PubMed Health⌕ Search

Biomedical subjects

Salman Khan

Publications and source records attributed to Salman Khan.

12 recordsLinked to original sources

N6-methyladenine identification using deep learning and discriminative feature integration.

N6-methyladenine (6 mA) is a pivotal DNA modification that plays a crucial role in epigenetic regulation, gene expression, and various biological processes. With advancements in sequencing technologies and computational biology, there is an increasing focus on developing accurate methods for 6 mA site identification to enhance early detection and understand its biological significance. Despite the rapid progress of machine learning in bioinformatics, accurately detecting 6 mA sites remains a challenge due to the limited generalizability and efficiency of existing approaches. In this study, we present Deep-N6mA, a novel Deep Neural Network (DNN) model incorporating optimal hybrid features for precise 6 mA site identification. The proposed framework captures complex patterns from DNA sequences through a comprehensive feature extraction process, leveraging k-mer, Dinucleotide-based Cross Covariance (DCC), Trinucleotide-based Auto Covariance (TAC), Pseudo Single Nucleotide Composition (PseSNC), Pseudo Dinucleotide Composition (PseDNC), and Pseudo Trinucleotide Composition (PseTNC). To optimize computational efficiency and eliminate irrelevant or noisy features, an unsupervised Principal Component Analysis (PCA) algorithm is employed, ensuring the selection of the most informative features. A multilayer DNN serves as the classification algorithm to identify N6-methyladenine sites accurately. The robustness and generalizability of Deep-N6mA were rigorously validated using fivefold cross-validation on two benchmark datasets. Experimental results reveal that Deep-N6mA achieves an average accuracy of 97.70% on the F. vesca dataset and 95.75% on the R. chinensis dataset, outperforming existing methods by 4.12% and 4.55%, respectively. These findings underscore the effectiveness of Deep-N6mA as a reliable tool for early 6 mA site detection, contributing to epigenetic research and advancing the field of computational biology.

Deep Learning↗

HIV-associated nephropathy.

Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is one of the most important causes of progressive kidney failure in HIV-1-seropositive patients. Since the 1980s, much has been published regarding the epidemiology, pathogenesis, and treatment of HIVAN. Our knowledge of the clinical features, pathologic manifestations, course, and potential outcome of HIVAN has increased considerably. The use of highly active antiretroviral therapy has shown significant improvement in the outcome of human immunodeficiency virus infection and is found to be effective in preventing end-stage renal disease. The purpose of this review is to summarize the data about the clinical manifestations, pathogenesis and pathophysiologic mechanisms of HIVAN with particular attention on treatment including pharmaceutical and renal replacement options.

AIDS-Associated Nephropathy↗

Variable response of conductance and resistance coronary arteries to endothelial stimulation in patients with heart failure due to nonischemic dilated cardiomyopathy.

UNLABELLED: Attenuation of endothelial-dependent coronary vasodilation has been reported in idiopathic dilated cardiomyopathy and anatomically normal coronaries; however, data are insufficient for understanding the incidence and extent of this finding. The response of conductance and resistance coronary arteries to endothelial stimulation with acetylcholine was examined in 25 patients. Coronary blood flow had a variable response to acetylcholine and suggested coronary endothelial dysfunction in approximately half of the patients. Abnormal endothelial dysfunction involved the large conductance epicardial coronary arteries and the small resistance vessels. Abnormal endothelial response of coronary blood flow to acetylcholine could not be predicted by demographic and hemodynamic data. CONCLUSIONS: Coronary artery endothelial function is heterogeneous in patients with idiopathic dilated cardiomyopathy. Endothelial dysfunction is present in approximately half of the cases and involves both resistance as well as conductance coronary blood vessels. Furthermore, coronary endothelial function cannot be predicted by demographic and hemo-dynamic parameters or left ventricular ejection fraction.

Acetylcholine↗

Pregnancy-associated cardiomyopathy: clinical characteristics and a comparison between early and late presentation.

