A First-in-Human Phase I Clinical Study with MVX-ONCO-1, a Personalized Active Immunotherapy, in Patients with Advanced Solid Tumors.

Unlabelled: Over two decades, most cancer vaccines failed clinical development. Key factors may be the lack of efficient priming with tumor-specific antigens and strong immunostimulatory signals. MVX-ONCO-1, a personalized cell-based cancer immunotherapy, addresses these critical steps utilizing clinical-grade material to replicate a successful combination seen in experimental models: inactivated patient's own tumor cells, providing the widest cancer-specific antigen repertoire and a standardized, sustained, local delivery over days of a potent adjuvant achieved by encapsulated cell technology.

A set of nematode rRNA cistron databases and a primer assessment tool to enable more flexible and comprehensive metabarcoding.

The ITS-2-rRNA has been particularly useful for nematode metabarcoding but does not resolve all phylogenetic relationships, and reference sequences are not available for many nematode species. This is a particular issue when metabarcoding complex communities such as wildlife parasites or terrestrial and aquatic free-living nematode communities. We have used markerDB to produce four databases of distinct regions of the rRNA cistron: the 18S rRNA gene, the 28S rRNA gene, the ITS-1 intergenic spacer and the region spanning ITS-1_5.

Erratum: Immortalized human myoblast cell lines for the delivery of therapeutic proteins using encapsulated cell technology.

[This corrects the article DOI: 10.1016/j.omtm.

Engineering a versatile and retrievable cell macroencapsulation device for the delivery of therapeutic proteins.

Encapsulated cell therapy holds a great potential to deliver sustained levels of highly potent therapeutic proteins to patients and improve chronic disease management. A versatile encapsulation device that is biocompatible, scalable, and easy to administer, retrieve, or replace has yet to be validated for clinical applications. Here, we report on a cargo-agnostic, macroencapsulation device with optimized features for protein delivery.

Immortalized human myoblast cell lines for the delivery of therapeutic proteins using encapsulated cell technology.

Despite many promising results obtained in previous preclinical studies, the clinical development of encapsulated cell technology (ECT) for the delivery of therapeutic proteins from macrocapsules is still limited, mainly due to the lack of an allogeneic cell line compatible with therapeutic application in humans. In our work, we generated an immortalized human myoblast cell line specifically tailored for macroencapsulation. In the present report, we characterized the immortalized myoblasts and described the engineering process required for the delivery of functional therapeutic proteins including a cytokine, monoclonal antibodies and a viral antigen.

The Challenge of Converting "Failed Spinal Cord Stimulation Syndrome" Back to Clinical Success, Using SCS Reprogramming as Salvage Therapy, through Neurostimulation Adapters Combined with 3D-Computerized Pain Mapping Assessment: A Real Life Retrospective Study.

While paresthesia-based Spinal Cord Stimulation (SCS) has been proven effective as treatment for chronic neuropathic pain, its initial benefits may lead to the development of "Failed SCS Syndrome' (FSCSS) defined as decrease over time related to Loss of Efficacy (LoE) with or without Loss of Coverage (LoC). Development of technologies associating new paresthesia-free stimulation waveforms and implanted pulse generator adapters provide opportunities to manage patients with LoE. The main goal of our study was to investigate salvage procedures, through neurostimulation adapters, in patients already implanted with SCS and experiencing LoE.

Vimentin Intermediate Filaments Mediate Cell Morphology on Viscoelastic Substrates.

The ability of cells to take and change shape is a fundamental feature underlying development, wound repair, and tissue maintenance. Central to this process is physical and signaling interactions between the three cytoskeletal polymeric networks: F-actin, microtubules, and intermediate filaments (IFs). Vimentin is an IF protein that is essential to the mechanical resilience of cells and regulates cross-talk among the cytoskeleton, but its role in how cells sense and respond to the surrounding extracellular matrix is largely unclear.

The Added Value of Subcutaneous Peripheral Nerve Field Stimulation Combined with SCS, as Salvage Therapy, for Refractory Low Back Pain Component in Persistent Spinal Pain Syndrome Implanted Patients: A Randomized Controlled Study (CUMPNS Study) Based on 3D-Mapping Composite Pain Assessment.

