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Diagnostics, Volume 10, Issue 8 (August 2020) – 101 articles

Cover Story (view full-size image): COVID-19 is especially severe in patients with cardiovascular disease. However, its severity among patients with certain forms of precapillary pulmonary hypertension is lower than expected. Both pathologies share common features. Could these common characteristics explain this good adaptation? Could these patients have obtained benefits from their specific therapies? This review will begin a dialogue to further explore the particular scenario of COVID-19 in precapillary pulmonary hypertension. View this paper
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19 pages, 5715 KiB  
Article
The Oncogenic Roles of PTTG1 and PTTG2 Genes and Pseudogene PTTG3P in Head and Neck Squamous Cell Carcinomas
by Inga Grzechowiak, Justyna Graś, Dominika Szymańska, Martyna Biernacka, Kacper Guglas, Paulina Poter, Andrzej Mackiewicz and Tomasz Kolenda
Diagnostics 2020, 10(8), 606; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080606 - 18 Aug 2020
Cited by 9 | Viewed by 2910
Abstract
Background: Head and neck squamous cell carcinomas are a group of heterogeneous diseases that occur in the mouth, pharynx and larynx and are characterized by poor prognosis. A low overall survival rate leads to a need to develop biomarkers for early head and [...] Read more.
Background: Head and neck squamous cell carcinomas are a group of heterogeneous diseases that occur in the mouth, pharynx and larynx and are characterized by poor prognosis. A low overall survival rate leads to a need to develop biomarkers for early head and neck squamous cell carcinomas detection, accurate prognosis and appropriate selection of therapy. Therefore, in this paper, we investigate the biological role of the PTTG3P pseudogene and associated genes PTTG1 and PTTG2 and their potential use as biomarkers. Methods: Based on TCGA data and the UALCAN database, PTTG3P, PTTG1 and PTTG2 expression profiles and clinicopathological features with TP53 gene status as well as expression levels of correlated genes were analyzed in patients’ tissue samples. The selected genes were classified according to their biological function using the PANTHER tool. Gene Set Enrichment Analysis software was used for functional enrichment analysis. All statistical analyses were performed using GraphPad Prism 5. Results: In head and neck squamous cell carcinomas, significant up-regulation of the PTTG3P pseudogene, PTTG1 and PTTG2 genes’ expression between normal and cancer samples were observed. Moreover, the expression of PTTG3P, PTTG1 and PTTG2 depends on the type of mutation in TP53 gene, and they correlate with genes from p53 pathway. PTTG3P expression was significantly correlated with PTTG1 as well as PTTG2, as was PTTG1 expression with PTTG2. Significant differences between expression levels of PTTG3P, PTTG1 and PTTG2 in head and neck squamous cell carcinomas patients were also observed in clinicopathological contexts. The contexts taken into consideration included: T-stage for PTTG3P; grade for PTTG3, PTTG1 and PTTG2; perineural invasion and lymph node neck dissection for PTTG1 and HPV p16 status for PTTG3P, PTTG1 and PTTG2. A significantly longer disease-free survival for patients with low expressions of PTTG3P and PTTG2, as compared to high expression groups, was also observed. Gene Set Enrichment Analysis indicated that the PTTG3 high-expressing group of patients have the most deregulated genes connected with DNA repair, oxidative phosphorylation and peroxisome pathways. For PTTG1, altered genes are from DNA repair groups, Myc targets, E2F targets and oxidative phosphorylation pathways, while for PTTG2, changes in E2F targets, G2M checkpoints and oxidative phosphorylation pathways are indicated. Conclusions: PTTG3P and PTTG2 can be used as a prognostic biomarker in head and neck squamous cell carcinomas diagnostics. Moreover, patients with high expressions of PTTG3P, PTTG1 or PTTG2 have worse outcomes due to upregulation of oncogenic pathways and more aggressive phenotypes. Full article
(This article belongs to the Special Issue Biomarkers of Oral Cancer)
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10 pages, 1517 KiB  
Article
Direct-RT-qPCR Detection of SARS-CoV-2 without RNA Extraction as Part of a COVID-19 Testing Strategy: From Sample to Result in One Hour
by Eva Kriegova, Regina Fillerova and Petr Kvapil
Diagnostics 2020, 10(8), 605; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080605 - 18 Aug 2020
Cited by 31 | Viewed by 8149
Abstract
Due to the lack of protective immunity in the general population and the absence of effective antivirals and vaccines, the Coronavirus disease 2019 (COVID-19) pandemic continues in some countries, with local epicentres emerging in others. Due to the great demand for effective COVID-19 [...] Read more.
Due to the lack of protective immunity in the general population and the absence of effective antivirals and vaccines, the Coronavirus disease 2019 (COVID-19) pandemic continues in some countries, with local epicentres emerging in others. Due to the great demand for effective COVID-19 testing programmes to control the spread of the disease, we have suggested such a testing programme that includes a rapid RT-qPCR approach without RNA extraction. The Direct-One-Step-RT-qPCR (DIOS-RT-qPCR) assay detects severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in less than one hour while maintaining the high sensitivity and specificity required of diagnostic tools. This optimised protocol allows for the direct use of swab transfer media (14 μL) without the need for RNA extraction, achieving comparable sensitivity to the standard method that requires the time-consuming and costly step of RNA isolation. The limit of detection for DIOS-RT-qPCR was lower than seven copies/reaction, which translates to 550 virus copies/mL of swab. The speed, ease of use and low price of this assay make it suitable for high-throughput screening programmes. The use of fast enzymes allows RT-qPCR to be performed under standard laboratory conditions within one hour, making it a potential point-of-care solution on high-speed cycling instruments. This protocol also implements the heat inactivation of SARS-CoV-2 (75 °C for 10 min), which renders samples non-infectious, enabling testing in BSL-2 facilities. Moreover, we discuss the critical steps involved in developing tests for the rapid detection of COVID-19. Implementing rapid, easy, cost-effective methods can help control the worldwide spread of the COVID-19 infection. Full article
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15 pages, 1372 KiB  
Article
Clinical Significance and Diagnostic Value of Pain Extent Extracted from Pain Drawings: A Scoping Review
by Marco Barbero, Marcos J. Navarro-Santana, María Palacios-Ceña, Ricardo Ortega-Santiago, Corrado Cescon, Deborah Falla and César Fernández-de-las-Peñas
Diagnostics 2020, 10(8), 604; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080604 - 18 Aug 2020
Cited by 18 | Viewed by 4295
Abstract
The current scoping review aimed to map current literature investigating the relationship between pain extent extracted from pain drawings with clinical, psychological, and psycho-physiological patient-reported outcome measures in people with pain. Electronic databases were searched for cross-sectional cohort studies that collected pain drawings [...] Read more.
The current scoping review aimed to map current literature investigating the relationship between pain extent extracted from pain drawings with clinical, psychological, and psycho-physiological patient-reported outcome measures in people with pain. Electronic databases were searched for cross-sectional cohort studies that collected pain drawings using digital technology or a pen-on-paper approach and assessed for correlations between pain extent and clinical, psychological or psycho-physical outcomes. Data were extracted by two different reviewers. The methodological quality of studies was assessed using the Newcastle–Ottawa Quality Assessment Scale. Mapping of the results included: 1, description of included studies; 2, summary of results; and 3, identification of gaps in the existing literature. Eleven cross-sectional cohort studies were included. The pain disorders considered were heterogeneous, ranging from musculoskeletal to neuropathic conditions, and from localized to generalized pain conditions. All studies included pain and/or pain-related disability as clinical outcomes. Psychological outcomes included depression and anxiety, kinesiophobia and catastrophism. Psycho-physical measures included pressure or thermal pain thresholds. Ten studies were considered of high methodological quality. There was heterogeneity in the associations between pain extent and patient-reported outcome measures depending on the pain condition. This scoping review found that pain extent is associated with patient-reported outcome measures more so in patients presenting with musculoskeletal pain, e.g., neck pain or osteoarthritis, rather than for those with neuropathic pain or headache. Full article
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13 pages, 4823 KiB  
Article
A Comparison of a Standard Macintosh Blade Laryngoscope, Pentax-AWS Videolaryngoscope and Intubrite Videolaryngoscope for Tracheal Intubation in Manikins in Sitting and Prone Positions: A Randomized Cross-Over Study
by Tomasz M. Gaszyński
Diagnostics 2020, 10(8), 603; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080603 - 18 Aug 2020
Cited by 8 | Viewed by 3060
Abstract
Background: Intubation of a patient in different positions may be done not only in emergency settings, but also in routine anesthesia (e.g., prone position for lumbar spine surgery). Methods: The aim of the study was to compare the classic Macintosh blade laryngoscope with [...] Read more.
