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Diagnostics, Volume 10, Issue 6 (June 2020) – 94 articles

Cover Story (view full-size image): Blue light cystoscopy is the most recent breakthrough in the diagnostics of bladder cancer, a common cancer with high rates of recurrence. The photodynamic diagnosis technique uses a photosensitizer as an adjunct to white light cystoscopy to enhance in vivo detection of malignant tissues based on their distinctive fluorescence. Although it has improved detection rates, fluorescence-assisted cystoscopy remains invasive and costly. In parallel, a variety of non-invasive tests and microdevices for the detection of urinary biomarkers of bladder cancer have been developed, none of which have yet entered routine clinical use due to unsatisfactory sensitivity. Following a brief description of the current approaches and their limitations, we provide a systematic review of a new niche research aiming to develop a non-invasive adaptation of photodynamic diagnosis. View this paper.
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20 pages, 888 KiB  
Review
Molecular and Serological Tests for COVID-19. A Comparative Review of SARS-CoV-2 Coronavirus Laboratory and Point-of-Care Diagnostics
by Robert Kubina and Arkadiusz Dziedzic
Diagnostics 2020, 10(6), 434; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060434 - 26 Jun 2020
Cited by 177 | Viewed by 31917
Abstract
Validated and accurate laboratory testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a crucial part of the timely management of Coronavirus Disease 2019 (COVID-19) disease, supporting the clinical decision-making process for infection control at the healthcare level and detecting asymptomatic cases. [...] Read more.
Validated and accurate laboratory testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a crucial part of the timely management of Coronavirus Disease 2019 (COVID-19) disease, supporting the clinical decision-making process for infection control at the healthcare level and detecting asymptomatic cases. This would facilitate an appropriate treatment, a prompt isolation and consequently deceleration of the pandemic. Various laboratory tests can identify the genetic material of SARS-CoV-2 that causes COVID-19 in specimens, or specific anti-viral antibodies in blood/serum. Due to the current pandemic situation, a development of point-of-care diagnostics (POCD) allows us to substantially accelerate taking clinical decisions and implement strategic planning at the national level of preventative measures. This review summarizes and compares the available POCD and those currently under development, including quantitative reverse transcription PCR (RT-qPCR), serology immunoassays (SIAs) and protein microarray method (PMM) designed for standard and rapid COVID-19 diagnosis. Full article
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12 pages, 970 KiB  
Article
Anthropometric Measurements and Frailty in Patients with Liver Diseases
by Hiroki Nishikawa, Kazunori Yoh, Hirayuki Enomoto, Naoto Ikeda, Nobuhiro Aizawa, Takashi Koriyama, Takashi Nishimura, Shuhei Nishiguchi and Hiroko Iijima
Diagnostics 2020, 10(6), 433; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060433 - 25 Jun 2020
Cited by 9 | Viewed by 2598
Abstract
There have been scarce data regarding the relationship between frailty and anthropometry measurements (AMs) in patients with chronic liver diseases (CLDs). We aimed to elucidate the influence of AMs on frailty in CLDs (median age = 66 years, 183 men and 192 women). [...] Read more.
There have been scarce data regarding the relationship between frailty and anthropometry measurements (AMs) in patients with chronic liver diseases (CLDs). We aimed to elucidate the influence of AMs on frailty in CLDs (median age = 66 years, 183 men and 192 women). AMs included arm circumference, triceps skinfold thickness, calf circumference (CC), waist circumference, and body mass index. Frailty assessment was done by using five phenotypes (body weight loss, exhaustion, decreased muscle strength, slow walking speed, and low physical activity). Robust (frailty point 0), prefrail (frailty point 1 or 2), and frailty (frailty point 3 or more) were observed in 63 (34.4%), 98 (53.6%), and 22 (12.0%) of males, respectively, and 63 (32.8%), 101 (52.6%), and 28 (14.6%) of females, respectively. In receiver operating characteristics (ROC) curve analyses for the presence of frailty, CC had the highest area under the ROC (AUC) both in male (AUC = 0.693, cutoff point = 33.7 cm) and female (AUC = 0.734, cutoff point = 33.4 cm) participants. In the multivariate analysis associated with frailty, for the male participants, only the presence of liver cirrhosis (p = 0.0433) was identified to be significant, while among the female participants, serum albumin (p = 0.0444) and CC (p = 0.0010) were identified to be significant. In conclusion, CC can be helpful for predicting frailty, especially in female CLD patients. Full article
(This article belongs to the Special Issue Skeletal Muscle Diagnostics and Managements)
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3 pages, 5565 KiB  
Interesting Images
Ultrasound-Guided Percutaneous Antegrade Varicocele Embolization with Cyanoacrylate Glue as an Alternative to the Standard Retrograde Approach
by Olivier Chevallier, Julie Pellegrinelli, Kevin Guillen and Romaric Loffroy
Diagnostics 2020, 10(6), 432; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060432 - 25 Jun 2020
Cited by 2 | Viewed by 2667
Abstract
We report a case of a 29-year-old male referred to our hospital for endovascular treatment of a left-sided painful varicocele. Standard retrograde embolization via the left renal vein was not possible because of the presence of a left circum-aortic renal vein making the [...] Read more.
We report a case of a 29-year-old male referred to our hospital for endovascular treatment of a left-sided painful varicocele. Standard retrograde embolization via the left renal vein was not possible because of the presence of a left circum-aortic renal vein making the catheterization of the testicular vein not feasible. The patient was successfully treated via ultrasound-guided percutaneous antegrade access of the testicular vein at the inguinal level with subsequent cyanoacrylate glue embolization as a minimally invasive alternative to surgical therapy. This is a new approach to varicocele embolization when the left renal vein does not feed the varicocele. Full article
(This article belongs to the Special Issue Endovascular Interventions for Venous Diseases)
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13 pages, 1434 KiB  
Article
Accuracy of a Semi-Quantitative Ultrasound Method to Determine Liver Fat Infiltration in Early Adulthood
by Camila Ibacahe, Paulina Correa-Burrows, Raquel Burrows, Gladys Barrera, Elissa Kim, Sandra Hirsch, Boris Jofré, Estela Blanco, Sheila Gahagan and Daniel Bunout
Diagnostics 2020, 10(6), 431; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060431 - 25 Jun 2020
Cited by 6 | Viewed by 5260
Abstract
An inexpensive and simple method to determine non-alcoholic fatty liver disease (NAFLD) is the abdominal ultrasound, but there are still doubts about its accuracy. We assessed the precision of a semi-quantitative ultrasound method to determine liver fat infiltration, using magnetic resonance spectroscopy (MRS) [...] Read more.
