Identification and surveillance of rare relapse-initiating stem cells during complete remission after transplantation.

ABSTRACT: Relapse after complete remission (CR) remains the main cause of mortality after allogeneic stem cell transplantation for hematological malignancies and, therefore, improved biomarkers for early prediction of relapse remains a critical goal toward development and assessment of preemptive relapse treatment. Because the significance of cancer stem cells as a source of relapses remains unclear, we investigated whether mutational screening for persistence of rare cancer stem cells would enhance measurable residual disease (MRD) and early relapse prediction after transplantation. In a retrospective study of patients who relapsed and patients who achieved continuous-CR with myelodysplastic syndromes and related myeloid malignancies, combined flow cytometric cell sorting and mutational screening for persistence of rare relapse-initiating stem cells was performed in the bone marrow at multiple CR time points after transplantation. In 25 CR samples from 15 patients that later relapsed, only 9 samples were MRD-positive in mononuclear cells (MNCs) whereas flowcytometric-sorted hematopoietic stem and progenitor cells (HSPCs) were MRD-positive in all samples, and always with a higher variant allele frequency than in MNCs (mean, 97-fold). MRD-positivity in HSPCs preceded MNCs in multiple sequential samples, in some cases preceding relapse by >2 years. In contrast, in 13 patients in long-term continuous-CR, HSPCs remained MRD-negative. Enhanced MRD sensitivity was also observed in total CD34+ cells, but HSPCs were always more clonally involved (mean, 8-fold). In conclusion, identification of relapse-initiating cancer stem cells and mutational MRD screening for their persistence consistently enhances MRD sensitivity and earlier prediction of relapse after allogeneic stem cell transplantation.

Congestive Heart Failure in an Adolescent With a Ruptured Sinus of Valsalva Aneurysm.

Sinus of Valsalva aneurysm (SVA) is an abnormal dilatation of the aortic root located between the aortic valve annulus and the sinotubular junction and is rare in the pediatric population. This case report describes a unique case of a 16-year-old adolescent patient admitted with progressive heart failure symptoms and diagnosed with a ruptured noncoronary SVA. He underwent surgical repair of the SVA with autologous pericardial patches and had an uncomplicated postoperative course. A genetic workup revealed an underlying 22q11.2 deletion that is infrequently associated with SVA.

Detection of Lung Tumors in CT Scan Images using Convolutional Neural Networks.

Changing the human being's lifestyle, has caused, or exacerbated many diseases. One of these diseases is cancer, and among all kind of cancers like, brain and pulmonary; lungs cancer is fatal. The cancers could be detected early to save lives using Computer Aided Diagnosis (CAD) systems. CT scans medical images are one the best images in detecting these tumors in lung that are especially accepted among doctors. However, location and random shape of tumors, and the poor quality of CT scans images are one the biggest challenges for physicians in identifying these tumors. Therefore, deep learning algorithms have been highly regarded by researchers. This paper presents a new method for identifying tumors and pulmonary nodules in CT scans images based on convolution neural network algorithm with which tumor is accurately identified. The active counter algorithm will show the detected tumor. The proposed method is qualitatively measured by the sensitivity assessment criteria and dice similarity criteria. The obtained results with 98.33% accuracy 99.25% validity and 98.18% dice similarity criterion show the superiority of the proposed method.

Carbon dioxide separation and capture by adsorption: a review.

Rising adverse impact of climate change caused by anthropogenic activities is calling for advanced methods to reduce carbon dioxide emissions. Here, we review adsorption technologies for carbon dioxide capture with focus on materials, techniques, and processes, additive manufacturing, direct air capture, machine learning, life cycle assessment, commercialization and scale-up.

Pouch Transfer for Single Coronary Artery With Nodal Artery Variant in Arterial Switch Operation.

The arterial switch operation with single coronary artery variance is an independent risk factor for increased operative mortality. There are reports of technical modifications, such as the double-barreled sinus pouch configuration, to improve geometric reimplantation of the single coronary into the neoaortic sinus. We describe the novel application of this technique for transferring a single coronary artery with a separate nodal artery emanating from the opposite sinus during an arterial switch operation.

Intraoperative Sapien S3 Valve Placement in 2 Patients With Multi-Valvar Disease Operation: A Unique Hybrid Procedure.