Background: Intubation of a patient in different positions may be done not only in emergency settings, but also in routine anesthesia (e.g., prone position for lumbar spine surgery). Methods: The aim of the study was to compare the classic Macintosh blade laryngoscope with two videolaryngoscopes: the Pentax-AWS and the Intubrite in a simulated scenario of a manikin placed in a sitting and prone position. Additionally, intubation with the use of all three devices was performed in a standard supine position as the control group. The time of intubation and the pressure exerted on the tongue was assessed. The ANOVA Friedman (analysis of variance) and Wilcoxon with Bonferroni correction tests were used for statistical analysis. Results: The time of intubation in a prone position was significantly shorter for the Pentax-AWS videolaryngoscope compared to the Macintosh and the Intubrite. There were no significant differences in the obtained results of the evaluated devices in sitting and standard positions. The lowest pressure exerted on the tongue was with the Pentax-AWS, followed by the Intubrite and the Macintosh laryngoscopes. Conclusions: The use of the Pentax-AWS was associated with faster tracheal intubation, creating lower pressure on tongue when compared with standard Macintosh and Intubrite laryngoscopes in both prone and sitting positions. Full article
(This article belongs to the Special Issue Advances in Tracheal Intubation)
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15 pages, 3222 KiB  
Article
An Adoptive Threshold-Based Multi-Level Deep Convolutional Neural Network for Glaucoma Eye Disease Detection and Classification
by Muhammad Aamir, Muhammad Irfan, Tariq Ali, Ghulam Ali, Ahmad Shaf, Alqahtani Saeed S, Ali Al-Beshri, Tariq Alasbali and Mater H. Mahnashi
Diagnostics 2020, 10(8), 602; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080602 - 18 Aug 2020
Cited by 35 | Viewed by 3814
Abstract
Glaucoma, an eye disease, occurs due to Retinal damages and it is an ordinary cause of blindness. Most of the available examining procedures are too long and require manual instructions to use them. In this work, we proposed a multi-level deep convolutional neural [...] Read more.
Glaucoma, an eye disease, occurs due to Retinal damages and it is an ordinary cause of blindness. Most of the available examining procedures are too long and require manual instructions to use them. In this work, we proposed a multi-level deep convolutional neural network (ML-DCNN) architecture on retinal fundus images to diagnose glaucoma. We collected a retinal fundus images database from the local hospital. The fundus images are pre-processed by an adaptive histogram equalizer to reduce the noise of images. The ML-DCNN architecture is used for features extraction and classification into two phases, one for glaucoma detection known as detection-net and the second one is classification-net used for classification of affected retinal glaucoma images into three different categories: Advanced, Moderate and Early. The proposed model is tested on 1338 retinal glaucoma images and performance is measured in the form of different statistical terms known as sensitivity (SE), specificity (SP), accuracy (ACC), and precision (PRE). On average, SE of 97.04%, SP of 98.99%, ACC of 99.39%, and PRC of 98.2% are achieved. The obtained outcomes are comparable to the state-of-the-art systems and achieved competitive results to solve the glaucoma eye disease problems for complex glaucoma eye disease cases. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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37 pages, 1074 KiB  
Review
Oxidative Stress Markers in Inflammatory Bowel Diseases: Systematic Review
by Małgorzata Krzystek-Korpacka, Radosław Kempiński, Mariusz A. Bromke and Katarzyna Neubauer
Diagnostics 2020, 10(8), 601; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080601 - 17 Aug 2020
Cited by 36 | Viewed by 4436
Abstract
Precise diagnostic biomarker in inflammatory bowel diseases (IBD) is still missing. We conducted a comprehensive overview of oxidative stress markers (OSMs) as potential diagnostic, differential, progression, and prognostic markers in IBD. A Pubmed, Web of Knowledge, and Scopus search of original articles on [...] Read more.
Precise diagnostic biomarker in inflammatory bowel diseases (IBD) is still missing. We conducted a comprehensive overview of oxidative stress markers (OSMs) as potential diagnostic, differential, progression, and prognostic markers in IBD. A Pubmed, Web of Knowledge, and Scopus search of original articles on OSMs in IBD, published between January 2000 and April 2020, was conducted. Out of 874 articles, 79 eligible studies were identified and used to prepare the interpretative synthesis. Antioxidants followed by lipid peroxidation markers were the most popular and markers of oxidative DNA damage the least popular. There was a disparity in the number of retrieved papers evaluating biomarkers in the adult and pediatric population (n = 6). Of the reviewed OSMs, a promising performance has been reported for serum total antioxidant status as a mucosal healing marker, mucosal 8-OHdG as a progression marker, and for multi-analyte panels of lipid peroxidation products assessed non-invasively in breath as diagnostic and differential markers in the pediatric population. Bilirubin, in turn, was the only validated marker. There is a desperate need for non-invasive biomarkers in IBD which, however, will not be met in the near future by oxidative stress markers as they are promising but mostly at the early research phase of discovery. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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17 pages, 2153 KiB  
Article
The Influence of Radical Prostatectomy on the Expression of Cell-Free MiRNA
by Maria Yu. Konoshenko, Olga E. Bryzgunova, Evgeniy A. Lekchnov, Evgeniya V. Amelina, Sergey V. Yarmoschuk, Svetlana V. Pak and Pavel P. Laktionov
Diagnostics 2020, 10(8), 600; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080600 - 17 Aug 2020
Cited by 13 | Viewed by 2496
Abstract
MiRNAs of blood and urine have been shown to represent a convenient source of biomarkers for prostate cancer (PCa) diagnosis and assessment of the therapy effectiveness due to their high stability and representation and the low invasiveness of sample collection. Here, we studied [...] Read more.
MiRNAs of blood and urine have been shown to represent a convenient source of biomarkers for prostate cancer (PCa) diagnosis and assessment of the therapy effectiveness due to their high stability and representation and the low invasiveness of sample collection. Here, we studied the influence of radical prostatectomy (RP) on the expression of 12 cell-free miRNAs previously shown as potential markers of PCa (i.e., miR-19b, miR-22, miR-92a, miR-378, miR-425, miR-30e, miR-31, miR-125b, miR-200b, miR-205, miR-375 and miR-660). The relative expression of the miRNAs combined into 31 paired ratios was evaluated in the urine extracellular vesicles (EVs), clarified urine (CU) and blood plasma of healthy donors, pre- and post-RP samples of PCa patients. Nineteen miRNA ratios based on combinations of ten of the miRNAs (miR-19b, miR-30e, miR-31, miR-125b, miR-200b, miR-205, miR-375, miR-378, miR-425, and miR-660) were altered by RP. The comparative expression analysis of the cell-free miRNA ratios between healthy donors and PCa patients revealed miR-125b/miR-30e and miR-375/miR-30e as potential markers for evaluating therapeutic efficacy. MiR-378/miR-19b, miR-425/miR-19b, miR-200/miR-30e, miR-660/miR-30e, and miR-205/miR-30e had minor prognostic value but could be used to increase the steadiness of the diagnostic system. The urine EVs had the highest potential as a source of markers. Full article
(This article belongs to the Special Issue Diagnostic Biomarkers in Prostate Cancer 2020)
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9 pages, 3226 KiB  
Article
Design of Liver Functional Reserve Estimation Technique Based on Optical Densitometry
by Ekaterina Savchenko, Ilya Kolokolnikov, Elena Velichko, Victor Osovskikh, Lyubov Kiseleva and Zhyldyz Musakulova
Diagnostics 2020, 10(8), 599; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080599 - 16 Aug 2020
Cited by 13 | Viewed by 2552
Abstract
This work is aimed at creating a modified invasive technique for assessing the liver’s functional reserves. A study of the degree of hepatodepression is carried out by measuring the plasma elimination of indocyanine green using the method of optical densitometry. This paper presents [...] Read more.