An inexpensive and simple method to determine non-alcoholic fatty liver disease (NAFLD) is the abdominal ultrasound, but there are still doubts about its accuracy. We assessed the precision of a semi-quantitative ultrasound method to determine liver fat infiltration, using magnetic resonance spectroscopy (MRS) as the reference. The study was conducted in youths from an ongoing cohort study. Clinical validation was performed, using receiver operating characteristic analysis, in n = 60 participants (22.6y; 50% males). Abdominal ultrasound was carried out with liver brightness (score 0–3), diaphragm attenuation (0–2) and liver vessel blurring (0–1) scored by two observers. Liver fat was estimated using MRS. Then, analytical validation was conducted in the remaining participants (n = 555; 22.7y; 51% males) using effects size estimates. An ultrasound score ≥4.0 had the highest sensitivity (78%) and specificity (85%) for NAFLD diagnosis. An area under the curve of 86% denotes a good diagnostic performance of the test, whereas a Kappa of 0.63 suggests substantial agreement of ultrasound vs. MRS. The analytical validation showed that participants having NAFLD according to ultrasound had an unhealthier cardiometabolic profile than participants without the condition. Abdominal ultrasound, combined with a semi-quantitative score system, is a reliable method to determine liver fat infiltration in young adults and should be encouraged whenever MRS is unavailable. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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22 pages, 9089 KiB  
Article
Development of a Deep Learning Algorithm for Periapical Disease Detection in Dental Radiographs
by Michael G. Endres, Florian Hillen, Marios Salloumis, Ahmad R. Sedaghat, Stefan M. Niehues, Olivia Quatela, Henning Hanken, Ralf Smeets, Benedicta Beck-Broichsitter, Carsten Rendenbach, Karim Lakhani, Max Heiland and Robert A. Gaudin
Diagnostics 2020, 10(6), 430; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060430 - 24 Jun 2020
Cited by 55 | Viewed by 8623
Abstract
Periapical radiolucencies, which can be detected on panoramic radiographs, are one of the most common radiographic findings in dentistry and have a differential diagnosis including infections, granuloma, cysts and tumors. In this study, we seek to investigate the ability with which 24 oral [...] Read more.
Periapical radiolucencies, which can be detected on panoramic radiographs, are one of the most common radiographic findings in dentistry and have a differential diagnosis including infections, granuloma, cysts and tumors. In this study, we seek to investigate the ability with which 24 oral and maxillofacial (OMF) surgeons assess the presence of periapical lucencies on panoramic radiographs, and we compare these findings to the performance of a predictive deep learning algorithm that we have developed using a curated data set of 2902 de-identified panoramic radiographs. The mean diagnostic positive predictive value (PPV) of OMF surgeons based on their assessment of panoramic radiographic images was 0.69 (±0.13), indicating that dentists on average falsely diagnose 31% of cases as radiolucencies. However, the mean diagnostic true positive rate (TPR) was 0.51 (±0.14), indicating that on average 49% of all radiolucencies were missed. We demonstrate that the deep learning algorithm achieves a better performance than 14 of 24 OMF surgeons within the cohort, exhibiting an average precision of 0.60 (±0.04), and an F1 score of 0.58 (±0.04) corresponding to a PPV of 0.67 (±0.05) and TPR of 0.51 (±0.05). The algorithm, trained on limited data and evaluated on clinically validated ground truth, has potential to assist OMF surgeons in detecting periapical lucencies on panoramic radiographs. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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12 pages, 1098 KiB  
Article
Budget Impact Analysis of EGFR Mutation Liquid Biopsy for First- and Second-Line Treatment of Metastatic Non-Small Cell Lung Cancer in Greece
by Mindy Cheng, Athanasios Akalestos and Sidney Scudder
Diagnostics 2020, 10(6), 429; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060429 - 24 Jun 2020
Cited by 5 | Viewed by 2983
Abstract
Within the European Union, Greece has the highest incidence of lung cancer among people under 45 years of age. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are indicated for the treatment of patients with EGFR mutation-positive metastatic non-small cell lung [...] Read more.
Within the European Union, Greece has the highest incidence of lung cancer among people under 45 years of age. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are indicated for the treatment of patients with EGFR mutation-positive metastatic non-small cell lung cancer (mNSCLC). Tumor tissue biopsy is the standard method for EGFR mutation detection but is invasive, is resource-intensive, and has risks of complications. The objective of this analysis was to estimate the financial impact on the Greek National Health System of adopting plasma biopsy and to identify the cost-optimal approach for EGFR mutation testing of patients with mNSCLC. We developed a budget impact model to estimate total costs for three EGFR mutation testing approaches: (1) plasma test, (2) combined testing (tissue and plasma test), and (3) reflex testing, compared to the current scenario of tissue biopsy only. One-way sensitivity and scenario analyses were conducted to evaluate the impact of uncertainty and variance of different input parameters on the results. In the first-line (1L) setting, base-case results showed that adopting plasma testing in a combined testing approach identified more EGFR mutation-positive patients and yielded cost savings (−€17 per correctly classified patient) relative to tissue testing alone. The reflex testing approach was the cost-optimal strategy in the second-line (2L) setting as it identified the most EGFR mutation-positive patients with cost savings of −€42 per correctly classified patient relative to tissue testing alone. This analysis suggests that access to both EGFR mutation tissue and plasma testing are important for optimizing mNSCLC treatment decisions in Greece. Inclusion of plasma testing in either a combined or reflex testing approach may be cost optimal for EGFR mutation plasma test implementation. Full article
(This article belongs to the Special Issue Lung Cancer Molecular Pathology)
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13 pages, 917 KiB  
Article
Metabolic Endotoxemia, Feeding Studies and the Use of the Limulus Amebocyte (LAL) Assay; Is It Fit for Purpose?
by Karma Pearce, Dianne Estanislao, Sinan Fareed and Kelton Tremellen
Diagnostics 2020, 10(6), 428; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060428 - 24 Jun 2020
Cited by 8 | Viewed by 2801
Abstract
The Limulus amebocyte assay (LAL) is increasingly used to quantify metabolic endotoxemia (ME), particularly in feeding studies. However, the assay was not intended to assess plasma at levels typically seen in ME. We aimed to optimize and validate the LAL assay under a [...] Read more.
The Limulus amebocyte assay (LAL) is increasingly used to quantify metabolic endotoxemia (ME), particularly in feeding studies. However, the assay was not intended to assess plasma at levels typically seen in ME. We aimed to optimize and validate the LAL assay under a range of pre-treatment conditions against the well-established lipopolysaccharide binding protein assay (LBP). Fifteen healthy overweight and obese males aged 28.8 ± 9.1years provided plasma. The LAL assay employed a range of pre-treatments; 70 °C for 15 and 30 min and 80 °C for 15 and 30 min, ultrasonication (70 °C for 10 min and then 40 °C for 10 min), and dilution (1:50, 1:75, 1:100, and 1:200 parts) or diluted using 0.5% pyrosperse. Seventeen different plasma pre-treatment methods employed prior to the use of the LAL analytical technique failed to show any relationships with either LBP, or body mass index (BMI; obesity), the biological trigger for ME (p > 0.05 for all). As expected, BMI positively correlated with LBP (r = 0.523, p = 0.052. No relationships were observed between LAL with any of the sample pre-treatments and LBP or BMI. In its current form, the LAL assay is unsuitable for detecting levels of endotoxin typically seen in ME. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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13 pages, 2579 KiB  
Review
Technical Assessment of Ultrasonic Cerebral Tomosphygmography and New Scientific Evaluation of Its Clinical Interest for the Diagnosis of Electrohypersensitivity and Multiple Chemical Sensitivity
by Frédéric Greco
Diagnostics 2020, 10(6), 427; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060427 - 24 Jun 2020
Cited by 4 | Viewed by 3368
Abstract
Ultrasonic cerebral tomosphygmography (UCTS), also known as “encephaloscan”, is an ultrasound-based pulsatile echoencephalography for both functional and anatomical brain imaging investigations. Compared to classical imaging, UCTS makes it possible to locate precisely the spontaneous brain tissue pulsations that occur naturally in temporal lobes. [...] Read more.
