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Glomerular diseases are often chronic or recurring and thus associated with a tremendous physical, psychological, and economic burden. Their etiologies are often unknown, and their pathogeneses are frequently poorly understood. The diagnoses and management of these diseases are therefore based on clinical features, traditional laboratory markers, and, often, kidney pathology. However, the clinical presentation can be highly variable, the kidney pathology may not establish a definitive diagnosis, and the therapeutic responses and resulting clinical outcomes are often unpredictable. To try to address these challenges, significant research efforts have been made over the last decade to identify potential biomarkers that can help clinicians optimize the diagnosis and prognosis at clinical presentation, as well as help predict long-term outcomes. Unfortunately, these efforts have to date only identified a single biomarker for glomerular disease that has been fully validated and developed for widespread clinical use (anti-PLA2R antibodies to diagnose membranous nephropathy). In this manuscript, we review the definitions and development of biomarkers, as well as the current knowledge on both historical and novel candidate biomarkers of glomerular disease, with an emphasis on those associated with idiopathic nephrotic syndrome., Author(s): Gabriel Cara-Fuentes [sup.1] , William E. Smoyer [sup.2] [sup.3] Author Affiliations: (1) grid.430503.1, 0000 0001 0703 675X, Department of Pediatrics, Division of Pediatric Nephrology, University of Colorado, , 12700 [...]

Purpose Activity/remission differentiation is a great challenge in the follow-up and treatment of sarcoidosis patients. Angiotensin-converting enzyme (ACE) and high sensitivity C-reactive protein (hs-CRP) were proposed as sarcoidosis biomarkers. More recently, chitotriosidase (CHITO) has been described as a better alternative. This study has the aim to evaluate the association of CHITO activity, ACE, hs-CRP or a combination of these biomarkers and to construct a clinical algorithm to differentiate between sarcoidosis activity/remission status. Methods Forty-six patients with either active sarcoidosis or sarcoidosis in remission and 21 healthy individuals were included. ACE, hs-CRP, and CHITO were evaluated in serum samples. Comparisons of the laboratory variable means among groups were performed by linear models. The cutoff points of the biomarkers for activity/remission differentiation were calculated using the Youden's index. Biomarker cutoff points and decision tree classifier (DTC) performance were estimated by their leave-one-out cross-validation (LOOCV) accuracy (Acc), sensitivity (Se), and specificity (Sp). Results A 55% mean Se and a 100% mean Sp were found for CHITO, while an 88% Se and a 47% Sp were found for ACE, and a 66% Se and a 68% Sp for hs-CRP cutoff points for activity/remission differentiation. The DTC algorithm with CHITO, hs-CRP, and ACE information had an LOOCV mean Acc of 82%, Se of 78%, and Sp of 89% for sarcoidosis activity/remission differentiation. Conclusions The algorithm involving CHITO, hs-CRP, and ACE could be a suitable strategy for differentiation between sarcoidosis activity/remission status., Author(s): Mariana Carneiro Lopes [sup.1] , Thaís Porto Amadeu [sup.1] , Marcelo Ribeiro-Alves [sup.2] , Claudia Henrique da Costa [sup.1] , Luciana Silva Rodrigues [sup.1] , Elisabeth Jauhar Cardoso Bessa [...]

* Context.--Phosphatase and tensin homolog (PTEN) is a promising prognostic and potentially predictive biomarker in prostate cancer. Objective.--To assess the effects of preanalytic variables on an analytically validated and fully automated PTEN immunohistochemistry assay. Design.--PTEN immunohistochemistry was performed on Ventana immunostaining systems. In benign prostate tissues, immunostaining intensity across variable conditions was assessed by digital image analysis. In prostate tumor tissues, immunostaining was scored visually. Results.--Delay of fixation for 4 hours or longer at room temperature or 48 hours or longer at 4[degrees]C and duration of formalin fixation did not significantly alter immunostaining intensity. Intensity of staining was highest in 10% formalin compared with other fixatives. Tumor tissues with PTEN loss processed using protocols from 11 academic institutions were all evaluable and scored identically. PTEN immunostaining of needle biopsies where tissue blocks had been stored for less than 10 years was more frequently scored as nonevaluable compared with blocks that had been stored for 10 years or longer. This effect was less evident for radical prostatectomy specimens, where low rates of nonevaluable staining were seen for 23 years or more of storage. Storage of unstained slides for 5 years at room temperature prior to immunostaining resulted in equivalent scoring compared with freshly cut slides. Machine-to-machine variability assessed across 3 Ventana platforms and 2 institutions was negligible in 12 tumors, and platform-to-platform variability was also minor comparing Ventana and Leica instruments across 77 tumors (k = 0.926). Conclusions.--Automated PTEN immunostaining is robust to most preanalytic variables in the prostate and may be performed on prostate tumor tissues subjected to a wide range of preanalytic conditions. These data may help guide assay development if PTEN becomes a key predictive biomarker. doi: 10.5858/arpa.2018-0068-OA, Tissue-based biomarkers hold great promise for the practice of personalized medicine in oncology. In particular, immunohistochemistry (IHC) assays, which enable the detection of proteins in situ in tissue specimens, are [...]

