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Sleep is an important indicator of a person’s health, and its accurate and cost-effective quantification is of great value in healthcare. The gold standard for sleep assessment and the clinical diagnosis of sleep disorders is polysomnography (PSG). However, PSG requires an overnight clinic visit and trained technicians to score the obtained multimodality data. Wrist-worn consumer devices, such as smartwatches, are a promising alternative to PSG because of their small form factor, continuous monitoring capability, and popularity. Unlike PSG, however, wearables-derived data are noisier and far less information-rich because of the fewer number of modalities and less accurate measurements due to their small form factor. Given these challenges, most consumer devices perform two-stage (i.e., sleep-wake) classification, which is inadequate for deep insights into a person’s sleep health. The challenging multi-class (three, four, or five-class) staging of sleep using data from wrist-worn wearables remains unresolved. The difference in the data quality between consumer-grade wearables and lab-grade clinical equipment is the motivation behind this study. In this paper, we present an artificial intelligence (AI) technique termed sequence-to-sequence LSTM for automated mobile sleep staging (SLAMSS), which can perform three-class (wake, NREM, REM) and four-class (wake, light, deep, REM) sleep classification from activity (i.e., wrist-accelerometry-derived locomotion) and two coarse heart rate measures—both of which can be reliably obtained from a consumer-grade wrist-wearable device. Our method relies on raw time-series datasets and obviates the need for manual feature selection. We validated our model using actigraphy and coarse heart rate data from two independent study populations: the Multi-Ethnic Study of Atherosclerosis (MESA; N = 808) cohort and the Osteoporotic Fractures in Men (MrOS; N = 817) cohort. SLAMSS achieves an overall accuracy of 79%, weighted F1 score of 0.80, 77% sensitivity, and 89% specificity for three-class sleep staging and an overall accuracy of 70-72%, weighted F1 score of 0.72-0.73, 64-66% sensitivity, and 89-90% specificity for four-class sleep staging in the MESA cohort. It yielded an overall accuracy of 77%, weighted F1 score of 0.77, 74% sensitivity, and 88% specificity for three-class sleep staging and an overall accuracy of 68-69%, weighted F1 score of 0.68-0.69, 60-63% sensitivity, and 88-89% specificity for four-class sleep staging in the MrOS cohort. These results were achieved with feature-poor inputs with a low temporal resolution. In addition, we extended our three-class staging model to an unrelated Apple Watch dataset. Importantly, SLAMSS predicts the duration of each sleep stage with high accuracy. This is especially significant for four-class sleep staging, where deep sleep is severely underrepresented. We show that, by appropriately choosing the loss function to address the inherent class imbalance, our method can accurately estimate deep sleep time (SLAMSS/MESA: 0.61±0.69 hours, PSG/MESA ground truth: 0.60±0.60 hours; SLAMSS/MrOS: 0.53±0.66 hours, PSG/MrOS ground truth: 0.55±0.57 hours;). Deep sleep quality and quantity are vital metrics and early indicators for a number of diseases. Our method, which enables accurate deep sleep estimation from wearables-derived data, is therefore promising for a variety of clinical applications requiring long-term deep sleep monitoring.