Ultrasonic cerebral tomosphygmography (UCTS), also known as “encephaloscan”, is an ultrasound-based pulsatile echoencephalography for both functional and anatomical brain imaging investigations. Compared to classical imaging, UCTS makes it possible to locate precisely the spontaneous brain tissue pulsations that occur naturally in temporal lobes. Scientific publications have recently validated the scientific interest of UCTS technique but clinical use and industrial development of this ancient brain imaging technique has been stopped notably in France, not for scientific or technical reasons but due to a lack of financing support. UCTS should be fundamentally distinguished from transcranial Doppler ultrasonography (TDU), which, although it also uses pulsed ultrasounds, aims at studying the velocity of blood flow (hemodynamics) in the cerebral arteries by using Doppler effect, especially in the middle cerebral artery of both hemispheres. Instead, UCTS has the technical advantage of measuring and locating spontaneous brain tissue pulsations in temporal lobes. Recent scientific work has shown the possibility to make an objective diagnosis of electrohypersensitivity (EHS) and multiple chemical sensitivity (MCS) by using UCTS, in conjunction with TDU investigation and the detection of several biomarkers in the peripheral blood and urine of the patients. In this paper, we independently confirm the clinical interest of using UCTS for the diagnosis of EHS and MCS. Moreover, it has been shown that repetitive use of UCTS in EHS and/or MCS patients can contribute to the objective assessment of their therapeutic follow-up. Since classical CT scan and MRI are usually not contributive for the diagnosis and are poorly tolerated by these patients, UCTS should therefore be considered as one of the best imaging technique to be used for the diagnosis of these new disorders and the follow-up of patients. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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13 pages, 733 KiB  
Article
Measuring Spinal Mobility Using an Inertial Measurement Unit System: A Validation Study in Axial Spondyloarthritis
by I. Concepción Aranda-Valera, Antonio Cuesta-Vargas, Juan L. Garrido-Castro, Philip V. Gardiner, Clementina López-Medina, Pedro M. Machado, Joan Condell, James Connolly, Jonathan M. Williams, Karla Muñoz-Esquivel, Tom O’Dwyer, M. Carmen Castro-Villegas, Cristina González-Navas, Eduardo Collantes-Estévez and on behalf of iMaxSpA Study Group
Diagnostics 2020, 10(6), 426; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060426 - 24 Jun 2020
Cited by 19 | Viewed by 3251
Abstract
Portable inertial measurement units (IMUs) are beginning to be used in human motion analysis. These devices can be useful for the evaluation of spinal mobility in individuals with axial spondyloarthritis (axSpA). The objectives of this study were to assess (a) concurrent criterion validity [...] Read more.
Portable inertial measurement units (IMUs) are beginning to be used in human motion analysis. These devices can be useful for the evaluation of spinal mobility in individuals with axial spondyloarthritis (axSpA). The objectives of this study were to assess (a) concurrent criterion validity in individuals with axSpA by comparing spinal mobility measured by an IMU sensor-based system vs. optical motion capture as the reference standard; (b) discriminant validity comparing mobility with healthy volunteers; (c) construct validity by comparing mobility results with relevant outcome measures. A total of 70 participants with axSpA and 20 healthy controls were included. Individuals with axSpA completed function and activity questionnaires, and their mobility was measured using conventional metrology for axSpA, an optical motion capture system, and an IMU sensor-based system. The UCOASMI, a metrology index based on measures obtained by motion capture, and the IUCOASMI, the same index using IMU measures, were also calculated. Descriptive and inferential analyses were conducted to show the relationships between outcome measures. There was excellent agreement (ICC > 0.90) between both systems and a significant correlation between the IUCOASMI and conventional metrology (r = 0.91), activity (r = 0.40), function (r = 0.62), quality of life (r = 0.55) and structural change (r = 0.76). This study demonstrates the validity of an IMU system to evaluate spinal mobility in axSpA. These systems are more feasible than optical motion capture systems, and they could be useful in clinical practice. Full article
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18 pages, 1524 KiB  
Article
Systemic Alterations of Immune Response-Related Proteins during Glaucoma Development in the Murine Model DBA/2J
by Andrés Fernández-Vega Cueto, Lydia Álvarez, Montserrat García, Enol Artime, Ana Álvarez Barrios, Ignacio Rodríguez-Uña, Miguel Coca-Prados and Héctor González-Iglesias
Diagnostics 2020, 10(6), 425; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060425 - 23 Jun 2020
Cited by 2 | Viewed by 2495
Abstract
Animal models of glaucoma, a neurodegenerative disease affecting the retina, offer the opportunity to study candidate molecular biomarkers throughout the disease. In this work, the DBA/2J glaucomatous mouse has been used to study the systemic levels of several proteins previously identified as potential [...] Read more.
Animal models of glaucoma, a neurodegenerative disease affecting the retina, offer the opportunity to study candidate molecular biomarkers throughout the disease. In this work, the DBA/2J glaucomatous mouse has been used to study the systemic levels of several proteins previously identified as potential biomarkers of glaucoma, along the pre- to post-glaucomatous transition. Serum samples obtained from glaucomatous and control mice at 4, 10, and 14 months, were classified into different experimental groups according to the optic nerve damage at 14 months old. Quantifications of ten serum proteins were carried out by enzyme immunoassays. Changes in the levels of some of these proteins in the transition to glaucomatous stages were identified, highlighting the significative decrease in the concentration of complement C4a protein. Moreover, the five-protein panel consisting of complement C4a, complement factor H, ficolin-3, apolipoprotein A4, and transthyretin predicted the transition to glaucoma in 78% of cases, and to the advanced disease in 89%. Our data, although still preliminary, suggest that disease development in DBA/2J mice is associated with important molecular changes in immune response and complement system proteins and demonstrate the utility of this model in identifying, at systemic level, potential markers for the diagnosis of glaucoma. Full article
(This article belongs to the Special Issue Corneal and Retinal Diseases: Diagnostic and Therapeutic Approaches)
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9 pages, 5577 KiB  
Case Report
Multifocal Amelanotic Melanoma of the Hard Palate: A Challenging Case
by Luisa Limongelli, Eliano Cascardi, Saverio Capodiferro, Gianfranco Favia, Massimo Corsalini, Angela Tempesta and Eugenio Maiorano
Diagnostics 2020, 10(6), 424; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060424 - 22 Jun 2020
Cited by 15 | Viewed by 3174
Abstract
Among all melanomas, the mucosal type is very rare and may occur in the sino-nasal mucosa, vagina, anus and the oral cavity. At variance with melanomas of the skin, no risk factors, such as familiarity, UV-exposure and skin phenotype, have been clearly identified [...] Read more.
Among all melanomas, the mucosal type is very rare and may occur in the sino-nasal mucosa, vagina, anus and the oral cavity. At variance with melanomas of the skin, no risk factors, such as familiarity, UV-exposure and skin phenotype, have been clearly identified for such neoplasms. Frequently, the diagnosis is delayed and achieved at advanced stages or when metastases have already occurred. The authors report on a case of mucosal melanoma of the oral cavity presenting as a mass of the hard palate in a 50-year old male, and the corresponding diagnostic-therapeutic pathway. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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7 pages, 2458 KiB  
Interesting Images
Simple and Accurate Border Detection Algorithm for Melanoma Computer Aided Diagnosis
by Cataldo Guaragnella and Maria Rizzi
Diagnostics 2020, 10(6), 423; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060423 - 22 Jun 2020
Cited by 7 | Viewed by 3206
Abstract
The interest of the scientific community for computer aided skin lesion analysis and characterization has been increased during the last years for the growing incidence of melanoma among cancerous pathologies. The detection of melanoma in its early stage is essential for prognosis improvement [...] Read more.