There has been a paradigm shift in the management of patients with congenital heart disease with a move away from conventional surgical treatment in favor of a percutaneous catheter-based approach across the spectrum of valvular heart diseases. The Sapien S3 valve implantation in the pulmonary position has been previously reported using a conventional transcatheter approach in patients with pulmonary insufficiency due to an enlarged right ventricular outflow tract. In this report, we present 2 unique cases of intraoperative hybrid implantation of Sapien S3 valves in patients with complex pulmonic and tricuspid valvular disease.

Hybrid approach for harmony transcatheter pulmonary valve replacement.

The Harmony™ Transcatheter Pulmonary Valve (Medtronic) was recently approved by the Food and Drug Administration for transcatheter pulmonary valve replacement in native right ventricular outflow tracts. Despite this milestone, some patients have main pulmonary arteries that are severely dilated and continue to require surgical pulmonary valve replacement. The hybrid approach combines surgical creation of a landing zone, transcatheter valve deployment, and suture stabilization of the implanted valve. In this case series, we report the first use of a hybrid approach for Harmony™ transcatheter pulmonary valve replacement. Two cases are reported with varying approaches for surgical creation of a landing zone followed by successful placement of a Harmony™ valve.

A Surgeon's Perspective on Blood Conservation Practice in Pediatric Cardiac Surgery.

Blood conservation practice in pediatric cardiac surgery has not been consistently adopted as quality improvement in many centers despite known risks associated with allogeneic blood products, shortage of donors, and costs. There are many blood conservation strategies available which collectively minimize exposure to allogeneic transfusion by maximizing the use of autologous red cells. These strategies are safe, reproducible, and have been implemented in clinical practice collectively with great efficacy for all patient ages and complexity levels. Institutional commitment to a set guideline will improve their blood conservation practice and quality outcome. The purpose of this article is to provide early career and practicing congenital cardiac surgeons with practical information concerning blood conservation strategies which can be considered for implementation in any pediatric cardiac surgery program, and which may be of particular value in resource-limited programs.

Set-shifting and inhibition interplay affect the rule-matching bias occurrence during conditional reasoning task.

The rule-matching bias is a common error during conditional reasoning tasks, which refers to a tendency to match responses with the lexical context in the conditional rule and leads to incorrect responses. Conditional reasoning is one of the higher-level cognitive abilities affected by many cognitive skills. We aimed to determine whether inhibition and set-shifting skills with rule-matching bias occurrence could be related and, if so, to what quantitative, at a statistically significant level. A total of 30 healthy university students aged 18 to 30 participated in this study. We used the Wason's Selection Task (WST) to measure conditional reasoning and investigated their inhibition and set-shifting skills with the Stroop and Wisconsin Card Sorting Test, respectively. Results showed a significant positive correlation between the number of correct responses to the Stroop test and the Wason Selection Card Test (p=0.614). There was a positive correlation between the number of correct responses to the Wisconsin Card Sorting Test and the Wason Selection Card Test (p=0.423). Participants with higher inhibition and set-shifting abilities showed better performance in the conditional reasoning test and lower rule-matching bias errors.

Single-Center Experience of Hybrid Pulmonary Valve Replacement Using Left Anterior Thoracotomy With Pulmonary Artery Plication in Patients With Large Right Ventricular Outflow Tract.

Background Until recently, a large right ventricle outflow tract interfered with the feasibility of standard transcatheter pulmonary valve replacement (PVR). We are describing our experience using a hybrid approach for PVR using a left anterior thoracotomy approach to allow for plication of the main pulmonary artery followed by a transcatheter PVR using a Sapien S3 valve. Methods and Results This is a single-center, retrospective review of patients who were evaluated to be appropriate for a hybrid PVR approach. The patients' demographics, procedure details, and follow-up data were collected. Between May 2018 and April 2021, a total of 11 patients presented for hybrid transcatheter PVR. The median age and weight were 24 years (interquartile range, 19-43 years) and 81.8 kg (interquartile range, 69-91 kg), respectively. Nine out of 11 patients received a transcatheter PVR after main pulmonary artery plication. There were no procedurally related deaths. One major complication was encountered in which the valve was malpositioned requiring successful surgical PVR. Minor complications included acute kidney injury (n=1) and a broken rib (n=1). The median length of stay was 4 days (interquartile range, 2-4 days), with median follow-up of 7 months (interquartile range, 3-18 months). A well-functioning pulmonary valve was observed in all patients at the last follow-up. Conclusions A hybrid approach using left anterior thoracotomy with pulmonary artery plication followed by transcatheter Sapien S3 PVR provides a less-invasive option for patients with an enlarged right ventricular outflow tract. Preliminary results demonstrated this to be a safe option with good short-term outcomes.

