Screening COVID-19 by Swaasa AI platform using cough sounds: a cross-sectional study.

The Advent of Artificial Intelligence (AI) has led to the use of auditory data for detecting various diseases, including COVID-19. SARS-CoV-2 infection has claimed more than six million lives to date and therefore, needs a robust screening technique to control the disease spread. In the present study we created and validated the Swaasa AI platform, which uses the signature cough sound and symptoms presented by patients to screen and prioritize COVID-19 patients. We collected cough data from 234 COVID-19 suspects to validate our Convolutional Neural Network (CNN) architecture and Feedforward Artificial Neural Network (FFANN) (tabular features) based algorithm. The final output from both models was combined to predict the likelihood of having the disease. During the clinical validation phase, our model showed a 75.54% accuracy rate in detecting the likely presence of COVID-19, with 95.45% sensitivity and 73.46% specificity. We conducted pilot testing on 183 presumptive COVID subjects, of which 58 were truly COVID-19 positive, resulting in a Positive Predictive Value of 70.73%. Due to the high cost and technical expertise required for currently available rapid screening methods, there is a need for a cost-effective and remote monitoring tool that can serve as a preliminary screening method for potential COVID-19 subjects. Therefore, Swaasa would be highly beneficial in detecting the disease and could have a significant impact in reducing its spread.

Development and clinical validation of Swaasa AI platform for screening and prioritization of pulmonary TB.

Acoustic signal analysis has been employed in various medical devices. However, studies involving cough sound analysis to screen the potential pulmonary tuberculosis (PTB) suspects are very few. The main objective of this cross-sectional validation study was to develop and validate the Swaasa AI platform to screen and prioritize at risk patients for PTB based on the signature cough sound as well as symptomatic information provided by the subjects. The voluntary cough sound data was collected at Andhra Medical College-India. An Algorithm based on multimodal convolutional neural network architecture and feedforward artificial neural network (tabular features) was built and validated on a total of 567 subjects, comprising 278 positive and 289 negative PTB cases. The output from these two models was combined to detect the likely presence (positive cases) of PTB. In the clinical validation phase, the AI-model was found to be 86.82% accurate in detecting the likely presence of PTB with 90.36% sensitivity and 84.67% specificity. The pilot testing of model was conducted at a peripheral health care centre, RHC Simhachalam-India on 65 presumptive PTB cases. Out of which, 15 subjects truly turned out to be PTB positive with a positive predictive value of 75%. The validation results obtained from the model are quite encouraging. This platform has the potential to fulfil the unmet need of a cost-effective PTB screening method. It works remotely, presents instantaneous results, and does not require a highly trained operator. Therefore, it could be implemented in various inaccessible, resource-poor parts of the world.

All Endocarditis Is Not Infective: Libman-Sacks Endocarditis.

Libman-Sacks endocarditis (LSE) is an uncommon disorder that might be confused with infective endocarditis. It is one of the systemic lupus erythematosus (SLE) manifestations that could present with heart failure. We report a 12-year-old girl who presented with a history of shortness of breath, joint pain for four weeks, and fever for about one week. On examination, she was pale, edematous, and febrile. Her cardiac exam revealed a pan-systolic murmur of mitral regurgitation, harsh, grade 3/6 best heard at the apex. She was diagnosed with systemic lupus erythematosus with lupus nephritis and carditis. Her echocardiography revealed severe mitral regurgitation with nodular thickening of the valve in keeping with a diagnosis of LSE. After appropriate management of her underlying disorder using immunosuppressive, we saw a dramatic clinical improvement and her heart failure symptoms resolved. This case proves that SLE can have significant cardiac involvement and a proper evaluation would help in overall management and prognosis.

Cardio-protective effect of regular transfusion in children with non-transfusion dependent thalassemia (NTDT): A cohort study.

