Diagnostics

18 pages, 1955 KiB

Open AccessReview

The Who, When, Why, and How of PET Amyloid Imaging in Management of Alzheimer’s Disease—Review of Literature and Interesting Images

by Subapriya Suppiah, Mellanie-Anne Didier and Sobhan Vinjamuri

Diagnostics 2019, 9(2), 65; https://doi.org/10.3390/diagnostics9020065 - 25 Jun 2019

Cited by 69 | Viewed by 7473

Abstract

Amyloid imaging using positron emission tomography (PET) has an emerging role in the management of Alzheimer’s disease (AD). The basis of this imaging is grounded on the fact that the hallmark of AD is the histological detection of beta amyloid plaques (Aβ) at [...] Read more.

Amyloid imaging using positron emission tomography (PET) has an emerging role in the management of Alzheimer’s disease (AD). The basis of this imaging is grounded on the fact that the hallmark of AD is the histological detection of beta amyloid plaques (Aβ) at post mortem autopsy. Currently, there are three FDA approved amyloid radiotracers used in clinical practice. This review aims to take the readers through the array of various indications for performing amyloid PET imaging in the management of AD, particularly using 18F-labelled radiopharmaceuticals. We elaborate on PET amyloid scan interpretation techniques, their limitations and potential improved specificity provided by interpretation done in tandem with genetic data such as apolipiprotein E (APO) 4 carrier status in sporadic cases and molecular information (e.g., cerebral spinal fluid (CSF) amyloid levels). We also describe the quantification methods such as the standard uptake value ratio (SUVr) method that utilizes various cutoff points for improved accuracy of diagnosing AD, such as a threshold of 1.122 (area under the curve 0.894), which has a sensitivity of 92.3% and specificity of 90.5%, whereas the cutoff points may be higher in APOE ε4 carriers (1.489) compared to non-carriers (1.313). Additionally, recommendations for future developments in this field are also provided. Full article

(This article belongs to the Special Issue Diagnosis of Dementia and Cognitive Impairment)

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1 pages, 146 KiB

Open AccessEditorial

Diagnostics Receives First Impact Factor

by Andreas Kjaer

Diagnostics 2019, 9(2), 64; https://doi.org/10.3390/diagnostics9020064 - 21 Jun 2019

Viewed by 3097

Abstract

It is with great pleasure we can announce that Diagnostics has received its first official impact factor, which has just been published in the 2018 edition of the Journal Citation Reports® [...] Full article

13 pages, 1483 KiB

Open AccessArticle

Decreased CTRP3 Plasma Concentrations Are Associated with Sepsis and Predict Mortality in Critically Ill Patients

by Eray Yagmur, Simone Otto, Ger H. Koek, Ralf Weiskirchen, Christian Trautwein, Alexander Koch and Frank Tacke

Diagnostics 2019, 9(2), 63; https://doi.org/10.3390/diagnostics9020063 - 21 Jun 2019

Cited by 6 | Viewed by 3470

Abstract

C1q/ tumor necrosis factor (TNF)-like protein 3 (CTRP3) represents a novel member of the adipokine family that exerts favorable metabolic actions in humans. However, the role of CTRP3 in critical illness and sepsis is currently unknown. Upon admission to the medical intensive care [...] Read more.

C1q/ tumor necrosis factor (TNF)-like protein 3 (CTRP3) represents a novel member of the adipokine family that exerts favorable metabolic actions in humans. However, the role of CTRP3 in critical illness and sepsis is currently unknown. Upon admission to the medical intensive care unit (ICU), we investigated CTRP3 plasma concentrations in 218 critically ill patients (145 with sepsis, 73 without sepsis). Results were compared with 66 healthy controls. CTRP3 plasma levels were significantly decreased in critically ill patients, when compared to healthy controls. In particular, low CTRP3 levels were highly associated with the presence of sepsis. CTRP3 levels were neither associated with obesity nor diabetes. In critically ill patients, CTRP3 plasma concentrations were inversely correlated with inflammatory cytokines and classical sepsis markers. Among a wide group of adipokines, CTRP3 only correlated with circulating resistin. Low CTRP3 plasma levels were associated with the overall mortality, and CTRP3 levels below 620.6 ng/mL indicated a particularly increased mortality risk in ICU patients. Our study demonstrates for the first time the role of circulating CTRP3 as a biomarker in critically ill patients that might facilitate diagnosis of sepsis as well as prognosis prediction. The association between low CTRP3 and increased inflammation warrants further pathophysiological investigations. Full article

(This article belongs to the Section Pathology and Molecular Diagnostics)

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11 pages, 907 KiB

Open AccessArticle

Solid Indeterminate Pulmonary Nodules of Less Than 300 mm³: Application of Different Volume Doubling Time Cut-offs in Clinical Practice

by Andrea Borghesi, Silvia Michelini, Alessandra Scrimieri, Salvatore Golemi and Roberto Maroldi

Diagnostics 2019, 9(2), 62; https://doi.org/10.3390/diagnostics9020062 - 20 Jun 2019

Cited by 10 | Viewed by 3455

Abstract

In the British Thoracic Society guidelines for incidental pulmonary nodules, volumetric analysis has become the recommended method for growth assessment in solid indeterminate pulmonary nodules (SIPNs) <300 mm³. In these guidelines, two different volume doubling time (VDT) cut-offs, 400 and 600 [...] Read more.

