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Background: People with single-sided deafness (SSD) or asymmetric hearing loss (AHL) have particular difficulty understanding speech in noisy listening situations and in sound localization. The objective of this multicenter study is to evaluate the effect of a cochlear implant (CI) in adults with single-sided deafness (SSD) or asymmetric hearing loss (AHL), particularly regarding sound localization and speech intelligibility with additional interest in electric-acoustic pitch matching. Methods: A prospective longitudinal study at 7 European tertiary referral centers was conducted including 19 SSD and 16 AHL subjects undergoing cochlear implantation. Sound localization accuracy was investigated in terms of root mean square error and signed bias before and after implantation. Speech recognition in quiet and speech reception thresholds in noise for several spatial configurations were assessed preoperatively and at several post-activation time points. Pitch perception with CI was tracked using pitch matching. Data up to 12 months post activation were collected. Results: In both SSD and AHL subjects, CI significantly improved sound localization for sound sources on the implant side, and thus overall sound localization. Speech recognition in quiet with the implant ear improved significantly. In noise, a significant head shadow effect was found for SSD subjects only. However, the evaluation of AHL subjects was limited by the small sample size. No uniform development of pitch perception with the implant ear was observed. Conclusion: The benefits shown in this study confirm and expand the existing body of evidence for the effectiveness of CI in SSD and AHL. Particularly, improved localization was shown to result from increased localization accuracy on the implant side.

Abstract Non-invasive assessment of the electrical activation pattern can significantly contribute to the diagnosis and treatment of cardiac arrhythmias, due to faster and safer diagnosis, improved surgical planning and easier follow-up. One promising path is to measure the mechanical contraction via echocardiography and utilize this as an indirect way of measuring the original activation pattern. To solve this demanding inversion task, we make use of physics-informed neural networks, an upcoming methodology to solve forward and inverse physical problems governed by partial differential equations. In this study, synthetic data sets were created, consisting of 2D excitation waves coupled to an isotropic and linearly deforming elastic medium. We show that for both focal and spiral patterns, the underlying excitation waves can be reconstructed accurately. We test the robustness of the method against Gaussian noise, reduced spatial resolution and projected tri-planar data. In situations where the data quality is heavily reduced, we show how to improve the reconstruction by additional regularization on the wave speed. Our findings suggest that physics-informed neural networks hold the potential to solve sparse and noisy bio-mechanical inversion problems and may offer a pathway to non-invasive assessment of certain cardiac arrhythmias.

Most pharmacological treatments for depression target monoamine transporters and about 50 % of treated patients attain symptomatic remission. Once remission is attained, it is hard to distinguish the changes on brain monoaminergic transmission induced by the antidepressants, from those associated to remission per se. In this study, we aimed at studying the brain of spontaneously remitted rats from repeated social defeat (RSD)-induced depression in terms of dopamine D2/D3 receptor and serotonin transporter (SERT) availability, showing absence of depressive symptoms 2 weeks after RSD. We combined behavioral tests and positron emission tomography (PET) with [11C]raclopride and [11C]DASB to explore the changes in dopamine D2/D3 receptor and serotonin transporter (SERT) availability, respectively. Male rats submitted to RSD showed increased peripheral corticosterone levels, decreased body weight and anhedonia, as measured with the sucrose preference test, 1 day after RSD, confirming depressive-like symptoms. These depressive-like symptoms were no longer present 2 weeks after RSD. Rats that recovered from depressive-like symptoms showed decreased D2/D3 receptor binding in the caudate putamen and increased SERT availability in the brainstem, insular cortex, midbrain and thalamus, compared to control non-stressed animals. Our study shows that remission of depressive-like symptoms does not just “normalize” monoaminergic transmission, as changes in dopaminergic and serotonergic neurotransmission linger in several brain regions even after depressive-like symptoms have already resolved. These results provide new insights into the brain changes associated to remission in the RSD-induced depression model in rats.