This work is aimed at creating a modified invasive technique for assessing the liver’s functional reserves. A study of the degree of hepatodepression is carried out by measuring the plasma elimination of indocyanine green using the method of optical densitometry. This paper presents test results for an aqueous solution and an albumin solution, as well as the results of measurements of plasma elimination of indocyanine green for patients with liver disease. Perfecting the proposed method will make an important scientific contribution to modern diagnostic medicine. Diagnosing the stages in the progression of the disease and its developing complications can make it possible to rapidly correct the patient’s treatment algorithm, achieving positive outcomes in medical practice. Full article
(This article belongs to the Special Issue Optical Diagnostics in Human Diseases)
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18 pages, 1258 KiB  
Review
Somatostatin Receptor PET/CT Imaging for the Detection and Staging of Pancreatic NET: A Systematic Review and Meta-Analysis
by Matteo Bauckneht, Domenico Albano, Salvatore Annunziata, Giulia Santo, Priscilla Guglielmo, Viviana Frantellizzi, Alessia Branca, Cristina Ferrari, Antonio Vento, Alessia Mirabile, Anna Giulia Nappi, Laura Evangelista, Pierpaolo Alongi and Riccardo Laudicella
Diagnostics 2020, 10(8), 598; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080598 - 16 Aug 2020
Cited by 32 | Viewed by 4398
Abstract
We investigated the diagnostic performance of Somatostatin Receptor Positron Emission Tomography/Computed Tomography (SSR-PET/CT) for the detection of primary lesion and initial staging of pancreatic neuroendocrine tumors (pNETs). A comprehensive literature search up to January 2020 was performed selecting studies in presence of: sample [...] Read more.
We investigated the diagnostic performance of Somatostatin Receptor Positron Emission Tomography/Computed Tomography (SSR-PET/CT) for the detection of primary lesion and initial staging of pancreatic neuroendocrine tumors (pNETs). A comprehensive literature search up to January 2020 was performed selecting studies in presence of: sample size ≥10 patients; index test (i.e., 68Ga-DOTATOC or 68Ga-DOTANOC or 68Ga-DOTATATE PET/CT); and outcomes (i.e., detection rate (DR), true positive, true negative, false positive, and false-negative). The methodological quality was evaluated with QUADAS-2. Pooled DR and pooled sensitivity and specificity for the identification of the primary tumor were assessed by a patient-based and a lesion-based analysis. Thirty-eight studies were selected for the qualitative analysis, while 18 papers were included in the meta-analysis. The number of pNET patients ranged from 10 to 142, for a total of 1143 subjects. At patient-based analysis, the pooled sensitivity and specificity for the assessment of primary pNET were 79.6% (95% confidence interval (95%CI): 71–87%) and 95% (95%CI: 75–100%) with a heterogeneity of 59.6% and 51.5%, respectively. Pooled DR for the primary lesion was 81% (95%CI: 65–90%) and 92% (95%CI: 80–97%), respectively, at patient-based and lesion-based analysis. In conclusion, SSR-PET/CT has high DR and diagnostic performances for primary lesion and initial staging of pNETs. Full article
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25 pages, 2283 KiB  
Guidelines
Recommendations for Lung Ultrasound in Internal Medicine
by Natalia Buda, Wojciech Kosiak, Marcin Wełnicki, Agnieszka Skoczylas, Robert Olszewski, Jakub Piotrkowski, Szymon Skoczyński, Elżbieta Radzikowska, Ewa Jassem, Elżbieta Magdalena Grabczak, Piotr Kwaśniewicz, Gebhard Mathis and Tudor P. Toma
Diagnostics 2020, 10(8), 597; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080597 - 16 Aug 2020
Cited by 41 | Viewed by 5743
Abstract
A growing amount of evidence prompts us to update the first version of recommendations for lung ultrasound in internal medicine (POLLUS-IM) that was published in 2018. The recommendations were established in several stages, consisting of: literature review, assessment of literature data quality (with [...] Read more.
A growing amount of evidence prompts us to update the first version of recommendations for lung ultrasound in internal medicine (POLLUS-IM) that was published in 2018. The recommendations were established in several stages, consisting of: literature review, assessment of literature data quality (with the application of QUADAS, QUADAS-2 and GRADE criteria) and expert evaluation carried out consistently with the modified Delphi method (three rounds of on-line discussions, followed by a secret ballot by the panel of experts after each completed discussion). Publications to be analyzed were selected from the following databases: Pubmed, Medline, OVID, and Embase. New reports published as of October 2019 were added to the existing POLLUS-IM database used for the original publication of 2018. Altogether, 528 publications were systematically reviewed, including 253 new reports published between September 2017 and October 2019. The new recommendations concern the following conditions and issues: pneumonia, heart failure, monitoring dialyzed patients’ hydration status, assessment of pleural effusion, pulmonary embolism and diaphragm function assessment. POLLUS-IM 2020 recommendations were established primarily for clinicians who utilize lung ultrasound in their everyday clinical work. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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13 pages, 1927 KiB  
Review
Recent Advances in Ultrasound Diagnosis of Carpal Tunnel Syndrome
by Yuichi Yoshii, Chunfeng Zhao and Peter C. Amadio
Diagnostics 2020, 10(8), 596; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080596 - 15 Aug 2020
Cited by 48 | Viewed by 11426
Abstract
With the widespread use of high-resolution ultrasonography, ultrasonic examination has been shown to be useful as a diagnostic method for carpal tunnel syndrome. The main advantages of ultrasonography are that it is simple, quick, non-invasive, and economical. Another advantage is that tissue dynamics [...] Read more.
With the widespread use of high-resolution ultrasonography, ultrasonic examination has been shown to be useful as a diagnostic method for carpal tunnel syndrome. The main advantages of ultrasonography are that it is simple, quick, non-invasive, and economical. Another advantage is that tissue dynamics can be observed with real-time imaging. In recent reports, it has been shown that ultrasonic examination can provide similar diagnostic accuracy as nerve conduction study in the diagnosis of carpal tunnel syndrome. It has been expected that ultrasound demand in daily medical care will continue to increase. Ultrasonography in carpal tunnel syndrome shows an enlarged median nerve in proximal carpal tunnel, thickening of the flexor retinaculum, and edema around flexor tendons in cross-sectional images. In addition, with the introduction of new technologies such as ultrasonic elastography and speckle tracking, it has become possible to quantify dynamics and material property changes of nerves, tendons, and their surrounding structures. In this review, we describe recent advancements of carpal tunnel syndrome diagnosis based on ultrasound dynamic images, and discuss its pathology. Full article
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12 pages, 3740 KiB  
Article
Clinicopathological Characteristics of Pleomorphic High-Grade Squamous Intraepithelial Lesion of the Uterine Cervix: A Single-Institutional Series of 31 Cases
by Hyunjin Kim, Sangjoon Choi, Sung-Im Do, Sang Hwa Lee, Nara Yoon and Hyun-Soo Kim
Diagnostics 2020, 10(8), 595; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080595 - 15 Aug 2020
Cited by 5 | Viewed by 4611
Abstract
We investigated the clinicopathological characteristics of 31 cases of pleomorphic high-grade squamous intraepithelial lesions (PHSIL) of the uterine cervix. We reviewed electronic medical records and all available slides to collect clinical and pathological information. PHSILs were histologically characterized by significant nuclear enlargement, marked [...] Read more.