In the British Thoracic Society guidelines for incidental pulmonary nodules, volumetric analysis has become the recommended method for growth assessment in solid indeterminate pulmonary nodules (SIPNs) <300 mm³. In these guidelines, two different volume doubling time (VDT) cut-offs, 400 and 600 days, were proposed to differentiate benign from malignant nodules. The present study aims to evaluate the performance of these VDT cut-offs in a group of SIPNs <300 mm³ which were incidentally detected in a routine clinical setting. During a 7-year period, we retrospectively selected 60 patients with a single SIPN <300 mm³. For each SIPN, the volume and VDT were calculated using semiautomatic software throughout the follow-up period, and the performance of the 400- and 600-day VDT cut-offs was compared. In the selected sample, there were 38 benign and 22 malignant nodules. In this group of nodules, the sensitivity, negative predictive value and accuracy of the 600-day VDT cut-off were higher than those of the 400-day VDT cut-off. Therefore, in the management of SIPNs <300 mm³ which were incidentally detected in a clinical setting, the 600-day VDT cut-off was better at differentiating benign from malignant nodules than the 400-day VDT cut-off, by reducing the number of false negatives. Full article

(This article belongs to the Section Medical Imaging and Theranostics)

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14 pages, 440 KiB

Open AccessReview

Hand-Held Ultrasound Devices Compared with High-End Ultrasound Systems: A Systematic Review

by Alexander Rykkje, Jonathan Frederik Carlsen and Michael Bachmann Nielsen

Diagnostics 2019, 9(2), 61; https://doi.org/10.3390/diagnostics9020061 - 15 Jun 2019

Cited by 60 | Viewed by 7348

Abstract

The aim of this study was to review the scientific literature available on the comparison of hand-held ultrasound devices with high-end systems for abdominal and pleural applications. PubMed, Embase, Web of Science and Cochrane were searched following Preferred Reporting Items for Systematic Reviews [...] Read more.

The aim of this study was to review the scientific literature available on the comparison of hand-held ultrasound devices with high-end systems for abdominal and pleural applications. PubMed, Embase, Web of Science and Cochrane were searched following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Original research describing hand-held ultrasound devices compared with high-end systems was included and assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2. The search was limited to articles published since 1 January 2012. A total of 2486 articles were found and screened by title and abstract. A total of 16 articles were chosen for final review. All of the included articles showed good overall agreement between hand-held and high-end ultrasound systems. Strong correlations were found when evaluating ascites, hydronephrosis, pleural cavities, in detection of abdominal aortic aneurysms and for use with obstetric and gynaecological patients. Other articles found good agreement for cholelithiasis and for determining the best site for paracentesis. QUADAS-2 analysis suggested few risks of bias and almost no concerns regarding applicability. For distinct clinical questions, hand-held devices may be a valuable supplement to physical examination. However, evidence is inadequate, and more research is needed on the abdominal and pleural use of hand-held ultrasound with more standardised comparisons, using only blinded reviewers. Full article

(This article belongs to the Special Issue Ultrasound Imaging in Medicine 2019)

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13 pages, 1167 KiB

Open AccessReview

Diagnostic Performance of PET or PET/CT Using ¹⁸F-FDG Labeled White Blood Cells in Infectious Diseases: A Systematic Review and a Bivariate Meta-Analysis

by Marie Meyer, Nathalie Testart, Mario Jreige, Christel Kamani, Mohammed Moshebah, Barbara Muoio, Marie Nicod-Lalonde, Niklaus Schaefer, Luca Giovanella, John O. Prior and Giorgio Treglia

Diagnostics 2019, 9(2), 60; https://doi.org/10.3390/diagnostics9020060 - 15 Jun 2019

Cited by 15 | Viewed by 4745

Abstract

Background: Diagnostic performance of positron emission tomography using white blood cells labeled with fluorine-18-fluorodeoxyglucose (¹⁸F-FDG-WBC PET or PET/CT) in patients with suspicious infectious diseases has been evaluated in several studies; however, there is no consensus about the diagnostic accuracy of this [...] Read more.

Background: Diagnostic performance of positron emission tomography using white blood cells labeled with fluorine-18-fluorodeoxyglucose (¹⁸F-FDG-WBC PET or PET/CT) in patients with suspicious infectious diseases has been evaluated in several studies; however, there is no consensus about the diagnostic accuracy of this method. Therefore, a systematic review and meta-analysis was carried out on this topic. Methods: A comprehensive computer literature search screening PubMed/MEDLINE, Embase and Cochrane library databases through March 2019 was performed. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR−), and diagnostic odds ratio (DOR) of ¹⁸F-FDG-WBC PET or PET/CT in patients with infectious diseases were calculated. Results: Eight studies on the use of ¹⁸F-FDG-WBC PET or PET/CT in suspicious infectious diseases were discussed in the systematic review. The meta-analysis of seven studies (236 patients) provided these pooled results on a per patient-based analysis: sensitivity was 86.3% [95% confidence interval (95%CI) 75–92.9%], specificity 92% (95%CI 79.8–97.1%), LR+ 6.6 (95%CI: 3.1–14.1), LR− 0.2 (95%CI: 0.12–0.33), DOR 43.5 (95%CI: 12.2–155). A statistically significant heterogeneity was not detected. Conclusions: Despite limited literature data, ¹⁸F-FDG-WBC PET or PET/CT demonstrated a good diagnostic accuracy for the diagnosis of infectious diseases; nevertheless, larger studies are needed. Full article

(This article belongs to the Section Medical Imaging and Theranostics)

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19 pages, 5218 KiB

Open AccessArticle

Expressions of HLA Class II Genes in Cutaneous Melanoma Were Associated with Clinical Outcome: Bioinformatics Approaches and Systematic Analysis of Public Microarray and RNA-Seq Datasets

by Yang-Yi Chen, Wei-An Chang, En-Shyh Lin, Yi-Jen Chen and Po-Lin Kuo

Diagnostics 2019, 9(2), 59; https://doi.org/10.3390/diagnostics9020059 - 12 Jun 2019

Cited by 12 | Viewed by 6885

Abstract

Major histocompatibility complex (MHC) class II molecules, encoded by human leukocyte antigen (HLA) class II genes, play important roles in antigen presentation and initiation of immune responses. However, the correlation between HLA class II gene expression level and patient survival and disease progression [...] Read more.