Rising obesity rates have become a major public health concern within the United States. Understanding the systemic and neural effects of obesity is crucial in designing preventive and therapeutic measures. In previous studies, administration of a high fat diet has induced significant weight gain for mouse models of obesity. Interestingly, sex differences in high-fat diet-induced weight gain have been observed, with female mice gaining significantly less weight compared to male mice on the same high-fat diet. It has also been observed that consumption of a high-fat diet can increase neurogliosis, but the mechanism by which this occurs is still not fully understood. Recent research has suggested that the gut microbiome may mediate diet-induced glial activation. The current study aimed to (1) analyze changes to the gut microbiome following consumption of a high fat (HF) diet as well as antibiotic treatment, (2) evaluate hippocampal microgliosis and astrogliosis, and (3) identify sex differences within these responses. We administered a low fat (Research Diets D12450 K) or high fat diet (Research Diets D12451) to male and female C57Bl/6 mice for sixteen weeks. Mice received an antibiotic cocktail containing 0.5g/L of vancomycin, 1.0 g/L ampicillin, 1.0 g/L neomycin, and 1.0 g/L metronidazole in their drinking water during the last six weeks of the study and were compared to control mice receiving normal drinking water throughout the study. We observed a significant reduction in gut microbiome diversity for groups that received the antibiotic cocktail, as determined by Illumina next-generation sequencing. Male mice fed the HF diet (± antibiotics) had significantly greater body weights compared to all other groups. And, female mice fed the low fat (LF) diet and administered antibiotics revealed significantly decreased microgliosis and astrogliosis in the hippocampus compared to LF-fed females without antibiotics. Interestingly, male mice fed the LF diet and administered antibiotics revealed significantly increased microgliosis, but decreased astrogliosis, compared to LF-fed males without antibiotics. The observed sex differences in LF-fed mice given antibiotics brings forward questions about sex differences in nutrient metabolism, gut microbiome composition, and response to antibiotics.

Nipah virus (NiV) is an emerging zoonotic virus that caused several serious outbreaks in the south asian region with high mortality rates ranging from 40 to 90% since 2001. NiV infection causes lethal encephalitis and respiratory disease with the symptom of endothelial cell-cell fusion. No specific and effective vaccine has yet been reported against NiV. To address the urgent need for a specific and effective vaccine against NiV infection, in the present study, we have designed two Multi-Epitope Vaccines (MEVs) composed of 33 Cytotoxic T lymphocyte (CTL) epitopes and 38 Helper T lymphocyte (HTL) epitopes. Out of those CTL and HTL combined 71 epitopes, 61 novel epitopes targeting nine different NiV proteins were not used before for vaccine design. Codon optimization for the cDNA of both the designed MEVs might ensure high expression potential in the human cell line as stable proteins. Both MEVs carry potential B cell linear epitope overlapping regions, B cell discontinuous epitopes as well as IFN-γ inducing epitopes. Additional criteria such as sequence consensus amongst CTL, HTL and B Cell epitopes was implemented for the design of final constructs constituting MEVs. Hence, the designed MEVs carry the potential to elicit cell-mediated as well as humoral immune response. Selected overlapping CTL and HTL epitopes were validated for their stable molecular interactions with HLA class I and II alleles and in case of CTL epitopes with human Transporter Associated with antigen Processing (TAP) cavity. The structure based epitope cross validation for interaction with TAP cavity was used as another criteria choosing final epitopes for NiV MEVs. Finally, human Beta-defensin 2 and Beta-defensin 3 were used as adjuvants to enhance the immune response of both the MEVs. Molecular dynamics simulation studies of MEVs-TLR3 ectodomain (Human Toll-Like Receptor 3) complex indicated the stable molecular interaction. We conclude that the MEVs designed and in silico validated here could be highly potential vaccine candidates to combat NiV infections, with great effectiveness, high specificity and large human population coverage worldwide.

