Densely Populated Cell and Organelles Segmentation With Multi-Plane Deep Learning Pipeline.

Here we develop a robust machine vision pipeline for cell and organelle segmentation within vEM datasets. We collect neural network predictions along multiple planes, capturing 3D correlations using only 2D neural networks. We segment and analyze hundreds of platelets and report quantitative morphological measurements.

Generative AI for Health Technology Assessment: Opportunities, Challenges, and Policy Considerations - an ISPOR Working Group Report.

Objective: To provide an introduction to the uses of generative Artificial Intelligence (AI) and foundation models, including large language models (LLMs), in the field of health technology assessment (HTA).

Methods: We reviewed applications of generative AI in three areas: systematic literature reviews, real world evidence (RWE) and health economic modeling.

Results: (1) Literature reviews: generative AI has the potential to assist in automating aspects of systematic literature reviews by proposing search terms, screening abstracts, extracting data and generating code for meta-analyses; (2) Real World Evidence (RWE): generative AI can facilitate automating processes and analyze large collections of real-world data (RWD) including unstructured clinical notes and imaging; (3) Health economic modeling: generative AI can aid in the development of health economic models, from conceptualization to validation.

Humoral Immunity Profiling to Pandemic and Bat-Derived Coronavirus Variants: A Geographical Comparison.

Dynamic pathogen exposure may impact the immunological response to SARS-CoV-2 (SCV2). One potential explanation for the lack of severe SCV2-related morbidity and mortality in Southeast Asia is prior exposure to related betacoronaviruses. Recent discoveries of SCV2-related betacoronaviruses from horseshoe bats (Rhinolophus sinicus) in Thailand, Laos, and Cambodia suggest the potential for bat-to-human spillover exposures in the region.

Curcumin attenuates smoking and drinking activated NF-κB/IL-6 inflammatory signaling axis in cervical cancer.

Background: High-risk strains of HPV are known to cause cervical cancer. Multiple clinical studies have emphasized that smoking and drinking are critical risk factors for cervical cancer and its high-grade precursors. In this study, we investigated if smoking and/or drinking augment the molecular mechanisms of cervical carcinogenesis and defined a potential therapeutic approach for their attenuation.

Altruistic feeding and cell-cell signaling during bacterial differentiation actively enhance phenotypic heterogeneity.

Starvation triggers bacterial spore formation, a committed differentiation program that transforms a vegetative cell into a dormant spore. Cells in a population enter sporulation nonuniformly to secure against the possibility that favorable growth conditions, which put sporulation-committed cells at a disadvantage, may resume. This heterogeneous behavior is initiated by a passive mechanism: stochastic activation of a master transcriptional regulator.

A Type I Photosensitizer-Polymersome Boosts Reactive Oxygen Species Generation by Forcing H-Aggregation for Amplifying STING Immunotherapy.

Activation of the innate immune Stimulator of Interferon Genes (STING) pathway potentiates antitumor immunity. However, delivering STING agonists systemically to tumors presents a formidable challenge, and resistance to STING monotherapy has emerged in clinical trials with diminishing natural killer (NK) cell proliferation. Here, we encapsulated the STING agonist diABZI within polymersomes containing a Type I photosensitizer (NBS), creating a nanoagonist (PNBS/diABZI) for highly responsive tumor immunotherapy.

Lineage-specific CDK activity dynamics characterize early mammalian development.

Cyclin-dependent kinases (CDK) are key regulatory enzymes that regulate proliferation dynamics and cell fate in response to extracellular inputs. It remains largely unknown how CDK activity fluctuates and influences cell commitment during early mammalian development. Here, we generated a transgenic mouse model expressing a CDK kinase translocation reporter (KTR) that enabled quantification of CDK activity in live single cells.

Non-invasive optical and laboratory hematologic biomarkers correlate in patients with sickle cell disease.

The goal of this study is to identify non-invasive optical hemodynamic biomarkers that can index laboratory hematology measurements in sickle cell disease (SCD). We acquired frequency-domain NIRS (FD-NIRS) and diffuse correlation spectroscopy (DCS) data from the forearms and foreheads of 17 participants in a randomized, double-blind, placebo-controlled trial evaluating effects of isoquercetin (IQ) on thromboinflammation in SCD. We observed multiple, significant correlations between optical and hematology biomarkers including cerebral tissue oxygen saturation (StO) and hematocrit (HCT); oxyhemoglobin ([OHb]) recovery rate and intercellular adhesion molecule 1 (ICAM-1); and blood flow index (BFI) reperfusion rate and coagulation index (CI).

Quantifying brain development in the HEALthy Brain and Child Development (HBCD) Study: The magnetic resonance imaging and spectroscopy protocol.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The acquisition of multimodal magnetic resonance-based brain development data is central to the study's core protocol. However, application of Magnetic Resonance Imaging (MRI) methods in this population is complicated by technical challenges and difficulties of imaging in early life.

Microbubbles bound to drug-eluting beads enable ultrasound imaging and enhanced delivery of therapeutics.

Transarterial chemoembolization (TACE) is an image-guided minimally invasive treatment for liver cancer which involves delivery of chemotherapy and embolic material into tumor-supplying arteries to block blood flow to a liver tumor and to deliver chemotherapy directly to the tumor. However, the released drug diffuses only less than a millimeter away from the beads. To enhance the efficacy of TACE, the development of microbubbles electrostatically bound to the surface of drug-eluting beads loaded with different amounts of doxorubicin (0-37.

