Brain Computer Interface Treatment for Motor Rehabilitation of Upper Extremity of Stroke Patients—A Feasibility Study

The main finding:The Brain-Computer Interface treatment used in this study was effective in promoting long-lasting functional improvements in the upper extremity in stroke survivors with severe, moderate and mild impairment. This functional improvement can be explained by improved neuroplasticity in the central nervous system.&nbsp;<img src="https://sum-bucket.nyc3.digitaloceanspaces.com/prod/images/sebastian_1.jpg">Photo by <a href="https://unsplash.com/@averey?utm_source=unsplash&amp;utm_medium=referral&amp;utm_content=creditCopyText" rel="noopener noreferrer" target="_blank">Robina Weermeijer</a> on <a href="https://unsplash.com/s/photos/brain?utm_source=unsplash&amp;utm_medium=referral&amp;utm_content=creditCopyText" rel="noopener noreferrer" target="_blank">Unsplash</a> The motivation:Stroke is the second largest cause of death worldwide and one of the most common causes of disability. Stroke causes devastating effects in many survivors, including severe motor and sensory impairment that hinder their activities of daily living. Stroke treatment may entail different devices and methods, but physical therapy is a central component of the rehabilitation process. The main objective of this process is to integrate the subject into daily living activities where the subject can end up actively participating in society. However, the standard rehabilitation techniques have some important limitations, especially for patients in the chronic stage with moderate or severe impairment.&nbsp;The big picture:The new technologies applied to the stroke rehabilitation process such as Brain-Computer Interfaces are showing promising results, bringing the patients' functional results to another level.The combination of Motor Imagery based BCIs with Functional Electrical Stimulation (FES) or Virtual Reality (VR) is an effective strategy to enhance brain plasticity and restore upper limb functionality. <a href="https://doi.org/10.3389/fnins.2020.591435" rel="noopener noreferrer" target="_blank">Dive deeper: Link to the full publication</a>

Rehabilitation and Therapy

Automated pharyngeal phase detection and bolus localization in videofluoroscopic swallowing study: Killing two birds with one stone?

The main finding:The detection of the pharyngeal phase of swallowing and the localization of the bolus in the videofluoroscopic swallowing study (VFSS) can be solved automatically with a convolutional neural network (CNN), without the need for manual annotation of bolus position. Our approach stems from the observation that the bolus presence in the pharynx is the most prominent visual characteristic upon which to infer whether a VFSS frame belongs to the pharyngeal phase or not. Hence, a CNN trained to detect the pharyngeal phase must rely on the presence of the bolus in the pharynx to make predictions, and its class activation maps should exhibit higher “attention” around the bolus region, providing a coarse bolus location.We also demonstrated that the pharyngeal phase can automatically be detected with accuracies close to the gold standards. These results pave the way for developing novel AI approaches for supporting clinicians during VFSS rating, with the end goal of providing objective clinical assessment and optimizing treatment planning for individuals with dysphagia.<img src="https://sum-bucket.nyc3.digitaloceanspaces.com/prod/images/a_bandini_12.gif">&nbsp;Oral, pharyngeal, and esophageal phases of swallowing.&nbsp; The motivation:The VFSS is a gold-standard imaging technique for assessing swallowing, but analysis and rating of VFSS recordings are time-consuming and require specialized training and expertise. Thus, it would be desirable if some parts of the VFSS rating could be automatized, to support clinicians in assessment and ease the clinical workload.Researchers have recently demonstrated that it is possible to automatically detect the pharyngeal phase of swallowing and to localize the bolus in VFSS recordings via computer vision approaches, fostering the development of novel techniques for automatic VFSS analysis. However, the training of algorithms to perform these tasks requires large amounts of annotated data that are seldom available.&nbsp;The big picture:Dysphagia may occur as a consequence of ageing and damage to the nervous system. Dysphagia has a negative impact on the quality of life of the affected individuals, and increases the risk of aspiration pneumonia, choking on food, malnutrition, and dehydration. Timely and accurate instrumental assessment is essential to prevent adverse events and plan appropriate interventions, such as diet texture modifications.The VFSS is a current gold standard clinical assessment for dysphagia. VFSS is an X-ray imaging technique that provides a dynamic view of the anatomical structures involved in the swallow, such as the oropharynx, pharynx, and oesophagus. During this exam, patients swallow food and liquid items prepared with a radiocontrast agent. Trained speech-language pathologists observe bolus motion and movements of the anatomical structures of interest (e.g., pharynx, hyoid bone, upper oesophagal sphincter, etc.) to make clinical decisions and plan interventions.VFSS is the only technique able to show the bolus throughout the three phases of the swallow: (1) the oral phase - where the food or liquid is being processed and transported through the oral cavity; (2) the pharyngeal phase - where a series of coordinated movements transport the bolus through the pharynx and upper oesophagal sphincter (UES) while simultaneously protecting the entrance to the lower airway from penetration-aspiration; and (3) the oesophagal phase - when the bolus passes through the oesophagus and travels towards the stomach. In particular, the pharyngeal phase is the time window of the swallow event that contains most of the clinical parameters of interest, and a thorough evaluation of it is essential for detecting the presence of penetration-aspiration. <a href="https://doi.org/10.1016/j.cmpb.2022.107058" rel="noopener noreferrer" target="_blank">Dive deeper: Link to the full publication</a>