BACKGROUND AND AIM OF THE WORK: Cardiac complications occur in patients with non-transfusion dependent thalassemia (NTDT). The study aimed to evaluate transfusion effect on systolic and diastolic cardiac function in young NTDT patients.  Methods:  Study design: Cohort study. Seventeen regularly-transfused patients with NTDT (12.5±5.3 years; group 1) and 15 none/minimally transfused patients (13.2±4.8 years; group 2) were followed up for 5 years and compared as regards their clinical parameters, echocardiographic and Tissue-Doppler-Imaging. RESULTS: Group 2 patients had significantly higher peak late-diastolic velocity of the left-ventricular-inflow Doppler (Am). Mitral-valve A-wave duration/pulmonary-veins, A-wave duration-ratio and pulmonary-vein S/D velocities-ratio were larger in group 2 as well (p = < 0.01). The diameters of right and left outflow-tract were larger with a higher cardiac-index in patients of group 2. Systolic-function was similar in the 2 studied groups. CONCLUSION: Diastolic function assessment revealed indicators of an abnormal relaxation of left-ventricle in non-transfused patients, which suggests a diastolic dysfunction. An increase in the diameter of the outflow-tract is likely attributed to high cardiac-output status in non-transfused NTDT patients as they have a higher cardiac index. Early start of regular transfusion for NTDT patients might prevent serious long-term cardiac complications.

Cor Triatriatum Sinistrum: A rare disease with a common presentation.

Cor triatriatum sinistrum (CTS) is a rare congenital cardiac anomaly characterised by an abnormal septum within the left atrium impairing blood flow to the left ventricle. We report the case of a two-month-old male infant who presented with symptoms of heart failure since the age of two weeks. He was admitted to a local hospital and was managed with antibiotics because of the impression of pneumonia. Due to persistent unresolved tachypnoea and tachycardia, he was referred to Sultan Qaboos University Hospital, Muscat, Oman, in 2019 for cardiac evaluation which confirmed a diagnosis of isolated CTS with severe stenosis and pulmonary hypertension. He underwent an urgent surgical excision of the membrane with uneventful recovery.

Anthracycline-related acute cardiotoxicity in a very young Omani patient with acute myeloid leukaemia.

Anthracycline-related cardiomyopathy is of concern in children treated for acute myeloid leukemia (AML). Risk is dose-dependent, increasing with higher doses. We aim to highlight the risk of early-onset cardiotoxicity with low-cumulative anthracycline dose in a young Omani boy with AML. We conclude in the presence of other known risk factors for cardiac dysfunction, there is probably no risk-free anthracycline dose.

Phenotypic spectrum of ALPK3-related cardiomyopathy.

Cardiomyopathies are clinically heterogeneous disorders and are the leading cause of cardiovascular morbidity and mortality. Different etiologies have a significant impact on prognosis. Recently, novel biallelic loss-of-function pathogenic variants in alpha-kinase 3 (ALPK3) were implicated in causing early-onset pediatric cardiomyopathy (cardiomyopathy, familial hypertrophic 27; OMIM 618052). To date, eight patients, all presented during early childhood, were reported with biallelic ALPK3 pathogenic variants. We describe the molecular and clinical phenotype characterization of familial cardiomyopathy on one family with six affected individuals. We identified homozygosity for an ALPK3 deleterious sequence variant (NM_020778.4:c.639G>A:p.Trp213*) in all the affected individuals. They presented with either dilated cardiomyopathy that progressed to hypertrophic cardiomyopathy (HCM) or HCM with left ventricular noncompaction. The age of presentation in our cohort extends between infancy to the fourth decade. The phenotypic severity decreases with the progression of age.

Management of Biotechnical Complications Associated with a Full-Arch Implant Restoration Using Digital and Conventional Workflows: A Clinical Report.

Full-arch implant-supported restorations using a metal-acrylic resin design have had a high success rate but are also associated with frequent technical complications including framework misfit due to casting errors, debonding of denture teeth, and fracture of the acrylic from the metal framework. This clinical report describes a case of maxillary and mandibular full-arch implant-supported rehabilitation associated with technical and biological complications and use of digital technology for fabricating monolithic restorations. The use of a bio-functional try-in and its subsequent use as a conversion prosthesis for fabricating a master cast is described. The use of the patient's existing metal bar to fabricate a retread type prosthesis is also described along with using digital technology for fabricating a new metal bar and a monolithic type of restoration. The integration of digital and conventional workflows to obtain an increased level of accuracy and simplicity is also discussed.

