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For this pilot study, the use of the digital 3D anatomy application Complete Anatomy was evaluated as a non-mandatory additional study tool throughout the semester. The aim of the study was to investigate if the Complete Anatomy usage time had an effect on final exam grades and how the app was used post-COVID-19. This cross-sectional study asked first year bachelor/freshman university students of Physical Therapy and Rehabilitation Sciences to fill out a questionnaire to gauge Complete Anatomy usage time, the student's exam results, and how the app was used, for example, in relation to other study tools. A positive correlation was found between the proportion of students that passed the final exam and the number of hours of Complete Anatomy usage (r[subscript s] (4) = 0.94, p = 0.016). Compared to students who didn't use Complete Anatomy, these positive effects were observed when students used Complete Anatomy for at least 10 h (p = 0.04). The app was well-used with almost half of the respondents reporting >10 h of usage time. The results from this study provide a good overview of how and how often Complete Anatomy is used. Although a positive correlation between the hours of use and the number of passing grades was found in this pilot study, a future study to prove the causality between these two factors is warranted to further investigate the effect of Complete Anatomy as an additional non-mandatory study tool.

Abstract Cell therapies, including tumor antigen-loaded dendritic cells used as therapeutic cancer vaccines, offer treatment options for patients with malignancies. We evaluated the feasibility, safety, immunogenicity, and clinical activity of adjuvant vaccination with Wilms’ tumor protein (WT1) mRNA-electroporated autologous dendritic cells (WT1-mRNA/DC) in a single-arm phase I/II clinical study of patients with advanced solid tumors receiving standard therapy. Disease status and immune reactivity were evaluated after 8 weeks and 6 months. WT1-mRNA/DC vaccination was feasible in all patients, except one. Vaccination was well tolerated without evidence of systemic toxicity. The disease control rate and overall response rate among a total of 39 evaluable patients were 74.4% and 12.8%, respectively. Median overall survival (OS) was 43.7 months among 13 patients with glioblastoma multiforme, 41.9 months among 12 patients with metastatic breast cancer, and 48.8 months among 10 patients with malignant pleural mesothelioma, comparing favourably with historical controls reported in the literature. OS was longer in patients with stable disease at 8 weeks and disease control at 6 months versus patients without disease control at either time point. Disease control and higher OS were associated with antigen-specific type 1 CD4+ and/or CD8+ T-lymphocyte responses, mainly induced by WT1-mRNA/DC vaccination. Antigen-nonspecific type 2 CD8+ T-cell responses were common before WT1-mRNA/DC vaccination but did not show any association with clinical outcome. Collectively, these data indicate that WT1-mRNA/DC vaccination is feasible, safe, and immunogenic and shows clinical activity in patients with advanced solid tumors, suggesting that it has the potential to help improve their survival.

Abstract The continuing emergence of immune evasive SARS-CoV-2 variants and the previous SARS-CoV-1 outbreak collectively underscore the need for broadly protective sarbecovirus vaccines. Targeting the conserved S2 subunit of SARS-CoV-2 is a particularly promising approach to elicit broad protection. Here, we describe a nanoparticle vaccine displaying multiple copies of the SARS-CoV-1 S2 subunit. This vaccine alone, or as a cocktail with a SARS-CoV-2 S2 subunit vaccine, protects female transgenic K18-hACE2 mice from challenges with Omicron subvariant XBB as well as several sarbecoviruses identified as having pandemic potential including the bat sarbecovirus WIV1, BANAL-236, and a pangolin sarbecovirus. Challenge studies in female Fc-γ receptor knockout mice reveal that antibody-based cellular effector mechanisms play a role in protection elicited by these vaccines. These results demonstrate that our S2-based vaccines provide broad protection against clade 1 sarbecoviruses and offer insight into the mechanistic basis for protection.

We present chromosome-level genome assemblies from representative species of three independently evolved seagrass lineages: Posidonia oceanica, Cymodocea nodosa, Thalassia testudinum and Zostera marina. We also include a draft genome of Potamogeton acutifolius, belonging to a freshwater sister lineage to Zosteraceae. All seagrass species share an ancient whole-genome triplication, while additional whole-genome duplications were uncovered for C. nodosa, Z. marina and P. acutifolius. Comparative analysis of selected gene families suggests that the transition from submerged-freshwater to submerged-marine environments mainly involved fine-tuning of multiple processes (such as osmoregulation, salinity, light capture, carbon acquisition and temperature) that all had to happen in parallel, probably explaining why adaptation to a marine lifestyle has been exceedingly rare. Major gene losses related to stomata, volatiles, defence and lignification are probably a consequence of the return to the sea rather than the cause of it. These new genomes will accelerate functional studies and solutions, as continuing losses of the 'savannahs of the sea' are of major concern in times of climate change and loss of biodiversity.