Major histocompatibility complex (MHC) class II molecules, encoded by human leukocyte antigen (HLA) class II genes, play important roles in antigen presentation and initiation of immune responses. However, the correlation between HLA class II gene expression level and patient survival and disease progression in cutaneous melanoma is still under investigation. In the present study, we analyzed microarray and RNA-Seq data of cutaneous melanoma from The Cancer Genome Atlas (TCGA) using different bioinformatics tools. Survival analysis revealed higher expression level of HLA class II genes in cutaneous melanoma, especially HLA-DP and -DR, was significantly associated with better overall survival. Furthermore, the expressions of HLA class II genes were most closely associated with survival in cutaneous melanoma as compared with other cancer types. The expression of HLA class II co-expressed genes, which were found to associate with antigen processing, immune response, and inflammatory response, was also positively associated with overall survival in cutaneous melanoma. Therefore, the results indicated that increased HLA class II expression may contribute to enhanced anti-tumor immunity and related inflammatory response via presenting tumor antigens to the immune system. The expression pattern of HLA class II genes may serve as a prognostic biomarker and therapeutic targets in cutaneous melanoma. Full article

(This article belongs to the Section Pathology and Molecular Diagnostics)

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Graphical abstract

9 pages, 751 KiB

Open AccessArticle

Codex (Cognitive Disorders Examination) Decision Tree Modified for the Detection of Dementia and MCI

by Besa Ziso and Andrew J. Larner

Diagnostics 2019, 9(2), 58; https://doi.org/10.3390/diagnostics9020058 - 01 Jun 2019

Cited by 7 | Viewed by 4588

Abstract

Many cognitive screening instruments are available to assess patients with cognitive symptoms in whom a diagnosis of dementia or mild cognitive impairment is being considered. Most are quantitative scales with specified cut-off values. In contrast, the cognitive disorders examination or Codex is a [...] Read more.

Many cognitive screening instruments are available to assess patients with cognitive symptoms in whom a diagnosis of dementia or mild cognitive impairment is being considered. Most are quantitative scales with specified cut-off values. In contrast, the cognitive disorders examination or Codex is a two-step decision tree which incorporates components from the Mini-Mental State Examination (MMSE) (three word recall, spatial orientation) along with a simplified clock drawing test to produce categorical outcomes defining the probability of dementia diagnosis and, by implication, directing clinician response (reassurance, monitoring, further investigation, immediate treatment). Codex has been shown to have high sensitivity and specificity for dementia diagnosis but is less sensitive for the diagnosis of mild cognitive impairment (MCI). We examined minor modifications to the Codex decision tree to try to improve its sensitivity for the diagnosis of MCI, based on data extracted from studies of two other cognitive screening instruments, the Montreal Cognitive Assessment and Free-Cog, which are more stringent than MMSE in their tests of delayed recall. Neither modification proved of diagnostic value for mild cognitive impairment. Possible explanations for this failure are considered. Full article

(This article belongs to the Special Issue Diagnosis of Dementia and Cognitive Impairment)

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6 pages, 4610 KiB

Open AccessCase Report

Detecting Synchronous Parathyroid Adenoma and False-Positive Findings on Technetium-99m MIBI Single Photon-Emission Computed Tomography/Computed Tomography

by Ji Young Lee, Hee-Sung Song, Jae Hyuck Choi, Chang Lim Hyun, Sang Ah Lee, Joon-Hyouk Choi and Seokjae Lee

Diagnostics 2019, 9(2), 57; https://doi.org/10.3390/diagnostics9020057 - 01 Jun 2019

Cited by 3 | Viewed by 4468

Abstract

Technetium (Tc)-99m-methoxyisobutylisonitrile (MIBI) single photon-emission computed tomography/computed tomography (SPECT/CT) is now being used increasingly for preoperative localization of parathyroid adenomas. Tc-99m-MIBI scintigraphy in a 52-year-old man with a diagnosis of primary hyperparathyroidism revealed two focal areas with retention of radioactivity in the left [...] Read more.

Technetium (Tc)-99m-methoxyisobutylisonitrile (MIBI) single photon-emission computed tomography/computed tomography (SPECT/CT) is now being used increasingly for preoperative localization of parathyroid adenomas. Tc-99m-MIBI scintigraphy in a 52-year-old man with a diagnosis of primary hyperparathyroidism revealed two focal areas with retention of radioactivity in the left lobe of the thyroid gland on the delayed phase of MIBI SPECT/CT but no significant focal radioactive uptake on MIBI planar images. The patient subsequently underwent left partial parathyroidectomy. Histological analysis identified one lesion to be thyroid hyperplasia and the other to be parathyroid adenoma. This case demonstrates the value of MIBI SPECT/CT for localization of a parathyroid lesion when compared with planar images and that false-positive findings can lead to misdiagnosis in a patient with coexisting thyroid disease. An appropriate diagnostic work-up that includes Tc-99m MIBI SPECT/CT in addition to ultrasonography is helpful for an accurate diagnosis in patients with concomitant thyroid disease. Full article

(This article belongs to the Section Medical Imaging and Theranostics)

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5 pages, 195 KiB

Open AccessCommunication

Feasibility of Direct Sputum Molecular Testing for Drug Resistance as Part of Tuberculosis Clinical Trials Eligibility Screening

by Narges Alipanah, Priya B. Shete, Hanh Nguyen, Nhung Viet Nguyen, Lien Luu, Thuong Pham, Hung Nguyen, Phuong Nguyen, Minh Chi Tran, Nam Pham, Ha Phan, Patrick P.J. Phillips, Adithya Cattamanchi and Payam Nahid

Diagnostics 2019, 9(2), 56; https://doi.org/10.3390/diagnostics9020056 - 30 May 2019

Cited by 4 | Viewed by 3714

Abstract

A rapid diagnosis of drug-resistant tuberculosis (TB) is critical for early initiation of effective therapy. Molecular testing with line probe assays (MTBDRplus and MTBDRsl) on culture isolates has been available for some time and significantly reduces the time to diagnosis [...] Read more.

