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Biologic agents and oral small molecules are the mainstays of inflammatory bowel disease [IBD] management. However, an unmet clinical need remains for additional agents with novel mechanism of action which are effective, safe, and disease-modifying; this is due to the substantial proportion of patients who do not respond, lose response, or develop intolerance to currently marketed products. microRNAs [miRNAs] that play a role in the modulation of signal transduction pathways implicated in the development of IBD hold the potential to be used as therapeutic targets. Recently, a novel first-in-class compound, obefazimod, originally conceived as a human immunodeficiency virus [HIV] infection drug, has shown great promise in phase II induction trials for ulcerative colitis [UC] patients. Findings from the maintenance phases of trials showed that long-term obefazimod treatment provides continued improvement in clinical symptoms of disease, with a substantial proportion of patients in clinical remission, and an overall good safety profile. With a novel mechanism of action, obefazimod is an orally available small molecule with anti-inflammatory properties through the specific and selective upregulation of miR-124 expression. The aim of this paper is to critically review the available evidence related to pharmacokinetics and pharmacodynamics, and to discuss the potential clinical implications of this first-in-class oral small molecule. [ABSTRACT FROM AUTHOR]

The 5GCHAMPION Europe–Korea collaborative project provides the first fully‐integrated and operational 5G prototype in 2018, in conjunction with the 2018 PyeongChang Winter Olympic Games. The corresponding technological advances comprise both an evolution and optimization of existing technological solutions and disruptive new features, which substantially outpace previous generations of technology. In this article, we focus on a subset of three disruptive technological solutions developed and experimented on by 5GCHAMPION during the 2018 PyeongChang Olympic Games: high speed communications, direct satellite‐user equipment communications, and post‐sale evolution of wireless equipment through software reconfiguration. Evaluating effectiveness and performing trials for these key 5G features permit us to learn about the actual maturity of 5G technology prototyping and the potential of new 5G services for vertical markets and end user enhanced experience two years before the launch of large‐scale 5G services. [ABSTRACT FROM AUTHOR]

Here are proposed two automatic detectors of Barau's petrel ( Pterodroma baraui ) and tropical shearwater ( Puffinus bailloni ) vocalisations in noisy audio recordings (1) trained with a low number of positive training instances, and (2) whose performances would be the highest possible. To do so, acoustic recordings were performed in one Barau's petrel colony between February and May 2014 (85 h) and in two tropical shearwater colonies in March and April (21 h). Manual and automatic methods of segmentation were combined. Manual segmentation allowed (1) to miss a very few number of positive segments and (2) to avoid introducing false positive instances. Automatic segmentation provided quickly a diversified set of negative instances. Manual labelling must be regarded as an investment, for current and future works. A random forest classifier and classical methods of acoustic signal characterisation (cepstral coefficients, spectral moments, etc.) were tested. Best models were able to discriminate each target species calls from other sounds of its colony with F1 scores of 88% (Barau's petrel, 1015 samples) and 85% (tropical shearwater, 1217 samples). The acoustic monitoring of nocturnal burrow-nesting seabirds based on (1) data collected by autonomous recording units in harsh, windy and wet environments and (2) automatic analysis tools is feasible. The size of our database was limited. Consequently further works will be necessary to study robustness of models on long time-series data. [ABSTRACT FROM AUTHOR]