We investigated the clinicopathological characteristics of 31 cases of pleomorphic high-grade squamous intraepithelial lesions (PHSIL) of the uterine cervix. We reviewed electronic medical records and all available slides to collect clinical and pathological information. PHSILs were histologically characterized by significant nuclear enlargement, marked pleomorphism, hyperchromasia, increased mitotic activity, and frequent atypical mitoses. In the majority of cases (24/31; 77.4%), this striking nuclear atypia involved both the surface epithelium and the endocervical glands. In the remaining seven cases, pleomorphic cells were observed in the surface epithelium only. PHSILs involving both the surface epithelium and glands showed higher mitotic counts and Ki-67 labelling indices than the surface-only PHSILs. Invasive squamous cell carcinoma was present in only one case (3.2%), and none developed recurrent disease. Our observations of striking nuclear atypia in cases of HSIL did not indicate increased aggressiveness. Further investigations are required for confirmation of our data in larger cohorts. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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8 pages, 1053 KiB  
Communication
Proposal of De Novo Antigen Test for COVID-19: Ultrasensitive Detection of Spike Proteins of SARS-CoV-2
by Yuta Kyosei, Mayuri Namba, Sou Yamura, Rikiya Takeuchi, Noriko Aoki, Kazunari Nakaishi, Satoshi Watabe and Etsuro Ito
Diagnostics 2020, 10(8), 594; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080594 - 14 Aug 2020
Cited by 37 | Viewed by 10156
Abstract
Polymerase chain reaction (PCR)-based antigen tests are technically difficult, time-consuming, and expensive, and may produce false negative results requiring follow-up confirmation with computed tomography. The global coronavirus disease 2019 (COVID-19) pandemic has increased the demand for accurate, easy-to-use, rapid, and cost-effective antigen tests [...] Read more.
Polymerase chain reaction (PCR)-based antigen tests are technically difficult, time-consuming, and expensive, and may produce false negative results requiring follow-up confirmation with computed tomography. The global coronavirus disease 2019 (COVID-19) pandemic has increased the demand for accurate, easy-to-use, rapid, and cost-effective antigen tests for clinical application. We propose a de novo antigen test for diagnosing COVID-19 using the combination of sandwich enzyme-linked immunosorbent assay and thio-nicotinamide adenine dinucleotide (thio-NAD) cycling. Our test takes advantage of the spike proteins specific to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The limit of detection of our test was 2.3 × 10−18 moles/assay. If the virus has ~25 spike proteins on its surface, our method should detect on the order of 10−20 moles of virus/assay, corresponding to ~104 copies of the virus RNA/assay. The detection sensitivity approaches that of PCR-based assays because the average virus RNA load used for PCR-based assays is ~105 copies per oro- or naso-pharyngeal swab specimen. To our knowledge, this is the first ultrasensitive antigen test for SARS-CoV-2 spike proteins that can be performed with an easy-to-use microplate reader. Sufficient sensitivity can be achieved within 10 min of thio-NAD cycling. Our antigen test allows for rapid, cost-effective, specific, ultrasensitive, and simultaneous multiple measurements of SARS-CoV-2, and has broad application for the diagnosis for COVID-19. Full article
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
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10 pages, 865 KiB  
Article
EDTA-Anticoagulated Whole Blood for SARS-CoV-2 Antibody Testing by Electrochemiluminescence Immunoassay (ECLIA) and Enzyme-Linked Immunosorbent Assay (ELISA)
by Marc Kovac, Lorenz Risch, Sarah Thiel, Myriam Weber, Kirsten Grossmann, Nadja Wohlwend, Thomas Lung, Dorothea Hillmann, Michael Ritzler, Susanna Bigler, Francesca Ferrara, Thomas Bodmer, Konrad Egli, Mauro Imperiali, Sonja Heer, Yacir Salimi, Harald Renz, Philipp Kohler, Pietro Vernazza, Christian R. Kahlert, Matthias Paprotny and Martin Rischadd Show full author list remove Hide full author list
Diagnostics 2020, 10(8), 593; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080593 - 14 Aug 2020
Cited by 18 | Viewed by 5469
Abstract
While lateral flow test formats can be utilized with whole blood and low sample volumes, their diagnostic characteristics are inferior to immunoassays based on chemiluminescence immunoassay (CLIA) or enzyme-linked immunosorbent assay (ELISA) technology. CLIAs and ELISAs can be automated to a high degree [...] Read more.
While lateral flow test formats can be utilized with whole blood and low sample volumes, their diagnostic characteristics are inferior to immunoassays based on chemiluminescence immunoassay (CLIA) or enzyme-linked immunosorbent assay (ELISA) technology. CLIAs and ELISAs can be automated to a high degree but commonly require larger serum or plasma volumes for sample processing. We addressed the suitability of EDTA-anticoagulated whole blood as an alternative sample material for antibody testing against SARS-CoV-2 by electro-CLIA (ECLIA; Roche, Rotkreuz, Switzerland) and ELISA (IgG and IgA; Euroimmun, Germany). Simultaneously drawn venous serum and EDTA-anticoagulated whole blood samples from 223 individuals were included. Correction of the whole blood results for hematocrit led to a good agreement with the serum results for weakly to moderately positive antibody signals. In receiver-operating characteristic curve analysis, all three assays displayed comparable diagnostic accuracy (area under the curve (AUC)) using corrected whole blood and serum (AUCs: 0.97 for ECLIA and IgG ELISA; 0.84 for IgA ELISA). In conclusion, our results suggest that the investigated assays can reliably detect antibodies against SARS-CoV-2 in hemolyzed whole blood anticoagulated with EDTA. Correction of these results for hematocrit is suggested. This study demonstrates that the automated processing of whole blood for identification of SARS-CoV-2 antibodies with common ECLIA and ELISA methods is accurate and feasible. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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10 pages, 1106 KiB  
Article
Anatomic Investigation of Two Cases of Aberrant Right Subclavian Artery Syndrome, Including the Effects on External Vascular Dimensions
by Mitchell H. Mirande, Madelyn R. Durhman and Heather F. Smith
Diagnostics 2020, 10(8), 592; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080592 - 14 Aug 2020
Cited by 2 | Viewed by 3373
Abstract
The retroesophageal aberrant right subclavian artery (ARSA) is a variation of the aortic arch that occurs asymptomatically in most patients. However, when symptomatic, it is most commonly associated with dysphagia. ARSA has also been noted as a location of potentially severe aneurysms in [...] Read more.