BackgroundFatigue is a common and debilitating side effect of chronic diseases, significantly impacting patients’ quality of life. While physical exercise and psychological treatments have been shown to reduce fatigue, patients often struggle with adherence to these interventions in clinical practice. Game-based eHealth interventions are believed to address adherence issues by making the intervention more accessible and engaging. ObjectiveThis study aims to compile empirical evidence on game-based eHealth interventions for fatigue in individuals with chronic diseases and to evaluate their effectiveness in alleviating fatigue. MethodsA comprehensive literature search was performed across Embase, MEDLINE ALL, PsycINFO, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and Google Scholar in August 2021. Study characteristics and outcomes from the included studies were extracted, and a random-effects meta-analysis was conducted. Sensitivity and subgroup analyses were performed to identify sources of heterogeneity. ResultsOf 1742 studies identified, 17 were included in the meta-analysis. These studies covered 5 different chronic diseases: multiple sclerosis (n=10), cancer (n=3), renal disease (n=2), stroke (n=1), and Parkinson disease (n=1). All but 1 study used exergaming interventions. The meta-analysis revealed a significant moderate effect size in reducing fatigue favoring the experimental interventions (standardized mean difference [SMD] –0.65, 95% CI –1.09 to –0.21, P=.003) compared with control conditions consisting of conventional care and no care. However, heterogeneity was high (I2=85.87%). Subgroup analyses were conducted for the 2 most prevalent diseases. The effect size for the multiple sclerosis subgroup showed a trend in favor of eHealth interventions (SMD –0.47, 95% CI –0.95 to 0.01, P=.05, I2=63.10%), but was not significant for the cancer group (SMD 0.61, 95% CI –0.36 to 1.58, P=.22). Balance exercises appeared particularly effective in reducing fatigue (SMD –1.19, 95% CI –1.95 to –0.42, P=.002). ConclusionsGame-based eHealth interventions appear effective in reducing fatigue in individuals with chronic diseases. Further research is needed to reinforce these findings and explore their impact on specific diseases. Additionally, there is a lack of investigation into interventions beyond exergaming within the field of game-based learning.

Abstract Background As pediatricians play a vital role in pediatric palliative care (PPC), understanding their perspectives toward PPC is important. PPC is established for a long time in Belgium, but has a shorter tradition in China, although it is growing in the last decade. Sampling and comparing the perspectives of these pediatricians could be insightful for both countries. Therefore, we sampled and compared perspectives of pediatricians in China and Belgium toward PPC, and explored factors influencing their perspectives. Methods We conducted a cross-sectional online survey using the validated Pediatric Palliative Care Attitude Scale (PPCAS). Over a five-month period, we recruited pediatricians practicing in China (C) and Flanders (F), Belgium. Convenience sampling and snowballing were used. We analyzed data with descriptive statistics, and evaluated group differences with univariate, multivariate and correlation tests. Results 440 complete surveys were analyzed (F: 115; C: 325). Pediatricians in both regions had limited PPC experience (F: 2.92 ± 0.94; C: 2.76 ± 0.92). Compared to Flemish pediatricians, Chinese pediatricians perceived receiving less unit support (F: 3.42 ± 0.86; C: 2.80 ± 0.89); perceived PPC less important (F: 4.70 ± 0.79; C: 4.18 ± 0.94); and faced more personal obstacles while practicing PPC (F: 3.50 ± 0.76; C: 2.25 ± 0.58). Also, select socio-demographic characteristics (e.g., experiences caring for children with life-threatening condition and providing PPC) influenced pediatricians’ perspectives. Correlational analyses revealed that pediatricians’ PPC experiences significantly correlated with perceived unit support (ρF = 0.454; ρC=0.661). Conclusions Chinese pediatricians faced more barriers in practicing PPC. Expanding PPC experiences can influence pediatricians’ perspectives positively, which may be beneficial for the child and their family.

BackgroundHTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is an incapacitating neuroinflammatory disorder for which no disease-modifying therapy is available, but corticosteroids provide some clinical benefit. Although HAM/TSP pathogenesis is not fully elucidated, older age, female sex and higher proviral load are established risk factors. We investigated systemic cytokines and a novel chronic inflammatory marker, GlycA, as possible biomarkers of immunopathogenesis and therapeutic response in HAM/TSP, and examined their interaction with established risk factors.Patients and methodsWe recruited 110 People living with HTLV-1 (PLHTLV-1, 67 asymptomatic individuals and 43 HAM/TSP patients) with a total of 946 person-years of clinical follow-up. Plasma cytokine levels (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, TNF) and GlycA were quantified by Cytometric Bead Array and 1NMR, respectively. Cytokine signaling and prednisolone response were validated in an independent cohort by nCounter digital transcriptomics. We used multivariable regression, machine learning algorithms and Bayesian network learning for biomarker identification.ResultsWe found that systemic IL-6 was positively correlated with both age (r = 0.50, p

Objectives To investigate if patients with early rheumatoid arthritis responding insufficiently to initial methotrexate (MTX) and bridging glucocorticoids (GCs) could benefit from early but temporary etanercept introduction as a second remission-induction attempt.Methods CareRA2020 (NCT03649061) was a 2-year, open-label, multicentre, pragmatic randomised controlled trial. Treatment-naïve patients started MTX and GC bridging (COBRA-Slim: CS). Within a time window from week (W) 8 until W32, early insufficient responders (28-joint Disease Activity Score – C-reactive Protein (DAS28-CRP) >3.2 between W8 and W32 or ≥2.6 at W32) were randomised to a Standard-CS strategy (adding leflunomide first) or Bio-induction-CS strategy (adding etanercept for 24 weeks). Additional treatment adaptations followed the treat-to-target principle. Longitudinal disease activity (DAS28-CRP) over 104 weeks (primary outcome), achievement of DAS28-CRP

