Maintaining sidedness and fluidity in cell membrane coatings supported on nano-particulate and planar surfaces.

Supported cell membrane coatings meet many requirements set to bioactive nanocarriers and materials, provided sidedness and fluidity of the natural membrane are maintained upon coating. However, the properties of a support-surface responsible for maintaining correct sidedness and fluidity are unknown. Here, we briefly review the properties of natural membranes and membrane-isolation methods, with focus on the asymmetric distribution of functional groups in natural membranes (sidedness) and the ability of molecules to float across a membrane to form functional domains (fluidity).

Ciprofloxacin-Loaded, pH-Responsive PAMAM-Megamers Functionalized with S-Nitrosylated Hyaluronic Acid Support Infected Wound Healing in Mice without Inducing Antibiotic Resistance.

Antimicrobial-resistant bacterial infections threaten to become the number one cause of death by the year 2050. Since the speed at which antimicrobial-resistance develops is exceeding the pace at which new antimicrobials come to the market, this threat cannot be countered by making more, new and stronger antimicrobials. Promising new antimicrobials should not only kill antimicrobial-resistant bacteria, but also prevent development of new bacterial resistance mechanisms in strains still susceptible.

A phase 2 trial combining afatinib with cetuximab in patients with EGFR exon 20 insertion-positive non-small cell lung cancer.

Background: Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations are the third most common EGFR mutations in patients with non-small cell lung cancer (NSCLC) and are associated with primary resistance to EGFR tyrosine kinase inhibitors (TKIs). There is evidence of activity of combining EGFR TKIs with monoclonal antibodies. This study reports on the efficacy and safety of afatinib in combination with cetuximab.

Taking the STING out of CIN.

Chromosomal instability (CIN), a hallmark of cancer, promotes cell-intrinsic inflammatory signaling. Although inflammation is generally considered tumor-suppressive, this relationship is more complex in cancers with CIN. We discuss new findings by Li et al.

Association between Low Vitamin D Status, Serotonin, and Clinico-Biobehavioral Parameters in Alzheimer's Disease.

Introduction: Studies suggest a role of vitamin D in the progression and symptomatology of Alzheimer's disease (AD), with few in vitro studies pointing to effects on serotonergic and amyloidogenic turnover. However, limited data exist in AD patients on the potential association with cognition and behavioral and psychological signs and symptoms of dementia (BPSD). In this retrospective cross-sectional study, we, therefore, explored potential correlations of serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations, indicative of vitamin D status, with serum serotonin (5-hydroxytryptamine, 5-HT) levels, cognitive/BPSD scorings, and cerebrospinal fluid (CSF) biomarker levels.

Magnetically-targetable outer-membrane vesicles for sonodynamic eradication of antibiotic-tolerant bacteria in bacterial meningitis.

Treatment of acute bacterial meningitis is difficult due to the impermeability of the blood-brain barrier, greatly limiting the antibiotic concentrations that can be achieved in the brain. Escherichia coli grown in presence of iron-oxide magnetic nanoparticles secrete large amounts of magnetic outer-membrane vesicles (OMVs) in order to remove excess Fe from their cytoplasm. OMVs are fully biomimetic nanocarriers, but can be inflammatory.

IL-33 Expression Is Lower in Current Smokers at both Transcriptomic and Protein Levels.

IL-33 is a proinflammatory cytokine thought to play a role in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). A recent clinical trial using an anti-IL-33 antibody showed a reduction in exacerbation and improved lung function in ex-smokers but not current smokers with COPD. This study aimed to understand the effects of smoking status on IL-33.

Rapid Bacterial Detection and Gram-Identification Using Bacterially Activated, Macrophage-Membrane-Coated Nanowired-Si Surfaces in a Microfluidic Device.

Bacterially induced sepsis requires rapid bacterial detection and identification. Hours count for critically ill septic patients, while current culture-based detection requires at least 10 h up to several days. Here, we apply a microfluidic device equipped with a bacterially activated, macrophage-membrane-coating on nanowired-Si adsorbent surfaces for rapid, bacterial detection and Gram-identification in bacterially contaminated blood.

Two or four implants for maxillary overdentures in edentulous patients: 1-year results of a randomized controlled trial.

Introduction: Maxillary implant overdenture therapy is a good treatment option for treating patients experiencing problems with their conventional maxillary denture. Retaining the overdenture with four implants and a bar attachment system serves as the current gold standard. However, there is a demand for less costly and less invasive treatment options.

MR-guided HDR prostate brachytherapy with teleoperated steerable needles.

Conformity of tumour volumes and dose plans in prostate brachytherapy (BT) can be constrained by unwanted needle deflections, needle access restrictions and visualisation limitations. This work validates the feasibility of teleoperated robotic control of an active steerable needle using magnetic resonance (MR) for guidance. With this system, perturbations can be counteracted and critical structures can be circumvented to access currently inaccessible areas.

Minimum and Optimal CA19-9 Response After Two Months Induction Chemotherapy in Patients With Locally Advanced Pancreatic Cancer: A Nationwide Multicenter Study.

Objective: This nationwide multicenter study aimed to define clinically relevant thresholds of relative serum CA19-9 response after 2 months of induction chemotherapy in patients with locally advanced pancreatic cancer (LAPC).

Background: CA19-9 is seen as leading biomarker for response evaluation in patients with LAPC, but early clinically useful cut-offs are lacking.

Methods: All consecutive patients with LAPC after 4 cycles (m)FOLFIRINOX or 2 cycles gemcitabine-nab-paclitaxel induction chemotherapy (±radiotherapy) with CA19-9 ≥5 U/mL at baseline were analyzed (2015-2019).

Practice variation in venous resection during pancreatoduodenectomy for pancreatic cancer: A nationwide cohort study.