The retroesophageal aberrant right subclavian artery (ARSA) is a variation of the aortic arch that occurs asymptomatically in most patients. However, when symptomatic, it is most commonly associated with dysphagia. ARSA has also been noted as a location of potentially severe aneurysms in some patients, as well as posing a risk during surgical interventions in the esophageal region. This case study analyzes two individuals with ARSA morphology in comparison to a normal sample in order to gain a better anatomical understanding of this anomaly, potentially leading to better risk assessment of ARSA patients going forward. The diameter of the ARSA vessel was found to be substantially larger than both the right subclavian artery and brachiocephalic trunk of the subjects with classic aortic arch anatomy. As many ARSA individuals are asymptomatic, we hypothesize that the relative size of the ARSA may dictate its contribution to the presence and/or severity of associated symptomatology. Full article
(This article belongs to the Special Issue Anatomical Variation and Clinical Diagnosis)
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14 pages, 1745 KiB  
Article
Diagnostic Reference Level of Radiation Dose and Image Quality among Paediatric CT Examinations in A Tertiary Hospital in Malaysia
by Nor Azura Muhammad, Muhammad Khalis Abdul Karim, Hasyma Abu Hassan, Mazliana Ahmad Kamarudin, Jeannie Hsiu Ding Wong and Kwan Hoong Ng
Diagnostics 2020, 10(8), 591; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080591 - 14 Aug 2020
Cited by 23 | Viewed by 4879
Abstract
Pediatrics are more vulnerable to radiation and are prone to dose compared to adults, requiring more attention to computed tomography (CT) optimization. Hence, diagnostic reference levels (DRLs) have been implemented as part of optimization process in order to monitor CT dose and diagnostic [...] Read more.
Pediatrics are more vulnerable to radiation and are prone to dose compared to adults, requiring more attention to computed tomography (CT) optimization. Hence, diagnostic reference levels (DRLs) have been implemented as part of optimization process in order to monitor CT dose and diagnostic quality. The noise index has recently been endorsed to be included as a part of CT optimization in the DRLs report. In this study, we have therefore set local DRLs for pediatric CT examination with a noise index as an indicator of image quality. One thousand one hundred and ninety-two (1192) paediatric patients undergoing CT brain, CT thorax and CT chest-abdomen-pelvis (CAP) examinations were analyzed retrospectively and categorized into four age groups; group 1 (0–1 year), group 2 (1–5 years), group 3 (5–10 years) and group 4 (10–15 years). For each group, data such as the volume-weighted CT dose index (CTDIvol), dose-length product (DLP) and the effective dose (E) were calculated and DRLs for each age group set at 50th percentile were determined. Both CT dose and image noise values between age groups have differed significantly with p-value < 0.05. The highest CTDIvol and DLP values in all age groups with the lowest noise index value reported in the 10–15 age group were found in CT brain examination. In conclusion, there was a significant variation in doses and noise intensity among children of different ages, and the need to change specific parameters to fit the clinical requirement. Full article
(This article belongs to the Special Issue Assessment of Radiation Dose in X-ray and CT Exams)
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3 pages, 168 KiB  
Editorial
MRI and Active Surveillance for Prostate Cancer
by Angelo Porreca, Michele Colicchia, Gian Maria Busetto and Matteo Ferro
Diagnostics 2020, 10(8), 590; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080590 - 14 Aug 2020
Cited by 1 | Viewed by 2041
Abstract
Since the introduction of Prostate-Specific Antigen (PSA) screening, prostate cancer mortality has decreased [...] Full article
(This article belongs to the Section Medical Imaging and Theranostics)
23 pages, 3532 KiB  
Review
Novel Approaches for Imaging-Based Diagnosis of Ocular Surface Disease
by Doreen Schmidl, Andreas Schlatter, Jacqueline Chua, Bingyao Tan, Gerhard Garhöfer and Leopold Schmetterer
Diagnostics 2020, 10(8), 589; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080589 - 13 Aug 2020
Cited by 20 | Viewed by 5495
Abstract
Imaging has become indispensable in the diagnosis and management of diseases in the posterior part of the eye. In recent years, imaging techniques for the anterior segment are also gaining importance and are nowadays routinely used in clinical practice. Ocular surface disease is [...] Read more.
Imaging has become indispensable in the diagnosis and management of diseases in the posterior part of the eye. In recent years, imaging techniques for the anterior segment are also gaining importance and are nowadays routinely used in clinical practice. Ocular surface disease is often synonymous with dry eye disease, but also refers to other conditions of the ocular surface, such as Meibomian gland dysfunction or keratitis and conjunctivitis with different underlying causes, i.e., allergies or infections. Therefore, correct differential diagnosis and treatment of ocular surface diseases is crucial, for which imaging can be a helpful tool. A variety of imaging techniques have been introduced to study the ocular surface, such as anterior segment optical coherence tomography, in vivo confocal microscopy, or non-contact meibography. The present review provides an overview on how these techniques can be used in the diagnosis and management of ocular surface disease and compares them to clinical standard methods such as slit lamp examination or staining of the cornea or conjunctiva. Although being more cost-intensive in the short term, in the long term, the use of ocular imaging can lead to more individualized diagnoses and treatment decisions, which in turn are beneficial for affected patients as well as for the healthcare system. In addition, imaging is more objective and provides good documentation, leading to an improvement in patient follow-up and education. Full article
(This article belongs to the Special Issue Dry Eye and Ocular Surface Disorders)
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13 pages, 1297 KiB  
Article
Quantitative Multiplex Real-Time Reverse Transcriptase–Polymerase Chain Reaction with Fluorescent Probe Detection of Killer Immunoglobulin-Like Receptors, KIR2DL4/3DL3
by Wipaporn Wongfieng, Rungtiwa Nutalai, Amonrat Jumnainsong and Chanvit Leelayuwat
Diagnostics 2020, 10(8), 588; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080588 - 13 Aug 2020
Cited by 1 | Viewed by 2141
Abstract
(1) Background: KIR2DL4/KIR3DL3 are the framework genes present in all KIR haplotypes, with unique expression patterns being present only in women and CD56bright NK cells. KIR genes have a high degree of DNA sequence identity. Consequently, they are one of the most challenging [...] Read more.
(1) Background: KIR2DL4/KIR3DL3 are the framework genes present in all KIR haplotypes, with unique expression patterns being present only in women and CD56bright NK cells. KIR genes have a high degree of DNA sequence identity. Consequently, they are one of the most challenging genes for molecular detection—especially regarding expressions; (2) Methods: We developed an effective method to determine KIR3DL3/KIR2DL4 expressions based on a multiplex quantitative real-time Reverse transcription polymerase chain reaction (qRT-PCR )with fluorescent probes using NK92; (3) Results: Standardizations of the singleplex KIR2DL4 and KIR3DL3 were performed to evaluate the sensitivity and specificity for further development of the multiplex assay. The limit of detection was at 500 copies each. There was cross-amplification with the presence of related KIR genes at a level of 5 × 107 copies. This is not biologically significant because this high level of KIR expression has not been found in clinical samples. The multiplex assay was reproducible equivalent to its singleplex (KIR2DL4; R2 = 0.995, KIR3DL3; R2 = 0.996, but lower sensitivity of 103 copies). Furthermore, the validation of the developed method on samples of blood donors showed high sensitivity (100%) and specificity (99.9%); (4) Conclusions: The developed method is reliable and highly specific suitable for evaluation of the KIR2DL4/3DL3 mRNA expressions in further applications. Full article
(This article belongs to the Collection Biomarkers in Medicine)
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12 pages, 722 KiB  
Article
The Role of Fecal Calprotectin in Patients with Systemic Sclerosis and Small Intestinal Bacterial Overgrowth (SIBO)
by Beata Polkowska-Pruszyńska, Agnieszka Gerkowicz, Karol Rawicz-Pruszyński and Dorota Krasowska
Diagnostics 2020, 10(8), 587; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080587 - 13 Aug 2020
Cited by 10 | Viewed by 3236
Abstract
Fecal calprotectin (FC) is a quick, cost-effective, and noninvasive test, which is used to diagnose patients with active inflammatory bowel diseases (IBD). Recent studies suggest the possible predictive role of FC in the diagnosis of small intestinal bacterial overgrowth (SIBO) in patients with [...] Read more.
