Cardiac matrix-bound Nanovesicles provide insight into mechanisms of clinical heart disease progression to failure.

Aims: Remodeling of the extracellular matrix (ECM) is critical for effective wound healing and maintaining organ homeostasis. The ECM of soft tissues, including cardiac, contains embedded nanovesicles; or matrix-bound nanovesicles (MBV). The luminal cargo of MBV consists of lipids, microRNAs (miRNAs), and proteins that influence the function of immune and stromal cells.

Point-cloud clustering and tracking algorithm for radar interferometry.

In data mining, density-based clustering, which entails classifying datapoints according to their distributions in some space, is an essential method to extract information from large datasets. With the advent of software-based radio, ionospheric radars are capable of producing unprecedentedly large datasets of plasma turbulence backscatter observations, and new automatic techniques are needed to sift through them. We present an algorithm to automatically identify and track clusters of radar echoes through time, using dbscan, a celebrated density-based clustering method for noisy point clouds.

Immunomodulation by the combination of statin and matrix-bound nanovesicle enhances optic nerve regeneration.

Modulating inflammation is critical to enhance nerve regeneration after injury. However, clinically applicable regenerative therapies that modulate inflammation have not yet been established. Here, we demonstrate synergistic effects of the combination of an HMG-CoA reductase inhibitor, statin/fluvastatin and critical components of the extracellular matrix, Matrix-Bound Nanovesicles (MBV) to enhance axon regeneration and neuroprotection after mouse optic nerve injury.

Matrix-bound nanovesicles alleviate particulate-induced periprosthetic osteolysis.

Aseptic loosening of orthopedic implants is an inflammatory disease characterized by immune cell activation, chronic inflammation, and destruction of periprosthetic bone, and is one of the leading reasons for prosthetic failure, affecting 12% of total joint arthroplasty patients. Matrix-bound nanovesicles (MBVs) are a subclass of extracellular vesicle recently shown to mitigate inflammation in preclinical models of rheumatoid arthritis and influenza-mediated "cytokine storm." The molecular mechanism of these anti-inflammatory properties is only partially understood.

Rapid Assessment of Biomarkers on Single Extracellular Vesicles Using "Catch and Display" on Ultrathin Nanoporous Silicon Nitride Membranes.

Extracellular vesicles (EVs) are particles released from cells that facilitate intercellular communication and have tremendous diagnostic and therapeutic potential. Bulk assays lack the sensitivity to detect rare EV subsets relevant to disease, and while single EV analysis techniques remedy this, they are often undermined by complicated detection schemes and prohibitive instrumentation. To address these issues, a microfluidic technique for EV characterization called "catch and display for liquid biopsy (CAD-LB)" is proposed.

Advances, challenges, and future directions in the clinical translation of ECM biomaterials for regenerative medicine applications.

Extracellular Matrix (ECM) scaffolds and biomaterials have been widely used for decades across a variety of diverse clinical applications and have been implanted in millions of patients worldwide. ECM-based biomaterials have been especially successful in soft tissue repair applications but their utility in other clinical applications such as for regeneration of bone or neural tissue is less well understood. The beneficial healing outcome with the use of ECM biomaterials is the result of their biocompatibility, their biophysical properties and their ability to modify cell behavior after injury.

Impact of the host immune response on the development of equine herpesvirus myeloencephalopathy in horses.

Herpesviruses establish a well-adapted balance with their host's immune system. Despite this co-evolutionary balance, infections can lead to severe disease including neurological disorders in their natural host. In horses, equine herpesvirus 1 (EHV-1) causes respiratory disease, abortions, neonatal foal death and myeloencephalopathy (EHM) in ~10 % of acute infections worldwide.

The MTIST platform: a microbiome time series inference standardized test.

The human gut microbiome is a promising therapeutic target, but interventions are hampered by our limited understanding of microbial ecosystems. Here, we present a platform to develop, evaluate, and score approaches to learn ecological interactions from microbiome time series data. The microbiome time series inference standardized test (MTIST) comprises: a simulation framework for the generation of microbiome study data akin to what is obtained with quantitative next-generation sequencing approaches, a compilation of a large curated data set generated by the simulation framework representing 648 simulated microbiome studies containing 18,360 time series, with a total of 2,182,800 species abundance measurements, and a scoring method to rank ecological inference algorithms.

Rapid Assessment of Biomarkers on Single Extracellular Vesicles Using 'Catch and Display' on Ultrathin Nanoporous Silicon Nitride Membranes.

Extracellular vesicles (EVs) are particles secreted by all cells that carry bioactive cargo and facilitate intercellular communication with roles in normal physiology and disease pathogenesis. EVs have tremendous diagnostic and therapeutic potential and accordingly, the EV field has grown exponentially in recent years. Bulk assays lack the sensitivity to detect rare EV subsets relevant to disease, and while single EV analysis techniques remedy this, they are undermined by complicated detection schemes often coupled with prohibitive instrumentation.

Modelling the Cost-Effectiveness of Hepatitis A in South Africa.

The World Health Organization (WHO) recommends the consideration of introducing routine hepatitis A vaccination into national immunization schedules for children ≥ 1 years old in countries with intermediate HAV endemicity. Recent data suggest that South Africa is transitioning from high to intermediate HAV endemicity, thus it is important to consider the impact and cost of potential routine hepatitis A vaccination strategies in the country. An age-structured compartmental model of hepatitis A transmission was calibrated with available data from South Africa, incorporating direct costs of hepatitis A treatment and vaccination.

Expanding the reach of vaccinology training in Africa: leveraging the success of the Annual African Vaccinology Course.

