CT Perfusion Map Synthesis from CTP Dynamic Images Using a Learned LSTM Generative Adversarial Network for Acute Ischemic Stroke Assessment.

Computed tomography perfusion (CTP) is a dynamic 4-dimensional imaging technique (3-dimensional volumes captured over approximately 1 min) in which cerebral blood flow is quantified by tracking the passage of a bolus of intravenous contrast with serial imaging of the brain. To diagnose and assess acute ischemic stroke, the standard method relies on summarizing acquired CTPs over the time axis to create maps that show different hemodynamic parameters, such as the timing of the bolus arrival and passage (Tmax and MTT), cerebral blood flow (CBF), and cerebral blood volume (CBV). However, producing accurate CTP maps requires the selection of an arterial input function (AIF), i.e. a time-concentration curve in one of the large feeding arteries of the brain, which is a highly error-prone procedure. Moreover, during approximately one minute of CT scanning, the brain is exposed to ionizing radiation that can alter tissue composition, and create free radicals that increase the risk of cancer. This paper proposes a novel end-to-end deep neural network that synthesizes CTP images to generate CTP maps using a learned LSTM Generative Adversarial Network (LSTM-GAN). Our proposed method can improve the precision and generalizability of CTP map extraction by eliminating the error-prone and expert-dependent AIF selection step. Further, our LSTM-GAN does not require the entire CTP time series and can produce CTP maps with a reduced number of time points. By reducing the scanning sequence from about 40 to 9 time points, the proposed method has the potential to minimize scanning time thereby reducing patient exposure to CT radiation. Our evaluations using the ISLES 2018 challenge dataset consisting of 63 patients showed that our model can generate CTP maps by using only 9 snapshots, without AIF selection, with an accuracy of 84.37 % .

Structural Anomalies Detection from Electrocardiogram (ECG) with Spectrogram and Handcrafted Features.

Cardiovascular diseases are the leading cause of death globally, causing nearly 17.9 million deaths per year. Therefore, early detection and treatment are critical to help improve this situation. Many manufacturers have developed products to monitor patients' heart conditions as they perform their daily activities. However, very few can diagnose complex heart anomalies beyond detecting rhythm fluctuation. This paper proposes a new method that combines a Short-Time Fourier Transform (STFT) spectrogram of the ECG signal with handcrafted features to detect heart anomalies beyond commercial product capabilities. Using the proposed Convolutional Neural Network, the algorithm can detect 16 different rhythm anomalies with an accuracy of 99.79% with 0.15% false-alarm rate and 99.74% sensitivity. Additionally, the same algorithm can also detect 13 heartbeat anomalies with 99.18% accuracy with 0.45% false-alarm rate and 98.80% sensitivity.

An Automatic Method to Reduce Baseline Wander and Motion Artifacts on Ambulatory Electrocardiogram Signals.

Today's wearable medical devices are becoming popular because of their price and ease of use. Most wearable medical devices allow users to continuously collect and check their health data, such as electrocardiograms (ECG). Therefore, many of these devices have been used to monitor patients with potential heart pathology as they perform their daily activities. However, one major challenge of collecting heart data using mobile ECG is baseline wander and motion artifacts created by the patient's daily activities, resulting in false diagnoses. This paper proposes a new algorithm that automatically removes the baseline wander and suppresses most motion artifacts in mobile ECG recordings. This algorithm clearly shows a significant improvement compared to the conventional noise removal method. Two signal quality metrics are used to compare a reference ECG with its noisy version: correlation coefficients and mean squared error. For both metrics, the experimental results demonstrate that the noisy signal filtered by our algorithm is improved by a factor of ten.

Cardiac rehabilitation in the paediatric Fontan population: development of a home-based high-intensity interval training programme.