A rapid diagnosis of drug-resistant tuberculosis (TB) is critical for early initiation of effective therapy. Molecular testing with line probe assays (MTBDRplus and MTBDRsl) on culture isolates has been available for some time and significantly reduces the time to diagnosis of drug resistance. However, routine use of this test directly on sputum is less common. As part of enrollment screening procedures for tuberculosis clinical trials conducted in Hanoi, Vietnam, we evaluated the feasibility and performance of line probe assay (LPA) testing directly on sputum samples from 315 participants with no prior history of TB treatment. Test performance characteristics for the detection of rifampin (RIF) and isoniazid (INH) drug resistance as compared to culture-based drug susceptibility testing (DST) reference standard were calculated. LPA demonstrated high sensitivity and specificity for the diagnosis of drug resistance. Scaling up molecular testing on sputum as part of time-sensitive clinical trial screening procedures in high TB burden settings is feasible and will reduce both time to initiation of appropriate therapy and the risk of late exclusions due to microbiologic ineligibility. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Tuberculosis)

29 pages, 402 KiB

Open AccessReview

PARP Inhibitors in Ovarian Cancer: The Route to “Ithaca”

by Stergios Boussios, Afroditi Karathanasi, Deirdre Cooke, Cherie Neille, Agne Sadauskaite, Michele Moschetta, Nikolaos Zakynthinakis-Kyriakou and Nicholas Pavlidis

Diagnostics 2019, 9(2), 55; https://doi.org/10.3390/diagnostics9020055 - 18 May 2019

Cited by 52 | Viewed by 7040

Abstract

Poly (ADP-ribose) polymerase (PARP) inhibitors are a novel class of therapeutic agents that target tumors with deficiencies in the homologous recombination DNA repair pathway. Genomic instability characterizes high-grade serous ovarian cancer (HGSOC), with one half of all tumors displaying defects in the important [...] Read more.

Poly (ADP-ribose) polymerase (PARP) inhibitors are a novel class of therapeutic agents that target tumors with deficiencies in the homologous recombination DNA repair pathway. Genomic instability characterizes high-grade serous ovarian cancer (HGSOC), with one half of all tumors displaying defects in the important DNA repair pathway of homologous recombination. Early studies have shown significant efficacy for PARP inhibitors in patients with germline breast related cancer antigens 1 and 2 (BRCA1/2) mutations. It has also become evident that BRCA wild-type patients with other defects in the homologous recombination repair pathway benefit from this treatment. Companion homologous recombination deficiency (HRD) scores are being developed to guide the selection of patients that are most likely to benefit from PARP inhibition. The choice of which PARP inhibitor is mainly based upon the number of prior therapies and the presence of a BRCA mutation or HRD. The identification of patients most likely to benefit from PARP inhibitor therapy in view of HRD and other biomarker assessments is still challenging. The aim of this review is to describe the current evidence for PARP inhibitors in ovarian cancer, their mechanism of action, and the outstanding issues, including the rate of long-term toxicities and the evolution of resistance. Full article

(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)

6 pages, 196 KiB

Open AccessCommunication

Ultrasound-Guided Core Needle Biopsies of Breast Invasive Carcinoma: When One Core is Sufficient for Pathologic Diagnosis and Assessment of Hormone Receptor and HER2 Status

by Hsin-Ni Li and Chuan-Han Chen

Diagnostics 2019, 9(2), 54; https://doi.org/10.3390/diagnostics9020054 - 13 May 2019

Cited by 1 | Viewed by 3203

Abstract

Ultrasound (US)-guided core needle biopsy is considered the gold standard procedure with regard to preoperative diagnosis of breast carcinomas. However, there is no clear standard for the number of cores considered to be sufficient for pathologic evaluation, including the expression of surface hormone [...] Read more.

Ultrasound (US)-guided core needle biopsy is considered the gold standard procedure with regard to preoperative diagnosis of breast carcinomas. However, there is no clear standard for the number of cores considered to be sufficient for pathologic evaluation, including the expression of surface hormone markers and HER2 status. Images and pathologic slides demonstrating breast invasive carcinoma from a single institution were thus retrospectively reviewed over a 12 month period. The results indicated that one core is sufficient for the diagnosis of invasive carcinomas, along with a reliable assessment of hormone receptor and HER2 status in many cases. The option of applying additional cores is recommended for some cases. Full article

(This article belongs to the Section Pathology and Molecular Diagnostics)

5 pages, 2146 KiB

Open AccessCase Report

Giant Hepatic Artery Aneurysm

by Farid Gossili and Helle D. Zacho

Diagnostics 2019, 9(2), 53; https://doi.org/10.3390/diagnostics9020053 - 13 May 2019

Cited by 3 | Viewed by 4507

Abstract

Hepatic artery aneurysm (HAA) is the second most common type of visceral aneurysm. Giant HAAs (larger than 5 cm) are very rare. We present a case of an asymptomatic giant hepatic artery aneurysm (diameter 10.7 cm) discovered as an incidental finding on an [...] Read more.

Hepatic artery aneurysm (HAA) is the second most common type of visceral aneurysm. Giant HAAs (larger than 5 cm) are very rare. We present a case of an asymptomatic giant hepatic artery aneurysm (diameter 10.7 cm) discovered as an incidental finding on an ¹⁸F-fludeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) scan of a patient admitted for pretreatment staging of urothelial carcinoma. Full article

(This article belongs to the Special Issue Atherosclerosis and Vascular Imaging)

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33 pages, 713 KiB

Open AccessArticle

Framework for the Development of Data-Driven Mamdani-Type Fuzzy Clinical Decision Support Systems

by Yamid Fabián Hernández-Julio, Martha Janeth Prieto-Guevara, Wilson Nieto-Bernal, Inés Meriño-Fuentes and Alexander Guerrero-Avendaño

Diagnostics 2019, 9(2), 52; https://doi.org/10.3390/diagnostics9020052 - 09 May 2019

Cited by 26 | Viewed by 6150

Abstract

Clinical decision support systems (CDSS) have been designed, implemented, and validated to help clinicians and practitioners for decision-making about diagnosing some diseases. Within the CDSSs, we can find Fuzzy inference systems. For the reasons above, the objective of this study was to design, [...] Read more.