Abstract Background The policy shift towards person-centred integrated primary care systems drives interest in primary care across higher education programs. In Flanders, the Primary Care Academy (PCA) is established to support this policy shift. The PCA focusses on the concepts of goal-oriented care, self-management, and interprofessional collaboration to support the shift towards integrated care and to integrate them in curricula in order to strengthen and develop a futureproof health system. Therefore, the aim of this study is if and how lecturers implement these concepts in the curriculum and what they need for a successful implementation. Methods A sequential explanatory mixed method study design was used combining quantitative and qualitative data. A cross-sectional survey was sent to 276 Flemish health care education programs. Qualitative data was collected through focus groups in which lecturers participated. Results The results showed that 89% of the higher education programs address goal-oriented care, self-management, and interprofessional collaboration with regard to primary care. Further analysis of courses within the programs reveals that the concept of self-management is covered in only 58%, while goal-oriented care (73%) and interprofessional collaboration (80%) appear more frequently. The level at which the themes are addressed in the courses are often limited to an introduction. The focus groups revealed that primary care is present in education programs, however lecturers are limited aware where primary care is integrated in their own and other programs. Lectures expressed a need for more collaboration between research, education and practice in developing educational content. When new concepts are introduced, lecturers want them to be translated into educational content, learning objectives and competencies. Conclusions The study shows that the concepts of goal-oriented care, self-management, and interprofessional collaboration are present in higher education programs to a varying degree. Lecturers are eager to implement these new primary concepts but they lack collaboration between education, research and practice. Lecturers indicate the need for a competence profile for primary care professionals as common framework to guide curriculum development.

Abstract Hypoxic tumors are radioresistant stemming from the fact that oxygen promotes reactive oxygen species (ROS) propagation after water radiolysis and stabilizes irradiation-induced DNA damage. Therefore, an attractive strategy to radiosensitize solid tumors is to increase tumor oxygenation at the time of irradiation, ideally above a partial pressure of 10 mm-Hg at which full radiosensitization can be reached. Historically, the many attempts to increase vascular O2 delivery have had limited efficacy, but mathematical models predicted that inhibiting cancer cell respiration would be more effective. Here, we report that mitochondria-targeted antioxidant MitoQ can radiosensitize human breast tumors in mice. This was not a class effect, as neither MitoTEMPO nor SKQ1 shared this property. At clinically relevant nanomolar concentrations, MitoQ completely abrogated the oxygen consumption of several human cancer cell lines of different origins, which was associated with a glycolytic switch. Using orthotopic breast cancer models in mice, we observed that pretreating hypoxic MDA-MB-231 tumors with MitoQ delayed tumor growth with both single dose irradiation and clinically relevant fractionated radiotherapy. Oxygenated MCF7 tumors were not radiosensitized, suggesting an oxygen enhancement effect of MitoQ. Because MitoQ already successfully passed Phase I clinical trials, our findings foster its clinical evaluation in combination with radiotherapy.

Abstract Esophageal adenocarcinoma (EAC) is an aggressive cancer characterized by a high risk of relapse post-surgery. Current follow-up methods (serum carcinoembryonic antigen detection and PET-CT) lack sensitivity and reliability, necessitating a novel approach. Analyzing cell-free DNA (cfDNA) from blood plasma emerges as a promising avenue. This study aims to evaluate the cost-effective and genome-wide cell-free reduced representation bisulfite sequencing (cfRRBS) method combined with computational deconvolution for effective disease monitoring in EAC patients. cfDNA methylation profiling with cfRRBS was performed on 162 blood plasma samples from 33 EAC cancer patients and 28 blood plasma samples from 20 healthy donors. The estimated tumor fraction for EAC patients at the time of diagnosis was significantly different from the healthy donor plasma samples (one-sided Wilcoxon rank-sum test: p-value = 0.032). Tumor fractions above 15% and focal gains/amplifications in MYC (chr8), KRAS (chr12), EGFR (chr7) and NOTCH2 (chr1) were observed in four samples of distinct patients at the time metastatic disease was detected. This study showed feasibility to estimate tumor fractions in blood plasma of EAC patients based on cfDNA methylation using cfRRBS and computational deconvolution. Nevertheless, in this study only cancer patients with evidence of metastatic disease show high tumor fractions and copy number alterations.