The interest of the scientific community for computer aided skin lesion analysis and characterization has been increased during the last years for the growing incidence of melanoma among cancerous pathologies. The detection of melanoma in its early stage is essential for prognosis improvement and for guaranteeing a high five-year relative survival rate of patients. The clinical diagnosis of skin lesions is challenging and not trivial since it depends on human vision and physician experience and expertise. Therefore, a computer method that makes an accurate extraction of important details of skin lesion image can assist dermatologists in cancer detection. In particular, the border detection is a critical computer vision issue owing to the wide range of lesion shapes, sizes, colours and skin texture types. In this paper, an automatic and effective pigmented skin lesion segmentation method in dermoscopic image is presented. The proposed procedure is adopted to extract a mask of the lesion region without the adoption of other signal processing procedures for image improvement. A quantitative experimental evaluation has been performed on a publicly available database. The achieved results show the method validity and its high robustness towards irregular boundaries, smooth transition between lesion and skin, noise and artifact presence. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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14 pages, 1274 KiB  
Article
Upstroke Time as a Novel Predictor of Mortality in Patients with Chronic Kidney Disease
by Wen-Hsien Lee, Po-Chao Hsu, Chun-Yuan Chu, Szu-Chia Chen, Ying-Chih Chen, Meng-Kuang Lee, Hung-Hao Lee, Chee-Siong Lee, Hsueh-Wei Yen, Tsung-Hsien Lin, Wen-Chol Voon, Wen-Ter Lai, Sheng-Hsiung Sheu and Ho-Ming Su
Diagnostics 2020, 10(6), 422; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060422 - 20 Jun 2020
Cited by 3 | Viewed by 2384
Abstract
Upstroke time (UT), measured from the foot-to-peak peripheral pulse wave, is a merged parameter used to assess arterial stiffness and target vascular injuries. In this study, we aimed to investigate UT for the prediction of cardiovascular and all-cause mortality in patients with chronic [...] Read more.
Upstroke time (UT), measured from the foot-to-peak peripheral pulse wave, is a merged parameter used to assess arterial stiffness and target vascular injuries. In this study, we aimed to investigate UT for the prediction of cardiovascular and all-cause mortality in patients with chronic kidney disease (CKD). This longitudinal study enrolled 472 patients with CKD. Blood pressure, brachial pulse wave velocity (baPWV), and UT were automatically measured by a Colin VP-1000 instrument. During a median follow-up of 91 months, 73 cardiovascular and 183 all-cause mortality instances were recorded. Multivariable Cox analyses indicated that UT was significantly associated with cardiovascular mortality (hazard ratio (HR) = 1.010, p = 0.007) and all-cause mortality (HR = 1.009, p < 0.001). The addition of UT into the clinical models including traditional risk factors and baPWV further increased the value in predicting cardiovascular and all-cause mortality (both p < 0.001). In the Kaplan–Meier analyses, UT ≥ 180 ms could predict cardiovascular and all-cause mortality (both log-rank p < 0.001). Our study found that UT was a useful parameter in predicting cardiovascular and all-cause mortality in CKD patients. Additional consideration of the UT might provide an extra benefit in predicting cardiovascular and all-cause mortality beyond the traditional risk factors and baPWV. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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18 pages, 3187 KiB  
Article
A Supervised Machine Learning Approach to Detect the On/Off State in Parkinson’s Disease Using Wearable Based Gait Signals
by Satyabrata Aich, Jinyoung Youn, Sabyasachi Chakraborty, Pyari Mohan Pradhan, Jin-han Park, Seongho Park and Jinse Park
Diagnostics 2020, 10(6), 421; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060421 - 20 Jun 2020
Cited by 32 | Viewed by 3261
Abstract
Fluctuations in motor symptoms are mostly observed in Parkinson’s disease (PD) patients. This characteristic is inevitable, and can affect the quality of life of the patients. However, it is difficult to collect precise data on the fluctuation characteristics using self-reported data from PD [...] Read more.
Fluctuations in motor symptoms are mostly observed in Parkinson’s disease (PD) patients. This characteristic is inevitable, and can affect the quality of life of the patients. However, it is difficult to collect precise data on the fluctuation characteristics using self-reported data from PD patients. Therefore, it is necessary to develop a suitable technology that can detect the medication state, also termed the “On”/“Off” state, automatically using wearable devices; at the same time, this could be used in the home environment. Recently, wearable devices, in combination with powerful machine learning techniques, have shown the potential to be effectively used in critical healthcare applications. In this study, an algorithm is proposed that can detect the medication state automatically using wearable gait signals. A combination of features that include statistical features and spatiotemporal gait features are used as inputs to four different classifiers such as random forest, support vector machine, K nearest neighbour, and Naïve Bayes. In total, 20 PD subjects with definite motor fluctuations have been evaluated by comparing the performance of the proposed algorithm in association with the four aforementioned classifiers. It was found that random forest outperformed the other classifiers with an accuracy of 96.72%, a recall of 97.35%, and a precision of 96.92%. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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9 pages, 1710 KiB  
Article
Carotid Stenosis Assessment with Vector Concentration before and after Stenting
by Andreas Hjelm Brandt, Tin-Quoc Nguyen, Henrik Gutte, Jonathan Frederik Carlsen, Ramin Moshavegh, Jørgen Arendt Jensen, Michael Bachmann Nielsen and Kristoffer Lindskov Hansen
Diagnostics 2020, 10(6), 420; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060420 - 20 Jun 2020
Cited by 6 | Viewed by 2703
Abstract
Digital subtraction angiography (DSA) is considered the reference method for the assessment of carotid artery stenosis; however, the procedure is invasive and accompanied by ionizing radiation. Velocity estimation with duplex ultrasound (DUS) is widely used for carotid artery stenosis assessment since no radiation [...] Read more.
Digital subtraction angiography (DSA) is considered the reference method for the assessment of carotid artery stenosis; however, the procedure is invasive and accompanied by ionizing radiation. Velocity estimation with duplex ultrasound (DUS) is widely used for carotid artery stenosis assessment since no radiation or intravenous contrast is required; however, the method is angle-dependent. Vector concentration (VC) is a parameter for flow complexity assessment derived from the angle independent ultrasound method vector flow imaging (VFI), and VC has shown to correlate strongly with stenosis degree. The aim of this study was to compare VC estimates and DUS estimated peak-systolic (PSV) and end-diastolic velocities (EDV) for carotid artery stenosis patients, with the stenosis degree obtained with DSA. Eleven patients with symptomatic carotid artery stenosis were examined with DUS, VFI, and DSA before and after stent treatment. Compared to DSA, VC showed a strong correlation (r = −0.79, p < 0.001), while PSV (r = 0.68, p = 0.002) and EDV (r = 0.51, p = 0.048) obtained with DUS showed a moderate correlation. VFI using VC calculations may be a useful ultrasound method for carotid artery stenosis and stent patency assessment. Full article
(This article belongs to the Special Issue New Trends in Vascular Imaging)
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9 pages, 754 KiB  
Article
Evaluation of BDNF as a Biomarker for Impulsivity in a Psychiatric Population
by Stanislav Pasyk, Nitika Sanger, Flavio Kapczinski and Zainab Samaan
Diagnostics 2020, 10(6), 419; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060419 - 20 Jun 2020
Cited by 7 | Viewed by 2145
Abstract
Impulsivity is an important risk factor for suicide and therefore, identifying biomarkers associated with impulsivity could be important in evaluating psychiatric patients. Currently, assessment of impulsivity is based solely on clinical evaluation. In this study, brain-derived neurotrophic factor (BDNF), a nerve growth factor, [...] Read more.
