 4-nitrobenzoate neither interfered with mitochondrial respiration nor induced oxidative stress, it should prove a valuable tool for studies on both Q deficiency and Q supplementation.

In this paper, we report on the creation of a publicly available, common evaluation framework for image and video visual interestingness prediction. We propose a robust data set, the Interestingness10k, with 9831 images and more than 4 h of video, interestigness scores determined based on more than 1M pair-wise annotations of 800 trusted annotators, some pre-computed multi-modal descriptors, and 192 system output results as baselines. The data were validated extensively during the 2016–2017 MediaEval benchmark campaigns. We provide an in-depth analysis of the crucial components of visual interestingness prediction algorithms by reviewing the capabilities and the evolution of the MediaEval benchmark systems, as well as of prominent systems from the literature. We discuss overall trends, influence of the employed features and techniques, generalization capabilities and the reliability of results. We also discuss the possibility of going beyond state-of-the-art performance via an automatic, ad-hoc system fusion, and propose a deep MLP-based architecture that outperforms the current state-of-the-art systems by a large margin. Finally, we provide the most important lessons learned and insights gained.

Background: Prospectively and systematically collected real-world data on vedolizumab are scarce. We aimed to assess the long-term clinical effectiveness of vedolizumab in inflammatory bowel disease (IBD). Methods: This study was a prospective, observational, multicentre study. Overall, 286 patients with active IBD were included (Crohn’s disease, n = 169; ulcerative colitis, n = 117). The primary outcomes were clinical response at week 12 and clinical remission at week 52, based on the Harvey Bradshaw Index and the partial Mayo Clinic score. Secondary outcomes included clinical remission at week 12, clinical response at week 52, corticosteroid-free clinical remission at week 52, changes in biochemical measures, and health-related quality of life (HRQoL). Results: At baseline, 88% of the patients were exposed to anti-TNF and 41% of the patients with Crohn’s disease had undergone ⩾1 surgical resection. At week 12, clinical response was 27% and remission 47% in Crohn’s disease; corresponding figures in ulcerative colitis were 52% and 34%. Clinical response, remission and corticosteroid-free remission at week 52 were 22%, 41% and 40% in Crohn’s disease and 49%, 47% and 46% in ulcerative colitis, respectively. A statistically significant decrease in median faecal-calprotectin and C-reactive protein was observed at 12 and 52 weeks in patients with Crohn’s disease and ulcerative colitis. The HRQoL measures Short Health Scale and EuroQol 5-Dimensions improved in both Crohn’s disease and ulcerative colitis patients (p < 0.001). Clinical disease activity at baseline was inversely associated with clinical remission at week 52. Conclusion: Vedolizumab proved effective for the treatment of refractory IBD in clinical practice.

Background: Real-world data on long-term outcomes of vedolizumab (VDZ) are scarce. Objective: To assess long-term outcomes (up to 3 years) of VDZ in treating inflammatory bowel disease (IBD). Design: A nationwide, prospective multicentre extension of a Swedish observational study on VDZ assessing Effectiveness And Healthcare resource utilization in patients with IBD (SVEAH). Methods: After re-consent, data of patients with Crohn’s disease (CD) (n = 68) and ulcerative colitis (UC) (n = 46) treated with VDZ were prospectively recorded using an electronic case report form integrated with the Swedish IBD Register (SWIBREG). The primary outcome was clinical remission (defined as Harvey–Bradshaw Index ⩽4 in CD and partial Mayo score ⩽2 in UC) at 104 and 156 weeks in patients with a response and/or remission 12 weeks after starting VDZ. Secondary outcomes included health-related quality of life (HRQoL) and biochemical outcomes. Results: VDZ continuation rates were high at weeks 104 and 156, 88% and 84%, respectively, for CD and 87% and 78%, respectively, for UC. Of the 53 CD patients with a response/remission at 12 weeks, 40 (75%) patients were in remission at 104 weeks and 42 (79%) patients at 156 weeks. For UC, these numbers were 25/31 (81%) and 22/31 (71%), respectively. Improvements were seen in the Short Health Scale (p < 0.01 for each dimension; CD, n = 51; UC, n = 33) and the EuroQol 5-Dimensions, 5-levels index value (p < 0.01; CD, n = 39; UC, n = 30). Median plasma-C-reactive protein concentrations (mg/L) decreased from 5 at baseline to 4 in CD (p = 0.01, n = 53) and from 5 to 4 in UC (p = 0.03, n = 34) at 156 weeks. Correspondingly, median faecal-calprotectin (µg/g) decreased from 641 to 114 in CD patients (p < 0.01, n = 26) and from 387 to 37 in UC patients (p = 0.02, n = 17). Conclusion: VDZ demonstrated high continuation rates and was associated with improvements in clinical outcomes, HRQoL measures and inflammatory markers at 2 and 3 years after treatment initiation in this prospective national SVEAH extension study. Registration: ENCePP registration number: EUPAS22735.