Microscopic retinal blood vessels detection and segmentation using support vector machine and K-nearest neighbors.

The retina is the deepest layer of texture covering the rear of the eye, recorded by fundus images. Vessel detection and segmentation are useful in disease diagnosis. The retina's blood vessels could help diagnose maladies such as glaucoma, diabetic retinopathy, and blood pressure. A mix of supervised and unsupervised strategies exists for the detection and segmentation of blood vessels images. The tree structure of retinal blood vessels, their random area, and different thickness have caused vessel detection difficulties at machine learning calculations. Since the green band of retinal images conveys more information about the vessels, they are utilized for microscopic vessels detection. The current research proposes an administered calculation for segmentation of retinal vessels, where two upgrading stages depending on filtering and comparative histogram were applied after pre-processing and image quality improvement. At that point, statistical features of vessel tracking, maximum curvature and curvelet coefficient are extracted for each pixel. The extracted features are classified by support vector machine and the k-nearest neighbors. The morphological operators then enhance the classified image at the final stage to segment with higher accuracy. The dice coefficient is utilized for the evaluation of the proposed method. The proposed approach is concluded to be better than different strategies with a normal of 92%.

Detection of Human Papillomavirus Integration in Brain Metastases from Oropharyngeal Tumors by Targeted Sequencing.

Human papillomavirus (HPV) positive and negative head and neck squamous cell carcinoma (HNSCC) are known to have differential phenotypes, including the incidence and location of metastases. HPV positive (HPV+) HNSCC are more likely to metastasize to distant sites, such as the lung, brain, and skin. Among these locations, metastasis to the brain is a rare event, and little is known about specific risk factors for this phenotype. In this report, we describe two patients who developed brain metastases from HNSCC. Both patient tumors had p16INK4a overexpression, suggesting these tumors were HPV+. This was confirmed after PCR, in situ hybridization, and mass spectrometry detected the presence of HPV type 16 (HPV16) DNA, RNA and protein. To further characterize the presence of HPV16, we used a target enrichment strategy on tumor DNA and RNA to isolate the viral sequences from the brain metastases. Analysis by targeted next generation sequencing revealed that both tumors had the HPV genome integrated into the host genome at known hotspots, 8q24.21 and 14q24.1. Applying a similar target enrichment strategy to a larger cohort of HPV+ HNSCC brain metastases could help to identify biomarkers that can predict metastasis and/or identify novel therapeutic options.

Towards enhancement of gas-liquid mass transfer in bioelectrochemical systems: Validation of a robust CFD model.

Mass transfer has been identified as a major bottleneck in gas fermentation and microbial conversion of carbon dioxide to chemicals. We present a pragmatic and validated Computational Fluid Dynamics (CFD) model for mass transfer in bioelectrochemical systems. Experiments were conducted to measure mixing times and mass transfer in a Duran bottle and an H-cell. An Eulerian-Eulerian framework with a simplified model for the bubble size distribution (BSD) was developed that utilized only one additional equation for the bubble number density while including the breakup and coalescence. Validations of the CFD model for mixing times showed that the predictions were within the confidence intervals of the measurements, verifying the model's capability in simulating the hydrodynamics. Further validations were performed using constant and varying bubble diameters for the mass transfer. The results showed the benefits of a simplified BSD model, as it yielded improvements of seven and four times in accuracy when assessed against the experimental data for the Duran bottle and H-cell, respectively. Modeling of the H-cell predicted that a lower stirring rate improves mass transfer compared with higher stirring rates, which is of great importance when designing microbial cultivation processes. The model offers a feasible framework for advanced modeling of gas fermentation and microbial electrosynthesis.

Authentication through gender classification from iris images using support vector machine.

Soft biometric information, such as gender, iris, and voice, can be helpful in various applications, such as security, authentication, and validation. Iris is secure biometrics with low forgery and error rates due to its highly certain features are being used in the last few decades. Iris recognition could be used both independently and in part for secure recognition and authentication systems. Existing iris-based gender classification techniques have low accuracy rates as well as high computational complexity. Accordingly, this paper presents an authentication approach through gender classification from iris images using support vector machine (SVM) that has an excellent response to sustained changes using the Zernike, Legendre invariant moments, and Gradient-oriented histogram. In this study, invariant moments are used as feature extraction from iris images. After extracting these descriptors' attributes, the attributes are categorized through keycode fusion. SVM is employed for gender classification using a fused feature vector. The proposed approach is evaluated on the CVBL data set and results are compared in state of the art based on local binary patterns and Gabor filters. The proposed approach came out with 98% gender classification rate with low computational complexity that could be used as an authentication measure.