Impulsivity is an important risk factor for suicide and therefore, identifying biomarkers associated with impulsivity could be important in evaluating psychiatric patients. Currently, assessment of impulsivity is based solely on clinical evaluation. In this study, brain-derived neurotrophic factor (BDNF), a nerve growth factor, was evaluated as a potential biomarker for impulsivity. We hypothesize that elevated BDNF may result in aberrantly high neurobiological activation, promoting impulsive behaviours. A total of 343 participants were recruited for the study and were divided into two groups, (i) elevated suicide risk (participants admitted to hospital with a recent suicide attempt), and (ii) average suicide risk (non-psychiatric participants and psychiatric participants without a history of suicide attempts). Impulsivity was measured by the Barratt Impulsiveness Scale, and serum BDNF levels were obtained. A regression analysis was performed to identify associations between BDNF and impulsivity. We identified a subtle but significant positive association between BDNF and impulsivity in the average risk for suicide group (B = 0.189, p = 0.014). The same association was not reproduced in the elevated risk group B = −0.086, p = 0.361). These findings lay the foundation to further explore the utility of BDNF as a biomarker for impulsivity to allow for early intervention. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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13 pages, 1998 KiB  
Article
Mammographic Breast Density and Urbanization: Interactions with BMI, Environmental, Lifestyle, and Other Patient Factors
by Nick Perry, Sue Moss, Steve Dixon, Sue Milner, Kefah Mokbel, Charlotte Lemech, Hendrik-Tobias Arkenau, Stephen Duffy and Katja Pinker
Diagnostics 2020, 10(6), 418; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060418 - 20 Jun 2020
Cited by 2 | Viewed by 3261
Abstract
Mammographic breast density (MBD) is an important imaging biomarker of breast cancer risk, but it has been suggested that increased MBD is not a genuine finding once corrected for age and body mass index (BMI). This study examined the association of various factors, [...] Read more.
Mammographic breast density (MBD) is an important imaging biomarker of breast cancer risk, but it has been suggested that increased MBD is not a genuine finding once corrected for age and body mass index (BMI). This study examined the association of various factors, including both residing in and working in the urban setting, with MBD. Questionnaires were completed by 1144 women attending for mammography at the London Breast Institute in 2012–2013. Breast density was assessed with an automated volumetric breast density measurement system (Volpara) and compared with subjective radiologist assessment. Multivariable linear regression was used to model the relationship between MBD and residence in the urban setting as well as working in the urban setting, adjusting for both age and BMI and other menstrual, reproductive, and lifestyle factors. Urban residence was significantly associated with an increasing percent of MBD, but this association became non-significant when adjusted for age and BMI. This was not the case for women who were both residents in the urban setting and still working. Our results suggest that the association between urban women and increased MBD can be partially explained by their lower BMI, but for women still working, there appear to be other contributing factors. Full article
(This article belongs to the Special Issue Multimodality Breast Imaging)
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22 pages, 2921 KiB  
Article
Efficient Pneumonia Detection in Chest Xray Images Using Deep Transfer Learning
by Mohammad Farukh Hashmi, Satyarth Katiyar, Avinash G Keskar, Neeraj Dhanraj Bokde and Zong Woo Geem
Diagnostics 2020, 10(6), 417; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060417 - 19 Jun 2020
Cited by 177 | Viewed by 19906
Abstract
Pneumonia causes the death of around 700,000 children every year and affects 7% of the global population. Chest X-rays are primarily used for the diagnosis of this disease. However, even for a trained radiologist, it is a challenging task to examine chest X-rays. [...] Read more.
Pneumonia causes the death of around 700,000 children every year and affects 7% of the global population. Chest X-rays are primarily used for the diagnosis of this disease. However, even for a trained radiologist, it is a challenging task to examine chest X-rays. There is a need to improve the diagnosis accuracy. In this work, an efficient model for the detection of pneumonia trained on digital chest X-ray images is proposed, which could aid the radiologists in their decision making process. A novel approach based on a weighted classifier is introduced, which combines the weighted predictions from the state-of-the-art deep learning models such as ResNet18, Xception, InceptionV3, DenseNet121, and MobileNetV3 in an optimal way. This approach is a supervised learning approach in which the network predicts the result based on the quality of the dataset used. Transfer learning is used to fine-tune the deep learning models to obtain higher training and validation accuracy. Partial data augmentation techniques are employed to increase the training dataset in a balanced way. The proposed weighted classifier is able to outperform all the individual models. Finally, the model is evaluated, not only in terms of test accuracy, but also in the AUC score. The final proposed weighted classifier model is able to achieve a test accuracy of 98.43% and an AUC score of 99.76 on the unseen data from the Guangzhou Women and Children’s Medical Center pneumonia dataset. Hence, the proposed model can be used for a quick diagnosis of pneumonia and can aid the radiologists in the diagnosis process. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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17 pages, 3137 KiB  
Article
Uncovering Potential Roles of Differentially Expressed Genes, Upstream Regulators, and Canonical Pathways in Endometriosis Using an In Silico Genomics Approach
by Zeenat Mirza and Umama A. Abdel-dayem
Diagnostics 2020, 10(6), 416; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060416 - 19 Jun 2020
Cited by 9 | Viewed by 3240
Abstract
Endometriosis is characterized by ectopic endometrial tissue implantation, mostly within the peritoneum, and affects women in their reproductive age. Studies have been done to clarify its etiology, but the precise molecular mechanisms and pathophysiology remain unclear. We downloaded genome-wide mRNA expression and clinicopathological [...] Read more.
Endometriosis is characterized by ectopic endometrial tissue implantation, mostly within the peritoneum, and affects women in their reproductive age. Studies have been done to clarify its etiology, but the precise molecular mechanisms and pathophysiology remain unclear. We downloaded genome-wide mRNA expression and clinicopathological data of endometriosis patients and controls from NCBI’s Gene Expression Omnibus, after a systematic search of multiple independent studies comprising 156 endometriosis patients and 118 controls to identify causative genes, risk factors, and potential diagnostic/therapeutic biomarkers. Comprehensive gene expression meta-analysis, pathway analysis, and gene ontology analysis was done using a bioinformatics-based approach. We identified 1590 unique differentially expressed genes (129 upregulated and 1461 downregulated) mapped by IPA as biologically relevant. The top upregulated genes were FOS, EGR1, ZFP36, JUNB, APOD, CST1, GPX3, and PER1, and the top downregulated ones were DIO2, CPM, OLFM4, PALLD, BAG5, TOP2A, PKP4, CDC20B, and SNTN. The most perturbed canonical pathways were mitotic roles of Polo-like kinase, role of Checkpoint kinase proteins in cell cycle checkpoint control, and ATM signaling. Protein–protein interaction analysis showed a strong network association among FOS, EGR1, ZFP36, and JUNB. These findings provide a thorough understanding of the molecular mechanism of endometriosis, identified biomarkers, and represent a step towards the future development of novel diagnostic and therapeutic options. Full article
(This article belongs to the Special Issue Diagnosis of Endometriosis: Biomarkers and Clinical Methods)
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17 pages, 1889 KiB  
Article
Comparison between Statistical Models and Machine Learning Methods on Classification for Highly Imbalanced Multiclass Kidney Data
by Bomi Jeong, Hyunjeong Cho, Jieun Kim, Soon Kil Kwon, SeungWoo Hong, ChangSik Lee, TaeYeon Kim, Man Sik Park, Seoksu Hong and Tae-Young Heo
Diagnostics 2020, 10(6), 415; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060415 - 18 Jun 2020
Cited by 16 | Viewed by 3140
Abstract
This study aims to compare the classification performance of statistical models on highly imbalanced kidney data. The health examination cohort database provided by the National Health Insurance Service in Korea is utilized to build models with various machine learning methods. The glomerular filtration [...] Read more.
