The development and impact of heterotopic ossification in burns: A review of four decades of research

Introduction: Heterotopic ossification (HO) is the formation of lamellar bone within connective and other tissue where bone should not form and is a rare complication after burn injury. However, it leads to severe pain and distress, marked reduction in joint range of motion (ROM), impaired function and increased hospital length of stay. The pathophysiology, incidence and risk factors of HO remain poorly understood in burns and other traumas and the management, controversial. The aim of this comprehensive review, therefore, was to synthesise the available evidence on the development and treatment of HO after acute burn injury. Methods: The review was based on a systematic search of five electronic databases PubMed, EMBASE, CINAHL, LILACS and Scopus. Results: Synthesis and analysis of the data highlighted that, despite the passage of time, little translatable evidence is available to guide any prevention, screening, diagnostic or pharmacological or physical management protocols. Discussion: Causes of HO remain confounded, therefore prevention is difficult. Although spontaneous resolution is possible, surgical resection remains the recommended treatment when ROM and activities of daily living are severely affected. Conclusion: The findings from this review indicate that multicentre data pooling is needed to understand the optimum pathway to prevention, identification and treatment of HO in acute burn patients

PromptonomyViT: Multi-Task Prompt Learning Improves Video Transformers using Synthetic Scene Data

Action recognition models have achieved impressive results by incorporating scene-level annotations, such as objects, their relations, 3D structure, and more. However, obtaining annotations of scene structure for videos requires a significant amount of effort to gather and annotate, making these methods expensive to train. In contrast, synthetic datasets generated by graphics engines provide powerful alternatives for generating scene-level annotations across multiple tasks. In this work, we propose an approach to leverage synthetic scene data for improving video understanding. We present a multi-task prompt learning approach for video transformers, where a shared video transformer backbone is enhanced by a small set of specialized parameters for each task. Specifically, we add a set of ``task prompts'', each corresponding to a different task, and let each prompt predict task-related annotations. This design allows the model to capture information shared among synthetic scene tasks as well as information shared between synthetic scene tasks and a real video downstream task throughout the entire network. We refer to this approach as ``Promptonomy'', since the prompts model a task-related structure. We propose the PromptonomyViT model (PViT), a video transformer that incorporates various types of scene-level information from synthetic data using the ``Promptonomy'' approach. PViT shows strong performance improvements on multiple video understanding tasks and datasets.Comment: Tech repor

Gene Editing of the Decoy Receptor LeEIX1 Increases Host Receptivity to Trichoderma Bio-Control

Fungal and bacterial pathogens generate devastating diseases and cause significant tomato crop losses worldwide. Due to chemical pesticides harming the environment and human health, alternative disease control strategies, including microorganismal bio-control agents (BCAs), are increasingly sought-after in agriculture. Bio-control microorganisms such as Trichoderma spp. have been shown to activate induced systemic resistance (ISR) in the host. However, examples of highly active bio-control microorganisms in agricultural settings are still lacking, due primarily to inconsistency in bio-control efficacy, often leading to widespread disease prior to the required ISR induction in the host. As part of its plant colonization strategy, Trichoderma spp. can secrete various compounds and molecules, which can effect host priming/ISR. One of these molecules synthesized and secreted from several species of Trichoderma is the family 11 xylanase enzyme known as ethylene inducing xylanase, EIX. EIX acts as an ISR elicitor in specific plant species and varieties. The response to EIX in tobacco and tomato cultivars is controlled by a single dominant locus, termed LeEIX, which contains two receptors, LeEIX1 and LeEIX2, both belonging to a class of leucine-rich repeat cell-surface glycoproteins. Both receptors are able to bind EIX, however, while LeEIX2 mediates plant defense responses, LeEIX1 acts as a decoy receptor and attenuates EIX induced immune signaling of the LeEIX2 receptor. By mutating LeEIX1 using CRISPR/Cas9, here, we report an enhancement of receptivity to T. harzianum mediated ISR and disease bio-control in tomato

Enhanced production yields of rVSV-SARS-CoV-2 vaccine using Fibra-Cel® macrocarriers