A review on preclinical studies conducted with Homeopathic medicine Cephalandra indica as an Anti-hyperglycemic agent

Background ­ Diabetes Mellitus a metabolic disorder affects the secretion of insulin from pancreas leading to hyperglycemia, if uncontrolled leads to complications triggered by free radical formed after oxidative stress. Homeopathic medicine Cephalandra Indica has shown antidiabetic activity in various potencies performed on preclinical studies on diabetic rat model. The present review highlights the pharmacological profile of homeopathic preparations Cephalandra Indica on preclinical studies and calculating the probable human equivalent dosage from preclinical studies for the pilot studies. Method ­ Articles published between January 1988 and December 2018 was included in review. Databases like PubMed ­ Medline, Google scholar were used for collecting the articles. Keywords like 'Homeopathy' or 'Homoeopathy', 'Invitro', 'Invivo' and 'Cephalandra Indica' were used. SABEH criteria were implemented for assessing methodology quality of articles. Results ­ Seven full text articles were included in review which had six Invivo studies and one Invitro study. This review article provided the scientific validation of high diluted homeopathic medicines pharmacological activity of Cephalandra Indica and probable mechanism of action confirmed through preclinical studies. Conversion of dosage from animal model to human dosage for pilot studies has been hypothetically proposed. Conclusion ­ Homeopathic medicine Cephalandra Indica has a therapeutic and safety profile with no toxicity observed in preclinical studies. The proposed hypothesis of conversion of dosage needs to be validated for further studies. (au)

Premature ventricular contractions as a side effect of filgrastim in a child with B-thalassaemia.

Premature ventricular contractions are a rare side effect of filgrastim, reported mainly in elderly men. Here we report the case of a 9-year-old child with thalassaemia who developed frequent premature ventricular contractions after three doses of filgrastim were given for deferiprone-induced agranulocytosis. The arrhythmia resolved 3 weeks after discontinuation of filgrastim. Children treated with filgrastim should be carefully monitored for potentially serious arrhythmia.

Mycobacterial Cultures Contain Cell Size and Density Specific Sub-populations of Cells with Significant Differential Susceptibility to Antibiotics, Oxidative and Nitrite Stress.

The present study shows the existence of two specific sub-populations of Mycobacterium smegmatis and Mycobacterium tuberculosis cells differing in size and density, in the mid-log phase (MLP) cultures, with significant differential susceptibility to antibiotic, oxidative, and nitrite stress. One of these sub-populations (~10% of the total population), contained short-sized cells (SCs) generated through highly-deviated asymmetric cell division (ACD) of normal/long-sized mother cells and symmetric cell divisions (SCD) of short-sized mother cells. The other sub-population (~90% of the total population) contained normal/long-sized cells (NCs). The SCs were acid-fast stainable and heat-susceptible, and contained high density of membrane vesicles (MVs, known to be lipid-rich) on their surface, while the NCs possessed negligible density of MVs on the surface, as revealed by scanning and transmission electron microscopy. Percoll density gradient fractionation of MLP cultures showed the SCs-enriched fraction (SCF) at lower density (probably indicating lipid-richness) and the NCs-enriched fraction (NCF) at higher density of percoll fractions. While live cell imaging showed that the SCs and the NCs could grow and divide to form colony on agarose pads, the SCF, and NCF cells could independently regenerate MLP populations in liquid and solid media, indicating their full genomic content and population regeneration potential. CFU based assays showed the SCF cells to be significantly more susceptible than NCF cells to a range of concentrations of rifampicin and isoniazid (antibiotic stress), H2O2 (oxidative stress),and acidified NaNO2 (nitrite stress). Live cell imaging showed significantly higher susceptibility of the SCs of SC-NC sister daughter cell pairs, formed from highly-deviated ACD of normal/long-sized mother cells, to rifampicin and H2O2, as compared to the sister daughter NCs, irrespective of their comparable growth rates. The SC-SC sister daughter cell pairs, formed from the SCDs of short-sized mother cells and having comparable growth rates, always showed comparable stress-susceptibility. These observations and the presence of M. tuberculosis SCs and NCs in pulmonary tuberculosis patients' sputum earlier reported by us imply a physiological role for the SCs and the NCs under the stress conditions. The plausible reasons for the higher stress susceptibility of SCs and lower stress susceptibility of NCs are discussed.