This study aims to compare the classification performance of statistical models on highly imbalanced kidney data. The health examination cohort database provided by the National Health Insurance Service in Korea is utilized to build models with various machine learning methods. The glomerular filtration rate (GFR) is used to diagnose chronic kidney disease (CKD). It is calculated using the Modification of Diet in Renal Disease method and classified into five stages (1, 2, 3A and 3B, 4, and 5). Different CKD stages based on the estimated GFR are considered as six classes of the response variable. This study utilizes two representative generalized linear models for classification, namely, multinomial logistic regression (multinomial LR) and ordinal logistic regression (ordinal LR), as well as two machine learning models, namely, random forest (RF) and autoencoder (AE). The classification performance of the four models is compared in terms of accuracy, sensitivity, specificity, precision, and F1-Measure. To find the best model that classifies CKD stages correctly, the data are divided into a 10-fold dataset with the same rate for each CKD stage. Results indicate that RF and AE show better performance in accuracy than the multinomial and ordinal LR models when classifying the response variable. However, when a highly imbalanced dataset is modeled, the accuracy of the model performance can distort the actual performance. This occurs because accuracy is high even if a statistical model classifies a minority class into a majority class. To solve this problem in performance interpretation, we not only consider accuracy from the confusion matrix but also sensitivity, specificity, precision, and F-1 measure for each class. To present classification performance with a single value for each model, we calculate the macro-average and micro-weighted values for each model. We conclude that AE is the best model classifying CKD stages correctly for all performance indices. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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15 pages, 3159 KiB  
Article
The Suitability of FGF21 and FGF23 as New Biomarkers in Endometrial Cancer Patients
by Aneta Cymbaluk-Płoska, Paula Gargulińska, Anita Chudecka-Głaz, Sebastian Kwiatkowski, Ewa Pius-Sadowska and Bogusław Machaliński
Diagnostics 2020, 10(6), 414; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060414 - 18 Jun 2020
Cited by 14 | Viewed by 2525
Abstract
Endometrial cancer is one of the most common cancers of the reproductive organ in women. The incidence of it increases from year to year. In our study we assessed role of FGF21 and FGF23 in the diagnostics of patients with endometrial cancer. The [...] Read more.
Endometrial cancer is one of the most common cancers of the reproductive organ in women. The incidence of it increases from year to year. In our study we assessed role of FGF21 and FGF23 in the diagnostics of patients with endometrial cancer. The study involved 182 patients, who were undergoing abrasion due to perimenopausal bleeding. FGF21, FGF23, and leptin concentration were quantified in serum by multiplex fluorescent bead-based immunoassays (Luminex Corporation). The median of FGF21 protein (181.8 pg/mL) as well as leptin (16.9 ng/mL) in patients with endometrial cancer was statistically significant higher compared to median of those proteins among patients from control group (152.1 pg/mL and 14.1 ng/mL, respectively). However, no significant differences were found in these groups at median FGF23 concentrations. For FGF21 and leptin, the AUC values were 0.81/0.79, while FGF23, the AUC values was 0.66 for all study patients. Leptin and FGF21 concentrations were statistically significantly higher in patients with poorly differentiated G3 tumors compared to patients with moderately differentiated G2 tumors and with moderately differentiated G2 with highly differentiated G1 respectively: p = 0.02/p = 0.03 and p = 0.02/p = 0.005. FGF21 appears to be useful as a diagnostic as well as prognostic factor in patients with endometrioid endometrial carcinoma. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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13 pages, 3252 KiB  
Article
The Application of Structural Retinal Biomarkers to Evaluate the Effect of Intravitreal Ranibizumab and Dexamethasone Intravitreal Implant on Treatment of Diabetic Macular Edema
by Ida Ceravolo, Giovanni William Oliverio, Angela Alibrandi, Ahsan Bhatti, Luigi Trombetta, Robert Rejdak, Mario Damiano Toro and Costantino John Trombetta
Diagnostics 2020, 10(6), 413; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060413 - 17 Jun 2020
Cited by 51 | Viewed by 3128
Abstract
Background: The aim of this study was to compare the therapeutic effect of intravitreal treatment with ranibizumab and dexamethasone using specific swept-source optical coherence tomography retinal biomarkers in patients with diabetic macular edema (DME). Methods: 156 treatment-naïve patients with DME were divided in [...] Read more.
Background: The aim of this study was to compare the therapeutic effect of intravitreal treatment with ranibizumab and dexamethasone using specific swept-source optical coherence tomography retinal biomarkers in patients with diabetic macular edema (DME). Methods: 156 treatment-naïve patients with DME were divided in two groups: 75 patients received 3 monthly intravitreal injections of ranibizumab 0.5 mg (Lucentis®) (Group 1) and 81 patients received an intravitreal implant of dexamethasone 0.7 mg (Ozurdex®) (Group 2). Patients were evaluated at baseline (V1), at three months post-treatment in Group 1, and at two months post-treatment in Group 2 (V2). Best-corrected visual acuity (BCVA) and swept source-OCT were recorded at each interval. Changes between V1 and V2 were analyzed using the Wilcoxon test and differences between the two groups of treatment were assessed using the Mann–Whitney test. Multiple regression analysis was performed to evaluate the possible OCT biomarker (CRT, ICR, CT, SND, HRS) as predictive factors for final visual acuity improvement. Results: In both groups, BCVA improved (p-value < 0.0001), and a significant reduction in central retinal thickness, intra-retinal cysts, red dots, hyper-reflective spots (HRS), and serous detachment of neuro-epithelium (SDN) was observed. A superiority of dexamethasone over ranibizumab in reducing the SDN height (p-value = 0.03) and HRS (p-value = 0.01) was documented. Conclusions: Ranibizumab and dexamethasone are effective in the treatment of DME, as demonstrated by functional improvement and morphological biomarker change. DME associated with SDN and HRS represents a specific inflammatory pattern for which dexamethasone appears to be more effective. Full article
(This article belongs to the Special Issue Corneal and Retinal Diseases: Diagnostic and Therapeutic Approaches)
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11 pages, 1154 KiB  
Review
Lactose Intolerance: What Your Breath Can Tell You
by Luelle Robles and Ronny Priefer
Diagnostics 2020, 10(6), 412; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060412 - 17 Jun 2020
Cited by 20 | Viewed by 10951
Abstract
Lactose intolerance has seen recognized as a clinical syndrome characterized by pain, abdominal distention, flatulence, and diarrhea after the consumption of lactose. Lactose is a common disaccharide found in dairy that requires lactase-phlorizin hydrolase (LPH) to break down into glucose and galactose. A [...] Read more.
