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Abstract In the present study, the chemical composition, mineralogy, and mechanisms of alteration of a cementitious grout based on a CEM III/C with addition of smectite, hydrotalcite, and silica fume, are studied using a combination of chemical and physical methods. This material was designed in the context of geological repository of radioactive wastes, with a twofold aim: first, to fill the technical voids left by drilling operations at the interface between the geological formation and the disposal galleries. Second, to neutralize a potential acidic transient due to pyrite oxidation, and to create an environment that favors low corrosion rates of carbon steels. The grout is mainly composed of calcium silicate hydrates having a Ca/Si ratio of ~0.8, incorporating Al in the bridging site of the Si chains (C-A-S-H), and accounting for 29–36 wt.% of the sample. It also contains silica fume (38–48 wt.%), smectite with interlayer Na (11–17 wt.%), hydrotalcite with interlayer CO3 2− (3–4 wt.%), and lower amounts of portlandite, calcite, and possibly gibbsite and gypsum. Upon alteration by water in a flow-through reactor, the main modifications affecting the sample are calcite and gypsum dissolution, hence releasing aqueous Ca2+ that is adsorbed in smectite interlayer by replacing Na+, and stoichiometric C-A-S-H dissolution. The evolution of solution chemistry and of the solid phase composition are reproduced successfully using a thermokinetic model.

Purpose: To retrospectively identify clinical, pathologic, or imaging factors predictive of local relapse (LR) after preoperative radiotherapy (RT) for soft tissue sarcomas (STS). Methods and Materials: This is a retrospective multicenter study of patients who underwent preoperative RT and surgery for limb or trunk wall STS between 2007 and 2018 in French Sarcoma Group centers and were enrolled in the “Conticabase”. Patterns of LR were investigated taking into account the multimodal response after preoperative RT. Diagnostic and surgical samples were compared after systematic review by expert pathologists and patients were stratified by tumor grade. Log-rank tests and Cox models were used to identify prognostic factors for radiation response and LR. Results: 257 patients were included; 17 % had low-grade (LG), 72.5 % had high-grade (HG) sarcomas. In HG group, tumors were larger, mostly undifferentiated, and displayed more necrosis and perilesional edema after RT. Median follow-up was 32 months. Five-year cumulative incidence of LR was 20.3 % in the HG group versus 9.7 % in the LG group (p = 0.026). In multivariate analysis, trunk wall location (HR 6.79, p = 0.012) and proportion of viable tumor cellularity ≥ 20 % (HR 3.15, p = 0.018) were associated with LR. After adjusting for tumor location, combination of histotype and cellularity rate significantly correlated with LR. We described three prognostic subgroups for HG sarcomas, listed from the highest to lowest risk: undifferentiated sarcoma (US) with cellularity rates ≥ 20 %; non-US (NUS) with cellularity rates ≥ 20 % or US with cellularity rates

Pentadesma butyracea is a medicinal plant of which bark decoctions are used in traditional medicine for the treatment of diarrhea symptoms in Gabon. The aim of the present work was to perform phytochemical and pharmacological analyses of decoctions of P. butyracea bark. In a principal approach, spectrophotometric analyses were used to quantify phenolic compounds, followed by liquid chromatography coupled to mass spectrometry analysis that allowed the identification of flavanone–flavone dimers as the main metabolites. Pharmacological analyses showed the absence of toxicity, thus confirming the safety of use of this decoction in traditional medicine. The antioxidant activity of the bark decoctions was demonstrated to depend on their phenolic contents. The decoction of stem barks harvested during the rainy season also induced a dose-dependent relaxation of isolated ileum fragments from Wistar rats. In addition, the antidiarrheal activity of P. butyracea barks was investigated against castor oil-induced diarrhea. The oral administration of different concentrations of this decoction led to a decrease in wet stools, indicating an antidiarrheal effect at the doses that were used. These results encourage the deepening of bio-guided research on P. butyracea bark decoctions in order to propose standard traditional medical treatments.

