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Abstract Background The COVID-19 pandemic immensely impacted care provision, including quality of care in general practice. This paper aimed: (1) to assess how Belgian general practices acted upon the six dimensions of quality of care during COVID-19; (2) to study differences between the three Belgian regions; and (3) to benchmark the performance of the Belgian practices against the performance in other European countries. Methods The data collected from 479 Belgian practices during 2020–2021 using an online survey as part of the international cross-sectional PRICOV-19 study were analyzed. Hereby, descriptive statistics, chi-squared tests, and binary logistic regression analyses were performed. Thirty-four survey questions related to the six dimensions of quality of care were selected as outcome variables. The adjusted regression models included four practice characteristics as covariates: practice type, being a teaching practice for GP trainees, multidisciplinarity of the team, and payment system. Results Belgian practices made important organizational changes to deliver high-quality care during COVID-19. Most practices (n = 259; 56.1%) actively reached out to vulnerable patients. Limitations to the practice building or infrastructure threatened high-quality care in 266 practices (55.5%). Infection prevention measures could not always be implemented during COVID-19, such as using a cleaning protocol (n = 265; 57.2%) and providing a separate doctor bag for infection-related home visits (n = 130; 27.9%). Three hundred and sixty practices (82.0%) reported at least one safety incident related to a delayed care process in patients with an urgent condition. The adjusted regression analysis showed limited significant differences between the Belgian regions regarding the quality of care delivered. Belgian practices demonstrated varied performance compared to other European countries. For example, they excelled in always checking the feasibility of isolation at home but reported more patient safety incidents related to timely care than at least three-quarters of the other European countries. Conclusions Future studies using different design methods are crucial to investigate which country and practice characteristics are associated with delivering high-quality care.

Abstract Background To design efficient mitigation measures against COVID-19, understanding the transmission dynamics between different age groups was crucial. The role of children in the pandemic has been intensely debated and involves both scientific and ethical questions. To design efficient age-targeted non-pharmaceutical interventions (NPI), a good view of the incidence of the different age groups was needed. However, using Belgian testing data to infer real incidence (RI) from observed incidence (OI) or positivity ratio (PR) was not trivial. Methods Based on Belgian testing data collected during the Delta wave of Autumn 2021, we compared the use of different estimators of RI and analyzed their effect on comparisons between age groups. Results We found that the RI estimator’s choice strongly influences the comparison between age groups. Conclusion The widespread implementation of testing campaigns using representative population samples could help to avoid pitfalls related to the current testing strategy in Belgium and worldwide. This approach would also allow a better comparison of the data from different countries while reducing biases arising from the specificities of each surveillance system.

Molecular tethers that mediate the immobilization of receptors to the sensor surface, carry critical ability to influence sensor outcomes by determining how the receptors are presented to the analyte in the biological medium. An aspect that has however been less explored is the role of flexibility of such tethers in enhancing the efficiency of analyte capture by the receptor, by enhancing its ability to “seek” the analytes in solution. In the enclosed study, we show the length and flexibility of PEG tethers to have a strong influence on the binding of gold nanoparticles (AuNP) or neutravidin (NAv) to tethered amine or biotin receptors respectively. The qualitative similarity in the influence of the tethers, despite the largely dissimilar interactions that drive binding of AuNPs and NAv implies a generic influence at play. The impact of tether length or flexibility is decoupled from that of the density and conformation of tethers, using real-time, quantitative measurements performed using quartz crystal microbalance (QCM) and surface plasmon resonance (SPR) sensors. Substituting neutravidin with neutravidin-conjugated gold nanoparticles accentuated the impact of the tether length, providing additional possibilities to harness the benefits of flexible tethers by increasing the analyte valency. The results emphasize the opportunity to enhance sensor performance by factoring in the influence of tether structure into the design of the sensor interface.

