Current Diagnostic Method Research Articles

End-to-end Deep Learning of Polysomnograms for Classification of REM Sleep Behavior Disorder.

Rapid eye movement (REM) sleep behavior disorder (RBD) is parasomnia and a prodromal manifestation of Parkinson's disease. The current diagnostic method relies on manual scoring of polysomnograms (PSGs), a procedure that is time and effort intensive, subject to interscorer variability, and requires high level of expertise. Here, we present an automatic and interpretable diagnostic tool for RBD that analyzes PSGs using end-to-end deep neural networks. We optimized hierarchical attention networks in a 5-fold cross validation directly to classify RBD from PSG data recorded in 143 participants with RBD and 147 age-and sex-matched controls. An ensemble model using logistic regression was implemented to fuse decisions from networks trained in various signal combinations. We interpreted the networks using gradient SHAP that attribute relevance of input signals to model decisions. The ensemble model achieved a sensitivity of 91.4 % and a specificity of 86.3 %. Interpretation showed that electroencephalography (EEG) and leg electromyography (EMG) exhibited most patterns with high relevance. This study validates a robust diagnostic tool for RBD and proposes an interpretable and fully automatic framework for end-to-end modeling of other sleep disorders from PSG data. Clinical relevance- This study presents a novel diagnostic tool for RBD that considers neurophysiologic biomarkers in multiple modalities.

Clinical predictors for nondiabetic kidney diseases in patients with type 2 diabetes mellitus: a retrospective study from 2017 to 2021

BackgroundNondiabetic kidney disease (NDKD), which is prevalent among patients with diabetes mellitus (DM), is considerably different from diabetic kidney disease (DKD) in terms of the pathological features, treatment strategy and prognosis. Although renal biopsy is the current gold-standard diagnostic method, it cannot be routinely performed due to a range of risks. The aim of this study was to explore the predictors for differentiating NDKD from DKD to meet the urgent medical needs of patients who cannot afford kidney biopsy.MethodsThis is a retrospective study conducted by reviewing the medical records of patients with type 2 DM who underwent percutaneous renal biopsy at the Affiliated Hospital of Guizhou Medical University between January 2017 and May 2021. The demographic data, clinical data, blood test results, and pathological examination results of the patients were obtained from their medical records. Multivariate regression analysis was performed to evaluate the predictive factors for NDKD.ResultsA total of 244 patients were analyzed. The median age at biopsy was 55 (46, 62) years. Patients diagnosed with true DKD, those diagnosed with NDKD and those diagnosed with NDKD superimposed DKD represented 48.36% (118/244), 45.9% (112/244) and 5.74% (14/244), respectively, of the patient population. Immunoglobulin A nephropathy was the most common type of lesion in those with NDKD (59, 52.68%) and NDKD superimposed DKD (10, 71.43%). Independent predictive indicators for diagnosing NDKD included a DM duration of less than 5 years (odds ratio [OR] = 4.476; 95% confidence interval [CI]: 2.257–8.877; P < 0.001), an absence of diabetic retinopathy (OR = 4.174; 95% CI: 2.049–8.502; P < 0.001), a high RBC count (OR = 1.901; 95% CI: 1.251–2.889; P = 0.003), and a negative of urinary glucose excretion test result (OR = 2.985; 95% CI: 1.474–6.044; P = 0.002)..ConclusionsA DM duration less than 5 years, an absence of retinopathy, a high RBC count and an absence of urinary glucose excretion were independent indicators for the diagnosis of NDKD, suggesting that patients with NDKD may require a different treatment regimen than those with DKD.

Usefulness of cellblock preparation in fine needle aspiration for the diagnosis of thyroid nodules.

