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Background: The alternative transcriptional isoform of Bruton's tyrosine kinase, BTK-C, is expressed in a wide variety of epithelial tumor types where it impacts apoptosis resistance, therapeutic escape, and glucose uptake. The initial exon in BTK-C encodes a 34 amino acid extension of the amino terminus of the canonical BTK-A isoform. Its function is unknown., Materials and Methods: Site-directed mutagenesis, acylation assays and expression studies in cancer cell lines were used to determine the effects that the BTK-C first exon sequence has on kinase activity, subcellular localization and cell physiology. Analysis of BTK-C expression in tumors was conducted using genomic databases., Results: BTK-C is palmitoylated on two cysteine residues. BTK-C localization at the plasma membrane is dependent upon phosphatidylinositol 3,4,5-triphosphate (PIP 3 ) levels as well as palmitoylation. In epithelial cancer cells, both BTK-A and BTK-C isoforms are recruited to the plasma membrane; however, BTK-A also localizes to the nucleus whereas BTK-C has a primarily perinuclear distribution. Transcription of the BTK-C isoform is inversely correlated with expression of commonly activated breast cancer signaling receptors in breast tumors. In MDA-MB-231 cells, BTK-C expression confers modest increases in proliferation and glucose uptake rates compared to BTK-A., Conclusion: Palmitoylation affects localization and regulation of BTK-C in epithelial tumor cells where it functions as an important survival factor. Expression of either palmitoylated or non-palmitoylated kinase isoforms that function in PI3K signaling may be a common regulatory feature as nine other soluble kinases in the human genome possess similarly encoded alternative N-termini (ANT)., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Coronavirus disease (COVID-19) has had a major and sometimes lethal effect on global public health. COVID-19 detection is a difficult task that necessitates the use of intelligent diagnosis algorithms. Numerous studies have suggested the use of artificial intelligence (AI) and machine learning (ML) techniques to detect COVID-19 infection in patients through chest X-ray image analysis. The use of medical imaging with different modalities for COVID-19 detection has become an important means of containing the spread of this disease. However, medical images are not sufficiently adequate for routine clinical use; there is, therefore, an increasing need for AI to be applied to improve the diagnostic performance of medical image analysis. Regrettably, due to the evolving nature of the COVID-19 global epidemic, the systematic collection of a large data set for deep neural network (DNN)/ML training is problematic. Inspired by these studies, and to aid in the medical diagnosis and control of this contagious disease, we suggest a novel approach that ensembles the feature selection capability of the optimized artificial immune networks (opt-aiNet) algorithm with deep learning (DL) and ML techniques for better prediction of the disease. In this article, we experimented with a DNN, a convolutional neural network (CNN), bidirectional long-short-term memory, a support vector machine (SVM), and logistic regression for the effective detection of COVID-19 in patients. We illustrate the effectiveness of this proposed technique by using COVID-19 image datasets with a variety of modalities. An empirical study using the COVID-19 image dataset demonstrates that the proposed hybrid approaches, named COVID-opt-aiNet, improve classification accuracy by up to 98%-99% for SVM, 96%-97% for DNN, and 70.85%-71% for CNN, to name a few examples. Furthermore, statistical analysis ensures the validity of our proposed algorithms. The source code can be downloaded from Github: https://github.com/faizakhan1925/COVID-opt-aiNet., Competing Interests: The authors declare no conflicts of interest., (© 2022 Wiley Periodicals LLC.)