INTRODUCTION: We evaluated the safety and feasibility of high-intensity interval training via a novel telemedicine ergometer (MedBIKE™) in children with Fontan physiology. METHODS: The MedBIKE™ is a custom telemedicine ergometer, incorporating a video game platform and live feed of patient video/audio, electrocardiography, pulse oximetry, and power output, for remote medical supervision and modulation of work. There were three study phases: (I) exercise workload comparison between the MedBIKE™ and a standard cardiopulmonary exercise ergometer in 10 healthy adults. (II) In-hospital safety, feasibility, and user experience (via questionnaire) assessment of a MedBIKE™ high-intensity interval training protocol in children with Fontan physiology. (III) Eight-week home-based high-intensity interval trial programme in two participants with Fontan physiology. RESULTS: There was good agreement in oxygen consumption during graded exercise at matched work rates between the cardiopulmonary exercise ergometer and MedBIKE™ (1.1 ± 0.5 L/minute versus 1.1 ± 0.5 L/minute, p = 0.44). Ten youth with Fontan physiology (11.5 ± 1.8 years old) completed a MedBIKE™ high-intensity interval training session with no adverse events. The participants found the MedBIKE™ to be enjoyable and easy to navigate. In two participants, the 8-week home-based protocol was tolerated well with completion of 23/24 (96%) and 24/24 (100%) of sessions, respectively, and no adverse events across the 47 sessions in total. CONCLUSION: The MedBIKE™ resulted in similar physiological responses as compared to a cardiopulmonary exercise test ergometer and the high-intensity interval training protocol was safe, feasible, and enjoyable in youth with Fontan physiology. A randomised-controlled trial of a home-based high-intensity interval training exercise intervention using the MedBIKE™ will next be undertaken.

A Survey of Heart Anomaly Detection Using Ambulatory Electrocardiogram (ECG).

Cardiovascular diseases (CVDs) are the number one cause of death globally. An estimated 17.9 million people die from CVDs each year, representing 31% of all global deaths. Most cardiac patients require early detection and treatment. Therefore, many products to monitor patient's heart conditions have been introduced on the market. Most of these devices can record a patient's bio-metric signals both in resting and in exercising situations. However, reading the massive amount of raw electrocardiogram (ECG) signals from the sensors is very time-consuming. Automatic anomaly detection for the ECG signals could act as an assistant for doctors to diagnose a cardiac condition. This paper reviews the current state-of-the-art of this technology discusses the pros and cons of the devices and algorithms found in the literature and the possible research directions to develop the next generation of ambulatory monitoring systems.

Deciphering critical amino acid residues to modify and enhance the binding affinity of ankyrin scaffold specific to capsid protein of human immunodeficiency virus type 1.

BACKGROUND: AnkGAG1D4 is an artificial ankyrin repeat protein which recognizes the capsid protein (CA) of the human immunodeficiency virus type 1 (HIV-1) and exhibits the intracellular antiviral activity on the viral assembly process. Improving the binding affinity of AnkGAG1D4 would potentially enhance the AnkGAG1D4-mediated antiviral activity. OBJECTIVE: To augment the affinity of AnkGAG1D4 scaffold towards its CA target, through computational predictions and experimental designs. METHOD: Three dimensional structure of the binary complex formed by AnkGAG1D4 docked to the CA was used as a model for van der Waals (vdW) binding energy calculation. The results generated a simple guideline to select the amino acids for modifications. Following the predictions, modified AnkGAG1D4 proteins were produced and further evaluated for their CA-binding activity, using ELISA-modified method and bio-layer interferometry (BLI). RESULTS: Tyrosine at position 56 (Y56) in AnkGAG1D4 was experimentally identified as the most critical residue for CA binding. Rational substitutions of this residue diminished the binding affinity. However, vdW calculation preconized to substitute serine for tyrosine at position 45. Remarkably, the affinity for the viral CA was significantly enhanced in AnkGAG1D4-S45Y mutant, with no alteration of the target specificity. CONCLUSIONS: The S-to-Y mutation at position 45, based on the prediction of interacting amino acids and on vdW binding energy calculation, resulted in a significant enhancement of the affinity of AnkGAG1D4 ankyrin for its CA target. AnkGAG1D4-S45Y mutant represented the starting point for further construction of variants with even higher affinity towards the viral CA, and higher therapeutic potential in the future.

Pharmacokinetics and metabolism of [14C]-tozadenant (SYN-115), a novel A2a receptor antagonist ligand, in healthy volunteers.