A Rare Inflammatory Myofibroblastic Tumor of the Mitral Valve With Systemic Embolism in a Child.

Inflammatory myofibroblastic tumors (IMTs) represent mesenchymal tumors that occur in the lungs, abdomen, or pelvis. Cardiac IMTs are rare, usually right-sided, and when left-sided can cause sudden cardiac death by coronary occlusion. We report a child with symptoms of embolization to the right kidney and the femoral artery, and a mobile mass in the left atrium attached to the mitral valve. Upon surgical removal, histopathology revealed IMT. Our case illustrates a unique presentation of systemic thromboembolism.

Exercise-induced electrocardiographic changes after treadmill exercise testing in healthy children: A comprehensive study.

Background: Treadmill exercise testing is a crucial diagnostic tool for evaluating congenital and acquired heart disease in the pediatric population. This study aimed to perform a comprehensive evaluation of exercise-induced electrocardiographic (ECG) changes in children. Although there are numerous studies on exercise testing in various cardiac pathologies, studies on exercise-induced ECG changes in normal children with coverage of all ECG parameters of atrial and ventricular depolarization and repolarization are very scant, if any. Aims and Objectives: This study aimed to investigate the exercise-induced ECG changes in healthy children and evaluate the effects of gender and four different formulas of heart rate correction of Bazett, Fridericia, Framingham and Hodges on ventricular repolarization parameters pre-and post-exercise. Materials and Methods: Between April 2019 and April 2020, all children with normal electrocardiogram, echocardiogram and exercise test, high-quality ECG tracings and consent for participation were enrolled in this prospective study. Twenty electrocardiographic parameters were measured and 25 indices were calculated. P-value < 0.05 was considered significant. Results: Seventy-four healthy children were studied. Amplitudes of P, S, and T waves increased significantly after the exercise. All durations, except P wave time to peak and T peak -T end /QT (Tp-e/QT) interval decreased significantly with exercise. Generally, the parameters of ventricular repolarization were not statistically significant between males and females. There were significant differences among the heart-rate corrected values of intervals of QTc, QoTc, JTc, J point to peak T and Tp-e/QTc by various formulas. There was no U wave either at pre-exercise or post-exercise. QT interval was shortened by 24.6 % ± 12.1 % with exercise. The ECG-derived estimated duration of mechanical systole and diastole decreased with exercise. The percentage of decrease in diastole was more than systole (43.79 %± 13.31% versus 33.74% ±15.79 %, respectively, P-value < 0.001). Conclusion: Diastolic time decreased more than systolic time with exercise and systolic time to diastolic time increased with exercise. Hodges' and Fridericia's formulas resulted in the longest and shortest QT and QoT, JT, and JTP, respectively. Thus, using a single value as the cut-off for long QT syndrome can lead to under or over-diagnosis. Nomograms incorporating data on age, heart rate, and heart rate correction formula are indispensable for accurate long QT diagnosis. Furthermore, gender differences in ventricular repolarization parameters are not generally present in 5 to 14-year-old healthy children. The lack of U wave in this study may implicate the need for more careful investigation in the presence of U wave in the treadmill exercise testing of healthy children.

De Novo Damaging Variants, Clinical Phenotypes, and Post-Operative Outcomes in Congenital Heart Disease.