Objective: An inclusive contemporary analysis of spinal cord injury (SCI) rates in patients undergoing aneurysm repair and the factors associated with complications has not been performed., Methods: Following a systematic literature search, studies from 2008 to 2018 on repair of descending thoracic aneurysm (DTA) and thoracoabdominal aortic aneurysm (TAAA) were pooled in a meta-analysis performed using the generic inverse variance method. The primary outcome was permanent SCI. Secondary outcomes were temporary SCI, operative mortality, long-term mortality, postoperative stroke, and cerebrospinal fluid (CSF) drain-related complications., Results: One-hundred sixty-nine studies (22,634 patients) were included. The pooled rate of permanent SCI was 4.5% (95% confidence interval [CI], 3.8-5.4); 3.5% (95% CI, 1.8-6.7) for DTA and 7.6% (96% CI, 6.2-9.3) for TAAA repair (P for subgroups = .02), 5.7% (95% CI, 4.3-7.5) for open repair and 3.9% (95% CI, 3.1-4.8) for endovascular repair (P for subgroups = .03). Rates for Crawford extents I, II, III, IV, and V aneurysms were 4.0% (95% CI, 3.0-5.0), 15.0% (95% CI, 10.0-22.0), 7.0% (95% CI, 6.0-9.0), 2.0% (95% CI, 2.0-4.0), and 7.0% (95% CI, 2.0-23.0) respectively (P for subgroups <.001). The pooled rates for operative mortality, late mortality at a mean follow-up of 5.0 years, stroke, and temporary SCI were 7.4% (95% CI, 6.1-9.4), 1.0% (95% CI, 0.0-1.0), 4.2% (95% CI, 3.6-4.8), and 3.7% (95% CI, 3.0-4.6), respectively. The pooled rates for severe, moderate, and minor CSF-drain related complications were 5.1% (95% CI, 2.23-11.1), 4.1% (95% CI, 0.6-22.0), and 3.6% (95% CI, 1.2-8.0) respectively., Conclusions: Despite improvement, both open and endovascular aneurysm repair remain associated with a substantial risk of permanent SCI. The risk is greater for TAAA repair, especially extent II, III, and V., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Main Conclusion: Salicylic acid (SA) and drought stress promote more flowering in sweet orange. The physiological response and molecular mechanism underlying stress-induced floral initiation were discovered by transcriptome profiling. Numerous flowering-regulated genes were identified, and ectopically expressed CsLIP2A promotes early flowering in Arabidopsis. Floral initiation is a critical developmental mechanism associated with external factors, and citrus flowering is mainly regulated by drought stress. However, little is known about the intricate regulatory network involved in stress-induced flowering in citrus. To understand the molecular mechanism of floral initiation in citrus, flower induction was performed on potted Citrus sinensis trees under the combined treatment of salicylic acid (SA) and drought (DR). Physiological analysis revealed that SA treatment significantly normalized the drastic effect of drought stress by increasing antioxidant enzyme activities (SOD, POD, and CAT), relative leaf water content, total chlorophyll, and proline contents and promoting more flowering than drought treatment. Analysis of transcriptome changes in leaves from different treatments showed that 1135, 2728 and 957 differentially expressed genes (DEGs) were revealed in response to DR, SD (SA + DR), and SA (SA + well water) treatments in comparison with the well watered plants, respectively. A total of 2415, 2318 and 1933 DEGs were expressed in DR, SD, and SA in comparison with water recovery, respectively. Some key flowering genes were more highly expressed in SA-treated drought plants than in DR-treated plants. GO enrichment revealed that SA treatment enhances the regulation and growth of meristem activity under drought conditions, but no such a pathway was found to be highly enriched in the control. Furthermore, we focused on various hormones, sugars, starch metabolism, and biosynthesis-related genes. The KEGG analysis demonstrated that DEGs enriched in starch sucrose metabolism and hormonal signal transduction pathways probably account for stress-induced floral initiation in citrus. In addition, a citrus LIPOYLTRANSFERSAE 2A homologous (LIP2A) gene was upregulated by SD treatment. Ectopic expression of CsLIP2A exhibited early flowering in transgenic Arabidopsis. Taken together, this study provides new insight that contributes to citrus tree floral initiation under the SA-drought scenario as well as an excellent reference for stress-induced floral initiation in woody trees., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Incidental IgA deposits in donor kidneys have unknown sequelae and may predate clinical kidney disease if primed by adverse immunologic or hemodynamic stimuli or may remain dormant., Methods: The presence of incidental IgA in post-implantation (T 0 ) biopsies from living (LDK) and deceased donor (DDK) kidneys, and its relationship to post-transplant patient and graft outcomes was investigated in an ethnically diverse US population at a large transplant center., Results: Mesangial IgA was present in 20.4% of 802 T 0 biopsies; 13.2% and 24.5% of LDK and DDK, respectively. Donors with incidental IgA deposits were more likely to have hypertension and be of Hispanic or Asian origin. Intensity of IgA staining was 1+ (57.3%), 2+ (26.8%), or 3+ (15.8%) of the T 0 IgA+ biopsies. Mesangial pathology correlated with higher-intensity IgA staining with less clearance on follow-up (53.8%) versus 79.2% without mesangial pathology. IgA cleared in 91%, 63%, and 40% of follow-up biopsies with 1+, 2+, and 3+ IgA staining, respectively. Early post-transplant rejection and rejection-related graft loss occurred more frequently in IgA+ kidney recipients; however, 5-year kidney function and graft survival were comparable to kidneys without IgA., Conclusion: This first and largest report of incidental IgA in T 0 biopsies of LDK and DDK in a US ethnically diverse population demonstrated no adverse association between the presence of IgA in donor kidneys and graft or patient survival. Whether IgA in donor kidneys represents latent IgA nephropathy (IgAN) is uncertain; nevertheless, living donors who demonstrate IgA on T 0 biopsy deserve careful follow-up., (© 2020 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.)