1. This phase-I study (NCT02240290) was designed to investigate the human absorption, disposition and mass balance of 14C-tozadenant, a novel A2a receptor antagonist in clinical development for Parkinson s disease. 2. Six healthy male subjects received a single oral dose of tozadenant (240 mg containing 81.47 KBq of [14C]-tozadenant). Blood, urine and feces were collected over 14 days. Radioactivity was determined by liquid scintillation counting or accelerator mass spectrometry (AMS). Tozadenant and metabolites were characterized using HPLC-MS/MS and HPLC-AMS with fraction collection. 3. At 4 h, the Cmax of tozadenant was 1.74 µg/mL and AUC(0-t) 35.0 h µg/mL, t1/2 15 h, Vz/F 1.82 L/kg and CL/F 1.40 mL/min/kg. For total [14C] radioactivity, the Cmax was 2.29 µg eq/mL at 5 h post-dose and AUC(0-t) 43.9 h µg eq/mL. Unchanged tozadenant amounted to 93% of the radiocarbon AUC(0-48h). At 312 h post-dose, cumulative urinary and fecal excretion of radiocarbon reached 30.5% and 55.1% of the dose, respectively. Unchanged tozadenant reached 11% in urine and 12% of the dose in feces. Tozadenant was excreted as metabolites, including di-and mono-hydroxylated metabolites, N/O dealkylated metabolites, hydrated metabolites. 4. The only identified species circulating in plasma was unchanged tozadenant. Tozadenant was primarily excreted in urine and feces in the form of metabolites.

Pseudomonas aeruginosa-induced apoptosis in airway epithelial cells is mediated by gap junctional communication in a JNK-dependent manner.

Chronic infection and inflammation of the airways is a hallmark of cystic fibrosis (CF), a disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. The response of the CF airway epithelium to the opportunistic pathogen Pseudomonas aeruginosa is characterized by altered inflammation and apoptosis. In this study, we examined innate immune recognition and epithelial responses at the level of the gap junction protein connexin43 (Cx43) in polarized human airway epithelial cells upon infection by PAO1. We report that PAO1 activates cell surface receptors to elicit an intracellular signaling cascade leading to enhancement of gap junctional communication. Expression of Cx43 involved an opposite regulation exerted by JNK and p38 MAPKs. PAO1-induced apoptosis was increased in the presence of a JNK inhibitor, but latter effect was prevented by lentiviral expression of a Cx43-specific short hairpin RNA. Moreover, we found that JNK activity was upregulated by pharmacological inhibition of CFTR in Calu-3 cells, whereas correction of a CF airway cell line (CF15 cells) by adenoviral expression of CFTR reduced the activation of this MAPK. Interestingly, CFTR inhibition in Calu-3 cells was associated with decreased Cx43 expression and reduced apoptosis. These results indicate that Cx43 expression is a component of the response of airway epithelial cells to innate immune activation by regulating the survival/apoptosis balance. Defective CFTR could alter this equilibrium with deleterious consequences on the CF epithelial response to P. aeruginosa.

Depth Perception of Surgeons in Minimally Invasive Surgery.

Minimally invasive surgery (MIS) poses visual challenges to the surgeons. In MIS, binocular disparity is not freely available for surgeons, who are required to mentally rebuild the 3-dimensional (3D) patient anatomy from a limited number of monoscopic visual cues. The insufficient depth cues from the MIS environment could cause surgeons to misjudge spatial depth, which could lead to performance errors thus jeopardizing patient safety. In this article, we will first discuss the natural human depth perception by exploring the main depth cues available for surgeons in open procedures. Subsequently, we will reveal what depth cues are lost in MIS and how surgeons compensate for the incomplete depth presentation. Next, we will further expand our knowledge by exploring some of the available solutions for improving depth presentation to surgeons. Here we will review the innovative approaches (multiple 2D camera assembly, shadow introduction) and devices (3D monitors, head-mounted devices, and auto-stereoscopic monitors) for 3D image presentation from the past few years.