Background: Practice variation exists in venous resection during pancreatoduodenectomy, but little is known about the potential causes and consequences as large studies are lacking. This study explores the potential causes and consequences of practice variation in venous resection during pancreatoduodenectomy for pancreatic cancer in the Netherlands.

Methods: This nationwide retrospective cohort study included patients undergoing pancreatoduodenectomy for pancreatic cancer in 18 centers from 2013 through 2017.

Efficient clearance of periodontitis pathogens by membrane-coated HO self-supplied nanocomposites in a "Jenga" style.

As a key pathogen of periodontitis, requires support of the initial colonizing bacterium ( preferably) to form symbiotic biofilms on gingival tissues with enhanced antibiotic resistance. Here, we report a new strategy to treat periodontitis biofilms with membrane-coated HO self-supplied nanocomposites (ZnO/FeO@MV NPs) in a "Jenga" style. Integration of our special MV coatings enables selectively enhanced internalization of the cargos in , thus inducing severe damage to the foundational bacterial layer and collapse/clearance of symbiotic biofilms consequently.

Reliability of panel-based mutational signatures for immune-checkpoint-inhibition efficacy prediction in non-small cell lung cancer.

Objectives: Mutational signatures (MS) are gaining traction for deriving therapeutic insights for immune checkpoint inhibition (ICI). We asked if MS attributions from comprehensive targeted sequencing assays are reliable enough for predicting ICI efficacy in non-small cell lung cancer (NSCLC).

Methods: Somatic mutations of m = 126 patients were assayed using panel-based sequencing of 523 cancer-related genes.

Characterization of soluble TLR2 and CD14 levels during acute dengue virus infection.

Dengue virus infection results in a broad spectrum of diseases ranging from mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Hitherto, there is no consensus biomarker for the prediction of severe dengue disease in patients. Yet, early identification of patients who progress to severe dengue is pivotal for better clinical management.

Enhancing longevity of immunoisolated pancreatic islet grafts by modifying both the intracapsular and extracapsular environment.

Type 1 diabetes mellitus (T1DM) is a chronic metabolic disease characterized by autoimmune destruction of pancreatic β cells. Transplantation of immunoisolated pancreatic islets might treat T1DM in the absence of chronic immunosuppression. Important advances have been made in the past decade as capsules can be produced that provoke minimal to no foreign body response after implantation.

SALL1 enforces microglia-specific DNA binding and function of SMADs to establish microglia identity.

Spalt-like transcription factor 1 (SALL1) is a critical regulator of organogenesis and microglia identity. Here we demonstrate that disruption of a conserved microglia-specific super-enhancer interacting with the Sall1 promoter results in complete and specific loss of Sall1 expression in microglia. By determining the genomic binding sites of SALL1 and leveraging Sall1 enhancer knockout mice, we provide evidence for functional interactions between SALL1 and SMAD4 required for microglia-specific gene expression.

Determinants of excessive weight gain after the initiation of insulin therapy in type 2 diabetes mellitus: Retrospective inception cohort study (ZODIAC 60).

Aims: To explore determinants of excessive weight gain after initiation of insulin therapy in type 2 diabetes mellitus (T2DM), in particular variables identified in the pre-insulin phase.

Methods: We performed a retrospective observational intervention cohort study, by means of a new user design/ inception cohort concerning n = 5086 patients. We studied determinants of excessive weight gain (5 kg or more) in the first year after initiation of insulin therapy, using both visualization and logistic regression analysis with subsequent receiver operation characteristic (ROC) analyses.

Universal gut microbial relationships in the gut microbiome of wild baboons.

Ecological relationships between bacteria mediate the services that gut microbiomes provide to their hosts. Knowing the overall direction and strength of these relationships is essential to learn how ecology scales up to affect microbiome assembly, dynamics, and host health. However, whether bacterial relationships are generalizable across hosts or personalized to individual hosts is debated.

Tribology of Pore-Textured Hard Surfaces under Physiological Conditions: Effects of Texture Scales.

Micro- and nanotexturing on hard biomaterials have shown advantages for tissue engineering and antifouling applications. However, a growing number of studies have also shown that texturing may cause an increase in friction, demanding further research on the tribological effects of texturing under physiological conditions. This study investigates the tribological effects of micro- and nanopore patterns on hard hydrophilic silicon sliding against soft hydrophobic polydimethylsiloxane (PDMS) immersed in aqueous liquids with various viscosities, simulating the sliding of a textured implant surface against soft tissues.

Targeting alarmin release reverses Sjogren's syndrome phenotype by revitalizing Ca signalling.

Background: Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease that is embodied by the loss of salivary gland function and immune cell infiltration, but the mechanism(s) are still unknown. The aim of this study was to understand the mechanisms and identify key factors that leads to the development and progression of pSS.

Methods: Immunohistochemistry staining, FACS analysis and cytokine levels were used to detect immune cells infiltration and activation in salivary glands.

Beyond personal space: Unveiling the transmission pattern of the human gut and oral microbiome.

Valles-Colomer et al. evaluated the rate of microbial strain sharing to infer person-to-person microbial transmission. The presence of shared strains does not necessarily indicate direct transmission between individuals.

Patient-reported outcomes in capmatinib-treated patients with METex14-mutated advanced NSCLC: Results from the GEOMETRY mono-1 study.

Introduction: Capmatinib, a MET inhibitor, showed substantial antitumour activity with manageable side effects in patients with MET exon 14 (METex14)-mutated advanced non-small cell lung cancer (aNSCLC) in the GEOMETRY mono-1 study. We report patient-reported outcomes (PROs) from this study.

Methods: Enrolled treatment-naïve (1L) or pre-treated (2L) patients with aNSCLC with a METex14-skipping mutation received 400 mg capmatinib twice daily during 21-day treatment cycles.