Thyroid nodules are common in the general population. The current diagnostic method for nodules is the ultrasound guided fine needle aspiration (US-FNA). The aim of the study was to evaluate the usefulness of cellblock preparation in addition to routine US-FNA in the diagnosis of thyroid nodules. A retrospective study of patients with thyroid nodules submitted to US-FNA, with collection of material using both smears and cellblock preparation. Two air-dried smears were prepared for each nodule. After centrifugation, the residual aspirate in the syringe and needle was processed as a standard histology specimen (cellblock). Then a pathologist reviewed the smears and cellblock slides of each case. A total of 12.360 thyroid nodules were submitted to US-FNA. Cellblock preparation was performed in 153 (1.2%) in addition to smears. Among the satisfactory cellblocks (80.5%, 120), 31.7% (38) provided additional morphological information in comparison with smears alone. No significant differences were found between the smear and the combined smear and cellblock evaluation concerning the number of unsatisfactory (12.1% vs. 11.4%, p=.85) and indeterminate (27.5% vs. 24.2%, p=.52) results. Overall, 10 samples (6.7%) had their diagnosis changed after cellblock evaluation, nine of them due to immunohistochemical studies. Immunohistochemistry confirmed parathyroid origin of the nodule in six cases. Cellblocks did not contribute to increase cellularity of the samples or to reduce indetermined results of FNA of thyroid nodules. Immunohistochemistry was essential to characterize rare cases without follicular histogenesis. Cellblock must only be prepared when considering performing immunohistochemistry.

Diagnostic accuracy of bilateral inferior petrosal sinus sampling using desmopressin or corticotropic- releasing hormone in ACTH-dependent Cushing's syndrome: A systematic review and meta-analysis.

The current gold standard diagnostic method for Cushing disease (CD) is bilateral inferior petrosal sinus sampling (BIPSS) after corticotropin-releasing hormone (CRH) stimulation. Due to shortages of CRH, BIPSS has been performed with desmopressin (DDAVP) instead. The objective of this systematic review and meta-analysis was to estimate the diagnostic accuracy of BIPSS using DDAVP or CRH for the differential diagnosis of Cushing's syndrome (CS). A literature review was done in PubMed, Scopus, EMBASE, and google scholar databases to derive summary estimates of the overall diagnostic sensitivity and accuracy of BIPSS using DDAVP or CRH in Cushing's syndrome. Pooled sensitivity, specificity, diagnostic odds ratio and summary receiver operating characteristic curves (SROC) for differential diagnosis of Cushing's syndrome in the random-effects models, were computed. Overall, 11 different studies with a total of 612 participants, were eligible for the analysis. Five articles with data on BIPSS using DDAVP, 5 papers on BIPSS using CRH, and another one evaluated the results of stimulation using DDAVP, with or without CRH, for differential diagnosis of Cushing's syndrome. The pooled (95% CI) sensitivity and specificity of BIPSS using DDAVP, were 96% (91-98%) and 1.00 (0.00-1.00), respectively. The area under the SROC curve was 0.95. The pooled (95% CI) sensitivity and specificity of BIPSS using CRH, were 98% (92-99%) and 1.00 (0.00-1.00), respectively, and the area under the SROC curve was 0.98. The I2 index (95% CI) was 0% (0-100%) for both BIPSS using DDAVP and using CRH. As a result, DDAVP stimulation is a safe, effective, less expensive, valuable and available alternative to CRH in the setting of BIPSS for all age groups of patients with CS. Registration code in PROSPERO: CRD42021292531.