Fatty acids (FAs) are the main components of lipids in corals. We examined FAs profiles from five symbiotic coral species belonging to five different genera (Acropora, Pavona, Turbinaria, Favites, and Platygyra) and four different families (Acroporidae, Agariciidae, Dendrophyllidae, Faviidae). We separated symbionts from the coral host tissue to investigate the interaction of FA between symbionts and host tissue. After separation, we used FA profiles, in particular specific FAs (e.g. 16:0, 18:0, 18:3n-3, 20:5n-3, 22:6n-3) and their ratios (EPA:DHA, PUFA:SFA) as biomarkers (i.e. signature lipids) to examine chemotaxonomy and trophic level (autotrophy vs. heterotrophy) of each coral species. Gas chromatography-mass spectrometry (GC-MS) was performed to identify and quantify FA. For quantification, the dry weight of total lipids was used to normalize FA concentration ([mu]g mg.sup.-1). We found that (1) the five different coral species showed define species-specific FA profiles; (2) certain FAs were valuable biomarkers to determine relative trophic strategies (i.e. autotrophy and/or heterotrophy; (3) the application of FA ratios to define trophic level requires caution in research application and data interpretation. Considering the limitations of FA ratios determined herein, we suggest it to be more appropriate to examine response to environmental change within species. Going forward, our study provides important FA baseline data that builds the foundation for future investigations on the impact of environmental changes related to nutrition and metabolism in symbiotic corals., Author(s): Taihun Kim [sup.1] [sup.2] [sup.3] , David M. Baker [sup.1] [sup.2] , Se-Jong Ju [sup.4] , Jetty Chung-Yung Lee [sup.1] Author Affiliations: (1) grid.194645.b, 0000000121742757, School of Biological Sciences, [...]

Microcystes (MC) produced by several cyanobacteria are potent hepatotoxins, whereas the toxicokinetics and subsequent detrimental effects of MC are not fully understood in marine bivalves. In this study, the accumulation and depuration pattern of MC-Leucine-Arginine (MC-LR) along with the antioxidant response were investigated in the gill tissue of Pacific oyster Crassostrea gigas and blue mussel Mytilus edulis exposed to 0.1, 1, 10, and 20 [micro]g [L.sup.-1] MC-LR for 7 days. Time- and concentration-dependent accumulation and depuration of MC-LR were observed in the gill tissue during the exposure and depuration phases. The values for maximum accumulation of MC-LR and malondialdehyde content were statistically significant (P < 0.05) at the end of exposure (day 7) to 20 [micro]g [L.sup.-1] MC-LR for both the bivalves, and at the beginning of the depuration period when M. edulis and C. gigas were exposed to 10 and 20 [micro]g [L.sup.-1], respectively. A significant level of glutathione (GSH) was detected in M. edulis in response to 20 [micro]g [L.sup.-1] MC-LR during the exposure and depuration periods, whereas no significant levels of GSH were detected in C. gigas. The MC-LR accumulation induced oxidative stress in the gill tissue through modulation of the activities of antioxidant enzymes, the antioxidant response being more significant in the mussel than in the oyster. The enzymatic activities of glutathione S-transferase, superoxide dismutase (SOD), glutathione peroxidase, and glutathione reductase (GR) increased significantly in M. edulis, whereas in C. gigas, significant increase in the activities of SOD, catalase, and GR were observed at the end of exposure (day 7) to 20 [micro]g [L.sup.-1] MC-LR. Similarly, during the depuration period, significant increases in the antioxidant activities were observed in M. edulis mostly at the beginning (day I and day 5) of exposure compared with the levels in C. gigas. The results obtained in this study will be useful in the understanding of MC-LR accumulation in bivalve gill tissues and the subsequent antioxidant defense response. KEY WORDS: Crassostrea gigas, Mytilus edulis, microcystin, bioconcentration, biomarker, bivalve, gill, oxidative stress, INTRODUCTION Cyanobacterial blooms in eutrophic aquatic systems can affect the water quality, which might cause toxicity in fresh, brackish, and marine water bodies as well as in the ecosystem of [...]