Mutation in mitochondrial complex IV subunit COX5A causes pulmonary arterial hypertension, lactic acidemia, and failure to thrive.

COX5A is a nuclear-encoded subunit of mitochondrial respiratory chain complex IV (cytochrome c oxidase). We present patients with a homozygous pathogenic variant in the COX5A gene. Clinical details of two affected siblings suffering from early-onset pulmonary arterial hypertension, lactic acidemia, failure to thrive, and isolated complex IV deficiency are presented. We show that the variant lies within the evolutionarily conserved COX5A/COX4 interface domain, suggesting that it alters the interaction between these two subunits during complex IV biogenesis. In patient skin fibroblasts, the enzymatic activity and protein levels of complex IV and several of its subunits are reduced. Lentiviral complementation rescues complex IV deficiency. The monomeric COX1 assembly intermediate accumulates demonstrating a function of COX5A in complex IV biogenesis. A potential therapeutic lead is demonstrated by showing that copper supplementation leads to partial rescue of complex IV deficiency in patient fibroblasts.

Computer-aided volumetric assessment of malignant pleural mesothelioma on CT using a random walk-based method.

OBJECTIVE: The aim of this study is to assess the performance of a computer-aided semi-automated algorithm we have adapted for the purpose of segmenting malignant pleural mesothelioma (MPM) on CT. METHODS: Forty-five CT scans were collected from 15 patients (M:F [Formula: see text] 10:5, mean age 62.8 years) in a multi-centre clinical drug trial. A computer-aided random walk-based algorithm was applied to segment the tumour; the results were then compared to radiologist-drawn contours and correlated with measurements made using the MPM-adapted Response Evaluation Criteria in Solid Tumour (modified RECIST). RESULTS: A mean accuracy (Sørensen-Dice index) of 0.825 (95% CI [0.758, 0.892]) was achieved. Compared to a median measurement time of 68.1 min (range [40.2, 102.4]) for manual delineation, the median running time of our algorithm was 23.1 min (range [10.9, 37.0]). A linear correlation (Pearson's correlation coefficient: 0.6392, [Formula: see text]) was established between the changes in modified RECIST and computed tumour volume. CONCLUSION: Volumetric tumour segmentation offers a potential solution to the challenges in quantifying MPM. Computer-assisted methods such as the one presented in this study facilitate this in an accurate and time-efficient manner and provide additional morphological information about the tumour's evolution over time.

Local characterization of neovascularization and identification of proliferative diabetic retinopathy in retinal fundus images.

Neovascularization (NV) is a characteristic of the onset of sight-threatening stage of DR, called proliferative DR (PDR). Identification of PDR requires modeling of these unregulated ill-formed vessels, and other associated signs of PDR. We present an approach that models the micro-pattern of local variations (using texture based analysis) and quantifies structural changes in vessel patterns in localized patches, to arrive at a score of neovascularity. The distribution of patch-level confidence scores is collated into an image-level decision of presence or absence of PDR. Evaluated on a dataset of 779 images combining public data and clinical data from local hospitals, the patch-level neovascularity prediction has a sensitivity of 92.4% at 92.6% specificity. For image-level PDR identification our method is shown to achieve sensitivity of 83.3% at a high specificity operating point of 96.1% specificity, and specificity of 83% at high sensitivity operating point of 92.2% sensitivity. Our approach could have potential application in DR grading where it can localize NVE regions and identify PDR images for immediate intervention.

Connecting Active-Site Loop Conformations and Catalysis in Triosephosphate Isomerase: Insights from a Rare Variation at Residue†96 in the Plasmodial Enzyme.