Abstract The International Staging System for multiple myeloma recently underwent a second revision (R2-ISS) to include gain/amplification of 1q21 and account for the additive prognostic significance of multiple high-risk features. The phase 3 ICARIA-MM (isatuximab–pomalidomide–dexamethasone vs. pomalidomide–dexamethasone) and IKEMA (isatuximab–carfilzomib–dexamethasone vs. carfilzomib–dexamethasone) studies provide large datasets for retrospectively validating the prognostic value of the R2-ISS in relapsed/refractory multiple myeloma. Of 609 pooled patients, 68 (11.2%) were reclassified as R2-ISS stage I, 136 (22.3%) as R2-ISS stage II, 204 (33.5%) as R2-ISS stage III, 55 (9.0%) as stage IV, and 146 (24.0%) “Not classified”. Median progression-free survival was shorter among those reclassified as R2-ISS stage II (HR 1.52, 95% CI 0.979–2.358), stage III (HR 2.59, 95% CI 1.709–3.923), and stage IV (HR 3.51, 95% CI 2.124–5.784) versus stage I. Adding isatuximab led to longer progression-free survival versus doublet therapy (adjusted HR 0.544 [95% CI 0.436–0.680]), with a consistent treatment effect observed across all R2-ISS stages. This is the first study to validate the R2-ISS with novel agents, including anti-CD38 monoclonal antibodies, and to show that R2-ISS, as a prognostic scoring system, can be applied to patients with relapsed/refractory multiple myeloma.

Abstract Background This study protocol outlines the phased construction of a questionnaire, data collection, and a strategy for analysis within the framework of the ATTAS project. This study has two primary objectives. First, it allows us to map the duration of the various phases of the abortion trajectory for women presenting for abortion in Flanders, Belgium. Second, it identifies barriers that cause delays within these phases. Methods The questionnaire was distributed to all women seeking abortion care at one of the five Flemish abortion centers; specifically, the LUNA centers, which are located in Ostend, Ghent, Antwerp, and Hasselt, as is the VUB-Dilemma center in Brussels during the fall and winter of 2023–2024. Ethical clearance for the described research was obtained from the University of Antwerp’s Ethics Committee for the Social Sciences and Humanities (reference numbers: SHW_2023_48_1 and SHW_2023_48_2). Discussion The collected data provide a dataset on the abortion trajectories of Flanders women who presented for abortion. This study protocol outlines the ATTAS project’s rationale, phased development, and implementation of the questionnaire, as well as the upcoming data analyses. To our knowledge, this is the first study within the Flemish context to investigate abortion trajectories, timing, and access. Furthermore, this study protocol provides a phased and systematic approach to adapt validated research instruments to fit within diverse legal and cultural contexts. Building on this protocol, future research will seek to advance reproductive justice for all women in Belgium.

Abstract Despite therapeutic advancements, multiple myeloma (MM) remains incurable. NK cells have emerged as a promising option for the treatment of MM. NK cells are heterogenous and typically classified based on the relative expression of their surface markers (e.g., CD56 and CD16a). These cells elicit an antitumor response in the presence of low mutational burden and without neoantigen presentation via germline-encoded activating and inhibitory receptors that identify the markers of transformation present on the MM cells. Higher NK cell activity is associated with improved survival and prognosis, whereas lower activity is associated with advanced clinical stage and disease progression in MM. Moreover, not all NK cell phenotypes contribute equally toward the anti-MM effect; higher proportions of certain NK cell phenotypes result in better outcomes. In MM, the proportion, phenotype, and function of NK cells are drastically varied between different disease stages; this is further influenced by the bone marrow microenvironment, proportion of activating and inhibitory receptors on NK cells, expression of homing receptors, and bone marrow hypoxia. Antimyeloma therapies, such as autologous stem cell transplant, immunomodulation, proteasome inhibition, and checkpoint inhibition, further modulate the NK cell landscape in the patients. Thus, NK cells can naturally work in tandem with anti-MM therapies and be strategically modulated for improved anti-MM effect. This review article describes immunotypic and phenotypic differences in NK cells along with the functional changes in homeostatic and malignant states and provides expert insights on strategies to harness the potential of NK cells for improving outcomes in MM.

Concepts such as participation and environment may differ across cultures. Consequently, to use a measure like the Young Children's Participation and Environment Measure (YC-PEM) in other than the original English-speaking contexts, cultural adaptation needs to be assured. The objective is to cross-culturally translate, adapt, and pilot test the YC-PEM into the Dutch language and culture. In total 3 cognitive interviews with caregivers and one focus group with Occupational Therapists (N = 5) working in early intervention were conducted to evaluate the cultural relevance of the YC-PEM content for use in a Dutch context. Data was analyzed by content analysis using semantic, idiomatic, content, and conceptual equivalence. The YC-PEM was pilot tested with 31 caregivers of children with and without disabilities. Setting specific estimates of internal consistency and test-retest reliability were obtained. Results show adaptations mainly focused on content and conceptual equivalence, with conceptual equivalence being the most challenging to reach. Internal consistency estimates varied from 0.42 to 0.93 for the participation scales and from 0.74 to 0.83 for the environmental scale. This study gives preliminary evidence for the use of a culturally adapted YC-PEM in Belgium and the Netherlands. Further validation in a larger sample is indicated to evaluate its psychometric properties.