BACKGROUND: Cardiomyopathy associated with pregnancy was first described more than half a century ago. However, because of its rare occurrence and geographical differences, the clinical profile of this condition has remained incompletely defined. METHODS AND RESULTS: Data obtained from 123 women with a history of cardiomyopathy diagnosed during pregnancy or the postpartum period were reviewed. One hundred women met traditional criteria of peripartum cardiomyopathy; 23 were diagnosed with pregnancy-associated cardiomyopathy earlier than the last gestational month. Peripartum cardiomyopathy patients had a mean age of 31+/-6 years and were mostly white (67%). Common associated conditions were gestational hypertension (43%), tocolytic therapy (19%), and twin pregnancy (13%). Left ventricular ejection fraction at the time of diagnosis was 29+/-11% and improved to 46+/-14% (P< or =0.0001) at follow-up. Normalization of left ventricular ejection fraction occurred in 54% and was more likely in patients with left ventricular ejection fraction >30% at diagnosis. Maternal mortality was 9%. A comparison between the peripartum cardiomyopathy and early pregnancy-associated cardiomyopathy groups revealed no differences in age, race, associated conditions, left ventricular ejection fraction at diagnosis, its rate and time of recovery, and maternal outcome. CONCLUSIONS: This study helps to define the clinical profile of patients with pregnancy-associated cardiomyopathy diagnosed in the United States. Clinical presentation and outcome of patients with pregnancy-associated cardiomyopathy diagnosed early in pregnancy are similar to those of patients with traditional peripartum cardiomyopathy. These 2 conditions may represent a continuum of a spectrum of the same disease.

Adolescent↗

Survey of the use of organic nitrates for the treatment of chronic congestive heart failure in the United States.

A survey of members of the Heart Failure Society of America revealed that despite their lack of approval by the United States Food and Drug Administration, nitrates are widely used in patients with chronic congestive heart failure (CHF). Most members reported using nitrates in patients with ischemic (90%) and nonischemic (81%) causes of chronic CHF, especially those with symptomatic CHF (43% reported using nitrates in >50% of their patients with ischemic and 25% with nonischemic causes). Ninety-six percent reported using nitrates to reduce symptoms, 74% for hemodynamic improvement, 65% for better exercise tolerance, and only 14% for left ventricular reversed remodeling. Nitrates were always combined with hydralazine in 25% of patients and occasionally combined with hydralazine in 67%.

Chronic Disease↗

Effect of elevated admission serum creatinine and its worsening on outcome in hospitalized patients with decompensated heart failure.

Renal insufficiency (RI), as represented by elevated serum creatinine (>1.5 mg/dl) on admission, is common and found in almost half of patients hospitalized with decompensated heart failure. This finding is associated with prolongation of length of stay and rate of rehospitalizations after discharge and also has an independent unfavorable effect on 6-month mortality. Similarly, an increase in serum creatinine (>0.5 mg/dl) in the hospital results in a significantly longer length of stay and has an independent effect on long-term mortality.

Aged↗

Comparison of effects on left ventricular filling pressure of intravenous nesiritide and high-dose nitroglycerin in patients with decompensated heart failure.

The results of this study showed an advantage of nesiritide compared with high-dose nitroglycerin in the treatment of patients with decompensated heart failure. Nesiritide resulted in an early decrease in pulmonary capillary wedge pressure (< or =15 minutes), which was sustained throughout the study period (24 hours) without the need for up-titration. In contrast, the onset of the nitroglycerin-mediated hemodynamic effect was delayed, and despite aggressive up-titration, the decrease in pulmonary capillary wedge pressure was gradually attenuated because of the early development of tolerance.

Cardiac Catheterization↗

Intravenous nitroglycerin in the treatment of decompensated heart failure: potential benefits and limitations.

Acute decompensated heart failure (ADHF) is a common cause of hospitalizations. Intravenous nitroglycerin is widely used in the treatment of this condition. The use of this drug is based on its nitric oxide-mediated vasodilatory effect, which can lead to beneficial hemodynamic effects as well as improvement of myocardial ischemia and reduction of mitral regurgitation. However, information regarding the use of nitroglycerin for ADHF is limited to mostly hemodynamic evaluations in small groups of patients without cardiovascular outcome data. A single randomized, placebo controlled study that evaluated commonly used doses of nitroglycerin in patients with ADHF was disappointing and failed to show a significant hemodynamic effect or improvement of symptoms compared with placebo. The potential benefit of nitroglycerin seems to be limited by a decreased vasodilatory response in patients with heart failure, which requires an active titration of the drug and the use of high doses (>120 microg/min). In addition, the initial beneficial hemodynamic effect achieved with the appropriate dose of nitroglycerin is associated with neurohumoral activation and limited by an early development of nitrate tolerance that leads to a marked attenuation of the initial effect. More information obtained in large-scale studies that are appropriately designed to evaluate the effect of variable doses of nitroglycerin on short- and long-term cardiovascular outcome, with and without interventions shown to prevent nitrate tolerance, is needed before intravenous nitroglycerin can be recommended as a standard therapy for ADHF.

Clinical Trials as Topic↗

Impaired endothelium-mediated vasodilation in heart failure: clinical evidence and the potential for therapy.