Author(s): Rosanna Coppo [sup.1] Author Affiliations: (1) grid.415778.8Fondazione Ricerca Molinette, Nephrology, Dialysis and Transplantation, Regina Margherita Hospital, Turin, Italy Introduction Among the conundrums surrounding immunoglobulin A nephropathy (IgAN) are its [...]

Background This study tested the hypothesis that during massive proteinuria, C-reactive protein (CRP) may be lost into the urine along with other proteins, making serum CRP (sCRP) level an unreliable marker of infection severity in nephrotic syndrome (NS). Methods Children with active NS (n = 23) were compared with two matched control groups: patients with febrile non-renal infectious disease (n = 30) and healthy subjects (n = 16). Laboratory measurements included sCRP, urine protein, creatinine, IgG, and protein electrophoresis. Urinary CRP (uCRP) was measured by ELISA. Results Sixty-nine patients were enrolled: 23 patients with NS, 30 patients with non-renal febrile infectious diseases, and 16 healthy children. Median uCRP concentrations were 0 mcg/gCr (0-189.7) in NS, 11 mcg/gCr (0-286) in the febrile group, and 0 mcg/gCr (0-1.8) in the healthy group. The uCRP/creatinine ratio was similar in the NS and healthy groups (p > 0.1) and significantly higher in the febrile group than the other two groups (p < 0.0001). There was no association of uCRP concentration with severity of proteinuria or IgG excretion. Conclusions NS in children is not characterized by significant loss of CRP into the urine. Therefore, sCRP may serve as a reliable marker of inflammation in this setting. The significant urinary excretion of CRP in children with transient non-renal infectious disease might be attributable to CRP synthesis in renal epithelial cells., Author(s): Eran Shostak[sup.1] [sup.4] , Irit Krause[sup.2] [sup.4] , Amit Dagan[sup.2] [sup.4] , Anat Ben-Dor[sup.3] , Meital Keidar[sup.2] , Miriam Davidovits[sup.2] [sup.4] Author Affiliations: (1) Pediatric Intensive Care Unit, Schneider [...]

Introduction The fractional excretion of sodium (FE.sub.Na) has been used as an index for the differential diagnosis of acute tubular necrosis (ATN) and prerenal acute kidney injury (AKI). The reliability of this index, however, decreases with the use of the diuretic agent furosemide. The fractional excretion of urea nitrogen (FE.sub.UN) has been shown to be useful in such settings in adults. The objective of this study was to examine whether FE.sub.UN is also useful in these settings in children. Methods We assessed 102 episodes of AKI in 74 children, classifying these into three groups based on history, physical examination, urine examination and subsequent clinical course: (1) prerenal AKI without furosemide (N = 37), (2) prerenal AKI with furosemide (N = 32) and (3) ATN (N = 33). Results Of the 37 prerenal AKI episodes without furosemide, 35 showed low FE.sub.Na of Conclusions FE.sub.UN is useful in detecting prerenal AKI in children administered furosemide., Author(s): Hisayo Fujita[sup.1] , Masayoshi Shinjoh[sup.2] , Tomohiro Ishii[sup.2] , Midori Awazu[sup.2] Author Affiliations: (1) Department of Pediatrics, Hiratsuka Kyosai Hospital, KanagawaJapan (2) Department of Pediatrics, Keio University School of [...]