While Spinal Cord Stimulation (SCS) provides satisfaction to almost 2/3 of Persistent Spinal Pain Syndrome-Type 2 (PSPS-T2) patients implanted for refractory chronic back and/or leg pain, when not adequately addressed the back pain component, leaves patients in a therapeutic cul-de-sac. Peripheral Nerve field Stimulation (PNfS) has shown interesting results addressing back pain in the same population. Far from placing these two techniques in opposition, we suggest that these approaches could be combined to better treat PSPS-T2 patients.

Professional Status of Persistent Spinal Pain Syndrome Patients after Spinal Surgery (PSPS-T2): What Really Matters? A Prospective Study Introducing the Concept of "Adapted Professional Activity" Inferred from Clinical, Psychological and Social Influence.

Persistent Spinal Pain Syndrome Type 2 (PSPS-T2) represents a main cause of work disruption. Beyond its societal consequences, occupational inactivity is responsible for a major decrease in physical/mental health in individuals but remains poorly analyzed. We designed a study to prospectively examine Professional Status (PS) evolution and its association with key bio-psychological markers.

A Novel Multi-Dimensional Clinical Response Index Dedicated to Improving Global Assessment of Pain in Patients with Persistent Spinal Pain Syndrome after Spinal Surgery, Based on a Real-Life Prospective Multicentric Study (PREDIBACK) and Machine Learning Techniques.

The multidimensionality of chronic pain forces us to look beyond isolated assessment such as pain intensity, which does not consider multiple key parameters, particularly in post-operative Persistent Spinal Pain Syndrome (PSPS-T2) patients. Our ambition was to produce a novel Multi-dimensional Clinical Response Index (MCRI), including not only pain intensity but also functional capacity, anxiety-depression, quality of life and quantitative pain mapping, the objective being to achieve instantaneous assessment using machine learning techniques. Two hundred PSPS-T2 patients were enrolled in the real-life observational prospective PREDIBACK study with 12-month follow-up and received various treatments.

Finite Mixture Models Based on Pain Intensity, Functional Disability and Psychological Distress Composite Assessment Allow Identification of Two Distinct Classes of Persistent Spinal Pain Syndrome after Surgery Patients Related to Their Quality of Life.

Persistent Spinal Pain Syndrome Type 2 (PSPS-T2), (Failed Back Surgery Syndrome), dramatically impacts on patient quality of life, as evidenced by Health-Related Quality of Life (HRQoL) assessment tools. However, the importance of functioning, pain perception and psychological status in HRQoL can substantially vary between subjects. Our goal was to extract patient profiles based on HRQoL dimensions in a sample of PSPS-T2 patients and to identify factors associated with these profiles.

A Novel Method to Make Polyacrylamide Gels with Mechanical Properties Resembling those of Biological Tissues.

Studies characterizing how cells respond to the mechanical properties of their environment have been enabled by the use of soft elastomers and hydrogels as substrates for cell culture. A limitation of most such substrates is that, although their elastic properties can be accurately controlled, their viscous properties cannot, and cells respond to both elasticity and viscosity in the extracellular material to which they bind. Some approaches to endow soft substrates with viscosity as well as elasticity are based on coupling static and dynamic crosslinks in series within polymer networks or forming gels with a combination of sparse chemical crosslinks and steric entanglements.

A Quantitative ELISA Protocol for Detection of Specific Human IgG against the SARS-CoV-2 Spike Protein.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic with at least 3.8 million deaths to date. For that reason, finding an efficient vaccine for this virus quickly became a global priority.

Persistent Spinal Pain Syndrome Type 2 (PSPS-T2), a Social Pain? Advocacy for a Social Gradient of Health Approach to Chronic Pain.

The Social Gradient of Health (SGH), or position in the social hierarchy, is one of the major determinants of health. It influences the development and evolution of many chronic diseases. Chronic pain dramatically affects individual and social condition.

Local Sustained GM-CSF Delivery by Genetically Engineered Encapsulated Cells Enhanced Both Cellular and Humoral SARS-CoV-2 Spike-Specific Immune Response in an Experimental Murine Spike DNA Vaccination Model.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic with recurrences. Therefore, finding a vaccine for this virus became a priority for the scientific community. The SARS-CoV-2 spike protein has been described as the keystone for viral entry into cells and effective immune protection against SARS-CoV-2 is elicited by this protein.

Cutting Edge: mTORC1 Inhibition in Metastatic Breast Cancer Patients Negatively Affects Peripheral NK Cell Maturation and Number.

