Multi-niche human bone marrow on-a-chip for studying the interactions of adoptive CAR-T cell therapies with multiple myeloma.

Multiple myeloma (MM), a cancer of bone marrow plasma cells, is the second-most common hematological malignancy. However, despite immunotherapies like chimeric antigen receptor (CAR)-T cells, relapse is nearly universal. The bone marrow (BM) microenvironment influences how MM cells survive, proliferate, and resist treatment.

Spatially resolved subcellular protein-protein interactomics in drug-perturbed lung-cancer cultures and tissues.

Protein-protein interactions (PPIs) regulate signalling pathways and cell phenotypes, and the visualization of spatially resolved dynamics of PPIs would thus shed light on the activation and crosstalk of signalling networks. Here we report a method that leverages a sequential proximity ligation assay for the multiplexed profiling of PPIs with up to 47 proteins involved in multisignalling crosstalk pathways. We applied the method, followed by conventional immunofluorescence, to cell cultures and tissues of non-small-cell lung cancers with a mutated epidermal growth-factor receptor to determine the co-localization of PPIs in subcellular volumes and to reconstruct changes in the subcellular distributions of PPIs in response to perturbations by the tyrosine kinase inhibitor osimertinib.

Spatial immunophenotyping using multiplexed imaging of immune follicles in secondary lymphoid tissues.

Secondary lymphoid organs (SLOs), including tonsils (TS), lymph nodes (LN), and Peyer's Patches, exhibit complementary immune functions. However, little is known about the spatial organization of immune cells and extracellular matrix (ECM) in the SLOs. Traditional imaging is limited to a few markers, confining our understanding of the differences between the SLOs.

Multi-Niche Human Bone Marrow On-A-Chip for Studying the Interactions of Adoptive CAR-T Cell Therapies with Multiple Myeloma.

Unlabelled: Multiple myeloma (MM), a cancer of bone marrow plasma cells, is the second-most common hematological malignancy. However, despite immunotherapies like chimeric antigen receptor (CAR)-T cells, relapse is nearly universal. The bone marrow (BM) microenvironment influences how MM cells survive, proliferate, and resist treatment.

Spatial Morphoproteomic Features Predict Uniqueness of Immune Microarchitectures and Responses in Lymphoid Follicles.

Multiplex imaging technologies allow the characterization of single cells in their cellular environments. Understanding the organization of single cells within their microenvironment and quantifying disease-status related biomarkers is essential for multiplex datasets. Here we proposed SNOWFLAKE, a graph neural network framework pipeline for the prediction of disease-status from combined multiplex cell expression and morphology in human B-cell follicles.

Single-cell spatial metabolomics with cell-type specific protein profiling for tissue systems biology.

Metabolic reprogramming in cancer and immune cells occurs to support their increasing energy needs in biological tissues. Here we propose Single Cell Spatially resolved Metabolic (scSpaMet) framework for joint protein-metabolite profiling of single immune and cancer cells in male human tissues by incorporating untargeted spatial metabolomics and targeted multiplexed protein imaging in a single pipeline. We utilized the scSpaMet to profile cell types and spatial metabolomic maps of 19507, 31156, and 8215 single cells in human lung cancer, tonsil, and endometrium tissues, respectively.

Subcellular spatially resolved gene neighborhood networks in single cells.

Image-based spatial omics methods such as fluorescence hybridization (FISH) generate molecular profiles of single cells at single-molecule resolution. Current spatial transcriptomics methods focus on the distribution of single genes. However, the spatial proximity of RNA transcripts can play an important role in cellular function.

Spatial subcellular organelle networks in single cells.

Organelles play important roles in human health and disease, such as maintaining homeostasis, regulating growth and aging, and generating energy. Organelle diversity in cells not only exists between cell types but also between individual cells. Therefore, studying the distribution of organelles at the single-cell level is important to understand cellular function.