Three-Dimensional Eye Tracking in a Surgical Scenario.

INTRODUCTION: Eye tracking has been widely used in studying the eye behavior of surgeons in the past decade. Most eye-tracking data are reported in a 2-dimensional (2D) fashion, and data for describing surgeons' behaviors on stereoperception are often missed. With the introduction of stereoscopes in laparoscopic procedures, there is an increasing need for studying the depth perception of surgeons under 3D image-guided surgery. METHODS: We developed a new algorithm for the computation of convergence points in stereovision by measuring surgeons' interpupillary distance, the distance to the view target, and the difference between gaze locations of the 2 eyes. To test the feasibility of our new algorithm, we recruited 10 individuals to watch stereograms using binocular disparity and asked them to develop stereoperception using a cross-eyed viewing technique. Participants' eye motions were recorded by the Tobii eye tracker while they performed the trials. Convergence points between normal and stereo-viewing conditions were computed using the developed algorithm. RESULTS: All 10 participants were able to develop stereovision after a short period of training. During stereovision, participants' eye convergence points were 14 ± 1 cm in front of their eyes, which was significantly closer than the convergence points under the normal viewing condition (77 ± 20 cm). CONCLUSION: By applying our method of calculating convergence points using eye tracking, we were able to elicit the eye movement patterns of human operators between the normal and stereovision conditions. Knowledge from this study can be applied to the design of surgical visual systems, with the goal of improving surgical performance and patient safety.

Crystal structure of an antiviral ankyrin targeting the HIV-1 capsid and molecular modeling of the ankyrin-capsid complex.

Ankyrins are cellular repeat proteins, which can be genetically modified to randomize amino-acid residues located at defined positions in each repeat unit, and thus create a potential binding surface adaptable to macromolecular ligands. From a phage-display library of artificial ankyrins, we have isolated Ank(GAG)1D4, a trimodular ankyrin which binds to the HIV-1 capsid protein N-terminal domain (NTD(CA)) and has an antiviral effect at the late steps of the virus life cycle. In this study, the determinants of the Ank(GAG)1D4-NTD(CA) interaction were analyzed using peptide scanning in competition ELISA, capsid mutagenesis, ankyrin crystallography and molecular modeling. We determined the Ank(GAG)1D4 structure at 2.2 Å resolution, and used the crystal structure in molecular docking with a homology model of HIV-1 capsid. Our results indicated that NTD(CA) alpha-helices H1 and H7 could mediate the formation of the capsid-Ank(GAG)1D4 binary complex, but the interaction involving H7 was predicted to be more stable than with H1. Arginine-18 (R18) in H1, and R132 and R143 in H7 were found to be the key players of the Ank(GAG)1D4-NTD(CA) interaction. This was confirmed by R-to-A mutagenesis of NTD(CA), and by sequence analysis of trimodular ankyrins negative for capsid binding. In Ank(GAG)1D4, major interactors common to H1 and H7 were found to be S45, Y56, R89, K122 and K123. Collectively, our ankyrin-capsid binding analysis implied a significant degree of flexibility within the NTD(CA) domain of the HIV-1 capsid protein, and provided some clues for the design of new antivirals targeting the capsid protein and viral assembly.

Neutrophil elastase degrades cystic fibrosis transmembrane conductance regulator via calpains and disables channel function in vitro and in vivo.

RATIONALE: Cystic fibrosis transmembrane conductance regulator (CFTR) protein is a chloride channel regulating fluid homeostasis at epithelial surfaces. Its loss of function induces hypohydration, mucus accumulation, and bacterial infections in CF and potentially other lung chronic diseases. OBJECTIVES: To test whether neutrophil elastase (NE) and neutrophil-mediated inflammation negatively impact CFTR structure and function, in vitro and in vivo. METHODS: Using an adenovirus-CFTR overexpression approach, we showed that NE degrades wild-type (WT)- and ΔF508-CFTR in vitro and WT-CFTR in mice through a new pathway involving the activation of intracellular calpains. MEASUREMENTS AND MAIN RESULTS: CFTR degradation triggered a loss of function, as measured in vitro by channel patch-clamp and in vivo by nasal potential recording in mice. Importantly, this mechanism was also shown to be operative in a Pseudomonas aeruginosa lung infection murine model, and was NE-dependent, because CFTR integrity was significantly protected in NE(-/-) mice compared with WT mice. CONCLUSIONS: These data provide a new mechanism and show for the first time a link between NE-calpains activation and CFTR loss of function in bacterial lung infections relevant to CF and to other chronic inflammatory lung conditions.