Purpose The IFA supplementation program under the Anemia Mukt Bharat (AMB) program is one of the most ambitious nutrient supplementation programs in India. The delivery of services often suffers due to frequent stock outs and shortages. It is critical to understand the bottleneck in the supply chain adversely affecting the performance and coverage of the program. The paper attempts to identify the bottlenecks of the IFA supply chain in key areas of supply chain i.e., forecasting, procurement, warehousing and inventory management, transportation, distribution, logistic information system and suggests a plan of action aimed at ensuring uninterrupted supplies to the end beneficiaries. Design/methodology/approach The data source for the present paper is the nationwide IFA Supply Chain Assessment (2018–19) conducted across 29 Indian states with a total of 58 districts, 116 blocks, 232 Sub-Centres, 232 Anganwadi centres and 232 schools covered under the assessment as a multi-partner collaborative initiative. Field insights from supply chain strengthening interventions under different public health programs in India and other developing countries were taken to arrive at corrective actions and recommendations. Findings were disseminated to government and an action plan was suggested for connecting service delivery points through an app-based system, developing a micro plan for ensuring fixed distribution schedule, followed by continuous monitoring and review meetings identified for follow up. Findings The average lead time across states was 35 weeks with top three performing states being Goa, Sikkim, and Telangana. The average per unit cost of procurement was Rs 0.35 for IFA Red, Rs 0.25 for IFA Blue, Rs 0.31 for IFA Pink and Rs 7.30 for IFA syrup. Out of the 704 districts in India, only 213 has IFA Red, only 140 had IFA Blue, 152 had IFA Pink and 163 had IFA Syrup available in four quarters of 2018–19. The key issues identified in the assessment were–a lack of standardized forecasting process, absence of inventory management techniques, no fixed distribution schedule, inadequate availability of transport vehicles and an absence of an integrated MIS. Originality/value The identification of bottlenecks in the IFA supply chain and its impact on the performance of the supply chain would provide policy guidelines for the government as well as development partner agencies to design an effective and efficient supply chain. It would also enable the policy planners to understand the challenges associated with managing different components of a supply chain, their interrelation and impact on the overall performance of the supply chain. The suggested recommendations would equip program managers with the tool to devise and implement field level solutions.

O-methylation of small molecules is a common modification widely present in most organisms. Type III polyketides undergo O-methylation at hydroxyl end to play a wide spectrum of roles in bacteria, plants, algae, and fungi. Mycobacterium marinum harbours a distinctive genomic cluster with a type III pks gene and genes for several polyketide modifiers including a methyltransferase gene, mmar_2193. This study reports functional analyses of MMAR_2193 and reveals multi-methylating potential of the protein. Comparative sequence analyses revealed conservation of catalytically important motifs in MMAR_2193 protein. Homology-based structure-function and molecular docking studies suggested type III polyketide cores as possible substrates for MMAR_2193 catalysis. In vitro enzymatic characterization revealed the capability of MMAR_2193 protein to utilize diverse polyphenolic substrates to methylate several hydroxyl positions on a single substrate molecule. High-resolution mass spectrometric analyses identified multi-methylations of type III polyketides in cell-free reconstitution assays. Notably, our metabolomics analyses identified some of these methylated molecules in biofilms of wild type Mycobacterium marinum. This study characterizes a novel mycobacterial O-methyltransferase protein with multi-methylating enzymatic ability that could be exploited to generate a palette of structurally distinct bioactive molecules.

Background Handgrip strength (HGS), lung function and health-related quality of life (HRQoL) are relevant indicators of future cardiovascular risk and mortality. The impact of cardiac surgery on these predictive variables has been under-explored. The aim of this study was to determine the acute (within hospital) changes in HGS, lung function and HRQoL, and their relationships, in adults undergoing elective cardiac surgery. Further, the study examined the relationship between these variables and the predictors for lung function and HRQoL in these patients. Methods The study was a prospective cohort study that involved 101 patients who completed pre-operative (1–2 days before surgery) and physiotherapy discharge (5–7 days after surgery) assessments. Handgrip strength, lung function and HRQoL were assessed using JAMAR dynamometers, Vitalograph-Alpha or EasyOne spirometer, and Short-Form 36 questionnaire, respectively. Changes in these variables and their relationships were analysed using paired t-test and Pearson correlation coefficients, respectively. Prediction of lung function and HRQoL using HGS and other co-variates was conducted using regression analysis. Results At the time of physiotherapy discharge, lung function, HGS and the physical component of HRQoL were significantly ( Conclusions Undergoing cardiac surgery acutely and significantly reduced lung function, HGS and physical component of HRQoL in adults with cardiac disease. Assessment of HGS at physiotherapy discharge may be a poor indicator of operative changes in lung function and HRQoL. Clinicians may consider HGS as an inadequate tool in predicting lung function and HRQoL following cardiac surgery.