Clinical decision support systems (CDSS) have been designed, implemented, and validated to help clinicians and practitioners for decision-making about diagnosing some diseases. Within the CDSSs, we can find Fuzzy inference systems. For the reasons above, the objective of this study was to design, to implement, and to validate a methodology for developing data-driven Mamdani-type fuzzy clinical decision support systems using clusters and pivot tables. For validating the proposed methodology, we applied our algorithms on five public datasets including Wisconsin, Coimbra breast cancer, wart treatment (Immunotherapy and cryotherapy), and caesarian section, and compared them with other related works (Literature). The results show that the Kappa Statistics and accuracies were close to 1.0% and 100%, respectively for each output variable, which shows better accuracy than some literature results. The proposed framework could be considered as a deep learning technique because it is composed of various processing layers to learn representations of data with multiple levels of abstraction. Full article

(This article belongs to the Section Point-of-Care Diagnostics and Devices)

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10 pages, 1390 KiB

Open AccessArticle

MACE for Diagnosis of Dementia and MCI: Examining Cut-Offs and Predictive Values

by Andrew J. Larner

Diagnostics 2019, 9(2), 51; https://doi.org/10.3390/diagnostics9020051 - 06 May 2019

Cited by 20 | Viewed by 4572

Abstract

The definition of test cut-offs is a critical determinant of many paired and unitary measures of diagnostic or screening test accuracy, such as sensitivity and specificity, positive and negative predictive values, and correct classification accuracy. Revision of test cut-offs from those defined in [...] Read more.

The definition of test cut-offs is a critical determinant of many paired and unitary measures of diagnostic or screening test accuracy, such as sensitivity and specificity, positive and negative predictive values, and correct classification accuracy. Revision of test cut-offs from those defined in index studies is frowned upon as a potential source of bias, seemingly accepting any biases present in the index study, for example related to sample bias. Data from a large pragmatic test accuracy study examining the Mini-Addenbrooke’s Cognitive Examination (MACE) were interrogated to determine optimal test cut-offs for the diagnosis of dementia and mild cognitive impairment (MCI) using either the maximal Youden index or the maximal correct classification accuracy. Receiver operating characteristic (ROC) and precision recall (PR) curves for dementia and MCI were also plotted, and MACE predictive values across a range of disease prevalences were calculated. Optimal cut-offs were found to be a point lower than those defined in the index study. MACE had good metrics for the area under the ROC curve and for the effect size (Cohen’s d) for both dementia and MCI diagnosis, but PR curves suggested the superiority for MCI diagnosis. MACE had high negative predictive value at all prevalences, suggesting that a MACE test score above either cut-off excludes dementia and MCI in any setting. Full article

(This article belongs to the Special Issue Diagnosis of Dementia and Cognitive Impairment)

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9 pages, 29542 KiB

Open AccessArticle

Four Virtual-Reality Simulators for Diagnostic Abdominal Ultrasound Training in Radiology

by Mia Louise Østergaard, Lars Konge, Niklas Kahr, Elisabeth Albrecht-Beste, Michael Bachmann Nielsen and Kristina Rue Nielsen

Diagnostics 2019, 9(2), 50; https://doi.org/10.3390/diagnostics9020050 - 06 May 2019

Cited by 19 | Viewed by 5965

Abstract

Ultrasound exams need skilled examiners, and simulation-based training could provide standardized and safe skill training. This study aims to give an overview of different types of virtual-reality simulators for use in abdominal diagnostic ultrasound training in radiology. Fifteen specialized radiologists and radiological residents [...] Read more.

Ultrasound exams need skilled examiners, and simulation-based training could provide standardized and safe skill training. This study aims to give an overview of different types of virtual-reality simulators for use in abdominal diagnostic ultrasound training in radiology. Fifteen specialized radiologists and radiological residents were presented with two similar cases on four different simulators for abdominal ultrasound training. A feedback sheet for each individual simulator and for an overall comparison was filled out by all participants. All means of scores were compared, and simulators were ranked from least to most favorable. One simulator was ranked most favorable in seven out of nine questions, but none of the mean scores had statistically significant differences. All simulators were recommended for training radiologists, and all simulators were perceived to benefit trainees more than experienced ultra-sonographers. Full article

(This article belongs to the Special Issue Ultrasound Imaging in Medicine 2019)

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17 pages, 2425 KiB

Open AccessReview

Current and Emerging Methods of Antibiotic Susceptibility Testing

by Zeeshan A. Khan, Mohd F. Siddiqui and Seungkyung Park

Diagnostics 2019, 9(2), 49; https://doi.org/10.3390/diagnostics9020049 - 03 May 2019

Cited by 222 | Viewed by 35898

Abstract

Antibiotic susceptibility testing (AST) specifies effective antibiotic dosage and formulates a profile of empirical therapy for the proper management of an individual patient’s health against deadly infections. Therefore, rapid diagnostic plays a pivotal role in the treatment of bacterial infection. In this article, [...] Read more.

Antibiotic susceptibility testing (AST) specifies effective antibiotic dosage and formulates a profile of empirical therapy for the proper management of an individual patient’s health against deadly infections. Therefore, rapid diagnostic plays a pivotal role in the treatment of bacterial infection. In this article, the authors review the socio-economic burden and emergence of antibiotic resistance. An overview of the phenotypic, genotypic, and emerging techniques for AST has been provided and discussed, highlighting the advantages and limitations of each. The historical perspective on conventional methods that have paved the way for modern AST like disk diffusion, Epsilometer test (Etest), and microdilution, is presented. Several emerging methods, such as microfluidic-based optical and electrochemical AST have been critically evaluated. Finally, the challenges related with AST and its outlook in the future are presented. Full article

(This article belongs to the Special Issue Diagnosis of Bacterial Pathogens)

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15 pages, 6470 KiB

Open AccessArticle

HAMP Downregulation Contributes to Aggressive Hepatocellular Carcinoma via Mechanism Mediated by Cyclin4-Dependent Kinase-1/STAT3 Pathway

by Ying Shen, Xin Li, Yanwei Su, Shaikh Atik Badshah, Bin Zhang, Yanru Xue and Peng Shang

Diagnostics 2019, 9(2), 48; https://doi.org/10.3390/diagnostics9020048 - 30 Apr 2019

Cited by 21 | Viewed by 4423

Abstract

Background: Hepcidin encoded by HAMP is vital to regulating proliferation, metastasis, and migration. Hepcidin is secreted specifically by the liver. This study sought to examine the functional role of hepcidin in hepatocellular carcinoma (HCC). Methods: Data in the Cancer Genome Atlas database was [...] Read more.