Combinatorial treatment rescues tumour-microenvironment-mediated attenuation of MALT1 inhibitors in B-cell lymphomas.

Activated B-cell-like diffuse large B-cell lymphomas (ABC-DLBCLs) are characterized by constitutive activation of nuclear factor κB driven by the B-cell receptor (BCR) and Toll-like receptor (TLR) pathways. However, BCR-pathway-targeted therapies have limited impact on DLBCLs. Here we used >1,100 DLBCL patient samples to determine immune and extracellular matrix cues in the lymphoid tumour microenvironment (Ly-TME) and built representative synthetic-hydrogel-based B-cell-lymphoma organoids accordingly.

Multiplexed protein profiling reveals spatial subcellular signaling networks.

Protein-protein interaction networks are altered in multi-gene dysregulations in many disorders. Image-based protein multiplexing sheds light on signaling pathways to dissect cell-to-cell heterogeneity, previously masked by the bulk assays. Herein, we present a rapid multiplexed immunofluorescence (RapMIF) method measuring up to 25-plex spatial protein maps from cultures and tissues at subcellular resolution, providing combinatorial 272 pairwise and 1,360 tri-protein signaling states across 33 multiplexed pixel-level clusters.

Spatially variant immune infiltration scoring in human cancer tissues.

The Immunoscore is a method to quantify the immune cell infiltration within cancers to predict the disease prognosis. Previous immune profiling approaches relied on limited immune markers to establish patients' tumor immunity. However, immune cells exhibit a higher-level complexity that is typically not obtained by the conventional immunohistochemistry methods.

Repair of complete atrioventricular septal defect between 2 and 3.5 kilograms: Defining the limits of safe repair.

Objectives: Repair of complete atrioventricular septal defect (cAVSD) is routinely performed at around 3 months of age with good results. However, some patients require earlier surgery due to heart failure or failure to thrive. It is uncertain whether cAVSD repair performed on patients ≤3.

Incidence and management of the left ventricular outflow obstruction in patients with atrioventricular septal defects.

Objectives: Left ventricular outflow tract obstruction (LVOTO) is a recognized complication after complete repair of atrioventricular septal defect (AVSD). This study reviewed the incidence and management of LVOTO following AVSD repair at a single institution.

Methods: From 1975 to 2019, 24 patients (3.

Propensity Score Matched Analysis of Cleft Closure in Complete Atrioventricular Septal Defect Repair.

Background: Repair of complete atrioventricular septal defect (cAVSD) is achieved with low mortality. However, there is a high rate of reoperation on the left atrioventricular valve (LAVV), which is often attributed to nonclosure of the cleft. Although nonclosure of the cleft has been reported to be a risk factor for reoperation, no randomized controlled or propensity-matched trials have ever been performed.

Spatially visualized single-cell pathology of highly multiplexed protein profiles in health and disease.

Deep molecular profiling of biological tissues is an indicator of health and disease. We used imaging mass cytometry (IMC) to acquire spatially resolved 20-plex protein data in tissue sections from normal and chronic tonsillitis cases. We present SpatialViz, a suite of algorithms to explore spatial relationships in multiplexed tissue images by visualizing and quantifying single-cell granularity and anatomical complexity in diverse multiplexed tissue imaging data.

Spatially resolved 3D metabolomic profiling in tissues.

Spatially resolved RNA and protein molecular analyses have revealed unexpected heterogeneity of cells. Metabolic analysis of individual cells complements these single-cell studies. Here, we present a three-dimensional spatially resolved metabolomic profiling framework (3D-SMF) to map out the spatial organization of metabolic fragments and protein signatures in immune cells of human tonsils.

Early repair of complete atrioventricular septal defect has better survival than staged repair after pulmonary artery banding: A propensity score-matched study.

Objectives: Complete atrioventricular septal defect (cAVSD) repair is usually performed between 3 and 6 months of age. However, some children present with early heart failure requiring intervention. It is unclear whether primary complete repair or initial pulmonary artery banding (PAB) provides better outcomes.