Lactose intolerance has seen recognized as a clinical syndrome characterized by pain, abdominal distention, flatulence, and diarrhea after the consumption of lactose. Lactose is a common disaccharide found in dairy that requires lactase-phlorizin hydrolase (LPH) to break down into glucose and galactose. A deficiency in this enzyme results in flora bacteria further along in the gastrointestinal tract (GI) tract to metabolize the excess lactose to numerous gases, including H2. Recent studies show that the risk of symptoms after lactose ingestion depends on the dose of lactose, LPH expression, intestinal flora, and sensitivity of the gastrointestinal tract. Currently, there are several diagnostic tests that investigate the biological mechanism of lactose intolerance such as blood, biopsy, genetic, and breath tests. Due to its relatively low cost, availability, and non-invasiveness, the hydrogen breath test (HBT) has become a popular technology to aid in the diagnosis of many gastroenterological diseases, specifically lactose intolerance. Additionally, while administering the HBT there seems to be a lack of uniform criteria amongst the various studies, with many using their own guidelines, which may in turn cause inconsistency with the analysis of the results. With ever improving nanotechnology, novel approaches to expedite and lower the costs of the HBT has become an area of research with significant advancements. Full article
(This article belongs to the Section Point-of-Care Diagnostics and Devices)
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15 pages, 3571 KiB  
Article
The Application of an Iterative Structure to the Delay-and-Sum and the Delay-Multiply-and-Sum Beamformers in Breast Microwave Imaging
by Tyson Reimer, Mario Solis-Nepote and Stephen Pistorius
Diagnostics 2020, 10(6), 411; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060411 - 17 Jun 2020
Cited by 26 | Viewed by 3491
Abstract
Breast microwave imaging (BMI) is a potential breast cancer screening method. This manuscript presents a novel iterative delay-and-sum (DAS) based reconstruction algorithm for BMI. This iterative-DAS (itDAS) algorithm uses a forward radar model to iteratively update an image estimate. A variation of the [...] Read more.
Breast microwave imaging (BMI) is a potential breast cancer screening method. This manuscript presents a novel iterative delay-and-sum (DAS) based reconstruction algorithm for BMI. This iterative-DAS (itDAS) algorithm uses a forward radar model to iteratively update an image estimate. A variation of the itDAS reconstruction algorithm that uses the delay-multiply-and-sum (DMAS) beamformer was also implemented (the itDMAS algorithm). Both algorithms were used to reconstruct images from experimental scans of an array of 3D-printed MRI-based breast phantoms performed with a clinical BMI system. The signal-to-clutter ratio (SCR) and signal-to-mean ratio (SMR) were used to compare the performance of the itDAS and itDMAS methods to the DAS and DMAS beamformers. While no significant difference between the itDAS and itDMAS methods was observed in most images, the itDAS algorithm produced reconstructions that had significantly higher SMR than the non-iterative methods, increasing contrast by as much as 19 dB over DAS and 13 dB over DMAS. The itDAS algorithm also increased the SCR of reconstructions by up to 5 dB over DAS and 4 dB over DMAS, indicating that both high-intensity and background clutter are reduced in images reconstructed by the itDAS algorithm. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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5 pages, 2044 KiB  
Interesting Images
Brain Metastases Unresponsive to Immunotherapy Detected by 18F-FDG-PET/CT in a Patient with Melanoma
by Rosa Fonti, Sara Pellegrino, Ciro Gabriele Mainolfi, Elide Matano and Silvana Del Vecchio
Diagnostics 2020, 10(6), 410; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060410 - 17 Jun 2020
Cited by 4 | Viewed by 3755
Abstract
Recently, newer therapies such as immunotherapy have been increasingly used in the treatment of several tumors, including advanced melanoma. In particular, several studies showed that the combination of ipilimumab, an anti-Cytotoxic T-lymphocyte Associated Protein 4 (CTLA-4) monoclonal antibody and nivolumab, an anti-Programmed Death [...] Read more.
Recently, newer therapies such as immunotherapy have been increasingly used in the treatment of several tumors, including advanced melanoma. In particular, several studies showed that the combination of ipilimumab, an anti-Cytotoxic T-lymphocyte Associated Protein 4 (CTLA-4) monoclonal antibody and nivolumab, an anti-Programmed Death 1 (PD-1) monoclonal antibody, leads to improved survival in patients with metastatic melanoma. Despite that, immunotherapeutic agents may not reach therapeutic concentration in the brain due to the blood–brain barrier. We report the case of a 50-year-old man with advanced melanoma who underwent whole-body 18F-FDG-PET/CT before and after treatment with immunotherapy showing resistant brain metastases confirmed by subsequent MRI of the brain. Moreover, 18F-FDG-PET/CT was able to detect an immune-related adverse event such as enterocolitis that contributed to the worsening of patient conditions. This case shows how a whole-body methodology such as 18F-FDG-PET/CT can be useful in identifying melanoma cancer patients unresponsive to immunotherapy that may benefit from traditional palliative therapy in the effort to improve their quality of life. Full article
(This article belongs to the Collection Interesting Images)
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33 pages, 5047 KiB  
Review
COVID-19 Diagnostics, Tools, and Prevention
by Mayar Allam, Shuangyi Cai, Shambavi Ganesh, Mythreye Venkatesan, Saurabh Doodhwala, Zexing Song, Thomas Hu, Aditi Kumar, Jeremy Heit, COVID-19 Study Group and Ahmet F. Coskun
Diagnostics 2020, 10(6), 409; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060409 - 16 Jun 2020
Cited by 57 | Viewed by 23526
Abstract
The Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), outbreak from Wuhan City, Hubei province, China in 2019 has become an ongoing global health emergency. The emerging virus, SARS-CoV-2, causes coughing, fever, muscle ache, and shortness of breath [...] Read more.
The Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), outbreak from Wuhan City, Hubei province, China in 2019 has become an ongoing global health emergency. The emerging virus, SARS-CoV-2, causes coughing, fever, muscle ache, and shortness of breath or dyspnea in symptomatic patients. The pathogenic particles that are generated by coughing and sneezing remain suspended in the air or attach to a surface to facilitate transmission in an aerosol form. This review focuses on the recent trends in pandemic biology, diagnostics methods, prevention tools, and policies for COVID-19 management. To meet the growing demand for medical supplies during the COVID-19 era, a variety of personal protective equipment (PPE) and ventilators have been developed using do-it-yourself (DIY) manufacturing. COVID-19 diagnosis and the prediction of virus transmission are analyzed by machine learning algorithms, simulations, and digital monitoring. Until the discovery of a clinically approved vaccine for COVID-19, pandemics remain a public concern. Therefore, technological developments, biomedical research, and policy development are needed to decipher the coronavirus mechanism and epidemiological characteristics, prevent transmission, and develop therapeutic drugs. Full article
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10 pages, 2967 KiB  
Brief Report
Mobile Laboratory Reveals the Circulation of Dengue Virus Serotype I of Asian Origin in Medina Gounass (Guediawaye), Senegal
by Idrissa Dieng, Boris Gildas Hedible, Moussa Moïse Diagne, Ahmed Abd El Wahed, Cheikh Tidiane Diagne, Cheikh Fall, Vicent Richard, Muriel Vray, Manfred Weidmann, Ousmane Faye, Amadou Alpha Sall and Oumar Faye
Diagnostics 2020, 10(6), 408; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060408 - 16 Jun 2020
Cited by 21 | Viewed by 3328
Abstract
With the growing success of controlling malaria in Sub-Saharan Africa, the incidence of fever due to malaria is in decline, whereas the proportion of patients with non-malaria febrile illness (NMFI) is increasing. Clinical diagnosis of NMFI is hampered by unspecific symptoms, but early [...] Read more.