Background: Hepcidin encoded by HAMP is vital to regulating proliferation, metastasis, and migration. Hepcidin is secreted specifically by the liver. This study sought to examine the functional role of hepcidin in hepatocellular carcinoma (HCC). Methods: Data in the Cancer Genome Atlas database was used to analyze HAMP expression as it relates to HCC prognosis. We then used the 5-ethynyl-20-deoxyuridine (EdU) incorporation assay, transwell assay, and flow cytometric analysis, respectively, to assess proliferation, migration, and the cell cycle. Gene set enrichment analysis (GSEA) was used to find pathways affected by HAMP. Results: HAMP expression was lower in hepatocellular carcinoma samples compared with adjacent normal tissue controls. Low HAMP expression was linked with a higher rate of metastasis and poor disease-free status. Downregulation of HAMP induced SMMC-7721 and HepG-2 cell proliferation and promoted their migration. HAMP could affect the cell cycle pathway and Western blotting, confirming that reduced HAMP levels activated cyclin-dependent kinase-1/stat 3 pathway. Conclusion: Our findings indicate that HAMP functions as a tumor suppressor gene. The role of HAMP in cellular proliferation and metastasis is related to cell cycle checkpoints. HAMP could be considered as a diagnostic biomarker and targeted therapy in HCC. Full article

(This article belongs to the Section Pathology and Molecular Diagnostics)

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11 pages, 256 KiB

Open AccessArticle

Health Predictors of Pain in Elderly—A Serbian Population-Based Study

by Milena Kostadinovic, Dejan Nikolic, Dragana Cirovic, Ljubica Konstantinovic, Milica Mitrovic-Jovanovic, Natasa Radosavljevic, Mirjana Kocic, Vesna Bjegovic-Mikanovic and Milena Santric Milicevic

Diagnostics 2019, 9(2), 47; https://doi.org/10.3390/diagnostics9020047 - 26 Apr 2019

Cited by 2 | Viewed by 3743

Abstract

Objectives: The aim of our study was to evaluate the association of health factors with the presence and different degrees of pain in elderly above 65 years of life. Methods: The population-based study included 3540 individuals above 65 years of age of life [...] Read more.

Objectives: The aim of our study was to evaluate the association of health factors with the presence and different degrees of pain in elderly above 65 years of life. Methods: The population-based study included 3540 individuals above 65 years of age of life from twofold stratified household sample representative for Serbia, during 2013 (the average age 73.9 ± 6.3 years; average Body Mass Index was 26.7 ± 4.4, females 56.8%, living with partner 55.5%, with primary education 55.3%, with poor wealth index 55.8% and from rural settings 46.2%). As health predictors of pain, we analyzed further health parameters: self-perceived general health, long-lasting health problems, diagnosed pulmonary disease, cardiovascular disease, musculoskeletal disease, diabetes, hyperlipidemia, hypertension and other chronic diseases. Pain domain of SF-36 version 2.0 was used for pain assessment. Results: Significant health predictors of pain were: self-perceived general health (OR 2.28), where bad perception of self-perceived general health in our study had greater risk of pain with higher degree of severity; long-lasting health problems (OR 1.60), where elderly with long-lasting health problems had almost twice the risk of moderate degree of pain, and above twice the risk for severe degree of pain; pulmonary disease (OR 1.38); musculoskeletal disease (OR 2.98) and other chronic diseases (OR 1.71). The presence of musculoskeletal disease increases the risk for pain, even more than double in severe versus mild degrees of pain. Conclusion: Bad self-perceived general health, long-lasting health problems, pulmonary, musculoskeletal diseases, cardiovascular disease and other chronic disease were significant health-related predictors of various degrees of pain in elderly. Full article

9 pages, 768 KiB

Open AccessArticle

Prostate Artery Embolization for Lower Urinary Tract Symptoms in Men Unfit for Surgery

by Brian Malling, Lars Lönn, Ruben Juhl Jensen, Mats Lindh, Susanne Frevert, Klaus Brasso and Martin Andreas Røder

Diagnostics 2019, 9(2), 46; https://doi.org/10.3390/diagnostics9020046 - 25 Apr 2019

Cited by 18 | Viewed by 4726

Abstract

Nearly one in three men develop lower urinary tract symptoms (LUTS) and 10% clinically progress despite medication. Transurethral resection of the prostate (TURP) is the reference standard for symptoms refractory to medical treatment. However, some patients cannot tolerate TURP for medical (e.g., comorbidity) [...] Read more.

Nearly one in three men develop lower urinary tract symptoms (LUTS) and 10% clinically progress despite medication. Transurethral resection of the prostate (TURP) is the reference standard for symptoms refractory to medical treatment. However, some patients cannot tolerate TURP for medical (e.g., comorbidity) or technical (e.g., large prostate) reasons. This study estimated the safety and effect of prostate artery embolization (PAE) in men unfit for surgery. A prospective, single-centre trial including men with LUTS or urinary retention secondary to benign prostatic hyperplasia (BPH) who were unfit for surgery. The primary objective was to treat urinary retention and LUTS. Outcome measures included International Prostate Symptom Score (IPSS), quality of life (IPSS-QoL), International Index of Erectile Function (IIEF-5), prostate volume (PV), prostate-specific antigen (PSA), peak void flow (Qmax), post-void residual (PVR), and complications. A p-value < 0.05 was considered statistically significant. Eleven consecutive patients with a mean age of 75.2 (SD ± 8.2) underwent PAE. Catheter removal was successful in 60%. IPSS-QoL improved 4.5 points (95% CI: −5.6; −3.4), and PV was reduced by 26.2 cm³ (95% CI: −50.9; −2.3). None of the remaining outcomes changed. No major complications occurred. PAE was effective and safe for LUTS and urinary retention associated with BPH in men unfit for surgery. Full article

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14 pages, 2876 KiB

Open AccessTechnical Note

Enhancement of Chest Radiograph in Emergency Intensive Care Unit by Means of Reverse Anisotropic Diffusion-Based Unsharp Masking Model

by Sheng Chen and Yuantao Cai

Diagnostics 2019, 9(2), 45; https://doi.org/10.3390/diagnostics9020045 - 24 Apr 2019

Cited by 4 | Viewed by 4094

Abstract

In intensive care units (ICUs), supporting devices play an important role, and the placement of these devices must be accurate, such as catheters and tubes. Taking portable chest radiograph (CXRs) for patients in ICU is a standard procedure. However, non-optimized exposure settings and [...] Read more.

