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Presentation of the Project "Inventory and Management Modeling of the Permanent Vegetation in a Forest Zone in Southern Senegal". Belgium has a long tradition in the field of agricultural and floristic research in humid tropical Africa. The studies that were once done in Congo and there after in Zaire can still be considered to be milestones. Recently, the introduction of new techniques like teledetection and Geographie Information systems software has created new possibilities for those researchers that want give their basic research effort some added value in the form of policy guidelines. This text presents''the work that is currently been done by the Laboratory of Tropical and Subtropical Plant Husbandry and Ethnobotany (University of Gent, Belgium) in the Moyenne Casajsnance Province (southern Senegal) on the evolution and management possibilities of its natural vegetation.

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Detrait et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Deep venous thrombosis (DVT) is a common postoperative complication in patients undergoing major orthopaedic surgery of the lower limbs, such as total hip or knee replacement (THR, TKR). Routine pharmacological thromboprophylaxis with low-molecular-weight heparin (LMWH) or a direct oral anticoagulant agent is strongly recommended in this setting. THR and TKR as well as ankle arthrodesis are frequently performed in people with haemophilia (PWH) and chronic haemophilic arthropathy. Pharmacological thromboprophylaxis in this population remains controversial., Methods: We report the results of a single-centre prospective study initiated in 2002 evaluating by systematic Doppler ultrasound the incidence of subclinical DVT in consecutive PWH referred for major orthopaedic surgery and not receiving pharmacological thromboprophylaxis., Results: We included 46 different PWH (39 Haemophilia A, 7 Haemophilia B, 27 severe, 15 moderate and 4 mild forms) undergoing 67 orthopaedic procedures. Most (89.5%) were performed with continuous infusion of clotting factor concentrates. Rehabilitation was usually started on day 1 post-op. No clinical DVT or pulmonary embolism was suspected. In total, there were 5 cases (3 severe, 1 moderate HA and 1 moderate HB) of subclinical DVT which were all distal. Two patients were treated with a short course (10-14 days) of LMWH. The overall incidence of DVT was 7.5%., Conclusions: These data provide imaging-based evidence that the risk of DVT following major orthopaedic surgery among PWH is low. Identified DVTs were distal and resolved spontaneously in most cases. Systematic pharmacological thromboprophylaxis in this specific population is probably for most patients not required., (© 2020 John Wiley & Sons Ltd.)

It was the aim of this study to elucidate the impact of the injection mold temperature upon the polymer crystallinity, its microstructure and the resulting drug release from immediate and sustained release tablets containing semi-crystalline polymers. The immediate release formulation contained 20% (w/w) ketoprofen (KETO) in poly (ethylene oxide) (PEO) and the sustained release formulation contained 20-40% (w/w) metoprolol tartrate (MPT) in polycaprolactone (PCL). Physical mixtures of drug-polymer were characterized via isothermal crystallization experiments using DSC and rheological measurements to elucidate the impact of the drug solid-state upon the crystallization kinetics. Tablets were prepared using various thermal histories (extrusion barrel temperature and injection mold temperatures). Polymer crystallinity and microstructure in the tablets was characterized via DSC and polarized optical microscopy. The polymer microstructure was altered by the various applied thermal histories. The differences in PEO crystallinity induced by the various mold temperatures did not affect the KETO dissolution from the tablets. On the other hand, MPT (20-40% w/w) dissolution from the PCL matrix when extruded at 80 °C and injection molded at 25 and 35 °C was significantly different due to the changes in the polymer microstructure. More perfect polymer crystals are obtained with higher mold temperatures, decreasing the drug diffusion rate through the PCL matrix. The results presented in this study imply that the injection mold temperature should be carefully controlled for sustained release formulations containing hydrophobic semi-crystalline polymers., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Burkholderia cenocepacia is an opportunistic pathogen responsible for life-threatening infections in cystic fibrosis patients. B. cenocepacia is extremely resistant towards antibiotics and therapy is complicated by its ability to form biofilms. We investigated the efficacy of an alternative antimicrobial strategy for B. cenocepacia lung infections using in vitro and in vivo models. A screening of the NIH Clinical Collection 1&2 was performed against B. cenocepacia biofilms formed in 96-well microtiter plates in the presence of tobramycin to identify repurposing candidates with potentiator activity. The efficacy of selected hits was evaluated in a three-dimensional (3D) organotypic human lung epithelial cell culture model. The in vivo effect was evaluated in the invertebrate Galleria mellonella and in a murine B. cenocepacia lung infection model. The screening resulted in 60 hits that potentiated the activity of tobramycin against B. cenocepacia biofilms, including four imidazoles of which econazole and miconazole were selected for further investigation. However, a potentiator effect was not observed in the 3D organotypic human lung epithelial cell culture model. Combination treatment was also not able to increase survival of infected G. mellonella. Also in mice, there was no added value for the combination treatment. Although potentiators of tobramycin with activity against biofilms of B. cenocepacia were identified in a repurposing screen, the in vitro activity could not be confirmed nor in a more sophisticated in vitro model, neither in vivo. This stresses the importance of validating hits resulting from in vitro studies in physiologically relevant model systems.

Agonists of Toll-like receptors (TLRs) are potent activators of the innate immune system and hold promise as vaccine adjuvant and for anticancer immunotherapy. Unfortunately, in soluble form they readily enter systemic circulation and cause systemic inflammatory toxicity. Here we demonstrate that by covalent ligation of a small-molecule imidazoquinoline-based TLR7/8 agonist to 50-nm-sized degradable polymeric nanogels the potency of the agonist to activate TLR7/8 in in vitro cultured dendritic cells is largely retained. Importantly, imidazoquinoline-ligated nanogels focused the in vivo immune activation on the draining lymph nodes while dramatically reducing systemic inflammation. Mechanistic studies revealed a prevalent passive diffusion of the nanogels to the draining lymph node. Moreover, immunization studies in mice have shown that relative to soluble TLR7/8 agonist, imidazoquinoline-ligated nanogels induce superior antibody and T-cell responses against a tuberculosis antigen. This approach opens possibilities to enhance the therapeutic benefit of small-molecule TLR agonist for a variety of applications.