Emerging evidence indicates periostin (POSTN) is upregulated in patients with OA, and studies have shown that it can induce the activation of inflammatory cytokines and catabolic enzymes, making it a potential therapeutic target. Link N (LN) is a peptide fragment derived from the link protein and has been demonstrated as an anabolic-like factor and anti-catabolic and anti-inflammatory factors both in vitro and in vivo. This study aims to determine if LN can regulate POSTN expression and function in OA cartilage. Articular cartilage was recovered from donors undergoing total knee replacements to isolate chondrocytes and prepare osteochondral explants. Cells and explants were treated with POSTN and LN (1 and 100 μg) and measured for changes in POSTN expression and various matrix proteins, catabolic and proinflammatory factors, and signaling. To determine the effects of POSTN expression in vivo, a rabbit OA model was used. Immunoprecipitation and in silico modeling were used to determine peptide/POSTN interactions. Western blotting, PCR, and immunohistochemistry demonstrated that LN decreased POSTN expression both in vitro and in vivo. LN was also able to directly inhibit POSTN signaling in OA chondrocytes. In silico docking suggested the direct interaction of LN with POSTN at residues responsible for its oligomerization. Immunoprecipitation experiments confirmed the direct interaction of LN with POSTN and the destabilization of its oligomerization. This study demonstrates the ability of a peptide, LN, to suppress the overexpression and function of POSTN in OA cartilage.

Pancreatic cancer is associated with a poor prognosis despite multimodal treatments. To improve the efficacy of radiotherapy, the use of nanoscintillators is emerging. Made of high‐Z elements, they absorb X‐rays more efficiently than tissues and can locally enhance the radiation dose provided they have accumulated near tumor cells. This study focuses on the role of the coating, a key parameter that controls both in vitro and in vivo properties of nanoparticles, including their internalization, biocompatibility, and therapeutic efficacy. Polyethylene glycol and tripolyphosphate molecules are used to coat lanthanum fluoride nanoscintillators, and their properties are evaluated on pancreatic cancer models. The experiments demonstrate a higher internalization of the nanoparticles when coated with tripolyphosphate, in both 2D and 3D culture models, correlating with greater efficacy under X‐rays, which may be associated with higher radiation dose‐enhancement. The nanoparticles are also injected intravenously in healthy or tumor‐bearing mice in order to study their toxicity, pharmacokinetics, and biodistribution. Despite a strong liver and spleen accumulation, especially for the tripolyphosphate‐coated nanoparticles, no toxicity is observed for either coating. Because they show promising radiation dose‐enhancement in vitro in both culture models and a limited toxicity in vivo, polyethylene glycol‐coated nanoparticles are good candidates for biomedical applications.

The emergence of embedded three‐dimensional (3D) bioprinting has revolutionized the biofabrication of free‐form constructs out of low‐viscosity and slow‐crosslinking hydrogels. Using gel‐based support baths has limitations including lack of proper oxygenation and nutrition and complications with bath removal. Herein, a novel‐embedded 3D bioprinting technique is developed with an albumin foam support bath as a promising substitute. The proposed technique, in‐foam bioprinting, offers excellent printability and convenience in bath removal while providing cells with easy access to oxygen and nutrients. The foam‐based support bath is characterized through foam stability and rheological tests. The bubble size in the foam is measured to study the change in the structure of the bath due to the coalescence of the bubbles over time. Free‐form structures are successfully 3D printed with thermoresponsive chitosan‐based bioinks to demonstrate the capability of the in‐foam bioprinting technique. The viability of bioprinted fibroblast L929 cells is studied over a seven‐day period, showing high cell viability of over 97%, which is attributed to the abundance of oxygen and nutrition in the foam support bath. Importantly, in‐foam bioprinting is beneficial for biofabricating large samples with a long printing time without jeopardizing cell viability.