Background In the ongoing COVID-19 pandemic, an increased incidence of ROCM was noted in India among those infected with COVID. We determined risk factors for rhino-orbito-cerebral mucormycosis (ROCM) post Coronavirus disease 2019 (COVID-19) among those never and ever hospitalized for COVID-19 separately through a multicentric, hospital-based, unmatched case-control study across India. Methods We defined cases and controls as those with and without post-COVID ROCM, respectively. We compared their socio-demographics, co-morbidities, steroid use, glycaemic status, and practices. We calculated crude and adjusted odds ratio (AOR) with 95% confidence intervals (CI) through logistic regression. The covariates with a p-value for crude OR of less than 0·20 were considered for the regression model. Results Among hospitalised, we recruited 267 cases and 256 controls and 116 cases and 231 controls among never hospitalised. Risk factors (AOR; 95% CI) for post-COVID ROCM among the hospitalised were age 45–59 years (2·1; 1·4 to 3·1), having diabetes mellitus (4·9; 3·4 to 7·1), elevated plasma glucose (6·4; 2·4 to 17·2), steroid use (3·2; 2 to 5·2) and frequent nasal washing (4·8; 1·4 to 17). Among those never hospitalised, age ≥ 60 years (6·6; 3·3 to 13·3), having diabetes mellitus (6·7; 3·8 to 11·6), elevated plasma glucose (13·7; 2·2 to 84), steroid use (9·8; 5·8 to 16·6), and cloth facemask use (2·6; 1·5 to 4·5) were associated with increased risk of post-COVID ROCM. Conclusions Hyperglycemia, irrespective of having diabetes mellitus and steroid use, was associated with an increased risk of ROCM independent of COVID-19 hospitalisation. Rational steroid usage and glucose monitoring may reduce the risk of post-COVID.

Genetic diversity studies provide important details on target trait availability and its variability, for the success of breeding programs. In this study, GBS approach was used to reveal a new structuration of genetic diversity and population structure of pigeonpea in Benin. We used a total of 688 high-quality Single Nucleotide Polymorphism markers for a total of 44 pigeonpea genotypes. The distribution of SNP markers on the 11 chromosomes ranged from 14 on chromosome 5 to 133 on chromosome 2. The Polymorphism Information Content and gene diversity values were 0.30 and 0.34 respectively. The analysis of population structure revealed four clear subpopulations. The Weighted Neighbor Joining tree agreed with structure analyses by grouping the 44 genotypes into four clusters. The PCoA revealed that genotypes from subpopulations 1, 2 and 3 intermixed among themselves. The Analysis of Molecular Variance showed 7% of the total variation among genotypes while the rest of variation (93%) was within genotypes from subpopulations indicating a high gene exchange (Nm = 7.13) and low genetic differentiation (PhiPT = 0.07) between subpopulations. Subpopulation 2 presented the highest mean values of number of different alleles (Na = 1.57), number of loci with private alleles (Pa = 0.11) and the percentage of polymorphic loci (P = 57.12%). We discuss our findings and demonstrate how the genetic diversity and the population structure of this specie can be used through the Genome Wide Association Studies and Marker-Assisted Selection to enhance genetic gain in pigeonpea breeding programs in Benin.

Bone marrow derived human Mesenchymal Stem Cells (hMSCs) are an attractive candidate for regenerative medicine. However, their harvest can be invasive, painful, and expensive, making it difficult to supply the enormous amount of pure hMSCs needed for future allogeneic therapies. Because of this, a robust method of scaled bioreactor culture must be designed to supply the need for high purity, high density hMSC yields. Here we test a scaled down model of a novel bioreactor consisting of an unsubmerged 3D printed Polylactic Acid (PLA) lattice matrix wetted by culture media. The growth matrix is uniform, replicable, and biocompatible, enabling homogenous cell culture in three dimensions. The goal of this study was to prove that hMSCs would culture well in this novel bioreactor design. The system tested resulted in comparable stem cell yields to other cell culture systems using bone marrow derived hMSCs, while maintaining viability (96.54% ±2.82), high purity (>98% expression of combined positive markers), and differentiation potential.