NK cells are cytotoxic lymphocytes displaying strong antimetastatic activity. Mouse models and in vitro studies suggest a prominent role of the mechanistic target of rapamycin (mTOR) kinase in the control of NK cell homeostasis and antitumor functions. However, mTOR inhibitors are used as chemotherapies in several cancer settings.

An Experimentally Defined Hypoxia Gene Signature in Glioblastoma and Its Modulation by Metformin.

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor, characterized by a high degree of intertumoral heterogeneity. However, a common feature of the GBM microenvironment is hypoxia, which can promote radio- and chemotherapy resistance, immunosuppression, angiogenesis, and stemness. We experimentally defined common GBM adaptations to physiologically relevant oxygen gradients, and we assessed their modulation by the metabolic drug metformin.

Elasticity-dependent response of malignant cells to viscous dissipation.

The stiffness of the cellular environment controls malignant cell phenotype and proliferation. However, the effect of viscous dissipation on these parameters has not yet been investigated, in part due to the lack of in vitro cell substrates reproducing the mechanical properties of normal tissues and tumors. In this article, we use a newly reported viscoelastic polyacrylamide gel cell substrate, and we characterize the impact of viscous dissipation on three malignant cell lines: DU145 and PC3 derived from prostate and LN229 from brain.

Comparison of conventional, burst and high-frequency spinal cord stimulation on pain relief in refractory failed back surgery syndrome patients: study protocol for a prospective randomized double-blinded cross-over trial (MULTIWAVE study).

Background: While the evolution of technology provides new opportunities to manage chronic refractory pain using different waveform modalities of spinal cord stimulation in failed back surgery syndrome (FBSS), there is no randomized controlled trial available to compare the efficacy of these different stimulations waveforms to date. MULTIWAVE is a prospective, randomized, double-blinded, crossover trial study designed to compare the clinical efficacy of tonic conventional stimulation (TCS), burst stimulation (BURST) and high-frequency stimulation (HF) in FBSS patients over a 15-month period in SCS implanted patients.

Methods/design: Twenty-eight patients will be recruited in the Poitiers University Hospital, in Niort and La Rochelle Hospitals in France.

A novel method to make viscoelastic polyacrylamide gels for cell culture and traction force microscopy.

Polyacrylamide hydrogels are commonly used in cell biology, notably to cultivate cells on soft surfaces. Polyacrylamide gels are purely elastic and well adapted to cell culture as they are inert and can be conjugated with adhesion proteins. Here, we report a method to make viscoelastic polyacrylamide gels with mechanical properties more closely resembling biological tissues and suitable for cell culture .

Loss of Vimentin Enhances Cell Motility through Small Confining Spaces.

The migration of cells through constricting spaces or along fibrous tracks in tissues is important for many biological processes and depends on the mechanical properties of a cytoskeleton made up of three different filaments: F-actin, microtubules, and intermediate filaments. The signaling pathways and cytoskeletal structures that control cell motility on 2D are often very different from those that control motility in 3D. Previous studies have shown that intermediate filaments can promote actin-driven protrusions at the cell edge, but have little effect on overall motility of cells on flat surfaces.

Deletion of Inflammasome Components Is Not Sufficient To Prevent Fatal Inflammation in Models of Familial Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a severe inflammatory condition that occurs in patients with genetic defects of cytotoxicity (familial HLH [FHL]) or secondary to other immunological disorders such as juvenile idiopathic arthritis. HLH is characterized by elevated levels of serum IL-18 and other cytokines. Moreover, a novel clinical entity has been recently identified in which constitutive NLRC4 inflammasome activation leads to severe HLH.

Matching material and cellular timescales maximizes cell spreading on viscoelastic substrates.

Recent evidence has shown that, in addition to rigidity, the viscous response of the extracellular matrix (ECM) significantly affects the behavior and function of cells. However, the mechanism behind such mechanosensitivity toward viscoelasticity remains unclear. In this study, we systematically examined the dynamics of motor clutches (i.

The desmin network is a determinant of the cytoplasmic stiffness of myoblasts.

Background Information: The mechanical properties of cells are essential to maintain their proper functions, and mainly rely on their cytoskeleton. A lot of attention has been paid to actin filaments, demonstrating their central role in the cells mechanical properties, but much less is known about the participation of intermediate filament (IF) networks. Indeed the contribution of IFs, such as vimentin, keratins and lamins, to cell mechanics has only been assessed recently.