P241

Abstract Background In recent decades, biological drugs targeting anti-tumour necrosis factor-α (TNF-α) have represented the cornerstone in the treatment of inflammatory bowel diseases. Currently, anti- TNF-α represents a breakthrough in patient care. However, 20–50% of patients experience primary or secondary loss of response. This may be due to pharmacodynamic and/or pharmacokinetic issues, resulting in subtherapeutic drug concentrations, frequently related to the development of anti-drug antibodies (ADA). In this context, therapeutic drug monitoring (TDM) is essential to patients’ management in order to pinpoint the basis of reduced efficacy. Indeed, a fast and reliable assessments of TDM is mandatory to allow rapid intervention, to avoid toxicity and improve treatment efficacy. In this study we assess the analytical performance of a novel fully automated chemiluminescent assay in measuring biological drugs levels and ADA serum concentration and to compare its performances to the current diagnostic method (ELISA). Methods Serum levels of biological drugs (Infliximab and Adalimumab) and their respective ADA were measured in twenty infliximab (IFX)-treated IBD patients and twenty adalimumab (ADL)-treated IBD patients using both the Promonitor® ELISA kits (Grifols) and the i-TRACKER chemiluminescent (CLIA) kits (Theradiag Results The CLIA method is a random-access platform that allows the continuous loading of samples, while the ELISA is a time-consuming manual method to be planned in advance to reduce expenses. Actually, in our laboratory is performed only twice a month. A very good correlation was observed both for Infliximab (Spearman r=0.9695, 95%CI = 0,92-0,99, p&amp;lt;0.0001) and Adalimumab serum levels (Spearman r=0.9476, 95%CI = 0,86-0,98, p&amp;lt;0.0001). Among the patients with undetectable IFX serum levels, 6/8 (75%) resulted ADA positive by ELISA versus 8/8 (100%) by CLIA. Moreover, CLIA disclosed very high ADA concentration in 3 samples compared to borderline results by ELISA. Regarding ADL, all the 9 patients with undetectable serum levels presented similar ADA concentration as tested with ELISA or CLIA. Conclusion In conclusion, the i-TRACKER CLIA Infliximab and Adalimumab assays showed a very good correlation for serum-based drugs level quantification as compared to the related ELISA methods. Furthermore, a good agreement was observed for ADA analysis, with a higher sensitivity against anti-IFX antibodies by CLIA compared to ELISA. Our data clearly highlighted that a fully automated assay for TDM would certainly reduce costs and significantly improve the management of IBD patients in terms of a shorter turn-around time.

BIOM-04. SENSITIVE DETECTION OF LEPTOMENINGEAL DISEASE USING CELL-FREE DNA FROM CEREBROSPINAL FLUID

Abstract Leptomeningeal disease is a devastating complication of cancer that is frequently underdiagnosed due to the low sensitivity of cerebrospinal fluid cytology, the current gold-standard diagnostic method. We performed genomic sequencing on cerebrospinal fluid specimens obtained from patients with suspected or confirmed leptomeningeal disease to identify tumor-derived cell-free DNA. From the same fluid draw, cerebrospinal fluid cytology was assayed for comparison. 30 patients underwent cytology and cell-free DNA analysis. This study consisted of two patient populations: 22 patients with cytology-confirmed leptomeningeal disease without parenchymal tumors abutting their cerebrospinal fluid and 8 patients with parenchymal brain metastases with no evidence of leptomeningeal disease. The primary outcome was the diagnostic accuracy of cell-free DNA, defined as the number of correct diagnoses out of the total number of tests assayed. A total of 30 patients, 23 female and 7 male, with a median age of 51 participated in this study. Participants mostly presented with metastatic solid malignancies. In patients previously diagnosed with leptomeningeal disease via cytology with no parenchymal tumor abutting cerebrospinal fluid, cell-free DNA was accurate in diagnosis of leptomeningeal disease in 45 of 48 follow-up samples (94%; 95% CI, 83%-99%). Cytology was accurate in 36 of 48 follow-up samples (75%; 95% CI, 60%-86%). Cell-free DNA was significantly more accurate (P=.02) and sensitive (P=.02) than cytology in patients without parenchymal tumors abutting the cerebrospinal fluid. In three patients with parenchymal brain metastases abutting the cerebrospinal fluid and no suspicion for leptomeningeal disease, cytology was negative in all three patients; whereas, cell-free DNA was positive in all three. This study demonstrates the improved sensitivity and accuracy of cell-free DNA in diagnosing leptomeningeal disease with the exception of parenchymal tumors abutting cerebrospinal fluid. Overall, these results will lead to improved diagnosis of leptomeningeal disease and potentially earlier intervention and clinical trial enrollment.

Deep-Learning-Based Coronary Artery Calcium Detection from CT Image.

One of the most common methods for diagnosing coronary artery disease is the use of the coronary artery calcium score CT. However, the current diagnostic method using the coronary artery calcium score CT requires a considerable time, because the radiologist must manually check the CT images one-by-one, and check the exact range. In this paper, three CNN models are applied for 1200 normal cardiovascular CT images, and 1200 CT images in which calcium is present in the cardiovascular system. We conduct the experimental test by classifying the CT image data into the original coronary artery calcium score CT images containing the entire rib cage, the cardiac segmented images that cut out only the heart region, and cardiac cropped images that are created by using the cardiac images that are segmented into nine sub-parts and enlarged. As a result of the experimental test to determine the presence of calcium in a given CT image using Inception Resnet v2, VGG, and Resnet 50 models, the highest accuracy of 98.52% was obtained when cardiac cropped image data was applied using the Resnet 50 model. Therefore, in this paper, it is expected that through further research, both the simple presence of calcium and the automation of the calcium analysis score for each coronary artery calcium score CT will become possible.