Insulin glargine is a long-acting analogue of human insulin that has been used to manage hyperglycemia in patients with diabetes mellitus (DM) for nearly 20 years. Insulin glargine has a relatively constant concentration-time profile that mimics basal levels of insulin and allows for once-daily administration. MYL-1501D is a biosimilar insulin glargine designed to offer greater access of insulin glargine to patients, with comparable efficacy and safety to the marketed reference product. We conducted a comprehensive panel of studies based on a formal analysis of critical quality attributes to characterize the structural and functional properties of MYL-1501D and reference insulin glargine products available in the United States and European Union. MYL-1501D was comprehensively shown to have high similarity to the reference products in terms of protein structure, metabolic activity (both in vitro cell-based assays and in vivo rabbit bioassays), and in vitro cell-based assays for mitogenic activity. The structural analyses demonstrated that the primary protein sequence was identical, and secondary and tertiary structures are similar between the proposed biosimilar and the reference products. Insulin receptor binding affinity and phosphorylation studies also established analytical similarity. MYL-1501D demonstrated high similarity in different metabolic assays of glucose uptake, adipogenesis activity, and inhibition of stimulated lipolysis. Rabbit bioassay studies showed MYL-1501D and EU-approved insulin glargine are highly similar to US-licensed insulin glargine. These product quality studies show high similarity between MYL-1501D and licensed or approved insulin glargine products and suggest the potential of MYL-1501D as an alternative cost-effective treatment option for patients and clinicians.

Introduction Government-sponsored health insurance schemes can play an important role in improving the reach of healthcare services. Launched in 2018 in India, Pradhan Mantri Jan Aarogya Yojana (PM-JAY) is one of the world’s largest government-sponsored health insurance schemes. The objective of this study is to understand beneficiaries’ experience of availing healthcare services at the empaneled hospitals in PM-JAY. This study examines the responsiveness of PM-JAY by measuring the prompt attention in service delivery, and access to information by the beneficiaries; financial burden experienced by the beneficiaries; and beneficiary’s satisfaction with the experience of hospitalization under PMJAY and its determinants. Methods The study was conducted during March-August 2019. Data were obtained through a survey conducted with 200 PM-JAY beneficiaries (or their caregivers) in the Indian states of Gujarat and Madhya Pradesh. The study population comprised of patients who received healthcare services at 14 study hospitals in April 2019. Prompt attention was measured in the form of a) effectiveness of helpdesk, and b) time taken at different stages of hospitalization and discharge events. Access to information by the beneficiaries was measured using the frequency and purpose of text messages and phone calls from the scheme authorities to the beneficiaries. The financial burden was measured in terms of the incidence and magnitude of out-of-pocket payments made by the beneficiaries separate from the cashless payment provided to hospitals by PMJAY. Beneficiaries’ satisfaction was measured on a five-point Likert scale. Results Socio-economically weaker sections of the society are availing healthcare services under PM-JAY. In Gujarat, the majority of the beneficiaries were made aware of the scheme by the government official channels. In Madhya Pradesh, the majority of the beneficiaries got to know about the scheme from informal sources. For most of the elements of prompt attention, access to information, and beneficiaries’ satisfaction, hospitals in Gujarat performed significantly better than the hospitals in Madhya Pradesh. Similarly, for most of the elements of prompt attention, access to information, and beneficiaries’ satisfaction, public hospitals performed significantly better than private hospitals. Incidence and magnitude of out-of-pocket payments were significantly higher in Madhya Pradesh as compared to Gujarat, and in private hospitals as compared to the public hospitals. Conclusion There is a need to focus on Information, Education, and Communication (IEC) activities for PM-JAY, especially in Madhya Pradesh. Capacity-building efforts need to be prioritized for private hospitals as compared to public hospitals, and for Madhya Pradesh as compared to Gujarat. There is a need to focus on enhancing the responsiveness of the scheme, and timely exchange of information with beneficiaries. There is also an urgent need for measures aimed at reducing the out-of-pocket payments made by the beneficiaries.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disorder worldwide and is increasing at an alarming rate. NAFLD is strongly associated with obesity and insulin resistance. The use of animal models remains a vital aspect for investigating the molecular mechanisms contributing to metabolic dysregulation and facilitating novel drug target identification. However, some differences exist between mouse and human hepatocyte physiology. Recently, chimeric mice with human liver have been generated, representing a step forward in the development of animal models relevant to human disease. Here we explored the feasibility of using one of these models (cDNA-uPA/SCID) to recapitulate obesity, insulin resistance and NAFLD upon feeding a Western-style diet. Furthermore, given the importance of a proper control diet, we first evaluated whether there are differences between feeding a purified ingredient control diet that matches the composition of the high-fat diet and feeding a grain-based chow diet. We show that mice fed chow have a higher food intake and fed glucose levels than mice that received a low-fat purified ingredient diet, suggesting that the last one represents a better control diet. Upon feeding a high-fat or matched ingredient control diet for 12 weeks, cDNA-uPA/SCID chimeric mice developed extensive macrovesicular steatosis, a feature previously associated with reduced growth hormone action. However, mice were resistant to diet-induced obesity and remained glucose tolerant. Genetic background is fundamental for the development of obesity and insulin resistance. Our data suggests that using a background that favors the development of these traits, such as C57BL/6, may be necessary to establish a humanized mouse model of NAFLD exhibiting the metabolic dysfunction associated with obesity.