Introduction Hepatic artery complications (HACs), such as a thrombosis or stenosis, are serious causes of morbidity and mortality after paediatric liver transplantation (LT). This study will investigate the incidence, current management practices and outcomes in paediatric patients with HAC after LT, including early and late complications.Methods and analysis The HEPatic Artery stenosis and Thrombosis after liver transplantation In Children (HEPATIC) Registry is an international, retrospective, multicentre, observational study. Any paediatric patient diagnosed with HAC and treated for HAC (at age

Abstract In recent years, the use of light to selectively and precisely activate drugs has been developed along the fundamental concepts of photopharmacology. One of the key methods in this field relies on transiently silencing the drug activity with photocleavable protecting groups (PPGs). To effectively utilize light‐activated drugs in future medical applications, physicians will require a reliable method to assess whether light penetrates deep enough into the tissues to activate the photoresponsive theragnostic agents. Here, we describe the development and evaluation of magnetic resonance (MR) imaging agents that allow for the detection of light penetration and drug activation in the tissues using non‐invasive whole‐body magnetic resonance imaging (MRI) and chemical exchange saturation transfer (CEST)‐MRI modalities. The approach relies on the use of PPG‐protected MR contrast agents, which upon irradiation with light change their imaging signal. A Gadolinium(III)‐based MRI contrast agent is presented that undergoes a significant change in relaxivity (25%) upon uncaging, providing a reliable indicator of light‐induced cargo release. Additionally, we introduce the first light‐responsive CEST‐MRI imaging agent, enabling positive signal enhancement (off‐to‐on) upon light activation, offering a novel approach to visualize the activation of photoactive agents in living tissues. This research provides a proof‐of‐principle for the non‐invasive, whole‐body imaging of light penetration and drug activation with high temporal resolution characteristic of MR methods.

Abstract Purpose To examine implications of the COVID-19 pandemic on eating disorder (ED) features and psychopathology in female adolescents with anorexia nervosa (AN). Method In total 79 females with first-onset AN (aged 12–22 years) were included and were followed up across a period of 1 year. We assessed AN participants recruited pre-pandemic (n = 49) to those recruited peri-pandemic (n = 30). Pre- (n = 37) and peri-pandemic (n = 38) age-, and education-matched typically developing (TD) girls (n = 75) were used as a reference cohort. ED features and psychopathology were assessed at baseline. After 1 year of follow-up the association between pandemic timing and clinical course was assessed. Analyses of covariance were used to examine differences in ED features and psychopathology. Results Peri-pandemic AN participants experienced less ED symptoms at baseline compared to pre-pandemic AN participants. In particular, they were less dissatisfied with their body shape, and experienced less interpersonal insecurity. In addition, the peri-pandemic AN group met fewer DSM-IV criteria for comorbid disorders, especially anxiety disorders. In contrast, peri-pandemic AN participants had a smaller BMI increase over time. In TD girls, there were no differences at baseline in ED features and psychopathology between the pre- and peri-pandemic group. Conclusion Overall, peri-pandemic AN participants were less severely ill, compared to pre-pandemic AN participants, which may be explained by less social pressure and peer contact, and a more protective parenting style during the pandemic. Conversely, peri-pandemic AN participants had a less favorable clinical course, which may be explained by reduced access to health care facilities during the pandemic. Level of evidence Level III: Evidence obtained from well-designed cohort or case–control analytic studies.

Abstract Introduction The synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare condition. Its treatment remains a challenge for clinicians, and often yields mixed results. Case We report the case of a 51-year-old Caucasian woman who presented with SAPHO syndrome with mainly axial involvement. She had been treated with sulfasalazine and anti-inflammatory drugs for many years without any success. A few weeks after starting treatment with tofacitinib, both clinical and biological parameters dramatically improved. Imaging also showed considerable regression of the vertebral and pelvic lesions. However, tofacitinib had to be discontinued due to the occurrence of pulmonary embolism. Consequently, recurrence of bone pain and biologic inflammation was rapidly observed. Conclusions Anti-JAKs are an interesting treatment option in the management of SAPHO syndrome that need further clinical trials and assessment for validating response.