MP44-06 ULTRASOUND CONTRAST-ENHANCED VOIDING CYSTOURETHROGRAM FOR DIAGNOSIS OF VESICOURETERAL REFLUX: SINGLE-INSTITUTION EXPERIENCE

You have accessJournal of UrologyPediatric Urology II (MP44)1 Sep 2021MP44-06 ULTRASOUND CONTRAST-ENHANCED VOIDING CYSTOURETHROGRAM FOR DIAGNOSIS OF VESICOURETERAL REFLUX: SINGLE-INSTITUTION EXPERIENCE Thomas Williams, Lane Palmer, John Amodio, and Jeffrey Palmer Thomas WilliamsThomas Williams More articles by this author , Lane PalmerLane Palmer More articles by this author , John AmodioJohn Amodio More articles by this author , and Jeffrey PalmerJeffrey Palmer More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002065.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The current standard diagnostic method for vesicoureteral reflux (VUR) is fluoroscopic voiding cystography (VCUG). However, exposure to this inherent ionizing radiation may increase the risk of developing a malignancy in this vulnerable population. The development of stable and reproducible intravesical ultrasound contrast agents and techniques offer an opportunity to diagnose VUR without radiation exposure. This study highlights a large volume, single-institution’s experience of ultrasound contrast-enhanced VCUG and reported outcomes. METHODS: Retrospective chart review for 143 pediatric patients who underwent ultrasound contrast-enhanced VCUG at a single children’s hospital between 2018 and 2020. Technique involved several voiding and filling cycles with 1cc of Lumason® microbubbles, mixed with normal saline, and instilled via catheter gravity drip. Primary outcomes measured grade of VUR (International Reflux Grading System) as interpreted by a trained pediatric radiologist. Additionally, related anatomical findings, indications for exam, and clinical outcomes were reported. RESULTS: Mean age ranged from newborn to 14 years of age (18.7 ± 33.6 months, mean ± SD). The predominant indication for examination was prenatal hydronephrosis, 85 patients (59.4%) followed by history of urinary tract infection, 46 patients (32.2%). Overall, VUR was detected in 41 patients (28.7%) with total of 58 renal units. VUR was more commonly noted on the left side - 31 renal units (53.4%) but without difference in reflux grade (3.1 vs 3.0). Reflux grade breakdown was Grade I (0), Grade II (19), Grade III (23), Grade IV (9), and Grade V (7). There were no complications. CONCLUSIONS: Ultrasound contrast-enhanced VCUG is a safe and efficient alternative to the diagnosis of VUR without exposure to ionizing radiation. Future studies should continue to explore exam reproducibility and comparison between that of fluoroscopic VCUG. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e794-e795 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Thomas Williams More articles by this author Lane Palmer More articles by this author John Amodio More articles by this author Jeffrey Palmer More articles by this author Expand All Advertisement Loading ...