Benoit Pétré,1,* Marine Paridans,1,* Nicolas Gillain,1 Eddy Husson,1 Anne-Françoise Donneau,1– 3 Nadia Dardenne,1,3 Christophe Breuer,4 Fabienne Michel,2,5 Margaux Dandoy,6 Fabrice Bureau,6,7 Laurent Gillet,6,8,9 Dieudonné Leclercq,1 Michèle Guillaume1,2 1Department of Public Health, Faculty of Medicine, Liège University, Liège, Belgium; 2Risk Assessment Group COVID-19, Liège University, Liège, Belgium; 3University and Hospital Biostatistics Center (B-STAT), Faculty of Medicine, Liège University, Liège, Belgium; 4Governance Support Unit, Rectorate, Liège University, Liège, Belgium; 5Collection and Analysis of Data and Information of Strategic Utility (RADIUS), Liège University, Liège, Belgium; 6Covid-19 Platform, Liège University, Liège, Belgium; 7Laboratory of Cellular and Molecular Immunology, GIGA Institute, Liège University, Liège, Belgium; 8Fundamental and Applied Research for Animal and Health (FARAH) Center, Liège University, Liège, Belgium; 9Laboratory of Immunology-Vaccinology, Liège University, Liège, Belgium*These authors contributed equally to this workCorrespondence: Benoit Pétré, Department of Public Health, Faculty of Medicine, Liège University, Quartier Hôpital, Avenue Hippocrate 13 (B23), Liège, 4000, Belgium, Tel +32 4 366 2505, Email benoit.petre@uliege.beAbstract: Current public health debate centers on COVID-19 testing methods and strategies. In some communities, high transmission risk may justify routine testing, and this requires test methods that are safe and efficient for both patients and the administrative or health-care workers administering them. Saliva testing appears to satisfy those criteria. There is, however, little documentation on the acceptability of this method among beneficiaries. This article presents the lessons learned from a pilot study on the use of saliva testing for routine screening of nursing home and secondary school personnel in Wallonia (the French-speaking part of Belgium), conducted in December 2020 to April 2021, respectively. Administrators at the facilities in question seemed to think highly of saliva testing and wished to continue it after the pilot study was over. This result reinforces the criteria (the noninvasive aspect, in particular) supporting a key role for saliva testing in monitoring community spread of the virus. Nevertheless, wider-scale deployment of this particular method will only be possible if the testing strategy as a whole takes a health promotion approach.Keywords: pandemic, COVID-19, community monitoring, preventive health behavior, saliva testing

The early modern period was an age marked by the forced migration and displacement of social groups and individuals around the world. Huguenots, conversos, Catholics, cavaliers, Jacobites, and French emigrés alike fled or were expelled from their homes and communities. Yet, exile is still usually considered only within the context of broader religious or political events by scholars working in sub‐fields rather than as a phenomenon worthy of study in its own right. Foregrounding displacement as a major facet of early modern society and culture, this special issue explores the experience, perception, and poetics of exile from 1500 to 1800 through the prism of innovation. It encompasses displaced individuals and communities, as well as writings that treat the theme of exile, to consider how forced migration shaped the social, cultural, political, and intellectual contours of the era – and thus led to innovative practices and ideas. [ABSTRACT FROM AUTHOR]

Introduction: Primary refractory disease affects 30–40% of patients diagnosed with DLBCL and is a significant challenge in disease management due to its poor prognosis. Predicting refractory status could greatly inform treatment strategies, enabling early intervention. Various options are now available based on patient and disease characteristics. Supervised machine-learning techniques, which can predict outcomes in a medical context, appear highly suitable for this purpose. Design: Retrospective monocentric cohort study. Patient population: Adult patients with a first diagnosis of DLBCL admitted to the hematology unit from 2017 to 2022. Aim: We evaluated in our Center five supervised machine-learning (ML) models as a tool for the prediction of primary refractory DLBCL. Main results: One hundred and thirty patients with Diffuse Large B-cell lymphoma (DLBCL) were included in this study between January 2017 and December 2022. The variables used for analysis included demographic characteristics, clinical condition, disease characteristics, first-line therapy and PET-CT scan realization after 2 cycles of treatment. We compared five supervised ML models: support vector machine (SVM), Random Forest Classifier (RFC), Logistic Regression (LR), Naïve Bayes (NB) Categorical classifier and eXtreme Gradient Boost (XGboost), to predict primary refractory disease. The performance of these models was evaluated using the area under the receiver operating characteristic curve (ROC-AUC), accuracy, false positive rate, sensitivity, and F1-score to identify the best model. After a median follow-up of 19.5 months, the overall survival rate was 60% in the cohort. The Overall Survival at 3 years was 58.5% (95%CI, 51–68.5) and the 3-years Progression Free Survival was 63% (95%CI, 54–71) using Kaplan-Meier method. Of the 124 patients who received a first line treatment, primary refractory disease occurred in 42 patients (33.8%) and 2 patients (1.6%) experienced relapse within 6 months. The univariate analysis on refractory disease status shows age (p = 0.009), Ann Arbor stage (p = 0.013), CMV infection (p = 0.012), comorbidity (p = 0.019), IPI score (p<0.001), first line of treatment (p<0.001), EBV infection (p = 0.008) and socio-economics status (p = 0.02) as influencing factors. The NB Categorical classifier emerged as the top-performing model, boasting a ROC-AUC of 0.81 (95% CI, 0.64–0.96), an accuracy of 83%, a F1-score of 0.82, and a low false positive rate at 10% on the validation set. The eXtreme Gradient Boost (XGboost) model and the Random Forest Classifier (RFC) followed with a ROC-AUC of 0.74 (95%CI, 0.52–0.93) and 0.67 (95%CI, 0.46–0.88) respectively, an accuracy of 78% and 72% respectively, a F1-score of 0.75 and 0.67 respectively, and a false positive rate of 10% for both. The other two models performed worse with ROC-AUC of 0.65 (95%CI, 0.40–0.87) and 0.45 (95%CI, 0.29–0.64) for SVM and LR respectively, an accuracy of 67% and 50% respectively, a f1-score of 0.64 and 0.43 respectively, and a false positive rate of 28% and 37% respectively. Conclusion: Machine learning algorithms, particularly the NB Categorical classifier, have the potential to improve the prediction of primary refractory disease in DLBCL patients, thereby providing a novel decision-making tool for managing this condition. To validate these results on a broader scale, multicenter studies are needed to confirm the results in larger cohorts. [ABSTRACT FROM AUTHOR]