Abstract Background Many rare genetic neurodevelopmental disorders (RGNDs) are characterized by intellectual disability (ID), severe cognitive and behavioral impairments, potentially diagnosed as a comorbid autism spectrum disorder or attention-deficit hyperactivity disorder. Quality of life is often impaired due to irritability, aggression and self-injurious behavior, generally refractory to standard therapies. There are indications from previous (case) studies and patient reporting that cannabidiol (CBD) may be an effective treatment for severe behavioral manifestations in RGNDs. However, clear evidence is lacking and interventional research is challenging due to the rarity as well as the heterogeneity within and between disease groups and interindividual differences in treatment response. Our objective is to examine the effectiveness of CBD on severe behavioral manifestations in three RGNDs, including Tuberous Sclerosis Complex (TSC), mucopolysaccharidosis type III (MPS III), and Fragile X syndrome (FXS), using an innovative trial design. Methods We aim to conduct placebo-controlled, double-blind, block-randomized, multiple crossover N-of-1 studies with oral CBD (twice daily) in 30 patients (aged ≥ 6 years) with confirmed TSC, MPS III or FXS and severe behavioral manifestations. The treatment is oral CBD up to a maximum of 25 mg/kg/day, twice daily. The primary outcome measure is the subscale irritability of the Aberrant Behavior Checklist. Secondary outcome measures include (personalized) patient-reported outcome measures with regard to behavioral and psychiatric outcomes, disease-specific outcome measures, parental stress, seizure frequency, and adverse effects of CBD. Questionnaires will be completed and study medication will be taken at the participants’ natural setting. Individual treatment effects will be determined based on summary statistics. A mixed model analysis will be applied for analyzing the effectiveness of the intervention per disorder and across disorders combining data from the individual N-of-1 trials. Discussion These N-of-1 trials address an unmet medical need and will provide information on the effectiveness of CBD for severe behavioral manifestations in RGNDs, potentially generating generalizable knowledge at an individual-, disorder- and RGND population level. Trial registration EudraCT: 2021-003250-23, registered 25 August 2022, https://www.clinicaltrialsregister.eu/ctr-search/trial/2021-003250-23/NL .

Abstract Background The apolipoprotein E-deficient (apoE −/− ) mouse is a well-established model for studying atherosclerosis. However, its small size limits its use in longitudinal positron emission tomography (PET) imaging studies. Recently, the apoE −/− rat has emerged as an alternative. With this study, we investigate the feasibility of using apoE −/− rats as an in vivo model for longitudinal atherosclerotic PET/CT imaging. Results ApoE −/− rats showed significantly higher [18F]FDG uptake than controls in the aortic arch (+ 18.5%, p

Abstract Aims Transthyretin amyloid cardiomyopathy (ATTR‐CM), a progressive and fatal cardiomyopathy, is frequently misdiagnosed or entails diagnostic delays, hindering patients from timely treatment. This study aimed to generate a systematic framework based on data from electronic health records (EHRs) to assess patients with ATTR‐CM in a real‐world population of heart failure (HF) patients. Predictive factors or combinations of predictive factors related to ATTR‐CM in a European population were also assessed. Methods and results Retrospective unstructured and semi‐structured data from EHRs of patients from OLV Hospital Aalst, Belgium (2012–20), were processed using natural language processing (NLP) to generate an Observational Medical Outcomes Partnership Common Data Model database. NLP model performance was assessed on a random subset of EHRs by comparing algorithm outputs to a physician‐generated standard (using precision, recall, and their harmonic mean, or F1‐score). Of the 3127 HF patients, 103 potentially had ATTR‐CM (age 78 ± 9 years; male 55%; ejection fraction of 48% ± 16). The mean diagnostic delay between HF and ATTR‐CM diagnosis was 1.8 years. Besides HF and cardiomyopathy‐related phenotypes, the strongest cardiac predictor was atrial fibrillation (AF; 72% in ATTR‐CM vs. 60% in non‐ATTR‐CM, P = 0.02), whereas the strongest non‐cardiac predictor was carpal tunnel syndrome (21% in ATTR‐CM vs. 3% in non‐ATTR‐CM, P

Despite the growing interest of academia in public outreach, little is known about what university students, among who are future researchers, take away from their academic education in terms of research dissemination opportunities. In this study, we analyzed social science students' discourses on creative dissemination practices in relation to standardized dissemination practices. Our findings reveal that student's conceptions of creative research dissemination (CRD) are diverse and influenced by varying perceptions of knowledge, the public, and creativity. Discourses on CRD are also strongly linked with values such as innovation and impact on society, but the concrete meaning of these values often remains undefined. We propose rethinking the academic context at the educational level so it offers a platform for multimodal formats of research dissemination. This would require encouraging students to take a stance toward how they envision a progressive academic future.