Background Annually, in India, millions of dog bite cases occur; most of them are inflicted by a stray dog. There are over 25 million dogs in the country. The rate of stray dog vaccination is suboptimal in India. This study aims to develop an intervention strategy, using Intervention Mapping framework, tailored for the target community to achieve canine rabies controlled zone. Methodology This is an exploratory, cross-sectional study conducted at a tertiary care Medical Institute at Jodhpur, Rajasthan, India, from 2018–2019. The semi-structured, In-Depth Discussion was conducted with a multidisciplinary planning group comprising of members from veterinary, health, and administrative sectors. The In-Depth Discussion focused on knowledge regarding complete stray dog vaccination schedule, self-efficacy (to prevent dog bites), challenges, and barriers faced by residents to achieve canine rabies controlled zone. Further, discussion with veterinary stakeholders focused on challenges faced for rigorous implementation of stray dog vaccination and sterilization. Results In-Depth Discussion revealed the following challenges: Lack of participation by the study population for canine vaccination, incomplete knowledge about annual canine vaccination schedule, lack of understanding of dog gestures, lack of infrastructure and resources at veterinary hospitals. The majority of the dogs in the study area were stray dogs that were partially or non-vaccinated and non-sterilized. An intersectoral collaboration was achieved between the community members, veterinary stakeholders both private and Non-Governmental organisations, and heath sector. Following which 35 (76.0%) stray dogs were vaccinated, and 17 (35.4%) were sterilized with community support. Burden of dog bite cases also decreased. The stray dog density map was prepared, and community engagement activity on dog gestures was conducted. Conclusion The present study demonstrates the feasibility of achieving canine rabies controlled zone. When implemented in a phase-wise manner across all Medical and Residential complex, this strategy would ensure achieving canine rabies controlled zone through multi-stakeholder engagement.

Hill's thistle (Cirsium hillii (Canby) Fernald) is a perennial plant endemic to the Great Lakes region of North America. Hill's thistle is listed as threatened in Ontario and Canada where it is found in globally rare alvar habitats. The main objective of this study was ex-situ conservation of Hill's thistle using in vitro culture techniques and reintroduction of micropropagated plants back to their natural habitat in Bruce Peninsula National Park, Ontario, Canada. Two out of twenty-nine available seeds were successfully germinated under in vitro condition. An efficient micropropagation protocol was optimized with 100% survival during acclimatization of plantlets in the greenhouse. Three hundred micropropagated plants were reintroduced to twelve different sites within Bruce Peninsula National Park in June and July 2017. Plants were monitored for survival, rosette growth, and flowering on all sites from 2017-2019. After four months of planting, 67 to 99% of the plants were alive in different sites and 90 to 99% of them survived over winter. In the following years, shoot regeneration and flowering were observed on most sites. This study further confirms the benefit of plant tissue culture techniques to ensure revival of Hill's thistle ecological biodiversity through the reintroduction of micropropagated plants. This approach consisting of the components of conservation, propagation, and reintroduction (CPR) may potentially serve as a model for saving and enriching other species at risk.