Background: While the number of emergency transfer of dementia elderlies to acute care hospitals has being increasing, paramedics are facing challenges to perform their duties promptly due to difficult communication with patients. Objectives: To develop the standardized educational system for paramedics specializing to dementia elderlies with the use of artificial intelligence. Design: Single arm, pre‐post study. Participants are paramedics in a metropolitan area of Japan. Exposure: The two sessions of standardized multimodal communication training program which contains lecture and workshop were provided twice, 1 month apart. The training consists three parts. 1: Mechanism and clinical manifestations of dementia, 2: Communication skills: face‐to‐face interaction; mutual gaze, geometric characteristics and duration of eye contact, verbal communication with phonetic elements, and touch interactions. 3: Interaction strategies with dementia elderlies in emergency situation. All participants performed the rescue simulation training before the training and 1 month after the completion of the training, which were video‐recorded and analyzed by artificial intelligence (AI). The video was taken by wearable camera with eye‐trackers (1st person camera) and fixed camera (3rd person camera). The satisfaction survey of effectiveness on their work and the Jefferson Scale of Empathy for healthcare professionals were also taken. Main Outcomes: The primary outcome is the change of communication skills in physical position, distance, eye contact with patients, phonetic elements and touch. The system to analyze face‐to‐face communication; mutual gaze, geometric characteristics and duration of eye contact by AI was developed by our team. Other elements of communications were evaluated manually. Secondary outcome were satisfaction and the empathy to patients. Result: 31 paramedics enrolled the study. Prior to the training, 88% had experienced any difficult condition taking care of dementia patients. The video analysis showed significant change of the interactive communication in the direction of approach, eye contacts and duration of mutual gaze. 96.7% considered the training was effective for their daily work and 97.5% of participants recommended this training to a colleague. The score of empathy scale showed no significant change. Conclusion: The educational system for paramedics specializing to dementia with the use of artificial intelligence is effective for their work. [ABSTRACT FROM AUTHOR]

Summary: Background: Despite the prevalence of complex ventral hernias, there is little agreement on the most appropriate technique or prosthetic to repair these defects, especially in contaminated fields. Our objective was to determine French surgical practice patterns among academic surgeons in complex ventral hernia repair (CVHR) with regard to indications, most appropriate techniques, choice of prosthesis, and experience with complications. Methods: A survey consisting of 21 questions and 6 case-scenarios was e-mailed to French practicing academic surgeons performing CVHR, representing all French University Hospitals. Results: Forty over 54 surgeons (74%) responded to the survey, representing 29 French University Hospitals. Regarding the techniques used for CVHR, primary closure without reinforcement was provided in 31.6% of cases, primary closure using the component separation technique without mesh use in 43.7% of cases, mesh positioned as a bridge in 16.5% of cases, size reduction of the defect by using aponeurotomy incisions without mesh use in 8.2% of cases. Among the 40 respondents, 36 had experience with biologic mesh. There was a strong consensus among surveyed surgeons for not using synthetic mesh in contaminated or dirty fields (100%), but for using it in clean settings (100%). There was also a strong consensus between respondents for using biologic mesh in contaminated (82.5%) or infected (77.5%) fields and for not using it in clean setting (95%). In clean-contaminated surgery, there was no consensus for defining the optimal therapeutic strategy in CVHR. Infection was the most common complication reported after biologic mesh used (58%). The most commonly reported influences for the use of biologic grafts included literature, conferences and discussion with colleagues (85.0%), personal experience (45.0%) and cost (40.0%). Conclusions: Despite a lack of level I evidence, biologic meshes are being used by 90% of surveyed surgeons for CVHR. Importantly, there was a strong consensus for using them in contaminated or infected fields and for not using them in clean setting. To better guide surgeons, prospective, randomized trials should be undertaken to evaluate the short- and long-term outcomes associated with these materials in various surgical wound classifications. [Copyright &y& Elsevier]

It has been recently shown how multitemporal data may be used to improve the radiometric resolution of Synthetic Aperture Radar (SAR) images. Yet even the optimal speckle reduction schemes may result in blurred images in featured zones. Structure detection is a prior requirement but complicates further the numerical treatments. Alternatively, it is shown that satisfactory results can be obtained using a simple adaptation of Lee's sigma filter, as illustrated by comparison with theoretically based methods. The proposed methodology combines temporal filtering with a subwindowing approach and appears to be a good compromise that smoothes efficiently the speckle in relatively homogeneous areas while carefully preserving the sharpness of the edges. It may be of particular interest for those concerned with the variations in time of backscatter, especially in an agricultural environment. [ABSTRACT FROM AUTHOR]