Despite extensive research into triosephosphate isomerases (TIMs), there exists a gap in understanding of the remarkable conjunction between catalytic loop-6 (residues 166-176) movement and the conformational flip of Glu165 (catalytic base) upon substrate binding that primes the active site for efficient catalysis. The overwhelming occurrence of serine at position 96 (98% of the 6277 unique TIM sequences), spatially proximal to E165 and the loop-6 residues, raises questions about its role in catalysis. Notably, Plasmodium falciparum TIM has an extremely rare residue--phenylalanine--at this position whereas, curiously, the mutant F96S was catalytically defective. We have obtained insights into the influence of residue 96 on the loop-6 conformational flip and E165 positioning by combining kinetic and structural studies on the PfTIM F96 mutants F96Y, F96A, F96S/S73A, and F96S/L167V with sequence conservation analysis and comparative analysis of the available apo and holo structures of the enzyme from diverse organisms.

Recommendations for screening and early detection of common cancers in India.

Cancers of the breast, uterine cervix, and lip or oral cavity are three of the most common malignancies in India. Together, they account for about 34% of more than 1 million individuals diagnosed with cancer in India each year. At each of these cancer sites, tumours are detectable at early stages when they are most likely to be cured with standard treatment protocols. Recognising the key role that effective early detection and screening programmes could have in reducing the cancer burden, the Indian Institute for Cytology and Preventive Oncology, in collaboration with the US National Cancer Institute Center for Global Health, held a workshop to summarise feasible options and relevant evidence for screening and early detection of common cancers in India. The evidence-based recommendations provided in this Review are intended to act as a guide for policy makers, clinicians, and public health practitioners who are developing and implementing strategies in cancer control for the three most common cancers in India.

Using implementation science to advance cancer prevention in India.

Oral, cervical and breast cancers, which are either preventable and/or amenable to early detection and treatment, are the leading causes of cancer-related morbidity and mortality in India. In this paper, we describe implementation science research priorities to catalyze the prevention and control of these cancers in India. Research priorities were organized using a framework based on the implementation science literature and the World Health Organization's definition of health systems. They addressed both community-level as well as health systems-level issues. Community-level or "pull" priorities included the need to identify effective strategies to raise public awareness and understanding of cancer prevention, monitor knowledge levels, and address fear and stigma. Health systems-level or "push" and "infrastructure" priorities included dissemination of evidence- based practices, testing of point-of-care technologies for screening and diagnosis, identification of appropriate service delivery and financing models, and assessment of strategies to enhance the health workforce. Given the extent of available evidence, it is critical that cancer prevention and treatment efforts in India are accelerated. Implementation science research can generate critical insights and evidence to inform this acceleration.

Computer-assisted grading of diabetic macular edema on retinal color fundus images.

Diabetic macular edema (DME) is one of the vision-impairing manifestations of Diabetic Retinopathy (DR). Early detection and treatment of DME can prevent permanent vision loss in people suffering from DR. However, the clinical detection through biomicroscopy is time-consuming. In this paper, a computer-assisted grading method has been proposed to determine the DME severity based on the spatial distribution of exudative lesions around macula. The region around macula is classified into zonal levels and severity of the DME is graded based on the presence of exudative lesions in each zone. The proposed method has been evaluated on diverse public and local databases, and produced the sensitivity of 89.54% for 9.1 false positive per image (FPPI) for exudate detection and 98.8% accuracy for DME grading.

Computer-assisted identification of proliferative diabetic retinopathy in color retinal images.

Advanced (proliferative) stage of diabetic retinopathy (DR) is indicated by the growth of thin, fragile and highly unregulated vessels, neovascularization (NV). In order to identify proliferative diabetic retinopathy (PDR), our approach models the micro-pattern of local variations using texture based analysis and quantifies the structural changes in vessel patterns in localized patches, to map them to the confidence score of being neovascular using supervised learning framework. Rule-based criteria on patch-level neovascularity scores in an image is used for the decision of absence or presence of PDR. Evaluated using 3 datasets, our method achieves 96% sensitivity and 92.6% specificity for localizing NV. Image-level identification of PDR achieves high sensitivity of 96.72% at 79.6% specificity and high specificity of 96.50% at 73.22% sensitivity. Our approach could have potential application in DR grading where it can localize NVE regions and identify PDR images for immediate intervention.