The COVID-19 pandemic has led to high global demand for vaccines to safeguard public health. To that end, our institute has developed a recombinant viral vector vaccine utilizing a modified vesicular stomatitis virus (VSV) construct, wherein the G protein of VSV is replaced with the spike protein of SARS-CoV-2 (rVSV-ΔG-spike). Previous studies have demonstrated the production of a VSV-based vaccine in Vero cells adsorbed on Cytodex 1 microcarriers or in suspension. However, the titers were limited by both the carrier surface area and shear forces. Here, we describe the development of a bioprocess for rVSV-ΔG-spike production in serum-free Vero cells using porous Fibra-Cel® macrocarriers in fixed-bed BioBLU®320 5p bioreactors, leading to high-end titers. We identified core factors that significantly improved virus production, such as the kinetics of virus production, the use of macrospargers for oxygen supply, and medium replenishment. Implementing these parameters, among others, in a series of GMP production processes improved the titer yields by at least two orders of magnitude (2e9 PFU/mL) over previously reported values. The developed process was highly effective, repeatable, and robust, creating potent and genetically stable vaccine viruses and introducing new opportunities for application in other viral vaccine platforms

Whole-Cell Multiparameter Assay for Ricin and Abrin Activity-Based Digital Holographic Microscopy

Ricin and abrin are ribosome-inactivating proteins leading to inhibition of protein synthesis and cell death. These toxins are considered some of the most potent and lethal toxins against which there is no available antidote. Digital holographic microscopy (DHM) is a time-lapse, label-free, and noninvasive imaging technique that can provide phase information on morphological features of cells. In this study, we employed DHM to evaluate the morphological changes of cell lines during ricin and abrin intoxication. We showed that the effect of these toxins is characterized by a decrease in cell confluence and changes in morphological parameters such as cell area, perimeter, irregularity, and roughness. In addition, changes in optical parameters such as phase-shift, optical thickness, and effective-calculated volume were observed. These effects were completely inhibited by specific neutralizing antibodies. An enhanced intoxication effect was observed for preadherent compared to adherent cells, as was detected in early morphology changes and confirmed by annexin V/propidium iodide (PI) apoptosis assay. Detection of the dynamic changes in cell morphology at initial stages of cell intoxication by DHM emphasizes the highly sensitive and rapid nature of this method, allowing the early detection of active toxins

Thrombin generation's role in predicting coronary disease severity.

BackgroundThrombin, a key enzyme of the clotting system, is involved in thrombus formation, platelet activation, and atherosclerosis, thereby possessing a central role in the pathogenesis of ischemic heart disease. Studies have shown an association between thrombin generation (TG) and cardiovascular morbidity and mortality, but results have been equivocal. Our aim was to study the predictive ability of TG assay in evaluating coronary stenosis severity.MethodsIn this prospective study we recruited patients with acute coronary syndrome (ACS) or acute chest pain (without evidence of myocardial injury) planned for coronary angiography. Thrombin generation was evaluated by Calibrated Automated Thrombogram (CAT) prior to angiography. Primary end points were significant coronary stenosis and the Syntax I score evaluated by coronary angiography.ResultsFrom April 2018 through September 2019, we recruited 128 patients. In the primary analysis there was no significant association between TG and significant coronary stenosis nor between TG and syntax I score, however, there was a positive correlation between peak height and troponin peak (Spearman correlation coefficient 0.194, P-value = 0.035). In sub-group analysis, the chest pain group bare no association between TG and coronary stenosis. In unstable angina group there was an association between peak height and significant coronary stenosis (P-value = 0.029), and in non ST-elevation myocardial infarction group, TG values possessed a relatively good predictive ability of significant coronary stenosis (area under the receiver operating characteristic curve of ~65%) and a positive correlation between both lag time and ttpeak with the syntax I score was noticed (Spearman correlation coefficient 0.31, P-value = 0.099 and Spearman correlation coefficient 0.37, P-value = 0.045 respectively).ConclusionIn patients with acute chest pain, TG values, evaluated by CAT, do not predict severity of coronary stenosis, nor do they possess prognostic value. Yet, in ACS patients, TG may have the ability to predict coronary disease severity

Light-induced MOF synthesis enabling composite photothermal materials

Abstract Metal-organic frameworks (MOFs) are a class of porous materials known for their large surface areas. Thus, over the past few decades the development of MOFs and their applications has been a major topic of interest throughout the scientific community. However, many current conventional syntheses of MOFs are lengthy solvothermal processes carried out at elevated temperatures. Herein, we developed a rapid light-induced synthesis of MOFs by harnessing the plasmonic photothermal abilities of bipyramidal gold nanoparticles (AuBPs). The generality of the photo-induced method was demonstrated by synthesizing four different MOFs utilizing three different wavelengths (520 nm, 660 nm and 850 nm). Furthermore, by regulating light exposure, AuBPs could be embedded in the MOF or maintained in the supernatant. Notably, the AuBPs-embedded MOF (AuBP@UIO-66) retained its plasmonic properties along with the extraordinary surface area typical to MOFs. The photothermal AuBP@UIO-66 demonstrated a significant light-induced heating response that was utilized for ultrafast desorption and MOF activation