A novel platform for virus-like particle-display of flaviviral envelope domain III: induction of Dengue and West Nile virus neutralizing antibodies.

CD16-RIgE is a chimeric human membrane glycoprotein consisting of the CD16 ectodomain fused to the transmembrane domain and cytoplasmic tail of the gamma chain of the high affinity receptor of IgE (RIgE). Coexpression of CD16-RIgE and HIV-1 Pr55Gag polyprotein precursor (Pr55GagHIV) in insect cells resulted in the incorporation of CD16-RIgE glycoprotein into the envelope of extracellular virus-like particles (VLPs), a phenomenon known as pseudotyping. Taking advantage of this property, we replaced the CD16 ectodomain of CD16-RIgE by the envelope glycoprotein domain III (DIII) of dengue virus serotype 1 (DENV1) or West Nile virus Kunjin (WNVKun). The two resulting chimeric proteins, DIII-DENV1-RIgE and DIII-WNVKun-RIgE, were addressed to the plasma membrane, exposed at the surface of human and insect cells, and incorporated into extracellular VLPs when coexpressed with Pr55GagHIV in insect cells. The DIII domains were accessible at the surface of retroviral VLPs, as shown by their reactivity with specific antibodies, and notably antibodies from patient sera. The DIII-RIgE proteins were found to be incorporated in VLPs made of SIV, MLV, or chimeric MLV-HIV Gag precursors, indicating that DIII-RIgE could pseudotype a wide variety of retroviral VLPs. VLP-displayed DIII were capable of inducing specific neutralizing antibodies against DENV and WNV in mice. Although the neutralization response was modest, our data confirmed the capability of DIII to induce a flavivirus neutralization response, and suggested that our VLP-displayed CD16-RIgE-based platform could be developed as a vaccine vector against different flaviviruses and other viral pathogens.

Exploring the Promise of Telemedicine Exercise Interventions in Children and Adolescents With Congenital Heart Disease.

Youth with congenital heart disease (CHD) have reduced exercise capacity via various physical and psychosocial mechanisms. In addition to limited physiologic exercise capacity, these patients experience lower levels of physical activity, physical activity self-efficacy, health-related quality of life, and endothelial function. The study of exercise interventions and cardiac rehabilitation programs in pediatric CHD populations remains limited, particularly home-based interventions that incorporate real-time physiologic monitoring. Home-based interventions provide improved access and convenience to patients. This is principally important for patients from geographically disperse regions who receive their care at centralized subspecialty centres, as is the case for Canadian pediatric cardiac care. These programs, however, have traditionally not permitted the supervision of safety, technique, and adherence that are afforded by hospital/facility-based programs. As such, telemedicine is an important evolving area that combines the benefits of traditional home and facility-based cardiac rehabilitation. An additional key area lacking study surrounds the types of exercise interventions in youth with CHD. To date, interventions have often centred around moderate-intensity continuous exercise. High-intensity interval training might offer superior cardiorespiratory advantages but remains understudied in the CHD population. In this review, we highlight the existing evidence basis for exercise interventions in youth with CHD, explore the promise of incorporating telemedicine home-based solutions, and highlight key knowledge gaps. To address identified knowledge gaps, we are undertaking a 12-week randomized crossover trial of a home-based telemedicine high-intensity interval training intervention in youth with repaired moderate-severe CHD using a video game-linked cycle ergometer (known as the MedBIKE; https://spaces.facsci.ualberta.ca/ahci/projects/medical-projects/remote-rehab-bike-projects).

Evaluating a Telemedicine Video Game-Linked High-Intensity Interval Training Exercise Programme in Paediatric Heart Transplant Recipients.