Fecal calprotectin (FC) is a quick, cost-effective, and noninvasive test, which is used to diagnose patients with active inflammatory bowel diseases (IBD). Recent studies suggest the possible predictive role of FC in the diagnosis of small intestinal bacterial overgrowth (SIBO) in patients with systemic sclerosis (SSc). This study aimed to assess the predictive value of FC in SSc patients and its’ possible use as a SIBO marker. A total of 40 SSc patients and 39 healthy volunteers were enrolled in the study. All subjects completed questionnaires evaluating gastrointestinal symptoms, FC measurements, and lactulose hydrogen breath test (LHBT) assessing SIBO presence. After rifaximin treatment, patients with SIBO underwent the same diagnostic procedures. Significantly higher FC values were observed in the study group compared to controls (97 vs. 20 μg/g; p < 0.0001) and in SSc patients diagnosed with SIBO compared to SSc patients without SIBO (206 vs. 24 μg/g; p = 0.0010). FC turned out to be a sensitive (94.12%) and specific (73.68%) marker in the detection of SIBO in patients with SSc (AUC = 0.82, 95% CI = 0.66–0.93; p < 0.0001). Our study suggests the potential value of FC in SSc in detecting gastrointestinal impairment and its promising role as an additional diagnostic tool for SIBO. Full article
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
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21 pages, 603 KiB  
Article
Identifying the Salient Genes in Microarray Data: A Novel Game Theoretic Model for the Co-Expression Network
by Papori Neog Bora, Vishwa Jyoti Baruah, Surajit Borkotokey, Loyimee Gogoi, Priyakshi Mahanta, Ankumon Sarmah, Rajnish Kumar and Stefano Moretti
Diagnostics 2020, 10(8), 586; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080586 - 13 Aug 2020
Cited by 2 | Viewed by 2966
Abstract
Microarray techniques are used to generate a large amount of information on gene expression. This information can be statistically processed and analyzed to identify the genes useful for the diagnosis and prognosis of genetic diseases. Game theoretic tools are applied to analyze the [...] Read more.
Microarray techniques are used to generate a large amount of information on gene expression. This information can be statistically processed and analyzed to identify the genes useful for the diagnosis and prognosis of genetic diseases. Game theoretic tools are applied to analyze the gene expression data. Gene co-expression networks are increasingly used to explore the system-level functionality of genes, where the roles of the genes in building networks in addition to their independent activities are also considered. In this paper, we develop a novel microarray network game by constructing a gene co-expression network and defining a game on this network. The notion of the Link Relevance Index (LRI) for this network game is introduced and characterized. The LRI successfully identifies the relevant cancer biomarkers. It also enables identifying salient genes in the colon cancer dataset. Network games can more accurately describe the interactions among genes as their basic premises are to consider the interactions among players prescribed by a network structure. LRI presents a tool to identify the underlying salient genes involved in cancer or other metabolic syndromes. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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13 pages, 710 KiB  
Article
Trends in Hospitalization of Patients with Potentially Serious Diseases Evaluated at a Quick Diagnosis Clinic
by Xavier Bosch, Andrea Ladino, Pedro Moreno-Lozano, Anna Jordán and Alfonso López-Soto
Diagnostics 2020, 10(8), 585; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080585 - 13 Aug 2020
Cited by 3 | Viewed by 1741
Abstract
Although quick diagnosis units (QDU) have become a cost-effective alternative to inpatient admission for diagnosis of potentially serious diseases, the rate of return hospitalizations among evaluated patients is unknown. This study examined the temporal trends in admissions of QDU patients through 15 years. [...] Read more.
Although quick diagnosis units (QDU) have become a cost-effective alternative to inpatient admission for diagnosis of potentially serious diseases, the rate of return hospitalizations among evaluated patients is unknown. This study examined the temporal trends in admissions of QDU patients through 15 years. Adult patients referred to QDU from 2004 to 2019 who were hospitalized between the first and last visit in the unit were eligible. Decisions about admissions were mainly based on the Appropriateness Evaluation Protocol and required independent validation by experienced clinicians using a customized tool. The final analysis included 825 patients. Patient characteristics and major reasons for admission were compared each year and linear trends were analyzed. Admission rates decreased from 7.2% in 2004–2005 to 4.3% in 2018–2019 (p < 0.0001). While a significant increasing trend was observed in the rate of admissions due to cancer-related complications (from 39.5% in 2004–2005 to 61.7% in 2018–2019; p < 0.0001), those due to anemia-related complications and scheduled invasive procedures experienced a significant downward trend. A likely explanation for these declining trends was the relocation of the unit to a new daycare center in 2013–2014 with recovery rooms and armchairs for IV treatments. The facts of this study could help in the provision of anticipatory guidance for the optimal management of patients at risk of clinical complications. Full article
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21 pages, 2010 KiB  
Article
Technique of Gene Expression Profiles Extraction Based on the Complex Use of Clustering and Classification Methods
by Sergii Babichev and Jiří Škvor
Diagnostics 2020, 10(8), 584; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080584 - 12 Aug 2020
Cited by 27 | Viewed by 2737
Abstract
In this paper, we present the results of the research concerning extraction of informative gene expression profiles from high-dimensional array of gene expressions considering the state of patients’ health using clustering method, ML-based binary classifiers and fuzzy inference system. Applying of the proposed [...] Read more.
In this paper, we present the results of the research concerning extraction of informative gene expression profiles from high-dimensional array of gene expressions considering the state of patients’ health using clustering method, ML-based binary classifiers and fuzzy inference system. Applying of the proposed stepwise procedure can allow us to extract the most informative genes taking into account both the subtypes of disease or state of the patient’s health for further reconstruction of gene regulatory networks based on the allocated genes and following simulation of the reconstructed models. We used the publicly available gene expressions data as the experimental ones which were obtained using DNA microarray experiments and contained two types of patients’ gene expression profiles—the patients with lung cancer tumor and healthy patients. The stepwise procedure of the data processing assumes the following steps—in the beginning, we reduce the number of genes by removing non-informative genes in terms of statistical criteria and Shannon entropy; then, we perform the stepwise hierarchical clustering of gene expression profiles at hierarchical levels from 1 to 10 using the SOTA (Self-Organizing Tree Algorithm) clustering algorithm with correlation distance metric. The quality of the obtained clustering was evaluated using the complex clustering quality criterion which is considered both the gene expression profiles distribution relative to center of the clusters where these gene expression profiles are allocated and the centers of the clusters distribution. The result of this stage execution was a selection of the optimal cluster at each of the hierarchical levels which corresponded to the minimum value of the quality criterion. At the next step, we have implemented a classification procedure of the examined objects using four well known binary classifiers—logistic regression, support-vector machine, decision trees and random forest classifier. The effectiveness of the appropriate technique was evaluated based on the use of ROC (Receiver Operating Characteristic) analysis using criteria, included as the components, the errors of both the first and the second kinds. The final decision concerning the extraction of the most informative subset of gene expression profiles was taken based on the use of the fuzzy inference system, the inputs of which are the results of the appropriate single classifiers operation and the output is the final solution concerning state of the patient’s health. To our mind, the implementation of the proposed stepwise procedure of the informative gene expression profiles extraction create the conditions for the increasing effectiveness of the further procedure of gene regulatory networks reconstruction and the following simulation of the reconstructed models considering the subtypes of the disease and/or state of the patient’s health. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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21 pages, 1632 KiB  
Review
Benefits and Risks of IgG Transplacental Transfer
by Anca Marina Ciobanu, Andreea Elena Dumitru, Nicolae Gica, Radu Botezatu, Gheorghe Peltecu and Anca Maria Panaitescu
Diagnostics 2020, 10(8), 583; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080583 - 12 Aug 2020
Cited by 43 | Viewed by 10172
Abstract
Maternal passage of immunoglobulin G (IgG) is an important passive mechanism for protecting the infant while the neonatal immune system is still immature and ineffective. IgG is the only antibody class capable of crossing the histological layers of the placenta by attaching to [...] Read more.