Background Urinary biomarkers may be indicators of acute kidney injury (AKI), although little is known of their developmental characteristics in healthy neonates across a full range of gestational age (GA). The purpose of this study was to examine patterns of urinary biomarkers across GA groups from birth to 3 months of age. Methods Fifty-two infants ranging from 24 to 41 weeks' GA had urine assayed from birth through 3 months of age for 7 biomarkers including albumin (ALB), beta-2-microglobulin (B2M), cystatin-C (CysC), epidermal growth factor (EGF), neutrophil-gelatinase-associated lipocalin (NGAL), osteopontin (OPN), and uromodulin (UMOD). Results Of the seven urinary biomarkers, EGF and UMOD increased while others decreased with advancing GA. By 3 months of age, EGF and UMOD had increased in preterm infants to levels similar to those of term infants. UMOD/ml and EGF/ml appeared to be predominantly developmental biomarkers distinguishing estimated glomerular filtration rate (GFR) Conclusions Among healthy neonates, urinary biomarkers vary with GA. These data support the use of urinary biomarkers in the assessment of normal kidney development in the absence of injury., Author(s): Marissa J. DeFreitas[sup.1] , Wacharee Seeherunvong[sup.1] , Chryso P. Katsoufis[sup.1] , Satish RamachandraRao[sup.2] , Shahnaz Duara[sup.3] , Salih Yasin[sup.4] , Gaston Zilleruelo[sup.1] , Maria M. Rodriguez[sup.5] , Carolyn L. [...]

Introduction The purpose of this study was to investigate the potential value of certain biomarkers in predicting the presence of malignant pleural mesothelioma (MPM) in individuals environmentally exposed to asbestos. Methods This prospective study investigated three groups; a control group composed of 41 healthy subjects, an asbestos exposure group consisting of 48 individuals, and a MPM group consisting of 42 patients. Serum levels of soluble mesothelin-related peptide (SMRP), thioredoxin-1 (TRX), epidermal growth factor receptor (EGFR), fibulin-3, syndecan-1 (SDC-1), and mesothelin were determined. Results Benign pleural plaques were present in 27 (58.3 %) of the individuals in the asbestos exposure group. The asbestos exposure group had significantly higher mean TRX, SMRP, and mesothelin levels compared to the control group (p = 0.023, p = 0.011, and p < 0.001, respectively). Compared to the asbestos exposure group, the MPM group had significantly higher mean EGFR, TRX, SMRP, and fibulin-3 levels (p = 0.041, p = 0.023, p = 0.002, and p = 0.001, respectively), and significantly lower mean SDC-1 levels (p = 0.002). Unlike the other biomarkers, SMRP and TRX levels increased in a graded fashion among the control, asbestos exposure, and MPM groups, respectively. Area under the curve values for SMRP and TRX were 0.86 and 0.72, respectively (95 % CI 0.79-0.92 and p < 0.001 for SMRP, and 95 % CI 0.62-0.81 and p < 0.001 for TRX). The cut-off value for SMRP was 0.62 nmol/l (sensitivity: 97.6 %, specificity: 68.9 %, positive predictive value (PPV): 56.2 %, and negative predictive value (NPV): 98.3 %) and for TRX was 156.67 ng/ml (sensitivity: 92.9 %, specificity: 77.6 %, PPV: 41.4 %, and NPV: 92.1 %). The combination of the biomarkers reached a sensitivity of 100 %, but had lower specificity (as high as 27.7 %). Conclusions Serum biomarkers may be helpful for early diagnosis of MPM in asbestos-exposed cases. SMRP and TRX increased in a graded fashion from the controls to asbestos exposure and MPM groups. These two seem to be the most valuable biomarkers for the diagnosis of MPM, both individually and in combination., Author(s): Melike Demir[sup.1] , Halide Kaya[sup.1] , Mahsuk Taylan[sup.1] , Aysun Ekinci[sup.2] , Sureyya Yilmaz[sup.1] , Fatma Teke[sup.3] , Cengizhan Sezgi[sup.1] , Abdullah Cetin Tanrikulu[sup.1] , Fatih Meteroglu[sup.4] , Abdurrahman [...]