Detection of Leptomeningeal Disease Using Cell-Free DNA From Cerebrospinal Fluid

Leptomeningeal disease (LMD) is a devastating complication of cancer that is frequently underdiagnosed owing to the low sensitivity of cerebrospinal fluid (CSF) cytologic assessment, the current benchmark diagnostic method. Improving diagnostic sensitivity may lead to improved treatment decisions. To assess whether cell-free DNA (cfDNA) analysis of CSF may be used to diagnose LMD more accurately than cytologic analysis. This diagnostic study conducted in a neuro-oncology clinic at 2 large, tertiary medical centers assessed the use of genomic sequencing of CSF samples obtained from 30 patients with suspected or confirmed LMD from 2015 through 2018 to identify tumor-derived cfDNA. From the same CSF samples, cytologic analyses were conducted, and the results of the 2 tests were compared. This study consisted of 2 patient populations: 22 patients with cytologically confirmed LMD without parenchymal tumors abutting their CSF and 8 patients with parenchymal brain metastases with no evidence of LMD. Patients were considered positive for the presence of LMD if previous CSF cytologic analysis was positive for malignant cells. The analysis was conducted from 2015 to 2018. The primary outcome was the diagnostic accuracy of cfDNA analysis, defined as the number of tests that resulted in correct diagnoses out of the total number of tests assayed. Hypotheses were formed before data collection. In total, 30 patients (23 women [77%]; median age, 51 years [range, 28-81 years]), primarily presenting with metastatic solid malignant neoplasms, participated in this study. For 48 follow-up samples from patients previously diagnosed via cytologic analysis as having LMD with no parenchymal tumor abutting CSF, cfDNA findings were accurate in the assessment of LMD in 45 samples (94%; 95% CI, 83%-99%), whereas cytologic analysis was accurate in 36 samples (75%; 95% CI, 60%-86%), a significant difference (P = .02). Of 43 LMD-positive samples, CSF cfDNA analysis was sensitive to LMD in 40 samples (93%; 95% CI, 81%-99%), and cytologic analysis was sensitive to LMD in 31 samples (72%; 95% CI, 56%-85%), a significant difference (P = .02). For 3 patients with parenchymal brain metastases abutting the CSF and no suspicion of LMD, cytologic findings were negative for LMD in all 3 patients, whereas cfDNA findings were positive in all 3 patients. This diagnostic study found improved sensitivity and accuracy of cfDNA CSF testing vs cytologic assessment for diagnosing LMD with the exception of parenchymal tumors abutting CSF, suggesting improved ability to diagnosis LMD. Consideration of incorporating CSF cfDNA analysis into clinical care is warranted.

Low saliva pH can yield false positives results in simple RT-LAMP-based SARS-CoV-2 diagnostic tests.

Diagnosis of any infectious disease is vital for opportune treatment and to prevent dissemination. RT-qPCR tests for detection of SARS-CoV-2, the causative agent for COVID-19, are ideal in a hospital environment. However, mass testing requires cheaper and simpler tests, especially in settings that lack sophisticated machinery. The most common current diagnostic method is based on nasopharyngeal sample collection, RNA extraction, and RT-qPCR for amplification and detection of viral nucleic acids. Here, we show that samples obtained from nasopharyngeal swabs in VTM and in saliva can be used with or without RNA purification in an isothermal loop-mediated amplification (LAMP)-based assay, with 60–93% sensitivity for SARS-CoV-2 detection as compared to standard RT-qPCR tests. A series of simple modifications to standard RT-LAMP published methods to stabilize pH fluctuations due to salivary acidity resulted in a significant improvement in reliability, opening new avenues for efficient, low-cost testing of COVID-19 infection.

Diagnostic value of high-frequency ultrasound in carpal tunnel syndrome during pregnancy: A case-control study

Background: Carpal tunnel syndrome (CTS) is the most prevalent entrapment syndrome in the upper limbs, for which pregnancy is a known risk factor. CTS diagnosis is confirmed via nerve conduction studies (NCSs), which sometimes is expensive, and the electrical stimulation makes it an unpleasant diagnostic modality, especially for pregnant subjects. Recently, high-frequency ultrasonography (HF-USG) is known as a diagnostic method. This study is concerned with determining the diagnostic value of this modality for CTS among pregnant women. Methods: This cross-sectional case-control study was conducted with 40 CTS cases and 40 matched controls. The HF-USG of wrists was performed bilaterally on all participants with a focus on the median nerve cross-sectional area (MNCSA) at the carpal tunnel (CT) inlet. Results: Mean MNCSA was statistically different between the CTS group (11.71 ± 1.86 mm2, range: 8 to 18 mm2) and the control group (6.75 ± 1.38 mm2, range: 4 to 11 mm2) (P < 0.001). The receiver operating characteristic (ROC) curve was drawn, and the cross-sectional area (CSA) cut-off point of 8.5 mm2 showed sensitivity and specificity of 98% and 93%, respectively. The positive predictive value (PPV) and the negative predictive value (NPV) were 95% and 98%, respectively, with the mentioned point as the diagnostic threshold. Conclusion: HF-USG of the median nerve can be utilized as a preferable alternative to NCS (the current gold standard diagnostic method) in pregnant women, due to its convenience and lower cost, or at least, it can be used as a screening tool among pregnant women with suspicious symptoms.