Introduction: It is estimated that one in five African children lack access to recommended life-saving vaccines. This situation has been exacerbated by the COVID-19 pandemic which disrupted routine immunization services in several parts of the region. To better support recovery efforts and get immunization programmes back on track, policy makers, programme managers, immunization providers and academics need continuous upskilling.

Measuring small-scale plasma irregularities in the high-latitude E- and F-regions simultaneously.

The ionosphere, Earth's space environment, exhibits widespread turbulent structuring, or plasma irregularities, visualized by the auroral displays seen in Earth's polar regions. Such plasma irregularities have been studied for decades, but plasma turbulence remains an elusive phenomenon. We combine scale-dependent measurements from a ground-based radar with satellite observations to characterize small-scale irregularities simultaneously in the bottomside and topside ionosphere and perform a statistical analysis on an aggregate from both instruments over time.

PhosphoDisco: A Toolkit for Co-regulated Phosphorylation Module Discovery in Phosphoproteomic Data.

Kinases are key players in cancer-relevant pathways and are the targets of many successful precision cancer therapies. Phosphoproteomics is a powerful approach to study kinase activity and has been used increasingly for the characterization of tumor samples leading to the identification of novel chemotherapeutic targets and biomarkers. Finding co-regulated phosphorylation sites which represent potential kinase-substrate sets or members of the same signaling pathway allows us to harness these data to identify clinically relevant and targetable alterations in signaling cascades.

The COVID-19 experience in Africa and the Middle East.

Aims: The experience of Africa and the Middle East with the COVID-19 pandemic has been unique, which can be attributed, in part, to disparities within these regions.

Methods: This review describes COVID-19 emergence, epidemiology, vaccination strategies and uptake, and lessons learned within Africa and the Middle East.

Results: For vaccines to be effective in curtailing COVID-19, a global approach to vaccination is required.

The TaxUMAP atlas: Efficient display of large clinical microbiome data reveals ecological competition in protection against bacteremia.

Longitudinal microbiome data provide valuable insight into disease states and clinical responses, but they are challenging to mine and view collectively. To address these limitations, we present TaxUMAP, a taxonomically informed visualization for displaying microbiome states in large clinical microbiome datasets. We used TaxUMAP to chart a microbiome atlas of 1,870 patients with cancer during therapy-induced perturbations.

Biocompatibility and biodistribution of matrix-bound nanovesicles in vitro and in vivo.

Matrix-bound nanovesicles (MBV) are a distinct subtype of extracellular vesicles that are firmly embedded within biomaterials composed of extracellular matrix (ECM). MBV both store and transport a diverse, tissue specific portfolio of signaling molecules including proteins, miRNAs, and bioactive lipids. MBV function as a key mediator in ECM-mediated control of the local tissue microenvironment.

3D Bioprinted Patient-Specific Extracellular Matrix Scaffolds for Soft Tissue Defects.

Soft tissue injuries such as volumetric muscle loss (VML) are often too large to heal normally on their own, resulting in scar formation and functional deficits. Decellularized extracellular matrix (dECM) scaffolds placed into these wounds have shown the ability to modulate the immune response and drive constructive healing. This provides a potential solution for functional tissue regeneration, however, these acellular dECM scaffolds are challenging to fabricate into complex geometries.

Matrix Bound Nanovesicles Have Tissue-Specific Characteristics That Suggest a Regulatory Role.

Recent studies have identified an extracellular vesicle population that is tightly anchored within the extracellular matrix (ECM) of tissues and organs until released by matrix turnover events. Evidence suggests that these matrix-bound nanovesicles (MBVs) are a ubiquitous component of the ECM, raising questions regarding their tissue-specific identity and their biologic function(s). The primary objective of this study was to examine MBVs isolated from six different tissues and compare their physical and compositional characteristics to determine the common and differentially expressed features.

Equine Herpesvirus-1 Myeloencephalopathy.

Although equine herpesvirus myeloencephalopathy (EHM) is a relatively uncommon manifestation of equine herpesvirus-1 (EHV-1) infection, it can cause devastating losses during outbreaks. Antemortem diagnosis of EHM relies mainly on the molecular detection of EHV-1 in nasal secretions and blood. Management of horses affected by EHM is aimed at supportive nursing and nutritional care, at reducing central nervous system inflammation and preventing thromboembolic sequelae.

Transcriptomic Regulation of Macrophages by Matrix-Bound Nanovesicle-Associated Interleukin-33.

The innate immune response, particularly the phenotype of responding macrophages, has significant clinical implications in the remodeling outcome following implantation of biomaterials and engineered tissues. In general, facilitation of an anti-inflammatory (M2-like) phenotype is associated with tissue repair and favorable outcomes, whereas pro-inflammatory (M1-like) activation can contribute to chronic inflammation and a classic foreign body response. Biologic scaffolds composed of extracellular matrix (ECM) and, more recently, matrix-bound nanovesicles (MBV) embedded within the ECM are known to direct macrophages toward an anti-inflammatory phenotype and stimulate a constructive remodeling outcome.

Contribution of the immune response to the pathogenesis of equine herpesvirus-1 (EHV-1): Are there immune correlates that predict increased risk or protection from EHV-1 myeloencephalopathy?

Equine herpesvirus-1 (EHV-1) myeloencephalopathy (EHM) is a devastating consequence of EHV-1 infection that has significant economic consequences. However, clinical EHM is relatively rare and occurs in only approximately 10% of infected horses. While there is a positive correlation between the duration and magnitude of viremia and incidence of EHM, it is likely that a combination of host and viral factors determine whether EHM occurs.