With the growing success of controlling malaria in Sub-Saharan Africa, the incidence of fever due to malaria is in decline, whereas the proportion of patients with non-malaria febrile illness (NMFI) is increasing. Clinical diagnosis of NMFI is hampered by unspecific symptoms, but early diagnosis is a key factor for both better patient care and disease control. The aim of this study was to determine the arboviral aetiologies of NMFI in low resource settings, using a mobile laboratory based on recombinase polymerase amplification (RPA) assays. The panel of tests for this study was expanded to five arboviruses: dengue virus (DENV), zika virus (ZIKV), yellow fever virus (YFV), chikungunya virus (CHIKV), and rift valley fever virus (RVFV). One hundred and four children aged between one month and 115 months were enrolled and screened. Three of the 104 blood samples of children <10 years presented at an outpatient clinic tested positive for DENV. The results were confirmed by RT-PCR, partial sequencing, and non-structural protein 1 (NS1) antigen capture by ELISA (Biorad, France). Phylogenetic analysis of the derived DENV-1 sequences clustered them with sequences of DENV-1 isolated from Guangzhou, China, in 2014. In conclusion, this mobile setup proved reliable for the rapid identification of the causative agent of NMFI, with results consistent with those obtained in the reference laboratory’s settings. Full article
(This article belongs to the Special Issue Mobile Diagnosis 2.0)
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13 pages, 2732 KiB  
Case Report
Quadruplicate Synchronous Adenocarcinoma of the Colon with Distant Metastases—Long-Term Molecular Follow-Up by KRAS and TP53 Mutational Profiling
by Emese Sarolta Bádon, Attila Mokánszki, Anikó Mónus, Csilla András, László Damjanovich and Gábor Méhes
Diagnostics 2020, 10(6), 407; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060407 - 16 Jun 2020
Cited by 2 | Viewed by 2585
Abstract
Anatomically independent tumor foci represent biologically distinct neoplasias, potentially featured by different progressivity and treatment responsiveness. To demonstrate the biological complexity, a metastatic colon adenocarcinoma patient originally presenting with four independent primary tumors of the right colon half and altogether eight distant metastases [...] Read more.
Anatomically independent tumor foci represent biologically distinct neoplasias, potentially featured by different progressivity and treatment responsiveness. To demonstrate the biological complexity, a metastatic colon adenocarcinoma patient originally presenting with four independent primary tumors of the right colon half and altogether eight distant metastases was followed by molecular testing. Next-generation sequencing results highlighted the mutational profile of the individual primaries and the dynamics of the different gene variants observed during follow-up. The four primary colon tumors presented with four different KRAS genotypes, one of them with a wild-type and three with pathogenic variants, without overlap. These were the following: c.35G > A; p.Gly12Asp with 40.6% variant allele frequency (VAF); c.34G > T; p.Gly12Cys with 16.2% VAF and c.35G > T; p.Gly12Val with 15.1% VAF. In metastatic tumors, with one exception where no mutation was detected, only the KRAS c.34G > T; p.Gly12Cys mutation could be detected. TP53 gene variants were variable in the primary tumors, with a single dominant variant evolving in the follow-up metastases (c.820G > T; p.Val274Phe). Genetic profiling of individually developing synchronous malignancies uncovers the clonal relations of metastatic tumors. NGS gene panels provide a solution to follow the dynamics of key oncogene variants during the course of the disease and greatly contribute to therapy optimization. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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17 pages, 3901 KiB  
Article
A CBCT Based Three-Dimensional Assessment of Mandibular Posterior Region for Evaluating the Possibility of Bypassing the Inferior Alveolar Nerve While Placing Dental Implants
by Mohammed G. Sghaireen, Kumar Chandan Srivastava, Deepti Shrivastava, Kiran Kumar Ganji, Santosh R. Patil, Anas Abuonq, Mohammed Assayed Mousa, Najla Dar-Odeh, Ghazi M. Sghaireen, Mohammad Amjad Kamal and Mohammad Khursheed Alam
Diagnostics 2020, 10(6), 406; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060406 - 14 Jun 2020
Cited by 21 | Viewed by 5384
Abstract
A high rate of nerve injury and related consequences are seen during implant placement in the posterior mandibular arch. An approach has been proposed to avoid nerve injury by dodging the inferior alveolar nerve (IAN) while placing an implant. A prospective study with [...] Read more.
A high rate of nerve injury and related consequences are seen during implant placement in the posterior mandibular arch. An approach has been proposed to avoid nerve injury by dodging the inferior alveolar nerve (IAN) while placing an implant. A prospective study with a total of 240 CBCT (cone beam computed tomography) images of patients with three dentate statuses, namely, edentulous (group I), partially edentulous (group II) and dentate (group III) were included in the study. The nerve path tracing was done on CBCT images with On-demand 3D software. The three dimensions, i.e., the linear distance from the outer buccal cortical plate to the inferior alveolar nerve (BCPN), linear distance from the outer lingual cortical plate to the inferior alveolar nerve (LCPN) and linear distance from the midpoint of the alveolar crest to the inferior alveolar nerve (ACN) were assessed. The data were presented and analyzed between variables using one-way ANOVA and independent t-test in SPSS version 21.LCPN of the right 1st premolar region (p < 0.05) was significantly different among the groups with edentulous subjects recorded with the minimum value (6.50 ± 1.20 mm). Females were found to have significantly (p < 0.05) less available bone (6.03 ± 1.46 mm) on the right side of the mandibular jaw compared to males in edentulous group of patients. On comparing age groups for partially edentulous subjects, LCPN of the right 1st premolar region had significantly (p < 0.05) less available bone (6.03 ± 0.38 mm) in subjects with age ≥54 years. The IAN follows a lingual course in the molar region and later flips to the buccal side in the premolar region. The LCPN dimension in the 1st and 2nd premolar region was found to be more than 6 mm irrespective of age, gender and side of the jaw. Thus, it can be considered as a suitable site for placing implants while bypassing the IAN with CBCT assessment remaining as the mainstay in the pre-surgical phase. Full article
(This article belongs to the Section Point-of-Care Diagnostics and Devices)
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10 pages, 1600 KiB  
Article
Pathogenic PSEN1 Thr119Ile Mutation in Two Korean Patients with Early-Onset Alzheimer’s Disease
by Eva Bagyinszky, Hyon Lee, Jung Min Pyun, Jeewon Suh, Min Ju Kang, Van Giau Vo, Seong Soo A. An, Kee Hyung Park and SangYun Kim
Diagnostics 2020, 10(6), 405; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10060405 - 14 Jun 2020
Cited by 2 | Viewed by 2713
Abstract
We report a probable pathogenic Thr119Ile mutation in presenilin-1 (PSEN1) in two unrelated Korean patients, diagnosed with early onset Alzheimer’s disease (EOAD). The first patient presented with memory decline when she was 64 years old. Magnetic resonance imaging (MRI) scans showed [...] Read more.
We report a probable pathogenic Thr119Ile mutation in presenilin-1 (PSEN1) in two unrelated Korean patients, diagnosed with early onset Alzheimer’s disease (EOAD). The first patient presented with memory decline when she was 64 years old. Magnetic resonance imaging (MRI) scans showed diffuse atrophy in the fronto-parietal regions. In addition, 18F-fludeoxyglucose positron emission tomography (FDG-PET) showed reduced tracer uptake in the parietal and temporal cortices, bilaterally. The second patient developed memory dysfunction at the age of 49, and his mother was also affected. Amyloid positron emission tomography (PET) was positive, but MRI scans did not reveal any atrophy. Targeted NGS and Sanger sequencing identified a heterozygous C to T exchange in PSEN1 exon 5 (c.356C>T), resulting in a p.Thr119Ile mutation. The mutation is located in the conserved HL-I loop, where several Alzheimer’s disease (AD) related mutations have been described. Structure analyses suggested that Thr119Ile mutation may result in a significant change inside conservative loop. Additional in vitro studies are needed to estimate the role of the PSEN1 Thr119Ile in AD disease progression. Full article
(This article belongs to the Special Issue Alzheimer’s Disease Pathophysiology)
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