Human Saliva Metabolome for Oral Lichen Planus Biomarker Identification.

Oral Lichen Planus (OLP) is one of the most common oral mucosal diseases. However, the current diagnostic method for OLP has limitations, and sometimes it is easy to be misdiagnosed. Salivary metabolomics may provide new ideas for the diagnosis of OLP. To identify the biomarkers for the early detection of OLP. A non-targeted metabolomic analysis method was established based on UHPLC-Q-Orbitrap HRMS (Ultra-performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry) to analyze the differential metabolites in saliva samples of patients with OLP and healthy subjects. Saliva samples were collected from 120 OLP patients and 125 healthy subjects. A total of 19 differential metabolites were identified, including 6 amino acid metabolites, 2 carnitines, 2 lipid metabolites and 9 other metabolites. The integrated biomarkers were constructed by 3 metabolites according to Receiver Operating Characteristic (ROC). Meanwhile, multiple metabolic pathways were found to be involved in the occurrence and development of OLP. Metabolomics can be used to characterize the characteristics of metabolic disorders in patients with OLP, which is also helpful to the early diagnosis of OLP and reveal the pathological process of OLP.

Rapid Quantitative PCR Assay for the Detection of the Three Vaginal Pathogens &amp;lt;i&amp;gt;Candida&amp;lt;/i&amp;gt;, &amp;lt;i&amp;gt;Gardnerella&amp;lt;/i&amp;gt; and &amp;lt;i&amp;gt;Atopobium&amp;lt;/i&amp;gt; as well as the Commensal &amp;lt;i&amp;gt;Lactobacillus&amp;lt;/i&amp;gt; Genera

The vaginal microbiota balance is quite fragile and susceptible to the development of vaginosis and candidiasis. The current diagnostic method for bacterial vaginosis relies on the evaluation of different bacterial morphotypes using the Nugent score. This method is only partially in correlation with a DNA sequencing-based diagnostic or Amsel criteria used by clinicians, suggesting the need for new molecular approaches dedicated to the diagnosis of BV. The objective of this study was to develop and validate a quantitative polymerase chain reaction (qPCR) assay for the specific and rapid detection of three vaginal pathogens, i.e. Candida, Gardnerella and Atopobium and the commensal Lactobacillus genera. For this purpose, four oligonucleotide primer pairs were designed and tested to obtain optimal amplification of the four target genera. The qPCR assay was also tested on the non-target genera and on human DNA. The designed primers allowed specific amplification of the target organisms in vitro and in clinical vaginal samples. The qPCR assay designed in this study is effective to specifically detect these genera in clinical samples as a molecular technique complementary to the Nugent score. It can be used in epidemiological studies for understanding the role of these pathogens and to follow their abundance in the microbiota in disease processes such as the development of vulvovaginal candidiasis and bacterial vaginosis.

Potential Metabolic Biomarkers for Early Detection of Oral Lichen Planus, a Precancerous Lesion.

Background: Oral lichen planus (OLP) is a T-cell-mediated chronic inflammatory disorder and precancerous oral lesion with high incidence. The current diagnostic method of OLP is very limited and metabolomics may provide a new approach for quantitative evaluation. Methods: The Ultra-Performance Liquid Chromatography-Quadrupole/Orbitrap High Resolution Mass Spectrometry (UHPLC-Q-Orbitrap HRMS) was applied to analyze the change of metabolites in serum of patients with OLP. A total of 115 OLP patients and 124 healthy controls were assigned to either a training set (n = 160) or a test set (n = 79). The potential biomarkers and the change of serum metabolites were profiled and evaluated by multivariate analysis. Results: Totally, 23 differential metabolites were identified in the training set between OLP group and healthy group. Three prominent metabolites in receiver operating characteristic (ROC) were selected as a panel to distinguish OLP or healthy individuals in the test set, and the diagnostic accuracy was 86.1%. Conclusions: This study established a new method for the early detection of OLP by analyzing serum metabolomics using UHPLC-Q-Orbitrap HRMS, which will help in understanding the pathological processes of OLP and identifying precancerous lesions in oral cavity.