As interest shifts to the development of models for predicting runoff quality, identification of the source areas for runoff becomes increasingly important. Active microwave remote sensing has a unique potential for surveying source areas at the catchment scale. Thresholdingof the back-scattering coefficient was initially proposed but provedunsatisfactory when applied to the ERS-1 SAR multitemporal images acquired during winter 1992 over Cote-Dan catchment, concomitantly withground observations. Difference images may, instead, allow the wettest part of the catchment to be identified provided that the two images encompass a marked hydrological event. A saturation plot could not however be obtained for each date; the use of a pair of images may befurther limited by the residual speckle (although carefully filteredusing the multitemporal information) and a slight inaccuracy in the SAR image calibration. It is therefore argued that considering the whole temporal back-scatter profile would be, at present, a safer approach to the remote sensing of saturated areas. The back-scatter temporal standard deviation appears, in this light, as a possible good indicator of the local saturation likelihood during the period of study: it is based on the fact that saturation develops on parts of the catchment that are wetter than the others through lateral recharge. Possible applications within the TOPMODEL framework are discussed. [ABSTRACT FROM AUTHOR]

Background: ABX464 (obefazimod) is a small molecule that upregulates a single microRNA (miR-124) in immune cells and reduces the production of various inflammatory cytokines and chemokines., Objective: We assessed the efficacy and safety of the standard of care (SoC) plus oral obefazimod (SoC plus ABX464), 50 mg once daily, versus the SoC plus placebo for prevention of severe acute respiratory syndrome in patients with coronavirus disease 2019 (COVID-19) who are at risk for severe disease., Methods: Eligible patients for this phase 2/3 double-blind, placebo-controlled miR-AGE study were randomized (2:1) into 2 groups: SoC-ABX464 (n = 339) and SoC-placebo (n = 170). The primary end point was the percentage of patients who did not require use of high-flow oxygen or invasive or noninvasive mechanical ventilation within 28 days. The safety analyses included patients who had been randomly assigned and had received at least 1 dose of the study treatment., Results: At the time of the interim analysis, obefazimod showed no benefit over placebo when added to the SoC; the study enrollment was stopped for futility. The evaluation of the safety of obefazimod in 505 patients showed significantly more treatment-emergent adverse events in the SoC-ABX464 group than in the SoC-placebo group ( P  = .007). Frequently reported AEs in the SoC-ABX464 group included headache (14.6%), abdominal pain (9.6%), diarrhea (9.0%), back pain (6.9%), and nausea (6.0%). No treatment-related changes in laboratory parameters were reported., Conclusion: For patients who have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and are at risk for severe COVID-19, obefazimod, 50 mg, provided no benefit over placebo when added to the SoC, although it did have a good safety profile (comparable to that reported in many therapeutic areas)., (© 2023 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.)

Advanced therapies have transformed the treatment of inflammatory bowel disease; however, many patients fail to respond, highlighting the need for therapies tailored to the underlying cell and molecular disease drivers. The first-in-class oral molecule ABX464 (obefazimod), which selectively upregulates miR-124, has demonstrated its ability to be a well-tolerated treatment with rapid and sustained efficacy in patients with ulcerative colitis (UC). Here, we provide evidence that ABX464 affects the immune system in vitro , in the murine model of inflammatory bowel disease, and in patients with UC. In vitro , ABX464 treatment upregulated miR-124 and led to decreases in proinflammatory cytokines including interleukin (IL) 17 and IL6, and in the chemokine CCL2. Consistently, miR-124 expression was upregulated in the rectal biopsies and blood samples of patients with UC, and a parallel reduction in Th17 cells and IL17a levels was observed in serum samples. In a mouse model of induced intestinal inflammation with dextran sulfate sodium, ABX464 reversed the increases in multiple proinflammatory cytokines in the colon and the upregulation of IL17a secretion in the mesenteric