Paediatric heart transplant recipients (HTRs) have reduced exercise capacity, physical activity (PA), health-related quality of life (HRQoL), and self-efficacy towards PA. Exercise interventions have demonstrated improvements in exercise capacity and functional status in adult HTRs, with a specific emerging interest in the role of high-intensity interval training (HIIT). Studies of exercise interventions in paediatric HTRs have been limited and nonrandomized to date. HIIT has not yet been evaluated in paediatric HTRs. We thus seek to evaluate the safety and feasibility of a randomized crossover trial of a 12-week, home-based, video game-linked HIIT intervention using a cycle ergometer with telemedicine and remote physiological monitoring capabilities (MedBIKE) in paediatric HTRs. The secondary objective is to evaluate the impact of the intervention on (1) exercise capacity, (2) PA, (3) HRQoL and self-efficacy towards PA, and (4) sustained changes in secondary outcomes at 6 and 12 months after intervention. After a baseline assessment of the secondary outcomes, participants will be randomized to receive the MedBIKE intervention (12 weeks, 36 sessions) or usual care. After the intervention and a repeated assessment, all participants will cross over. Follow-up assessments will be administered at 6 and 12 months after the MedBIKE intervention. We anticipate that the MedBIKE intervention will be feasible and safely yield sustained improvements in exercise capacity, PA, HRQoL, and self-efficacy towards PA in paediatric HTRs. This study will serve as the foundation for a larger, multicentre randomized crossover trial and will help inform exercise rehabilitation programmes for paediatric HTRs.

La tolérance à l'effort, le niveau d'activité physique (AP), le score de la qualité de vie liée à la santé (QVLS) ainsi que l'auto-efficacité à la pratique d'une AP se trouvent diminués chez les patients pédiatriques ayant reçu une transplantation cardiaque. Il a été montré que les exercices physiques permettent d'améliorer la tolérance à l'effort ainsi que le statut fonctionnel chez les patients adultes ayant reçu une transplantation cardiaque. D'ailleurs, le rôle de l'entraînement par intervalles de haute intensité (EIHI) suscite depuis peu un nouvel intérêt à cet égard. Les études réalisées à ce jour sur les programmes d'activité physique chez les patients pédiatriques ayant reçu une transplantation cardiaque sont toutefois peu nombreuses et ne reposent pas sur une répartition aléatoire. De plus, l'EIHI n'a pas encore été évalué chez ce groupe de patients. La présente étude a donc pour objectif d'évaluer la faisabilité et l'innocuité d'un essai clinique croisé à répartition aléatoire d'une durée de 12 semaines chez des patients pédiatriques ayant reçu une transplantation cardiaque. Le programme d'activité physique prendra la forme d'un EIHI à la maison au moyen d'un jeu vidéo et d'une bicyclette ergométrique permettant une assistance et une surveillance des données physiologiques à distance (MedBIKE). Les objectifs secondaires de l'étude consistent à évaluer les effets du programme sur : 1) la tolérance à l'effort; 2) le niveau d'AP; 3) la QVLS ainsi que l'auto-efficacité à la pratique d'une AP; et 4) le maintien des améliorations relatives aux critères d'évaluation se-condaires à 6 et 12 mois. Après une évaluation initiale des critères d'évaluation secondaires, les participants seront répartis aléatoirement dans le groupe suivant le programme à l'aide du vélo MedBIKE (36 séances réparties sur 12 semaines) ou dans le groupe recevant le traitement usuel. Tous les participants changeront ensuite de groupe, et une nouvelle évaluation des critères d'évaluation se-condaires sera effectuée. Les évaluations de suivi auront lieu 6 et 12 mois après la fin du programme. On s'attend à ce que ce dernier soit sûr, facile à suivre et accompagné d'améliorations soutenues de la tolérance à l'effort, du niveau d'AP, de la QVLS et de l'auto-efficacité à la pratique d'une AP chez les patients pédiatriques ayant reçu une transplantation cardiaque. Cette étude servira de modèle à un essai clinique croisé, multicentrique, à répartition aléatoire de plus grande envergure. Elle permettra aussi de générer des renseignements utiles pour les programmes de réadaptation destinés aux patients pédiatriques ayant reçu une transplantation cardiaque.