Numerous studies in the last decade have clearly shown an attenuated endothelium-dependent vasodilation in patients with chronic heart failure. This abnormality has been demonstrated in the peripheral, pulmonary, and coronary circulation in patients with both ischemic and nonischemic cardiomyopathy; its magnitude correlates with the severity of symptoms. Endothelial dysfunction in patients with cardiomyopathy and a relatively new onset of symptoms suggests that change in endothelial function occurs early in the course of the disease. In contrast to other circulatory beds, renal circulation has shown significant vasodilatory response to endothelial stimulation. The development of endothelial dysfunction may not be homogeneous, and its magnitude may differ among circulatory systems. Although the clinical implications of the attenuated endothelium-dependent vasodilation in heart failure are not clear, this condition may lead to decreased organ perfusion, impaired exercise tolerance, and progression of disease. Many therapeutic interventions have resulted in improvement of endothelial function in patients with heart failure. Some of these interventions have also proven effective in enhancing exercise capacity, symptoms, and survival in patients with heart failure. This association suggests a therapeutic role for improvement of endothelial function in patients with chronic heart failure.

Endothelium, Vascular↗

Nesiritide: a new drug for the treatment of decompensated heart failure.

Nesiritide, a recombinant human B-type natriuretic peptide, is the first in a new drug class for the treatment of decompensated heart failure. The drug binds to receptors in the vasculature, kidney, adrenal gland, and brain, and overcomes resistance to endogenous BNP present in patients with CHF. Nesiritide administration leads to a rapid and balanced vasodilatory effect, which results in a significant decrease in right and left ventricular filling pressures and systemic vascular resistance and at the same time in an increase in stroke volume and cardiac output without a change in heart rate. These early hemodynamic changes result in a rapid improvement in symptoms of heart failure. In addition, nesiritide lowers aldosterone, catecholamines, and endothelin-1 levels and its effect on the kidney leads to an increased natriuresis and diuresis without effect on serum potassium or renal function. Prior to its approval for clinical use, nesiritide was studied in 10 different clinical trials involving 941 patients with moderate and severe CHF, including elderly patients, patients with both systolic and diastolic dysfunction, and patients with arrhythmias, renal insufficiency, and acute ischemic syndrome. In comparative studies with available vasoactive therapies frequently used for treatment of patients with decompensated heart failure, nesiritide was proven comparable in efficacy to inotropic drugs such as dobutamine, but superior in safety. In a recent study, nesiritide was found to be more effective and better tolerated than the vasodilator, nitroglycerin. The most common side effects expected with the use of nesiritide are headaches and decrease in blood pressure. At the recommended dose of nesiritide, headache was reported during the first 24 hours of treatment in 8% of patients and symptomatic hypotension in 4% of patients, compared to 20% and 5% in nitroglycerin-treated patients.

Animals↗

Prevalence of type III secretion genes in clinical and environmental isolates of Pseudomonas aeruginosa.

The type III secretion system of Pseudomonas aeruginosa transports four known effector proteins: ExoS, ExoT, ExoU and ExoY. However, the prevalence of the type III secretion system genes or the effector-encoding genes in clinical and environmental isolates of P. aeruginosa has not been well studied. Southern hybridization analyses and PCR were performed on over 100 P. aeruginosa isolates to determine the distribution of these genes. Clinical isolates were obtained from urine, endotracheal, blood and wound specimens, from the sputum of cystic fibrosis (CF) patients, and from non-hospital environmental sites. The popB gene was used as a marker for the presence of the large chromosomal locus encoding the type III secretion machinery proteins. Each isolate contained the popB gene, indicating that at least a portion of this large chromosomal locus was present in all isolates. Likewise, each isolate contained exoT-like sequences. In contrast, the exoS, exoU and exoY genes were variable traits. Overall, 72% of examined isolates contained the exoS gene, 28% contained the exoU gene, and 89% contained the exoY gene. Interestingly, an inverse correlation was noted between the presence of the exoS and exoU genes in that all isolates except two contained either exoS or exoU but not both. No significant difference in exoS, exoU or exoY prevalence was observed between clinical and environmental isolates or between isolates cultured from different disease sites except for CF respiratory isolates. CF isolates harboured the exoU gene less frequently and the exoS gene more frequently than did isolates from some of the other sites of infection, including the respiratory tract of patients without CF. These results suggest that the P. aeruginosa type III secretion system is present in nearly all clinical and environmental isolates but that individual isolates and populations of isolates from distinct disease sites differ in their effector genotypes. The ubiquity of type III secretion genes in clinical isolates is consistent with an important role for this system in human disease.

Bacterial Proteins↗