Abstract Cell wall homeostasis in bacteria is tightly regulated by balanced synthesis and degradation of peptidoglycan (PG), allowing cells to expand their sacculus during growth while maintaining physical integrity. In rod-shaped bacteria, actin-like MreB proteins are key players of the PG elongation machinery known as the Rod complex. In the Gram-positive model bacterium Bacillus subtilis depletion of the essential MreB leads to loss of rod shape and cell lysis. However, millimolar concentrations of magnesium in the growth medium rescue the viability and morphological defects of mreB mutants by an unknown mechanism. Here, we used a combination of cytological, biochemical and biophysical approaches to investigate the cell surface properties of mreB null mutant cells and the interactions of Mg2+ with the cell wall of B. subtilis. We show that ∆mreB cells have rougher and softer surfaces, and changes in PG composition indicative of increased DL- and DD-endopeptidase activities as well as increased deacetylation of the sugar moieties. Increase in DL-endopeptidase activity is mitigated by excess Mg2+ while DD-endopeptidase activity remains high. Visualization of PG degradation in pulse-chase experiments showed anisotropic PG hydrolase activity along the sidewalls of ∆mreB cells, in particular at the sites of increased cell width and bulging, while PG synthesis remained isotropic. Overall, our data support a model in which divalent cations maintain rod shape in ∆mreB cells by inhibiting PG hydrolases, possibly through the formation of crosslinks with carboxyl groups of the PG meshwork that affect the capacity of PG hydrolases to act on their substrate.

Abstract Background Fibromyalgia is a chronic multidimensional pain disease with no curative treatment currently available. Its management relies on a multimodal approach involving pharmacologic and non-pharmacologic elements. Because a suggested factor in its etiology is a central sensitization phenomenon involving the N-methyl-D-aspartate receptor (NMDAR), NMDAR antagonists have been proposed as a treatment target. Ketamine and its levogyre form, S-ketamine, have been used to treat chronic pain for many years without consensus about their therapeutic efficiency. We aim to assess the efficacy of S-ketamine as a co-treatment for fibromyalgia. Methods This prospective, randomized, single-center, double-blind, parallel-group, dose-escalation trial will compare a co-treatment with S-ketamine (intervention) to a control treatment without S-ketamine (control). It will consist of two successive cohorts with 2:1 randomization ratio (S-ketamine at two different doses: control) with 105 participants in each cohort. The protocol follow-up time will be 12 weeks, including 3 visits for the treatment (week 0, week 2, and week 4) and 3 visits for follow-up (week 6, week 9, and week 12). Our primary outcome, pain relief and/or better patient function, will be assessed with the Brief Pain Inventory questionnaire. The statistical analysis will be performed on an intention-to-treat basis. If the primary outcome is reached at the end of follow-up in the first cohort with low-dose S-ketamine (0.2 mg/kg), the trial will end. If not, the trial will continue with the second cohort and high-dose S-ketamine (0.4 mg/kg). Discussion The challenge of our trial is the inclusion of a large number of participants in comparison to other trials involving ketamine or S-ketamine infusions for chronic pain management. The originality of our protocol is to include functionality in addition to pain relief as a primary outcome because these two endpoints are not linked in a linear way. For some patients, functional status is more important than pain relief. Trial registration EudraCT reference: 2020-000473-25, ClinicalTrials.gov : NCT04436250, first posted June 18, 2020; last updated July 21, 2020. Protocol version 2.2 issued on September 30, 2020, after a revision by the ethics committee. https://clinicaltrials.gov/ct2/show/NCT04436250