Antiviral activity of recombinant ankyrin targeted to the capsid domain of HIV-1 Gag polyprotein.

BACKGROUND: Ankyrins are cellular mediators of a number of essential protein-protein interactions. Unlike intrabodies, ankyrins are composed of highly structured repeat modules characterized by disulfide bridge-independent folding. Artificial ankyrin molecules, designed to target viral components, might act as intracellular antiviral agents and contribute to the cellular immunity against viral pathogens such as HIV-1. RESULTS: A phage-displayed library of artificial ankyrins was constructed, and screened on a polyprotein made of the fused matrix and capsid domains (MA-CA) of the HIV-1 Gag precursor. An ankyrin with three modules named Ank(GAG)1D4 (16.5 kDa) was isolated. Ank(GAG)1D4 and MA-CA formed a protein complex with a stoichiometry of 1:1 and a dissociation constant of K(d) ~ 1 µM, and the Ank(GAG)1D4 binding site was mapped to the N-terminal domain of the CA, within residues 1-110. HIV-1 production in SupT1 cells stably expressing Ank(GAG)1D4 in both N-myristoylated and non-N-myristoylated versions was significantly reduced compared to control cells. Ank(GAG)1D4 expression also reduced the production of MLV, a phylogenetically distant retrovirus. The Ank(GAG)1D4-mediated antiviral effect on HIV-1 was found to occur at post-integration steps, but did not involve the Gag precursor processing or cellular trafficking. Our data suggested that the lower HIV-1 progeny yields resulted from the negative interference of Ank(GAG)1D4-CA with the Gag assembly and budding pathway. CONCLUSIONS: The resistance of Ank(GAG)1D4-expressing cells to HIV-1 suggested that the CA-targeted ankyrin Ank(GAG)1D4 could serve as a protein platform for the design of a novel class of intracellular inhibitors of HIV-1 assembly based on ankyrin-repeat modules.

Automatic Bone Segmentation from MRI for Real-Time Knee Tracking in Fluoroscopic Imaging.

Recent progress in real-time tracking of knee bone structures from fluoroscopic imaging using CT templates has opened the door to studying knee kinematics to improve our understanding of patellofemoral syndrome. The problem with CT imaging is that it exposes patients to extra ionising radiation, which adds to fluoroscopic imaging. This can be solved by segmenting bone templates from MRI instead of CT by using a deep neural network architecture called 2.5D U-Net. To train the network, we used the SKI10 database from the MICCAI challenge; it contains 100 knee MRIs with their corresponding annotated femur and tibia bones as the ground truth. Since patella tracking is essential in our application, the SKI10 database was augmented with a new label named UofA Patella. Using 70 MRIs from the database, a 2.5D U-Net was trained successfully after 75 epochs with an excellent final Dice score of 98%, which compared favourably with the best state-of-the-art algorithms. A test set of 30 MRIs were segmented using the trained 2.5D U-Net and then converted into 3D mesh templates by using a marching cube algorithm. The resulting 3D mesh templates were compared to the 3D mesh model extracted from the corresponding labelled data from the augmented SKI10. Even though the final Dice score (98%) compared well with the state-of-the-art algorithms, we initially found that the Euclidean distance between the segmented MRI and SKI10 meshes was over 6 mm in many regions, which is unacceptable for our application. By optimising many of the hyper-parameters of the 2.5D U-Net, we were able to find that, by changing the threshold used in the last layer of the network, one can significantly improve the average accuracy to 0.2 mm with a variance of 0.065 mm for most of the MRI mesh templates. These results illustrate that the Dice score is not always a good predictor of the geometric accuracy of segmentation and that fine-tuning hyper-parameters is critical for improving geometric accuracy.

Deep Learning using Pre-Brachytherapy MRI to Automatically Predict Applicator Induced Complex Uterine Deformation.