Teleost fishes, which are the largest and most diverse group of living vertebrates, have a rich history of ancient and recent polyploidy. Previous studies of allotetraploid common carp and goldfish (cyprinids) reported a dominant subgenome, which is more expressed and exhibits biased gene retention. However, the underlying mechanisms contributing to observed subgenome dominance remains poorly understood. Here we report high-quality genomes of twenty-one cyprinids to investigate the origin and subsequent subgenome evolution patterns following three independent allopolyploidy events. We identify the closest extant relatives of the diploid progenitor species, investigate genetic and epigenetic differences among subgenomes, and conclude that observed subgenome dominance patterns are likely due to a combination of maternal dominance and transposable element densities in each polyploid. These findings provide an important foundation to understanding subgenome dominance patterns observed in teleost fishes, and ultimately the role of polyploidy in contributing to evolutionary innovations.

The wide adoption of occupational shoulder exoskeletons in industrial settings remains limited. Passive exoskeletons were proved effective in a limited amount of application scenarios, such as (quasi-)static overhead handling tasks. Quasi-active devices, albeit representing an improved version of their passive predecessors, do not allow full modulation of the amount of assistance delivered to the user, lacking versatility and adaptability in assisting various dynamic tasks. Active occupational shoulder exoskeletons could overcome these limitations by controlling the shape of the delivered torque profile according to the task they aim to assist. However, most existing active devices lack compactness and wearability. This prevents their implementation in working environments. In this work, we present a new active shoulder exoskeleton, named Active Exo4Work (AE4W). It features a new flexible shaft-driven remote actuation unit that allows the positioning of the motors close to the wearer’s center of mass while it maintains a kinematic structure that is compatible with the biological motion of the shoulder joint. in vitro and in vivo experiments have been conducted to investigate the performance of AE4W. Experimental results show that the exoskeleton is kinematically compatible with the user’s workspace since it does not constrain the natural range of motion of the shoulder joint. Moreover, this device can effectively provide different types of assistance while the user executes various dynamic tasks, without altering perceived comfort.

Objective: Patients with therapy-refractory chronic spinal pain after spinal surgery experience increased disability, resulting in substantial loss of employment and consequently lower quality of life. Despite findings that rehabilitation improves socio-economic outcomes in other chronic pain conditions, evidence for patients with chronic spinal pain after spinal surgery is limited. A systematic review was conducted to provide an overview of rehabilitation interventions and their effectiveness to improve work participation for patients with chronic spinal pain after spinal surgery. Methods: MEDLINE (via PubMed), Scopus, Embase, and Web of Science, were systematically searched. Risk of bias was assessed using the modified Downs and Black checklist and GRADE was used to assess certainty of evidence. The review protocol was prospectively registered on PROSPERO (CRD42022346091). Results: The search yielded 1,289 publications. Full-text screening of 48 articles resulted in the inclusion of 6 publications. The included interventions comprised multiple treatment components, consisting of back school, self-care, functional restoration, multidisciplinary rehabilitation, physiotherapy, and digital care programmes to improve work participation. Conclusion: Rehabilitation to improve return to work for patients with chronic spinal pain after spinal surgery was supported only by low-certainty evidence. Rehabilitation therapies that are personalized and that integrate the patient’s work seem most suitable.

Surra and Dourine are widespread diseases caused by two protozoan parasites Trypanosoma brucei evansi and Trypanosoma brucei equiperdum, respectively. A wide range of animals including camels, horses, cattle and buffaloes are susceptible to infection. These diseases pose a significant socio-economic burden, primarily due to the limited therapeutic options and the complications associated with toxicity and drug resistance, making disease management particularly challenging. This study evaluated the potential of 3′-deoxytubercidin, a previously identified antitrypanosomal nucleoside, as a therapeutic candidate for Surra and Dourine using mouse models. Mice infected with either T. b. evansi or T. b. equiperdum were treated with 3′-deoxytubercidin at a dosage of 6.25 mg kg−1 administrated intraperitoneally once daily for five consecutive days. The treatment resulted in full cure, as confirmed by both microscopic examination and quantitative PCR, without any observed toxicity. Given the importance of considering the One Health concept in developing new antiparasitic drugs for veterinary use, the environmental impact of 3′-deoxytubercidin was assessed through the ecotoxicity tests on aquatic organisms, conducted in accordance with OECD guidelines. The compound showed some toxicity to Daphnia (EC50 = 0.54 mg L−1 in acute Daphnia test) but had no significant adverse effects on green alga at concentrations tested (up to 50 mg L−1). This study confirms the suitability of 3′-deoxytubercidin as an effective and safe therapeutic candidate for further development in the treatment of Surra and Dourine, highlighting its potential for improving disease management in affected regions.