lymph nodes. By upregulating miR-124, ABX464 acts as "a physiological brake" of inflammation, which may explain the efficacy of ABX464 with a favorable tolerability and safety profile in patients with UC., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background and Aims: Low anti-HBc serum levels at the time of therapy cessation were linked to a higher relapse risk in predominantly HBeAg-positive cohorts. We investigated the association of anti-HBc levels with relapse in HBeAg-negative patients., Methods: Serum levels of anti-HBc, HBsAg and HBcrAg were determined in 136 HBeAg-negative patients, participating in a vaccination trial (ABX-203, NCT02249988), before treatment cessation or vaccination. Importantly, vaccination showed no impact on relapse. The correlation between the biomarkers and their predictive value for relapse (HBV DNA >2000 IU/ml ± ALT >2xULN) was investigated., Results: After therapy cessation 50% (N = 68) of patients relapsed. Median anti-HBc prior to treatment stop was significantly higher among relapsers compared to off-treatment responders (520 IU/ml vs. 330 IU/mL, p = .0098). The optimal anti-HBc cut-off to predict relapse was 325 IU/ml according to the Youden-Index. About 35% of patients with anti-HBc level < 325 IU/ml versus 60% of those with values ≥325 IU/mL relapsed (p = .0103; sensitivity 50%, specificity 75%). Combining the optimal cut-offs of HBsAg (>3008 IU/mL) or HBcrAg (≥1790 U/ml) with anti-HBc increased the proportion of patients with relapse to 80% (p < .0001) and 74% (p = .0006), respectively., Conclusion: In contrast to predominantly HBeAg-positive cohorts, in our cohort of HBeAg-negative patients lower anti-HBc levels are associated with a significantly lower relapse risk after nucleos(t)ide analogue cessation. The vast majority of included patients were either genotype B or C and the applicability to other genotypes has to be further evaluated. However, anti-HBc level as an indicator of the host response might be prospectively further explored for prediction models., (© 2022 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: ABX464 (obefazimod) is a small molecule that selectively upregulates miR-124 in immune cells. We aimed to assess ABX464 as a treatment for patients with moderate-to-severe, active ulcerative colitis., Methods: In this phase 2b, double-blind, randomised, placebo-controlled induction trial, patients were recruited from 95 centres (hospitals and health-care centres) in 16 countries. Eligible patients were aged 18-75 years, with a diagnosis of moderate-to-severe, active ulcerative colitis and a modified Mayo Score (MMS) of 5 points or higher, and a documented non-response or intolerance to previous treatment. Enrolled patients were randomly assigned (1:1:1:1) via an interactive voice and web response system to receive once daily oral ABX464 100 mg, ABX464 50 mg, ABX464 25 mg, or matched placebo. Randomisation was stratified according to study site (US vs non-US) and to whether the patient had previous exposure to second-line treatment with biologics or JAK inhibitors. The primary endpoint was the change from baseline in MMS at week 8. The primary efficacy analysis was done in the full analysis set (FAS), defined as all randomly assigned patients who received at least one dose of study treatment and had baseline data for at least one efficacy variable, and was analysed according to the principles of intention-to-treat. Safety analyses included patients who had been randomly assigned and who received at least one dose of study treatment. The 96 week open-label extension is ongoing. This study is registered with ClinicalTrials.gov, NCT04023396., Findings: Between Aug 13, 2019, and April 16, 2021, 254 patients were randomly allocated to ABX464 100 mg (n=64), ABX464 50 mg (n=63), ABX464 25 mg (n=63), or placebo (n=64). Two patients, both in the ABX464 25 mg group, were excluded from the FAS. In the FAS at week 8, the least squares mean (LSM) change from baseline in MMS was -2·9 (95% CI -3·4 to -2·5) for the ABX464 100 mg group, -3·2 (-3·7 to -2·7) for the ABX464 50 mg group, -3·1 (-3·6 to -2·6) for the ABX464 25 mg group, and -1·9 (-2·4 to -1·5) for placebo group; the magnitude of the difference in MMS from baseline was significantly greater in all three ABX464 groups compared with placebo (p=0·0039 for ABX464 100 mg vs placebo, p=0·0003 for ABX464 50 mg vs placebo, and p=0·0010 for ABX464 25 mg vs placebo). The most frequently reported adverse event was headache, which was reported for 27 (42%) of 64 patients in the ABX464 100 mg group, 19 (30%) of 63 in the 50 mg group, 13 (21%) of 62 in the 25 mg group, and five (8%) of 64 in the placebo group. Severe (grade 3) headache was reported for three (5%) patients in the ABX464 group 100 mg group, two (3%) in the