Maternal passage of immunoglobulin G (IgG) is an important passive mechanism for protecting the infant while the neonatal immune system is still immature and ineffective. IgG is the only antibody class capable of crossing the histological layers of the placenta by attaching to the neonatal Fc receptor expressed at the level of syncytiotrophoblasts, and it offers protection against neonatal infectious pathogens. In pregnant women with autoimmune or alloimmune disorders, or in those requiring certain types of biological therapy, transplacental passage of abnormal antibodies may cause fetal or neonatal harm. In this review, we will discuss the physiological mechanisms and benefits of transplacental transfer of maternal antibodies as well as pathological maternal situations where this system is hijacked, potentially leading to adverse neonatal outcomes. Full article
(This article belongs to the Special Issue Fetal Medicine)
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11 pages, 1284 KiB  
Case Report
Low-Grade Gliomas in Patients with Noonan Syndrome: Case-Based Review of the Literature
by Mariachiara Lodi, Luigi Boccuto, Andrea Carai, Antonella Cacchione, Evelina Miele, Giovanna Stefania Colafati, Francesca Diomedi Camassei, Luca De Palma, Alessandro De Benedictis, Elisabetta Ferretti, Giuseppina Catanzaro, Agnese Pò, Alessandro De Luca, Martina Rinelli, Francesca Romana Lepri, Emanuele Agolini, Marco Tartaglia, Franco Locatelli and Angela Mastronuzzi
Diagnostics 2020, 10(8), 582; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080582 - 12 Aug 2020
Cited by 19 | Viewed by 3940
Abstract
Noonan syndrome (NS) is a congenital autosomic dominant condition characterized by a variable spectrum from a clinical and genetical point of view. Germline mutations in more than ten genes involved in RAS–MAPK signal pathway have been demonstrated to cause the disease. An higher [...] Read more.
Noonan syndrome (NS) is a congenital autosomic dominant condition characterized by a variable spectrum from a clinical and genetical point of view. Germline mutations in more than ten genes involved in RAS–MAPK signal pathway have been demonstrated to cause the disease. An higher risk for leukemia and solid malignancies, including brain tumors, is related to NS. A review of the published literature concerning low grade gliomas (LGGs) in NS is presented. We described also a 13-year-old girl with NS associated with a recurrent mutation in PTPN11, who developed three different types of brain tumors, i.e., an optic pathway glioma, a glioneuronal neoplasm of the left temporal lobe and a cerebellar pilocytic astrocytoma. Molecular characterization of the glioneuronal tumor allowed to detect high levels of phosphorylated MTOR (pMTOR); therefore, a therapeutic approach based on an mTOR inhibitor (everolimus) was elected. The treatment was well tolerated and proved to be effective, leading to a stabilization of the tumor, which was surgical removed. The positive outcome of the present case suggests considering this approach for patients with RASopathies and brain tumors with hyperactivated MTOR signaling. Full article
(This article belongs to the Special Issue Advances in Pediatric Neuro-Oncology)
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27 pages, 525 KiB  
Review
A Systematic Review of Cerebral Functional Near-Infrared Spectroscopy in Chronic Neurological Diseases—Actual Applications and Future Perspectives
by Augusto Bonilauri, Francesca Sangiuliano Intra, Luigi Pugnetti, Giuseppe Baselli and Francesca Baglio
Diagnostics 2020, 10(8), 581; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080581 - 12 Aug 2020
Cited by 28 | Viewed by 4741
Abstract
Background: The management of people affected by age-related neurological disorders requires the adoption of targeted and cost-effective interventions to cope with chronicity. Therapy adaptation and rehabilitation represent major targets requiring long-term follow-up of neurodegeneration or, conversely, the promotion of neuroplasticity mechanisms. However, affordable [...] Read more.
Background: The management of people affected by age-related neurological disorders requires the adoption of targeted and cost-effective interventions to cope with chronicity. Therapy adaptation and rehabilitation represent major targets requiring long-term follow-up of neurodegeneration or, conversely, the promotion of neuroplasticity mechanisms. However, affordable and reliable neurophysiological correlates of cerebral activity to be used throughout treatment stages are often lacking. The aim of this systematic review is to highlight actual applications of functional Near-Infrared Spectroscopy (fNIRS) as a versatile optical neuroimaging technology for investigating cortical hemodynamic activity in the most common chronic neurological conditions. Methods: We reviewed studies investigating fNIRS applications in Parkinson’s Disease (PD), Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI) as those focusing on motor and cognitive impairment in ageing and Multiple Sclerosis (MS) as the most common chronic neurological disease in young adults. The literature search was conducted on NCBI PubMed and Web of Science databases by PRISMA guidelines. Results: We identified a total of 63 peer-reviewed articles. The AD spectrum is the most investigated pathology with 40 articles ranging from the traditional monitoring of tissue oxygenation to the analysis of functional resting-state conditions or cognitive functions by means of memory and verbal fluency tasks. Conversely, applications in PD (12 articles) and MS (11 articles) are mainly focused on the characterization of motor functions and their association with dual-task conditions. The most investigated cortical area is the prefrontal cortex, since reported to play an important role in age-related compensatory mechanism and neurofunctional changes associated to these chronic neurological conditions. Interestingly, only 9 articles applied a longitudinal approach. Conclusion: The results indicate that fNIRS is mainly employed for the cross-sectional characterization of the clinical phenotypes of these pathologies, whereas data on its utility for longitudinal monitoring as surrogate biomarkers of disease progression and rehabilitation effects are promising but still lacking. Full article
(This article belongs to the Special Issue Biomarkers of Vascular Diseases)
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8 pages, 2553 KiB  
Case Report
Primary Retroperitoneal Mucinous Carcinoma with Carcinosarcomatous Mural Nodules: A Case Report with Emphasis on Its Histological Features and Immunophenotype
by Sujin Park and Hyun-Soo Kim
Diagnostics 2020, 10(8), 580; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080580 - 11 Aug 2020
Cited by 7 | Viewed by 2299
Abstract
Mucinous carcinoma of the retroperitoneal origin is extremely rare. The existence of mural nodules in association with retroperitoneal mucinous carcinoma is an even rarer condition and indicates a worse prognosis. We present a case of primary retroperitoneal mucinous carcinoma with carcinosarcomatous mural nodules [...] Read more.