Domesticated lentil has a relatively narrow genetic base globally and most released varieties are susceptible to severe biotic and abiotic stresses. The crop wild relatives could provide new traits of interest for tailoring novel germplasm and cultivated lentil improvement. The primary objective of this study was to evaluate wild lentil accessions for identification of economically viable agro-morphological traits and resistance against major biotic stresses. The study has revealed substantial variations in seed yield and its important component characters. Further, the diversity analysis of wild accessions showed two major clusters which were bifurcated into sub-clusters, thereby suggesting their wider genetic divergence. However, principal component analysis exhibited that seed yield plant-1, number of seeds plant-1, number of pods plant-1, harvest index and biological yield plant-1 contributed significantly to the total genetic variation assessed in wild lentil taxa. Moreover, some of the wild accessions collected from Syria and Turkey regions showed resistance against more than one disease indicating rich diversity of lentil genetic resources. The identification of most promising genotypes carrying resistance against major biotic stresses could be utilized in the cultivated or susceptible varieties of lentil for enhancing genetic gains. The study has also identified some trait specific accessions, which could also be taken into the consideration while planning distant hybridization in lentil.

ObjectiveCurrent urinary tract infection (UTI) diagnostic strategies that rely on leukocyte esterase have limited accuracy. We performed an aptamer-based proteomics pilot study to identify urine protein levels that could differentiate a culture proven UTI from culture negative samples, regardless of pyuria status.MethodsWe analyzed urine from 16 children with UTIs, 8 children with culture negative pyuria and 8 children with negative urine culture and no pyuria. The urine levels of 1,310 proteins were quantified using the Somascan™ platform and normalized to urine creatinine. Machine learning with support vector machine (SVM)-based feature selection was performed to determine the combination of urine biomarkers that optimized diagnostic accuracy.ResultsEight candidate urine protein biomarkers met filtering criteria. B-cell lymphoma protein, C-X-C motif chemokine 6, C-X-C motif chemokine 13, cathepsin S, heat shock 70kDA protein 1A, mitogen activated protein kinase, protein E7 HPV18 and transgelin. AUCs ranged from 0.91 to 0.95. The best prediction was achieved by the SVMs with radial basis function kernel.ConclusionsBiomarkers panel can be identified by the emerging technologies of aptamer-based proteomics and machine learning that offer the potential to increase UTI diagnostic accuracy, thereby limiting unneeded antibiotics.

Background Risk factors for the development of severe COVID-19 disease and death have been widely reported across several studies. Knowledge about the determinants of severe disease and mortality in the Indian context can guide early clinical management. Methods We conducted a hospital-based case control study across nine sites in India to identify the determinants of severe and critical COVID-19 disease. Findings We identified age above 60 years, duration before admission >5 days, chronic kidney disease, leucocytosis, prothrombin time > 14 sec, serum ferritin >250 ng/mL, d-dimer >0.5 ng/mL, pro-calcitonin >0.15 μg/L, fibrin degradation products >5 μg/mL, C-reactive protein >5 mg/L, lactate dehydrogenase >150 U/L, interleukin-6 >25 pg/mL, NLR ≥3, and deranged liver function, renal function and serum electrolytes as significant factors associated with severe COVID-19 disease. Interpretation We have identified a set of parameters that can help in characterising severe COVID-19 cases in India. These parameters are part of routinely available investigations within Indian hospital settings, both public and private. Study findings have the potential to inform clinical management protocols and identify patients at high risk of severe outcomes at an early stage.