Detection and Classification of Immature Leukocytes for Diagnosis of Acute Myeloid Leukemia Using Random Forest Algorithm.

Acute myeloid leukemia (AML) is a fatal blood cancer that progresses rapidly and hinders the function of blood cells and the immune system. The current AML diagnostic method, a manual examination of the peripheral blood smear, is time consuming, labor intensive, and suffers from considerable inter-observer variation. Herein, a machine learning model to detect and classify immature leukocytes for efficient diagnosis of AML is presented. Images of leukocytes in AML patients and healthy controls were obtained from a publicly available dataset in The Cancer Imaging Archive. Image format conversion, multi-Otsu thresholding, and morphological operations were used for segmentation of the nucleus and cytoplasm. From each image, 16 features were extracted, two of which are new nucleus color features proposed in this study. A random forest algorithm was trained for the detection and classification of immature leukocytes. The model achieved 92.99% accuracy for detection and 93.45% accuracy for classification of immature leukocytes into four types. Precision values for each class were above 65%, which is an improvement on the current state of art. Based on Gini importance, the nucleus to cytoplasm area ratio was a discriminative feature for both detection and classification, while the two proposed features were shown to be significant for classification. The proposed model can be used as a support tool for the diagnosis of AML, and the features calculated to be most important serve as a baseline for future research.

COVID-19 rapid diagnostic test could contain transmission in low- and middle-income countries.

BackgroundCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has impacted heavily on global health. Although real-time polymerase chain reaction (RT-PCR) is the current diagnostic method, challenges for low- and middle-income countries (LMICs) necessitate cheaper, higher-throughput, reliable rapid diagnostic tests (RDTs).ObjectiveWe reviewed the documented performance characteristics of available COVID-19 RDTs to understand their public health utility in the ongoing pandemic, especially in resource-scarce LMIC settings.MethodsUsing a scoping review methodology framework, common literature databases and documentary reports were searched up to 22 April 2020, irrespective of geographical location. The search terms included ‘SARS-CoV-2 AND serological testing’ and ‘COVID-19 AND serological testing’.ResultsA total of 18 RDTs produced in eight countries, namely China (6; 33.33%), the United States (4; 22.22%), Germany (2; 11.11%), Singapore (2; 11.11%), Canada, Kenya, Korea and Belgium (1 each; 5.56%), were evaluated. Reported sensitivity ranged from 18.4% to 100% (average = 84.7%), whereas specificity ranged from 90.6% to 100% (average = 95.6%). The testing time ranged from 2 min to 30 min. Of the 12 validated RDTs, the IgM/IgG duo kit with non-colloidal gold labelling system was reported to elicit the highest sensitivity (98% – 100%) and specificity (98% – 99% for IgG and 96% – 99% for IgM).ConclusionWe found reports of high sensitivity and specificity among the developed RDTs that could complement RT-PCR for the detection of SARS-CoV-2 antibodies, especially for screening in LMICs. However, it is necessary to validate these kits locally.

Identification of lipid biomarker from serum in patients with chronic obstructive pulmonary disease

BackgroundChronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States with no effective treatment. The current diagnostic method, spirometry, does not accurately reflect the severity of COPD disease status. Therefore, there is a pressing unmet medical need to develop noninvasive methods and reliable biomarkers to detect early stages of COPD. Lipids are the fundamental components of cell membranes, and dysregulation of lipids was proven to be associated with COPD. Lipidomics is a comprehensive approach to all the pathways and networks of cellular lipids in biological systems. It is widely used for disease diagnosis, biomarker identification, and pathology disorders detection relating to lipid metabolism.MethodsIn the current study, a total of 25 serum samples were collected from 5 normal control subjects and 20 patients with different stages of COPD according to the global initiative for chronic obstructive lung disease (GOLD) (GOLD stages I ~ IV, 5 patients per group). After metabolite extraction, lipidomic analysis was performed using electrospray ionization mass spectrometry (ESI-MS) to detect the serum lipid species. Later, the comparisons of individual lipids were performed between controls and patients with COPD. Orthogonal projections to latent structures discriminant analysis (OPLS-DA) and receiver operating characteristic (ROC) analysis were utilized to test the potential biomarkers. Finally, correlations between the validated lipidomic biomarkers and disease stages, age, FEV1% pack years and BMI were evaluated.ResultsOur results indicate that a panel of 50 lipid metabolites including phospholipids, sphingolipids, glycerolipids, and cholesterol esters can be used to differentiate the presence of COPD. Among them, 10 individual lipid species showed significance (p < 0.05) with a two-fold change. In addition, lipid ratios between every two lipid species were also evaluated as potential biomarkers. Further multivariate data analysis and receiver operating characteristic (ROC: 0.83 ~ 0.99) analysis suggest that four lipid species (AUC:0.86 ~ 0.95) and ten lipid ratios could be potential biomarkers for COPD (AUC:0.94 ~ 1) with higher sensitivity and specificity. Further correlation analyses indicate these potential biomarkers were not affected age, BMI, stages and FEV1%, but were associated with smoking pack years.ConclusionUsing lipidomics and statistical methods, we identified unique lipid signatures as potential biomarkers for diagnosis of COPD. Further validation studies of these potential biomarkers with large population may elucidate their roles in the development of COPD.