In intensive care units (ICUs), supporting devices play an important role, and the placement of these devices must be accurate, such as catheters and tubes. Taking portable chest radiograph (CXRs) for patients in ICU is a standard procedure. However, non-optimized exposure settings and misaligned body positions usually mean that portable CXRs are not in acceptable working condition. The purpose of this study was to enhance ICU CXRs to assist radiologists in the positioning of endotracheal, feeding, and nasogastric tubes in ICU patients. The unsharp masking model (USM) was a classical image enhancement technique. Because of the isotropic diffusion filter applied in this model, USM enhanced the edge information and noise simultaneously. In this paper, we proposed a reverse anisotropic diffusion (RAD)-based USM technique for enhancement of line structures in ICU CXRs. First, a RAD algorithm was applied to replace the Gaussian filter in the classical USM. The RAD algorithm only produced a smoothed image, in which edge information was smoothed while the noise was preserved. Then, the smoothed image was subtracted from the original image to produce the unsharp mask whereby only the edges were retained. Consequently, only edge information was enhanced in the final enhanced image by using the RAD-based USM model. The proposed method was tested for 87 ICU CXRs and the findings indicate that this approach can enhance image edges efficiently while suppressing noise. Full article

(This article belongs to the Section Medical Imaging and Theranostics)

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15 pages, 1329 KiB

Open AccessArticle

Preimplantation Genetic Diagnosis of Neurodegenerative Diseases: Review of Methodologies and Report of Our Experience as a Regional Reference Laboratory

by Chun-Hua Liao, Ming-Yuh Chang, Gwo-Chin Ma, Shun-Ping Chang, Chi-Fang Lin, Wen-Hsiang Lin, Hsin-Fu Chen, Shee-Uan Chen, Yi-Chung Lee, Chi-Chao Chao, Ming Chen and Sung-Tsang Hsieh

Diagnostics 2019, 9(2), 44; https://doi.org/10.3390/diagnostics9020044 - 23 Apr 2019

Cited by 7 | Viewed by 4826

Abstract

Preimplantation genetic diagnosis (PGD) has become a crucial approach in helping carriers of inherited disorders to give birth to healthy offspring. In this study, we review PGD methodologies and explore the use of amplification refractory mutation system quantitative polymerase chain reaction (ARMS-qPCR) and/or [...] Read more.

Preimplantation genetic diagnosis (PGD) has become a crucial approach in helping carriers of inherited disorders to give birth to healthy offspring. In this study, we review PGD methodologies and explore the use of amplification refractory mutation system quantitative polymerase chain reaction (ARMS-qPCR) and/or linkage analysis for PGD in neurodegenerative diseases that are clinically relevant with typical features, such as late onset, and which are severely debilitating. A total of 13 oocyte retrieval cycles were conducted in 10 cases with various neurodegenerative diseases. Among the 59 embryos analyzed, 49.2% (29/59) were unaffected and 50.8% (30/59) were affected. Of the 12 embryo transfer cycles, three resulted in pregnancy, and all pregnancies were delivered. The implantation rate and livebirth rate were 23.1% (3/13) per oocyte retrieval cycle and 25.0% (3/12) per embryo transfer cycle. Allele dropout (ADO) was noted in two embryos that were classified as unaffected by ARMS-qPCR but were evidenced as affected after prenatal diagnosis, rendering the false negative rate as 6.3% (2/32). Four among the 13 cycles underwent PGD by ARMS-qPCR coupled with linkage analysis, and all were correctly diagnosed. We conclude that PGD by ARMS-qPCR and/or linkage analysis is a feasible strategy, whereas ADO is a concern when ARMS-qPCR is used as the sole technology in PGD, especially in autosomal dominant diseases. Full article

(This article belongs to the Section Pathology and Molecular Diagnostics)

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8 pages, 422 KiB

Open AccessArticle

Association of Non-Carious Cervical Lesions with Oral Hygiene Habits and Dynamic Occlusal Parameters

by Satheesh B. Haralur, Abdulrahman Saad Alqahtani, Mohammed Shaya AlMazni and Mohammad Khalid Alqahtani

Diagnostics 2019, 9(2), 43; https://doi.org/10.3390/diagnostics9020043 - 12 Apr 2019

Cited by 13 | Viewed by 6453

Abstract

Dentists routinely encounter non-carious cervical lesions (NCCLs) in daily clinical practices. The dental literature is contradictory regarding the occlusal etiology of NCCLs. NCCL is defined as the loss of dental structure at the cemento–enamel junction, with no association of bacteria. The aim of [...] Read more.

Dentists routinely encounter non-carious cervical lesions (NCCLs) in daily clinical practices. The dental literature is contradictory regarding the occlusal etiology of NCCLs. NCCL is defined as the loss of dental structure at the cemento–enamel junction, with no association of bacteria. The aim of this study was to evaluate the association of dynamic occlusal factors and dental hygiene practices with NCCLs. In total, 100 participants were selected by the random stratified sampling method, 50 each for control and NCCL groups. Information regarding oral hygiene practices, including frequency, duration, force, and technique of brushing, was recorded. Dynamic occlusal parameters like initial contact, occlusion time (OT), disocclusion time (DT), and center of force were recorded with T-scan analysis. The obtained data were analyzed with Pearson’s correlation and binary logistic regression. We found that 68% of participants in the NCCL group and 31% in the control group utilized the horizontal brushing technique; 46% of NCCL group participants used hard brush against 7% of participants in the control group. The mean OT was 0.727 and 0.516 s for NCCL and control groups, respectively. The OT and left and right lateral DT were strongly related to NCCL, with r-values of 0.661, 0.642, and 0.534, respectively, with p ≤ 0.001. Using a hard toothbrush was found to be associated with NCCL. The NCCL group had extended mean occlusion time and disocclusion time in all eccentric mandibular movements. Full article