BACKGROUND: De novo genic and copy number variants are enriched in patients with congenital heart disease, particularly those with extra-cardiac anomalies. The impact of de novo damaging variants on outcomes following cardiac repair is unknown. METHODS: We studied 2517 patients with congenital heart disease who had undergone whole-exome sequencing as part of the CHD GENES study (Congenital Heart Disease Genetic Network). RESULTS: Two hundred ninety-four patients (11.7%) had clinically significant de novo variants. Patients with de novo damaging variants were 2.4 times more likely to have extra-cardiac anomalies (P=5.63×10-12). In 1268 patients (50.4%) who had surgical data available and underwent open-heart surgery exclusive of heart transplantation as their first operation, we analyzed transplant-free survival following the first operation. Median follow-up was 2.65 years. De novo variants were associated with worse transplant-free survival (hazard ratio, 3.51; P=5.33×10-04) and longer times to final extubation (hazard ratio, 0.74; P=0.005). As de novo variants had a significant interaction with extra-cardiac anomalies for transplant-free survival (P=0.003), de novo variants conveyed no additional risk for transplant-free survival for patients with these anomalies (adjusted hazard ratio, 1.96; P=0.06). By contrast, de novo variants in patients without extra-cardiac anomalies were associated with worse transplant-free survival during follow-up (hazard ratio, 11.21; P=1.61×10-05) than that of patients with no de novo variants. Using agnostic machine-learning algorithms, we identified de novo copy number variants at 15q25.2 and 15q11.2 as being associated with worse transplant-free survival and 15q25.2, 22q11.21, and 3p25.2 as being associated with prolonged time to final extubation. CONCLUSIONS: In patients with congenital heart disease undergoing open-heart surgery, de novo variants were associated with worse transplant-free survival and longer times on the ventilator. De novo variants were most strongly associated with adverse outcomes among patients without extra-cardiac anomalies, suggesting a benefit for preoperative genetic testing even when genetic abnormalities are not suspected during routine clinical practice. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01196182.

A three-dimensional in vitro model of erythropoiesis recapitulates erythroid failure in myelodysplastic syndromes.

Established cell culture systems have failed to accurately recapitulate key features of terminal erythroid maturation, hampering our ability to in vitro model and treat diseases with impaired erythropoiesis such as myelodysplastic syndromes with ring sideroblasts (MDS-RS). We developed an efficient and robust three-dimensional (3D) scaffold culture model supporting terminal erythroid differentiation from both mononuclear (MNC) or CD34+-enriched primary bone marrow cells from healthy donors and MDS-RS patients. While CD34+ cells did not proliferate beyond two weeks in 2D suspension cultures, the 3D scaffolds supported CD34+ and MNC erythroid proliferation over four weeks demonstrating the importance of the 3D environment. CD34+ cells cultured in 3D facilitated the highest expansion and maturation of erythroid cells, including generation of erythroblastic islands and enucleated erythrocytes, while MNCs supported multi-lineage hemopoietic differentiation and cytokine secretion relevant for MDS-RS. Importantly, MDS-RS 3D-cultures supported de novo generation of ring sideroblasts and maintenance of the mutated clone. The 3D cultures effectively model a clonal disease characterized by terminal erythroid failure and can be used to assess therapeutic compounds.

Predictors of Cardiac Surgery Patients Who Tolerate Blood Conservation in Cardiac Surgery.

BACKGROUND: Whether there is a cardiac surgical patient population that does not incur harm from blood conservation is unknown. This study aimed to identify patient characteristics associated with patients who safely tolerate blood conservation. METHODS: We conducted a retrospective review of consecutive patients undergoing isolated coronary artery bypass graft surgery or isolated aortic valve replacement, or concomitant coronary artery bypass graft surgery and aortic valve replacement between 2011 and 2016, during which blood conservation intervention took place. Logistic regression derived from the preintervention cohort was applied to the postintervention cohort to identify patient characteristics associated with those predicted to be transfused in the preintervention era but were not in the postintervention era. RESULTS: In this series of 2,701 adult patients undergoing cardiac operations, blood conservation intervention in 2014 led to a 52% reduction in red blood cell transfusion. Between preintervention and postintervention cohorts, there was no significant difference in the measured outcomes. A regression model derived from the preintervention cohort was applied to the postintervention cohort to identify predictors of cohort that do not derive benefit from liberal transfusion. This model demonstrated such patient characteristics to be age more than 75 years (odds ratio [OR] 1.71, 95% confidence interval [CI]: 1.09 to 2.68, p = 0.033), body mass index less than 30 kg/m2 (OR 1.5, 95% CI: 1.02 to 2.20, p = 0.044), lowest intraoperative hematocrit between 22 and 25 (OR 1.77, 95% CI: 1.16 to 2.68, p < 0.001), and cardiopulmonary bypass use (OR 4.50, 95% CI: 2.25 to 9.01, p < 0.001). CONCLUSIONS: Blood conservation can successfully yield reduction in perioperative blood product use, with associated decrease in the risk of postoperative renal failure. A select patient population who may tolerate blood conservation safely was identified, and that may guide a targeted blood conservation effort.