Background: Surgical animal models are used in pre-clinical scientific studies. To date there has not been an analysis of how effective these data are when translated to human/clinical research. In this retrospective review, we evaluate the impact of studies using surgical animal models on human/clinical research through study-level analysis of citations., Methods: The top two ranking clinical journals based on impact factor for the top ten surgical specialties were identified and a search was run on PubMed to identify studies using surgical animal models published in the years 2007 and 2008. The translation to human/clinical research of each study was evaluated by analyzing the frequency of citation in human studies over the ten years following publication. Regression was used to identify predictors of citation in human/clinical research., Results: 411 animal studies using surgical models were identified. Over the course of the 10 years following publication the original animal studies were cited 6063 times, with 1300 (21.4%) citations in human/clinical studies and 4763 (78.6%) in animal/basic science studies. The median number of citations in human/clinical research was 1 (IQR 0-5). Regression showed an association between citation in human/clinical research and the use of porcine models and the specialties of general surgery, oral and maxillofacial surgery, orthopedic surgery, transplant, and plastic surgery., Conclusion: The use of animal models in surgical research shows poor translation to human/clinical research. Alternative surgical models should urgently be explored., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2020 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Purpose of Review: The severity of low-flow, low-gradient aortic stenosis cases continue to be misunderstood because of challenging diagnosis, and treatment remains complex. We discuss current diagnostic and treatment modalities for low-flow, low-gradient aortic stenosis., Recent Findings: This article summarizes current guidelines and best practices for the management of low-flow, low-gradient aortic stenosis., Summary: Low-flow, low-gradient aortic stenosis is a difficult entity to diagnose and treat. Various diagnostic modalities are needed to accurately determine the severity of aortic stenosis and potential treatment benefit. True-severe classical and paradoxical low-flow, low-gradient aortic stenosis can be distinguished from pseudo-severe aortic stenosis by dobutamine stress echocardiography and/or multidetector computed tomography. Once the distinction is made, aortic valve replacement results in better outcomes compared with conservative management. Although both surgical and transcatheter aortic valve replacement result in adequate outcomes, the decision between the two treatment strategies is based on patient characteristics, valve morphology, and other risk factors.

Animal models have provided invaluable information in the pursuit of medical knowledge and alleviation of human suffering. The foundations of our basic understanding of disease pathophysiology and human anatomy can largely be attributed to preclinical investigations using various animal models. Recently, however, the scientific community, citing concerns about animal welfare as well as the validity and applicability of outcomes, has called the use of animals in research into question. In this review, we seek to summarize the current state of the use of animal models in research., (Copyright © 2019 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Studies on the association between care quality, case volume, and outcomes in coronary artery bypass grafting (CABG) have concluded that consistent adherence to quality measures improves mortality rates and outcomes. However, the quality metrics are not well-defined, and their significance to surgeons and healthcare providers remains uncertain. We review the concept of "quality and quality metrics" and discuss their importance in the context of CABG., (Copyright © 2019 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Clinical quality measures (CQMs) are important tools for the assessment and improvement of health care quality. Federal requirements initially set forth in the American Recovery and Reinvestment Act, and advanced in subsequent stages of the requirements, codified electronic health record (EHR)-based CQM reporting, and have made automated CQM implementation a priority amongst the clinical and informatics communities. Nevertheless, the processes surrounding CQM implementation and validation remain complex, time-consuming, and largely undefined. We collected issue-tracking data during the course of an agile and rigorous collaborative project to build an analytics platform for the Knight Cardiovascular Institute at OHSU, with nine heart failure CQMs defined by the American College of Cardiology (ACC) as an exemplar. Using a mixed methods approach we provide an overview of our CQM implementation and validation process, identify major roadblocks and bottlenecks, and make recommendations for other professionals working in the area of health care quality assessment and improvement.

Spontaneous coronary artery dissection is an unusual cause of acute coronary syndrome, most commonly seen in the peripartum patient with no overt cardiovascular risk factors. Hormonal and hemodynamic changes play a role in the pathogenesis. Early management is known to improve the survival rate. We report the case of a 27 year old healthy pregnant woman (24 weeks) presenting with respiratory distress, chest pain and late decelerations. She had an emergency caesarean section due to fetal decelerations and was subsequently diagnosed with a left main dissection on angiography. Management included conservative measures followed by coronary artery bypass graft.

Objective: To determine the frequency of anxiety and depression among medical students of Wah Medical College and their associations with sociodemographic and educational characteristics if any., Study Design: Cross-sectional survey., Place and Duration of Study: Wah Medical College, from September 2007 to March 2008., Methodology: A sample of 279 students was included in the study after excluding first year medical students because they were admitted for less than 6 months. A self administered Encounter Form was administered. Sociodemographic and educational characteristics included age, gender, birth order, number of siblings, monthly income, monthly expenditure on education, academic performance in professional examination, past medical and past psychiatric history, substance abuse and family history of psychiatric illness. Beck depression inventory and beck anxiety inventory were used to assess the level of depression and anxiety. The chi-square test was applied at 5% level of significance to determine associated factors for anxiety and depression respectively., Results: The mean age of students was 21.4+/-1.41 years with female preponderance i.e. 202 (72.4%). Anxiety was present in 133 (47.7%) students and depression in 98 (35.1%) students. Both were found concomitantly in 68 (24.37%) students. Age (p=0.013), gender (p=0.016), examination criteria dissatisfaction (p=0.002) and overburden with test schedule (p=0.002) were significantly associated with depression. Anxiety was significantly associated with gender (p=0.007), birth order (p=0.049), year of study (p=0.001), examination criteria dissatisfaction (p=0.010) and overburden with test schedule (p=0.006)., Conclusion: One third of students were found to have anxiety and depression which was associated with the sociodemographic and educational factors as stated above.