Background The evaluation of the role of novel biomarkers in the management of cardiac and pulmonary conditions has received particular attention in recent years. A further particular perspective is the use of biomarker panels in the evaluation of patients presenting with acute dyspnea. Methods We prospectively evaluated three biomarkers (MR-proANP, PCT, and MR-proADM) in consecutive patients presenting with acute dyspnea in a medical emergency unit during a 4-week period. Patients received a final diagnosis. Biomarkers were tested for their potential to predict diagnoses and survival. No intervention was done. Results Overall, n = 172 patients were included. Of these, 32.6 % had acute heart failure, 16.9 % pneumonia, and 5.8 % died. MR-proANP was the highest in patients with acute heart failure and lung embolism. Dyspnea scores and levels of MR-pro-ANP correlated positively. MR-proANP achieved an AUC of 0.83 for the diagnosis of acute heart failure. Using a cut-off of 120 pmol/l, sensitivity was 91.1 % and specificity 50 %. PPV was 46.8 % and NPV 92.1 %. In patients with MR-proANP >300 pmol/l, PPV raised to 67.3 %. MR-proADM had an AUC of 0.84 for the prediction of death. PPV was 16 % and NPV 98.4 %. The AUC of PCT was 0.74 for the diagnosis of pneumonia. Using a cut-off of 0.25 ng/ml, PCT had a sensitivity of 44.8 % and a specificity of 85.3 %. PPV was 38.2 and NPV 88.4 %. Using a lower cut-off of Conclusions A panel of three biomarkers (MR-proANP, PCT, and MR-proADM) in patients presenting to the emergency unit with acute dyspnea provides information about the probability of acute heart failure, nonsurvival, and pneumonia. These biomarkers achieve low to moderate positive predictive values (PPV) and high negative predictive values (NPV)., Author(s): Lars Heining[sup.1] , Christian Giesa[sup.1] , Santiago Ewig[sup.1] Author Affiliations: (1) Thoraxzentrum Ruhrgebiet, Kliniken für Pneumologie und Infektiologie, EVK Herne und Augusta-Kranken-Anstalt Bochum, Bergstrasse 26, 44791, Bochum, Germany Introduction [...]

Kidney disease and its related comorbidities impose a large public health burden. Despite this, the number of clinical trials in nephrology lags behind many other fields. An important factor contributing to the relatively slow pace of nephrology trials is that existing clinical endpoints have significant limitations. 'Hard' endpoints for chronic kidney disease, such as progression to end-stage renal disease, may not be reached for decades. Traditional biomarkers, such as serum creatinine in acute kidney injury, may lack sensitivity and predictive value. Finding new biomarkers to serve as surrogate endpoints is therefore an important priority in kidney disease research and may help to accelerate nephrology clinical trials. In this paper, I first review key concepts related to the selection of clinical trial endpoints and discuss statistical and regulatory considerations related to the evaluation of biomarkers as surrogate endpoints. This is followed by a discussion of the challenges and opportunities in developing novel biomarkers and surrogate endpoints in three major areas of nephrology research: acute kidney injury, chronic kidney disease, and autosomal dominant polycystic kidney disease., Author(s): Erum A. Hartung[sup.1] [sup.2] Author Affiliations: (1) Division of Nephrology, Children's Hospital of Philadelphia, 34th and Civic Center Boulevard, 19104, Philadelphia, PA, USA (2) Department of Pediatrics, Perelman School [...]

Filler disfluencies-uh and um-are thought to serve distinct discourse functions. We examined fillers in spontaneous speech by youth with autism spectrum disorder (ASD), who struggle with pragmatic language, and by youth with ASD who have achieved an 'optimal outcome' (OO), as well as in peers with typical development (TD). While uh rates did not differ, participants with ASD produced um less frequently than OO or TD groups. Um rate was associated with autism symptom severity, but not executive function or language abilities, suggesting that um serves a pragmatic, listener-oriented function. Moreover, in contrast to minimal production in ASD, the typical OO um production substantiates the normalization of subtle social communication in this population., Author(s): Christina A. Irvine[sup.1] , Inge-Marie Eigsti[sup.1] , Deborah A. Fein[sup.1] [sup.2] Author Affiliations: (1) Department of Psychology, University of Connecticut, Storrs, CT, USA (2) Department of Pediatrics, University of [...]

We examined prenatal screening markers and offspring autism spectrum disorder (ASD) using California statewide data on singleton births in 1996 and 2002. Second trimester levels of unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and maternal serum alpha-fetoprotein (MSAFP) were compared between mothers of children with ASD (n = 2586) and of non-cases (n = 600,103). Adjusted odds ratios (AOR) were calculated by logistic regression. Lower uE3 (AOR for 90th percentile) were significantly associated with ASD. A U-shaped relationship was seen for hCG (AOR = 1.16, 95 % CI 1.02-1.32 for 90th percentile). Our results further support prenatal hormone involvement in ASD risk., Author(s): Gayle C. Windham[sup.1] , Kristen Lyall[sup.1] [sup.4] , Meredith Anderson[sup.2] , Martin Kharrazi[sup.3] [sup.5] Author Affiliations: (1) California Department of Public Health, Division of Environmental and Occupational Disease Control, [...]