In vivo dynamic characterization of the human tympanic membrane using pneumatic optical coherence tomography.

Decreased mobility of the human eardrum, the tympanic membrane (TM), is an essential indicator of a prevalent middle ear infection. The current diagnostic method to assess TM mobility is via pneumatic otoscopy, which provides subjective and qualitative information of subtle motion. In this study, a handheld spectral-domain pneumatic optical coherence tomography system was developed to simultaneously measure the displacement of the TM, air pressure inputs applied to a sealed ear canal, and to perform digital pneumatic otoscopy. A novel approach based on quantitative parameters is presented to characterize spatial and temporal variations of the dynamic TM motion. Furthermore, the TM motions of normal middle ears are compared with those of ears with middle ear infections. The capability of noninvasively measuring the rapid motion of the TM is beneficial to understand the complex dynamics of the human TM, and can ultimately lead to improved diagnosis and management of middle ear infections.

One-step nested RT-PCR for COVID-19 detection: A flexible, locally developed test for SARS-CoV2 nucleic acid detection.

Due to the coronavirus pandemic, identifying the infected individuals has become key to limiting its spread. Virus nucleic acid real-time RT-PCR testing has become the current standard diagnostic method but high demand could lead to shortages. Therefore, we propose a detection strategy using a one-step nested RT-PCR. The nucleotide region in the ORF1ab gene that has the greatest differences between the human coronavirus and the bat coronavirus was selected. Primers were designed after that sequence. All diagnostic primers are species-specific since the 3´ end of the sequence differs from that of other species. A primer set also creates a synthetic positive control. Amplified products were seen in a 2.5% agarose gel, as well as in an SYBR Green-Based Real-Time RT-PCR. Amplification was achieved for the positive control and specific regions in both techniques. This new technique is flexible and easy to implement. It does not require a real-time thermocycler and can be interpreted in agarose gels, as well as adapted to quantify the viral genome. It has the advantage that if the coronavirus mutates in one of the key amplification nucleotides, at least one pair can still amplify, thanks to the four diagnostic primers.

Mouthwash to Deliver Indocyanine Green for Near Infrared Dental Fluorescence Imaging

Dental diseases significantly impact the quality of life and human populations; the current X-ray diagnostic dental imaging method may also bring the potential health risks to humans. This study used human extracted teeth and rats as animal model to test a new near-infrared (NIR) dental fluorescence imaging system with a painless mouthwash for administering indocyanine green (ICG). Our results show that the mouthwash delivery of ICG enables better image contrast than subcutaneous injection at short imaging time (1-10 minutes after ICG administration): for the erupted rat model, in vivo mouthwash (live rat) showed better imaging quality than injection method or ex vivo mouthwash (dead rat); for the unerupted molar, both mouthwash and injection showed the clear dental structures of the unerupted molars through endoscopic imaging; the dosage of mouthwash was at least 10 times lower than injection method. For human teeth, efficient image contrast was obtained in as short as 1 minute of ICG immersion; caries lesions were represented as a bright dot in the NIR windows. Overall, mouthwash serves as a painless and convenient method for administration of ICG; ICG-assisted NIR mouthwash dental imaging provides a low-cost and safe dental imaging tool for the diagnosis of dental diseases.