This novel deep-learning (DL) algorithm addresses the challenging task of predicting uterine shape and location when deformed from its natural anatomy by the presence of an intrauterine (tandem)/intravaginal (ring) applicator during brachytherapy (BT) treatment for locally advanced cervical cancer. Paired pelvic MRI datasets from 92 subjects, acquired without (pre-BT) and with (at-BT) applicators, were used. We propose a novel automated algorithm to segment the uterus in pre-BT MR images using a deep convolutional neural network (CNN) incorporated with autoencoders. The proposed neural net is based on a pre-trained CNN Inception V4 architecture. It predicts a compressed vector by applying a multi-layer autoencoder, which is then back-projected into the segmentation contour of the uterus. Following this, another transfer learning approach using a modified U-net model is employed to predict the at-BT uterus shape from pre-BT MRI. The complex and large deformations of the uterus are quantified using free form deformation method. The proposed algorithm yielded an average Dice Coefficient (DC) of 94.1±3.3 and an average Hausdorff Distance (HD) of 4.0±3.1 mm compared to the manually defined ground truth by expert clinicians. Further, the modified U-net prediction of the at-BT uterus resulted in a DC accuracy of 88.1±3.8 and HD of 5.8±3.6 mm. The mean uterine surface point-to-point displacement was 25.0 [10.0-62.5] mm from the pre-BT position. Our unique DL method can thus successfully predict tandem-deformed uterine shape and position from MR images taken before the BT implant procedure i.e. without the applicator in place. Clinical relevance-The proposed DL-based framework can be incorporated as an automatic prediction tool of uterine deformation due to applicator insertion for personalized BT treatments. It holds promise for more streamlined clinical/technical decision-making before BT applicator insertion resulting in improved dosimetric outcomes.

Do agri-food market incentives improve food security and nutrition indicators? a microsimulation evaluation for Kenya.

The sustainable development goal #2 aims at ending hunger and malnutrition by 2030. Given the numbers of food insecure and malnourished people on the rise, the heterogeneity of nutritional statuses and needs, and the even worse context of COVID-19 pandemic, this has become an urgent challenge for food-related policies. This paper provides a comprehensive microsimulation approach to evaluate economic policies on food access, sufficiency (energy) and adequacy (protein, fat, carbohydrate) at household level. The improvement in market access conditions in Kenya is simulated as an application case of this method, using original insights from households' surveys and biochemical and nutritional information by food item. Simulation's results suggest that improving market access increases food purchasing power overall the country, with a pro-poor impact in rural areas. The daily energy consumption per capita and macronutrients intakes per capita increase at the national level, being the households with at least one stunted child under 5 years old, and poor households living areas outside Mombasa and Nairobi, those which benefit the most. The developed method and its Kenya's application contribute to the discussion on how to evaluate nutrition-sensitive policies, and how to cover most households suffering food insecurity and nutrition deficiencies in any given country. Supplementary Information: The online version contains supplementary material available at 10.1007/s12571-021-01215-2.

A New Semi-automated Algorithm for Volumetric Segmentation of the Left Ventricle in Temporal 3D Echocardiography Sequences.

PURPOSE: Echocardiography is commonly used as a non-invasive imaging tool in clinical practice for the assessment of cardiac function. However, delineation of the left ventricle is challenging due to the inherent properties of ultrasound imaging, such as the presence of speckle noise and the low signal-to-noise ratio. METHODS: We propose a semi-automated segmentation algorithm for the delineation of the left ventricle in temporal 3D echocardiography sequences. The method requires minimal user interaction and relies on a diffeomorphic registration approach. Advantages of the method include no dependence on prior geometrical information, training data, or registration from an atlas. RESULTS: The method was evaluated using three-dimensional ultrasound scan sequences from 18 patients from the Mazankowski Alberta Heart Institute, Edmonton, Canada, and compared to manual delineations provided by an expert cardiologist and four other registration algorithms. The segmentation approach yielded the following results over the cardiac cycle: a mean absolute difference of 1.01 (0.21) mm, a Hausdorff distance of 4.41 (1.43) mm, and a Dice overlap score of 0.93 (0.02). CONCLUSION: The method performed well compared to the four other registration algorithms.