Bioimaging and Biomedical Optics

Brachypodium Antifreeze Protein Gene Products Inhibit Ice Recrystallisation, Attenuate Ice Nucleation, and Reduce Immune Response

The main finding:Antifreeze proteins from the wild grass, Brachypodium distachyon, are secreted into the extracellular apoplast following translation. Once in the apoplast, the proteins are cleaved into two independently functioning domains, a leucine-rich repeat domain and an ice-binding domain.The leucine-rich repeat domain presents an extracellular component of plant immune systems that may interact with pathogen-associated molecular patterns, or small epitopes that elicit an energy costly host immune response which can kill plant tissue and disrupt growth. The interaction may block host recognition of pathogenic epitopes and dampen the host immune response, allowing continued growth.The ice-binding domain functions to directly and irreversibly bind to molecular ice crystals in the apoplast and prevent ice recrystallization, keeping ice crystals from growing large and causing damage to cells. These ice-binding domains are also capable of attacking the source of the apoplastic ice crystals, ice nucleating proteins expressed by ice-nucleation active pathogens that use ice as a weapon to to gain access to intracellular nutrients. By binding to ice crystals and ice nucleating proteins, the ice-binding proteins are able to combat not only the ice but also their direct origin as well.Taken together, these three distinct functions produce an amazing “jab-cross-lead hook” combination to defy pathogens and freezing conditions alike.<img src="https://sum-bucket.nyc3.digitaloceanspaces.com/prod/images/c_juurakko_1.jpg">&nbsp;Photo by <a href="https://unsplash.com/@unjay?utm_source=unsplash&amp;utm_medium=referral&amp;utm_content=creditCopyText" rel="noopener noreferrer" target="_blank">Unjay Markiewicz</a> on <a href="https://unsplash.com/s/photos/wild-grass?utm_source=unsplash&amp;utm_medium=referral&amp;utm_content=creditCopyText" rel="noopener noreferrer" target="_blank">Unsplash</a> The motivation:To reduce the loss of crops due to frost and ice nucleation pathogens.&nbsp;The big picture:Aid food security under changing climates. <a href="https://www.doi.org/10.3390/plants11111475" rel="noopener noreferrer" target="_blank">Dive deeper: Link to the full publication</a>

Molecular Genetics

Three-dimensional CRISPR screening reveals epigenetic interaction with anti-angiogenic therapy

The backgroundAberrant angiogenesis underlies the pathogenesis of many human diseases. Inhibiting this process using anti-angiogenic therapy has been successful in the clinical treatment of various types of cancer and eye conditions such as age-related macular degeneration. However, the clinical benefit of anti-angiogenic therapy is largely limited by the highly variable and unpredictable patient response and inevitable resistance due to a lack of quality biomarkers and knowledge of resistance mechanisms. <img src="https://sum-bucket.nyc3.digitaloceanspaces.com/prod/images/m_he_angio_image.jpg">﻿Angiogenesis. Image from <a href="https://www.scientificanimations.com/wiki-images/" rel="noopener noreferrer" target="_blank" style="background-color: transparent; color: rgb(79, 113, 138);">Scientific Animations</a>. The highlightsIn this study, we report a novel 3D microcarrier-based CRISPR – Cas9 screening platform in human blood endothelial cells, which are the main cell type contributing to angiogenesis and one of the key cell populations within a tumor. This helps us understand better the cell response to one of the most commonly used anti-angiogenic therapies, the VEGFA neutralizing monoclonal antibody bevacizumab. Several novel genes and their new functions have been revealed to either help cells become more resistant or sensitize them to drug treatment. For example, the main target identified in this study is a group of proteins called the BET proteins whose functions are well-known in epigenetic regulation. We further show that the epigenetic interaction between BET inhibition and anti-angiogenesis may change the chromatin structure and activity to affect cell response to drug treatment. Why it matters?Anti-angiogenic therapy is an important and successful treatment option. For example, since the FDA's approval of bevacizumab in 2004, it has been continuously reported as a top drug by sales and obtained $7.1 billion in 2019 sales (as the top 4th monoclonal antibody therapeutics). Understanding better the drug response is a key to maximizing the clinical benefit of using anti-angiogenic therapy. Notably, combining 3D microcarrier-based cell culture and the cutting-edge gene-editing technology CRISPR – Cas9, we have established a novel functional genomic screening platform to evaluate cell response to drug treatment. This technological advance enables pre-clinical investigation to become feasible in difficult-to-culture cell types such as blood endothelial cells and stem cells which are highly relevant to human diseases. In addition, the validated targets identified from our study play important roles in key biological processes, including regulation of transcription, chromatin structure, cell cycle progression, DNA repair, translation, and cytoskeleton. Several targets share common functions in these activities, potentially indicating a common signature for controlling blood endothelial cell response to anti-angiogenic therapy. Further studies on these targets and biological processes could enhance our understanding of resistance mechanisms and facilitate the development of novel biomarkers as well as more effective therapeutic options in the clinical setting. The big pictureOverall, our study provides useful biological models and technical advances to explore an important clinical problem, which could be applicable to other platforms and systems. Our data offer an entry point for understanding the therapeutic response to anti-angiogenic therapy and establishing a new connection between epigenetic regulation and anti-angiogenesis. These could eventually enable the rational use of anti-angiogenic therapy and/or other therapeutic approaches in treating many human diseases. <a href="https://www.doi.org/10.1038/s42003-021-02397-3" rel="noopener noreferrer" target="_blank">Dive deeper: Link to the full publication</a>

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