COVID-19 Diagnostics, Tools, and Prevention.

The Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), outbreak from Wuhan City, Hubei province, China in 2019 has become an ongoing global health emergency. The emerging virus, SARS-CoV-2, causes coughing, fever, muscle ache, and shortness of breath or dyspnea in symptomatic patients. The pathogenic particles that are generated by coughing and sneezing remain suspended in the air or attach to a surface to facilitate transmission in an aerosol form.

Suprascapular Nerve Blockade for Postoperative Pain Control After Arthroscopic Shoulder Surgery: A Systematic Review and Meta-analysis.

Background: Regional nerve blocks are commonly used to manage postoperative pain after arthroscopic shoulder procedures. The interscalene brachial plexus block (ISB) is commonly used; however, because of the reported side effects of ISB, the use of a suprascapular nerve block (SSNB) has been described as an alternative strategy with fewer reported side effects.

Purpose: To examine the efficacy of SSNB for pain control after shoulder arthroscopy compared with ISB as well as anesthesia without a nerve block.

Multivariate Analysis of Hemicelluloses in Bleached Kraft Pulp Using Infrared Spectroscopy.

The hemicellulose composition of a pulp significantly affects its chemical and physical properties and thus represents an important process control variable. However, complicated steps of sample preparation make standard methods for the carbohydrate analysis of pulp samples, such as high performance liquid chromatography (HPLC), expensive and time-consuming. In contrast, pulp analysis by attenuated total internal reflection Fourier transform infrared spectroscopy (ATR FT-IR) requires little sample preparation.

Modification of xylan in alkaline treated bleached hardwood kraft pulps as classified by attenuated total-internal-reflection (ATR) FTIR spectroscopy.

The glucuronoxylan composition of a pulp affects the bonding between cellulosic fibres, and thus correlates with such network properties as tensile strength. Here, we demonstrate the promise of attenuated total-internal-reflection (ATR) FTIR spectroscopy as a rapid means for classifying the xylan contained in commercial bleached kraft pulps. This study draws upon samples composed of bleached eucalyptus kraft pulps and combinations of eucalyptus with other commercial bleached kraft pulps.

Extreme strain localization and sliding friction in physically associating polymer gels.

Model physically associating gels deformed in shear over a wide range of reduced rates displayed evidence of strain localization. The nonlinear stress responses and inhomogeneous velocity profiles observed during shear rheometry coupled with particle tracking velocimetry were associated with the occurrence of rate-dependent banding and fracture-like responses in the gel. Scaling law analysis from traditional sliding friction studies suggests that, at the molecular level, deformation is confined to a shear zone with thickness comparable to the mesh size of the gel, the smallest structurally relevant length scale in the gel.

Interaction of tertiary phosphines with lignin-type, alpha,beta-unsaturated aldehydes in water.

To learn more about the bleaching action of pulps by (hydroxymethyl)phosphines, lignin chromophores, such as the alpha,beta-unsaturated aromatic aldehydes, sinapaldehyde, coniferylaldehyde, and coumaraldehyde, were reacted with the tertiary phosphines R2R'P [R = R' = Me, Et, (CH2)3OH, iPr, cyclo-C6H11, (CH2)2CN; R = Me or Et, R' = Ph; R = Ph, R' = Me, m-NaSO3-C6H4] in water at room temperature under argon. In all cases, initial nucleophilic attack of the phosphine occurs at the activated C=C bond to form a zwitterionic monophosphonium species. With the phosphines PR3 [R = Me, Et, (CH2)3OH] and with R2R'P (R = Me or Et, R' = Ph), the zwitterion undergoes self-condensation to give a bisphosphonium zwitterion that can react with aqueous HCl to form the corresponding dichloride salts (as a mixture of R,R- and S,S-enantiomers); X-ray structures are presented for the bisphosphonium chlorides synthesized from the Et3P and Me3P reactions with sinapaldehyde.