Radiotherapy is recommended for the treatment of brain tumors such as glioblastoma (GBM) and brain metastases. Various curative and palliative scenarios suggest improved local-regional control. Although the underlying mechanisms are not yet clear, additional therapeutic effects have been described, including proximity and abscopal reactions at the treatment site. Clinical and preclinical data suggest that the immune system plays an essential role in regulating the non-targeted effects of radiotherapy for GBM. This article reviews current biological mechanisms for regulating the non-targeted effects caused by external and internal radiotherapy, and how they might be applied in a clinical context. Optimization of therapeutic regimens requires assessment of the complexity of the host immune system on the activity of immunosuppressive or immunostimulatory cells, such as glioma-associated macrophages and microglia. This article also discusses recent preclinical models adapted to post-radiotherapy responses.This narrative review explores and discusses the current status of immune responses both locally via the ''bystander effect'' and remotely via the ''abscopal effect''. Preclinical and clinical observations demonstrate that unirradiated cells, near or far from the irradiation site, can control the tumor response. Nevertheless, previous studies do not address the problem in its global context, and present gaps regarding the link between the role of the immune system in the control of non-targeted effects for different types of radiotherapy and different fractionation schemes applied to GBM. This narrative synthesis of the scientific literature should help to update and critique available preclinical and medical knowledge. Indirectly, it will help formulate new research projects based on the synthesis and interpretation of results from a non-systematic selection of published studies.

Summary: Background: Insufficient infection prevention and control (IPC) practices in healthcare settings increase the SARS-CoV-2 infection risk among health workers. This study aimed to examine the level of preparedness for future outbreaks. Methods: We modelled the experience from the COVID-19 pandemic and assessed the return on investment on a global scale of three IPC interventions to prevent SARS-CoV-2 infections among health workers: enhancing hand hygiene; increasing access to personal protective equipment (PPE); and combining PPE, with a scale-up of IPC training and education (PPE+). Our analysis covered seven geographic regions, representing a combination of World Health Organization (WHO) regions and the Organisation for Economic Co-operation and Development (OECD) countries. Across all regions, we focused on the first 180 days of the pandemic in 2020 between January 1st and June 30th. We used an extended version of a susceptible-infectious-recovered compartmental model to measure the level of IPC preparedness. Data were sourced from the WHO COVID-19 Detailed Surveillance Database. Findings: In all regions, the PPE + intervention would have averted the highest number of new SARS-CoV-2 infections compared to the other two interventions, ranging from 6562 (95% CI 4873–8779) to 38,170 (95% CI 33,853–41,901) new infections per 100,000 health workers in OECD countries and in the South-East Asia region, respectively. Countries in the South-East Asia region and non-OECD countries in the Western Pacific region were poised to achieve the highest level of savings by scaling up the PPE + intervention. Interpretation: Our results not only support efforts to make an economic case for continuing investments in IPC interventions to halt the COVID-19 pandemic and protect health workers, but could also contribute to efforts to improve preparedness for future outbreaks. Funding: This work was funded by WHO, with support by the German Federal Ministry of Health for the WHO Research and Development Blueprint for COVID-19.

The COVID-19 pandemic has underscored the need for rapid and cost-effective diagnostic tools. Serological tests, particularly those measuring antibodies targeting the receptor-binding domain (RBD) of the virus, play a pivotal role in tracking infection dynamics and vaccine effectiveness. In this study, we aimed to develop a simple enzyme-linked immunosorbent assay (ELISA) for measuring RBD-specific antibodies, comparing two plant-based platforms for diagnostic reagent production. We chose to retain RBD in the endoplasmic reticulum (ER) to prevent potential immunoreactivity issues associated with plant-specific glycans. We produced ER-retained RBD in two plant systems: a stable transformation of BY-2 plant cell culture (BY2-RBD) and a transient transformation in Nicotiana benthamiana using the MagnICON system (NB-RBD). Both systems demonstrated their suitability, with varying yields and production timelines. The plant-made proteins revealed unexpected differences in N-glycan profiles, with BY2-RBD displaying oligo-mannosidic N-glycans and NB-RBD exhibiting a more complex glycan profile. This difference may be attributed to higher recombinant protein synthesis in the N. benthamiana system, potentially overloading the ER retention signal, causing some proteins to traffic to the Golgi apparatus. When used as diagnostic reagents in ELISA, BY2-RBD outperformed NB-RBD in terms of sensitivity, specificity, and correlation with a commercial kit. This discrepancy may be due to the distinct glycan profiles, as complex glycans on NB-RBD may impact immunoreactivity. In conclusion, our study highlights the potential of plant-based systems for rapid diagnostic reagent production during emergencies. However, transient expression systems, while offering shorter timelines, introduce higher heterogeneity in recombinant protein forms, necessitating careful consideration in serological test development.