Mucinous carcinoma of the retroperitoneal origin is extremely rare. The existence of mural nodules in association with retroperitoneal mucinous carcinoma is an even rarer condition and indicates a worse prognosis. We present a case of primary retroperitoneal mucinous carcinoma with carcinosarcomatous mural nodules in a 27-year-old woman. We found a histological spectrum of mucinous tumors encompassing a mucinous borderline tumor, microinvasive carcinoma, and overt carcinoma with an expansile invasive pattern. The mural nodules had two morphological components. The sarcomatous component consisted of diffusely proliferating pleomorphic spindle or polygonal cells, while the carcinomatous component exhibited infiltrative glands showing a complex and cribriform architecture as well as distorted and poorly formed small glands. The carcinomatous component, comprising approximately 20% of the entire tumor volume of the mural nodules, was randomly distributed within the sarcomatous component. In a few areas, the carcinomatous component transformed and merged into the sarcomatous component. Immunostaining revealed a mutually exclusive pattern of expression of cytokeratin and vimentin in the carcinomatous and sarcomatous components, respectively, supporting the presence of a dual tumor cell population and confirming the diagnosis of carcinosarcoma. In summary, our case exhibited a histological spectrum of mucinous tumors and a metaplastic transformation from the carcinomatous to sarcomatous component in mural nodules. The immunostaining results of a mutually exclusive expression pattern of epithelial and mesenchymal markers confirmed the histological evidence of a dual population. Although rare, the specific histological features and immunophenotype are helpful in establishing the diagnosis of carcinosarcomatous mural nodules. Since the pathogenetic mechanism and treatment strategies for primary retroperitoneal mucinous carcinoma remain unclear, pathologists have an essential role to play in correctly evaluating the presence of mural nodules and determining their nature, to be later utilized to predict patients’ outcomes and provide appropriate treatment. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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17 pages, 1131 KiB  
Review
Surveillance of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease
by Yoshio Sumida, Masashi Yoneda, Yuya Seko, Hiroshi Ishiba, Tasuku Hara, Hidenori Toyoda, Satoshi Yasuda, Takashi Kumada, Hideki Hayashi, Takashi Kobayashi, Kento Imajo, Masato Yoneda, Toshifumi Tada, Takumi Kawaguchi, Yuichiro Eguchi, Satoshi Oeda, Hirokazu Takahashi, Eiichi Tomita, Takeshi Okanoue, Atsushi Nakajima and Japan Study Group of NAFLD (JSG-NAFLD)add Show full author list remove Hide full author list
Diagnostics 2020, 10(8), 579; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080579 - 10 Aug 2020
Cited by 24 | Viewed by 5398
Abstract
Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of hepatocellular carcinoma (HCC), liver-related mortality, and liver transplantation. There is sufficient epidemiological cohort data to recommend the surveillance of patients with NAFLD based upon the incidence of HCC. The American Gastroenterology Association [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of hepatocellular carcinoma (HCC), liver-related mortality, and liver transplantation. There is sufficient epidemiological cohort data to recommend the surveillance of patients with NAFLD based upon the incidence of HCC. The American Gastroenterology Association (AGA) expert review published in 2020 recommends that NAFLD patients with cirrhosis or advanced fibrosis estimated by non-invasive tests (NITs) consider HCC surveillance. NITs include the fibrosis-4 (FIB-4) index, the enhanced liver fibrosis (ELF) test, FibroScan, and MR elastography. The recommended surveillance modality is abdominal ultrasound (US), which is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with NAFLD. In NAFLD patients with a high likelihood of having an inadequate US, or if an US is attempted but inadequate, CT or MRI may be utilized. The GALAD score, consisting of age, gender, AFP, the lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and the protein induced by the absence of vitamin K or antagonist-II (PIVKA-II), can help identify a high risk of HCC in NAFLD patients. Innovative parameters, including a Mac-2 binding protein glycated isomer, type IV collagen 7S, free apoptosis inhibitor of the macrophage, and a combination of single nucleoside polymorphisms, are expected to be established. Considering the large size of the NAFLD population, optimal screening tests must meet several criteria, including high sensitivity, cost effectiveness, and availability. Full article
(This article belongs to the Special Issue Fatty Liver Disease: Diagnostic, Predictive and Prognostic Markers)
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18 pages, 1107 KiB  
Article
Evaluation of MicroRNAs as Non-Invasive Diagnostic Markers in Urinary Cells from Patients with Suspected Prostate Cancer
by Angelika Borkowetz, Andrea Lohse-Fischer, Jana Scholze, Ulrike Lotzkat, Christian Thomas, Manfred P. Wirth, Susanne Fuessel and Kati Erdmann
Diagnostics 2020, 10(8), 578; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080578 - 09 Aug 2020
Cited by 16 | Viewed by 2494
Abstract
Currently used tumor markers for early diagnosis of prostate cancer (PCa) are often lacking sufficient specificity and sensitivity. Therefore, the diagnostic potential of selected microRNAs in comparison to serum PSA levels and PSA density (PSAD) was explored. A panel of 12 PCa-associated microRNAs [...] Read more.
Currently used tumor markers for early diagnosis of prostate cancer (PCa) are often lacking sufficient specificity and sensitivity. Therefore, the diagnostic potential of selected microRNAs in comparison to serum PSA levels and PSA density (PSAD) was explored. A panel of 12 PCa-associated microRNAs was quantified by qPCR in urinary sediments from 50 patients with suspected PCa undergoing prostate biopsy, whereupon PCa was detected in 26 patients. Receiver operating characteristic (ROC) curve analyses revealed a potential for non-invasive urine-based PCa detection for miR-16 (AUC = 0.744, p = 0.012; accuracy = 76%) and miR-195 (AUC = 0.729, p = 0.017; accuracy = 70%). While serum PSA showed an insufficient diagnostic value (AUC = 0.564, p = 0.656; accuracy = 50%) in the present cohort, PSAD displayed an adequate diagnostic performance (AUC = 0.708, p = 0.031; accuracy = 70%). Noteworthy, the combination of PSAD with the best candidates miR-16 and miR-195 either individually or simultaneously improved the diagnostic power (AUC = 0.801–0.849, p < 0.05; accuracy = 76–90%). In the sub-group of patients with PSA ≤ 10 ng/mL (n = 34), an inadequate diagnostic power of PSAD alone (AUC = 0.595, p = 0.524; accuracy = 68%) was markedly surpassed by miR-16 and miR-195 individually as well as by their combination with PSAD (AUC = 0.772–0.882, p < 0.05; accuracy = 74–85%). These findings further highlight the potential of urinary microRNAs as molecular markers with high clinical performance. Overall, these results need to be validated in a larger patient cohort. Full article
(This article belongs to the Special Issue Diagnostic Biomarkers in Prostate Cancer 2020)
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26 pages, 7428 KiB  
Article
Melanoma Diagnosis Using Deep Learning and Fuzzy Logic
by Shubhendu Banerjee, Sumit Kumar Singh, Avishek Chakraborty, Atanu Das and Rajib Bag
Diagnostics 2020, 10(8), 577; https://0-doi-org.brum.beds.ac.uk/10.3390/diagnostics10080577 - 09 Aug 2020
Cited by 60 | Viewed by 5007
Abstract
Melanoma or malignant melanoma is a type of skin cancer that develops when melanocyte cells, damaged by excessive exposure to harmful UV radiations, start to grow out of control. Though less common than some other kinds of skin cancers, it is more dangerous [...] Read more.
Melanoma or malignant melanoma is a type of skin cancer that develops when melanocyte cells, damaged by excessive exposure to harmful UV radiations, start to grow out of control. Though less common than some other kinds of skin cancers, it is more dangerous because it rapidly metastasizes if not diagnosed and treated at an early stage. The distinction between benign and melanocytic lesions could at times be perplexing, but the manifestations of the disease could fairly be distinguished by a skilled study of its histopathological and clinical features. In recent years, deep convolutional neural networks (DCNNs) have succeeded in achieving more encouraging results yet faster and computationally effective systems for detection of the fatal disease are the need of the hour. This paper presents a deep learning-based ‘You Only Look Once (YOLO)’ algorithm, which is based on the application of DCNNs to detect melanoma from dermoscopic and digital images and offer faster and more precise output as compared to conventional CNNs. In terms with the location of the identified object in the cell, this network predicts the bounding box of the detected object and the class confidence score. The highlight of the paper, however, lies in its infusion of certain resourceful concepts like two phase segmentation done by a combination of the graph theory using minimal spanning tree concept and L-type fuzzy number based approximations and mathematical extraction of the actual affected area of the lesion region during feature extraction process. Experimented on a total of 20250 images from three publicly accessible datasets—PH2, International Symposium on Biomedical Imaging (ISBI) 2017 and The International Skin Imaging Collaboration (ISIC) 2019, encouraging results have been obtained. It achieved a Jac score of 79.84% on ISIC 2019 dataset and 86.99% and 88.64% on ISBI 2017 and PH2 datasets, respectively. Upon comparison of the pre-defined parameters with recent works in this area yielded comparatively superior output in most cases. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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