Byline: Lucía. Ferreiro, Óscar. Lado-Baleato, Juan. Suárez-Antelo, María. Toubes, María. San José, Adriana. Lama, Nuria. Rodríguez-Núñez, José. Álvarez-Dobaño, Francisco. González-Barcala, Jorge. Ricoy, Francisco. Gude, Luis. Valdés INTRODUCTION: Diagnosis of pleural [...]

Byline: Joo. Lee, Jin. Huh, Sang-Bum. Hong, Yeon-Mok. Oh, Tae. Shim, Chae-Man. Lim, Sang-Do. Lee, Younsuck. Koh, Woo. Kim, Jae. Lee BACKGROUND: Better outcomes have been observed in patients with [...]

Background The World Health Organization (WHO) and Foundation for Innovative New Diagnostics (FIND) have published target product profiles (TPPs) calling for non-sputum-based diagnostic tests for the diagnosis of active tuberculosis (ATB) disease and for predicting the progression from latent tuberculosis infection (LTBI) to ATB. A large number of host-derived blood-based gene-expression biomarkers for diagnosis of patients with ATB have been proposed to date, but none have been implemented in clinical settings. The focus of this study is to directly compare published gene signatures for diagnosis of patients with ATB across a large, diverse list of publicly available gene expression datasets, and evaluate their performance against the WHO/FIND TPPs. Methods and findings We searched PubMed, Gene Expression Omnibus (GEO), and ArrayExpress in June 2018. We included all studies irrespective of study design and enrollment criteria. We found 16 gene signatures for the diagnosis of ATB compared to other clinical conditions in PubMed. For each signature, we implemented a classification model as described in the corresponding original publication of the signature. We identified 24 datasets containing 3,083 transcriptome profiles from whole blood or peripheral blood mononuclear cell samples of healthy controls or patients with ATB, LTBI, or other diseases from 14 countries in GEO. Using these datasets, we calculated weighted mean area under the receiver operating characteristic curve (AUROC), specificity at 90% sensitivity, and negative predictive value (NPV) for each gene signature across all datasets. We also compared the diagnostic odds ratio (DOR), heterogeneity in DOR, and false positive rate (FPR) for each signature using bivariate meta-analysis. Across 9 datasets of patients with culture-confirmed diagnosis of ATB, 11 signatures had weighted mean AUROC > 0.8, and 2 signatures had weighted mean AUROC [less than or equal to] 0.6. All but 2 signatures had high NPV (>98% at 2% prevalence). Two gene signatures achieved the minimal WHO TPP for a non-sputum-based triage test. When including datasets with clinical diagnosis of ATB, there was minimal reduction in the weighted mean AUROC and specificity of all but 3 signatures compared to when using only culture-confirmed ATB data. Only 4 signatures had homogeneous DOR and lower FPR when datasets with clinical diagnosis of ATB were included; other signatures either had heterogeneous DOR or higher FPR or both. Finally, 7 of 16 gene signatures predicted progression from LTBI to ATB 6 months prior to sputum conversion with positive predictive value > 6% at 2% prevalence. Our analyses may have under- or overestimated the performance of certain ATB diagnostic signatures because our implementation may be different from the published models for those signatures. We re-implemented published models because the exact models were not publicly available. Conclusions We found that host-response-based diagnostics could accurately identify patients with ATB and predict individuals with high risk of progression from LTBI to ATB prior to sputum conversion. We found that a higher number of genes in a signature did not increase the accuracy of the signature. Overall, the Sweeney3 signature performed robustly across all comparisons. Our results provide strong evidence for the potential of host-response-based diagnostics in achieving the WHO goal of ending tuberculosis by 2035, and host-response-based diagnostics should be pursued for clinical implementation., Author(s): Hayley Warsinske 1,2, Rohit Vashisht 1,2, Purvesh Khatri 1,2,* Introduction The World Health Organization (WHO) has identified the need for a non-sputum-based triage test to rule out active tuberculosis [...]