The HEALthy Brain and Child Development Study (HBCD): NIH collaboration to understand the impacts of prenatal and early life experiences on brain development.

The human brain undergoes rapid development during the first years of life. Beginning in utero, a wide array of biological, social, and environmental factors can have lasting impacts on brain structure and function. To understand how prenatal and early life experiences alter neurodevelopmental trajectories and shape health outcomes, several NIH Institutes, Centers, and Offices collaborated to support and launch the HEALthy Brain and Child Development (HBCD) Study.

Eosinophils Respond to Extracellular Matrix Treated Muscle Injuries but are Not Required for Macrophage Polarization.

The immune response to decellularized extracellular matrix (ECM) muscle injury is characterized by Th2 T cells, Tregs, M2-like macrophages, and an abundance of eosinophils. Eosinophils have previously been described as mediators of muscle regeneration but inhibit skin wound healing. In addition to response to wounding, a large number of eosinophils respond to biomaterial-treated muscle injury, specifically in response to decellularized ECM.

Exosomes derived from tumor adjacent fibroblasts efficiently target pancreatic tumors.

The application of extracellular vesicles, particularly exosomes (EXs), is rapidly expanding in the field of medicine, owing to their remarkable properties as natural carriers of biological cargo. This study investigates utilization of exosomes derived from stromal cells of tumor adjacent normal tissues (NAF-EXs) for personalized medicine, which can be derived at the time of diagnosis by endoscopic ultrasound. Herein, we show that exosomes (EXs) derived from NAFs demonstrate differential bio-physical characteristics, efficient cellular internalization, drug loading efficiency, pancreatic tumor targeting and delivery of payloads.

Variations in Microwave Ablation Zones as a Function of Probe Spacing, Angulation, and Geometry.

Despite advancements in precision and effectiveness of microwave ablation for tumor management, accurately predicting ablation zone geometry and minimum ablation margin remains a major challenge. This pilot study aimed to elucidate the influence of probe configuration on the morphometry of resulting ablation zones using tissue-mimicking thermochromic phantoms. In vitro results from 12 ablations were analyzed: (a) a single-probe ablation (n = 1) and (b) dual-probe ablations (n = 11).

Flotation Coefficient Distributions of Lipid Nanoparticles by Sedimentation Velocity Analytical Ultracentrifugation.

The robust characterization of lipid nanoparticles (LNPs) encapsulating therapeutics or vaccines is an important and multifaceted translational problem. Sedimentation velocity analytical ultracentrifugation (SV-AUC) has proven to be a powerful approach in the characterization of size-distribution, interactions, and composition of various types of nanoparticles across a large size range, including metal nanoparticles (NPs), polymeric NPs, and also nucleic acid loaded viral capsids. Similar potential of SV-AUC can be expected for the characterization of LNPs, but is hindered by the flotation of LNPs being incompatible with common sedimentation analysis models.

Modulation of biophysical properties of nucleocapsid protein in the mutant spectrum of SARS-CoV-2.

Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage of the uniquely large genomic database of SARS-CoV-2, we examine the impact of mutations across the spectrum of viable amino acid sequences on the biophysical phenotypes of the highly expressed and multifunctional nucleocapsid protein. We find variation in the physicochemical parameters of its extended intrinsically disordered regions (IDRs) sufficient to allow local plasticity, but also observe functional constraints that similarly occur in related coronaviruses.

Distributable, metabolic PET reporting of tuberculosis.

Tuberculosis remains a large global disease burden for which treatment regimens are protracted and monitoring of disease activity difficult. Existing detection methods rely almost exclusively on bacterial culture from sputum which limits sampling to organisms on the pulmonary surface. Advances in monitoring tuberculous lesions have utilized the common glucoside [F]FDG, yet lack specificity to the causative pathogen Mycobacterium tuberculosis (Mtb) and so do not directly correlate with pathogen viability.

Engineering Tumor Stroma Morphogenesis Using Dynamic Cell-Matrix Spheroid Assembly.

The tumor microenvironment consists of resident tumor cells organized within a compositionally diverse, three-dimensional (3D) extracellular matrix (ECM) network that cannot be replicated in vitro using bottom-up synthesis. We report a new self-assembly system to engineer ECM-rich 3D MatriSpheres wherein tumor cells actively organize and concentrate microgram quantities of decellularized ECM dispersions which modulate cell phenotype. 3D colorectal cancer (CRC) MatriSpheres were created using decellularized small intestine submucosa (SIS) as an orthotopic ECM source that had greater proteomic homology to CRC tumor ECM than traditional ECM formulations such as Matrigel.

Development of a predictive algorithm for patient survival after traumatic injury using a five analyte blood panel.

Severe trauma can induce systemic inflammation but also immunosuppression, which makes understanding the immune response of trauma patients critical for therapeutic development and treatment approaches. By evaluating the levels of 59 proteins in the plasma of 50 healthy volunteers and 1000 trauma patients across five trauma centers in the United States, we identified 6 novel changes in immune proteins after traumatic injury and further new variations by sex, age, trauma type, comorbidities, and developed a new equation for prediction of patient survival. Blood was collected at the time of arrival at Level 1 trauma centers and patients were stratified based on trauma level, tissues injured, and injury types.