ABX464 50 mg group, one (2%) in the ABX464 25 mg group, and none in the placebo group. The only serious adverse event reported for two or more patients in any group was ulcerative colitis (one in each of the ABX464 100 mg and 50 mg groups, and three [5%] in the placebo group)., Interpretation: All doses of ABX464 significantly improved moderate-to-severe, active ulcerative colitis compared with placebo, as measured by changes in MMS from baseline to week 8. A phase 3 clinical programme is ongoing., Funding: Abivax., Competing Interests: Declaration of interests All authors have received support from Abivax for the study with regard to trial administration, provision of study materials, and medical writing support. SV, BS, and WJS have received consultancy fees from Abivax. JN, JS, DS, SB, HJE, J-MS, and PG are employees of Abivax. J-MS is former Abivax Chief Medical Officer (September, 2015, to June, 2021) and has received payments for lectures, expert testimony, and as a drug safety monitoring board member for Abivax. PG, HJE, and J-MS own Abivax stock. SV has received grants or consulting fees from AbbVie, AbolerIS Pharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, CVasThera, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, GSK, Hospira, Imidomics, Janssen, Johnson & Johnson, Eli Lilly, Materia Prima, MiroBio, Morphic, MrMHealth, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillots Pharma, and Zealand Pharma; and lecture or writing fees from AbbVie, Galapagos, Genentech-Roche, Janssen, Pfizer, and Takeda. BS has received grants or personal fees from Abbvie/Alimenti/Amgen, Arena Pharmaceuticals, AstraZeneca, Bausch Health (Salix Pharmaceuticals), Boehringer lngelheim, Boston Pharmaceuticals, Bristol Meyer Squibb, Celgene, Celltrion, Clostrabio, Equillium, Galapagos, Genentech (Roche), Gilead Sciences, GlaxoSmithKline, Gossamer Bio, lmmunic, Index Pharmaceuticals, lnotrem, Janssen, Eli Lilly, Morphic Therapeutics, Novartis, Oppilan Pharma (acquired by Ventyx), Otuska, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonists Therapeutics, Seres Therapeutics, Shire Pharmaceuticals, Surrozen, Takeda, Theravance Biopharma, Teva, UCB, Vedanta Biosciences, Ventyx Biosciences, Vivelix Pharmaceuticals, Ironwood Pharmaceuticals, OSE lmmunotherapeutics, Redhill Biopharma, Target RWE, Bacainn Therapeutics, Capella Bioscience, Palatin Technologies, Rheos Medicines, USWM Enterprises, Viela Bio, Artugen Therapeutics, Calibr, Entera, Evommune, Innovation Pharmaceuticals, Kaleido, Merck, MRM Health, Q32 Bio, Sun Pharma, and TLL Pharmaceutical; has received writing support from Arena Pharmaceuticals, Bristol Meyer Squibb, Celgene, Janssen, Eli Lilly, Pfizer, and Takeda; and owns stock options from Ventyx Biosciences and Vivante Health. WJS has received grants or personal fees from Alfasigma, Alimentiv (previously Robarts Clinical Trials), Alivio Therapeutics, Allakos, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, AstraZeneca, Atlantic Pharmaceuticals, Bausch Health (Salix Pharmaceuticals), BeiGene, Bellatrix Pharmaceuticals, Boehringer lngelheim, Boston Pharmaceuticals, Bristol Meyer Squibb, Celgene (Receptos), Celltrion, Celularity, Clostrabio, Codexis, Cosmo Pharmaceuticals, Escalier Biosciences, Equillium, Forbion, Galapagos, Genentech (Roche), Gilead Sciences, GSK, Glenmark Pharmaceuticals, Gossamer Bio, lmmunic (Vital Therapies), Index Pharmaceuticals, lnotrem, Intact Therapeutics, Iota Biosciences, Janssen, Kiniksa Pharmaceuticals, Kyvema Therapeutics, Landos Biopharma, Eli Lilly, Morphic Therapeutics, Novartis, Ono Pharmaceuticals, Oppilan Pharma (acquired by Ventyx Biosciences), Otsuka, Pandion Therapeutics, Pfizer, PharmOlam, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonists Therapeutics, Provention Bio, PTM Therapeutics, Quell Therapeutics, Reistone Biopharma, Series Therapeutics, Shanghai Pharma Biotherapeutics, Shire Pharmaceuticals, Shoreline Biosciences, Sterna Biologicals, Sublimity Therapeutics, Surrozen, Takeda, Theravance Biopharma, Thetis Pharmaceuticals, Tillotts Pharma, UCB, Vedanda Biosciences, Ventix Biosciences, Vimalan Biosciences, Vivelix Pharmaceuticals, Vividion Therapeutics, Vivreon Gastrosciences, Xencor, and Zealand Pharmaceuticals; and owns stock options from Allakos, BeiGene, Gossamer Bio, Oppilan Pharma, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonists Therapeutics, Shoreline Biosciences (also an employee), Ventix Biosciences, Vimalan Biosciences, and Vivreon Gastrosciences. SD has received consulting fees from Abbvie, Allergan, Alimentiv, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Mondipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity, Therapeutics, Takeda, TiGenix, UCB, and Vifor., (Copyright © 2022 Elsevier Ltd. All rights reserved.)