BackgroundCyclosporine (CsA) or infliximab (IFX) are used as rescue therapies in steroid-refractory, severe attacks of ulcerative colitis (UC). There are no data comparing the efficacy of these two alternatives.MethodsOutcome of rescue therapy was retrospectively studied in two cohorts of patients hospitalized due to steroid-refractory moderate to severe UC: 1) a Swedish-Danish cohort (n = 49) treated with a single infusion of IFX; 2) an Austrian cohort (n = 43) treated with intravenous CsA. After successful rescue therapy, maintenance immunomodulator treatment was given to 27/33 (82%) of IFX patients and to 31/40 (78%) of CsA patients. Endpoints were colectomy-free survival at 3 and 12 months. Kaplan–Meier and Cox regression models were used to evaluate the association between treatment groups and colectomy.ResultsAt 15 days, colectomy-free survival in the IFX cohort was 36/49 (73%) versus 41/43 (95%) in the CsA cohort (P = 0.005), at 3 months 33/49 (67%) versus 40/43 (93%) (P = 0.002), and at 12 months 28/49 (57%) versus 33/43 (77%) (P = 0.034). After adjusting for potential confounding factors, Cox regression analysis yielded adjusted hazard ratios for risk of colectomy in IFX-treated patients of 11.2 (95% confidence interval [CI] 2.4–53.1, P = 0.002) at 3 months and of 3.0 (95% CI 1.1–8.2, P = 0.030) at 12 months in comparison with CsA-treated patients. There were no opportunistic infections or mortality.ConclusionsColectomy frequencies were significantly lower after rescue therapy with CsA than with a single infusion of IFX both at 3 and 12 months' follow-up. The superiority of CsA was seen principally during the first 15 days.

The amount of digital visual information available in the world today is enormous, and the rate at which more is continuously generated is simply unbelievable. For example YouTube gets 100 hours of new video every minute, and Facebook more than 350 million new photos every day. At best, this represents the creativity and knowledge of millions or even billions of people, made available to the entire world thanks to the Internet. The problem is of course: how do we find the \"needle\" that is relevant to us in this enormous \"haystack\"? Web search engines such as Google and Bing are decent solutions to find textual content, but finding relevant visual content is as yet an unsolved problem. The core issue is the semantic gap between the raw visual data processed by computers, and the abstract concepts and ideas humans use to communicate. This thesis studies one approach to this problem, namely using mid-level concepts to bridge the semantic gap. These semantic concepts are e.g. objects, locations, persons or events which are relatively concrete and thus comparatively easy to associate with the raw visual data. These can then be used to formulate more abstract queries, or used to index and further organise an image or video database. An overview of semantic concept detection using machine learning techniques is presented here, together with some applications. A central issue is keeping the computational speed and efficiency at a practical level for huge amounts of visual data, while still producing accurate and relevant results. To this end, this thesis studies several fast approximative versions of the popular Support Vector Machine (SVM) algorithm, and proposes some improvements to the fast Self-Organising Map (SOM) algorithm to improve its accuracy. Several large-scale real-world experimental applications are presented including image retrieval using social network tags, video search, indoor location recognition, and semantic visualisation of large image and video databases. The empirical evidence presented in this thesis shows that while the semantic gap problem is still not solved, the semantic concept approach produces concrete improvements to real-world applications. The improvements proposed and evaluated contribute to making the machine learning algorithms faster and thus more practically useful for processing huge amounts of visual data.