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9 pages, 3376 KiB

Open AccessCase Report

Complete and Durable Response to Combined Chemo/Radiation Therapy in EGFR Wild-Type Lung Adenocarcinoma with Diffuse Brain Metastases

by Davide Adriano Santeufemia, Giuseppe Palmieri, Antonio Cossu, Valli De Re, Laura Caggiari, Mariangela De Zorzi, Milena Casula, Maria Cristina Sini, Giovanni Baldino, Maria Filomena Dedola, Giuseppe Corona and Gianmaria Miolo

Diagnostics 2019, 9(2), 42; https://doi.org/10.3390/diagnostics9020042 - 11 Apr 2019

Cited by 1 | Viewed by 3998

Abstract

Most non-small-cell lung cancer (NSCLC) patients are likely to develop brain metastases during the course of their illness. Currently, no consensus on NSCLC patients’ treatment with brain metastasis has been established. Although whole brain radiotherapy prolongs the median survival time of approximately 4 [...] Read more.

Most non-small-cell lung cancer (NSCLC) patients are likely to develop brain metastases during the course of their illness. Currently, no consensus on NSCLC patients’ treatment with brain metastasis has been established. Although whole brain radiotherapy prolongs the median survival time of approximately 4 months, a cisplatin-pemetrexed combination may also represent a potential option in the treatment of asymptomatic NSCLC patients with brain metastases. Herein, we report the case of a non-smoker male patient with multiple, large and diffuse brain metastases from an “epidermal growth factor receptor (EGFR) wild-type” lung adenocarcinoma who underwent an overly aggressive chemo/radiation therapy. This approach led to a complete and durable remission of the disease and to a long survival of up to 58 months from diagnosis of primary tumor. The uncommon course of this metastatic disease induced us to describe its oncological management and to investigate the molecular features of the tumor. Full article

(This article belongs to the Special Issue Brain Imaging)

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16 pages, 1124 KiB

Open AccessArticle

Evidence of Clinical Pathology Abnormalities in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) from an Analytic Cross-Sectional Study

by Luis Nacul, Barbara de Barros, Caroline C. Kingdon, Jacqueline M. Cliff, Taane G. Clark, Kathleen Mudie, Hazel M. Dockrell and Eliana M. Lacerda

Diagnostics 2019, 9(2), 41; https://doi.org/10.3390/diagnostics9020041 - 10 Apr 2019

Cited by 26 | Viewed by 12910

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease presenting with extreme fatigue, post-exertional malaise, and other symptoms. In the absence of a diagnostic biomarker, ME/CFS is diagnosed clinically, although laboratory tests are routinely used to exclude alternative diagnoses. In this analytical cross-sectional [...] Read more.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease presenting with extreme fatigue, post-exertional malaise, and other symptoms. In the absence of a diagnostic biomarker, ME/CFS is diagnosed clinically, although laboratory tests are routinely used to exclude alternative diagnoses. In this analytical cross-sectional study, we aimed to explore potential haematological and biochemical markers for ME/CFS, and disease severity. We reviewed laboratory test results from 272 people with ME/CFS and 136 healthy controls participating in the UK ME/CFS Biobank (UKMEB). After corrections for multiple comparisons, most results were within the normal range, but people with severe ME/CFS presented with lower median values (p < 0.001) of serum creatine kinase (CK; median = 54 U/L), compared to healthy controls (HCs; median = 101.5 U/L) and non-severe ME/CFS (median = 84 U/L). The differences in CK concentrations persisted after adjusting for sex, age, body mass index, muscle mass, disease duration, and activity levels (odds ratio (OR) for being a severe case = 0.05 (95% confidence interval (CI) = 0.02–0.15) compared to controls, and OR = 0.16 (95% CI = 0.07–0.40), compared to mild cases). This is the first report that serum CK concentrations are markedly reduced in severe ME/CFS, and these results suggest that serum CK merits further investigation as a biomarker for severe ME/CFS. Full article

(This article belongs to the Special Issue Biomedical Insights that Inform the Diagnosis of ME/CFS)

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8 pages, 212 KiB

Open AccessArticle

Dual-Time-Point FDG Uptake Correlates with Prognostic Factors of Invasive Breast Cancer: Clinical Usefulness of Early Delayed Scanning

by Ji Young Lee, Hee-Sung Song, Jae Hyuck Choi and Chang Lim Hyun

Diagnostics 2019, 9(2), 40; https://doi.org/10.3390/diagnostics9020040 - 09 Apr 2019

Cited by 4 | Viewed by 4044

Abstract

This study investigated correlations between fluorodeoxyglucose (FDG) uptake in tumors as assessed by modified dual-time-point (mDTP) FDG positron emission tomography/computed tomography (PET/CT) in invasive breast cancer (iBC) and several prognostic parameters. Thirty-two women who underwent mastectomies for iBC were retrospectively evaluated. mDTP scanning [...] Read more.

This study investigated correlations between fluorodeoxyglucose (FDG) uptake in tumors as assessed by modified dual-time-point (mDTP) FDG positron emission tomography/computed tomography (PET/CT) in invasive breast cancer (iBC) and several prognostic parameters. Thirty-two women who underwent mastectomies for iBC were retrospectively evaluated. mDTP scanning was performed using standard FDG PET/CT (PET1), followed by early delayed acquisition (PET2) without repositioning and additional CT scanning. Using maximal standardized uptake values on PET1 (SUV1) and PET2 (SUV2) in the primary breast tumor, the percentage changes between SUV1 and SUV2 (retention index, (RI)) were calculated. Prognostic parameters (e.g., tumor size and stage; number of metastatic lymph nodes; histologic grade; expression of estrogen receptor (ER), progesterone, epidermal growth factor receptor (HER-2), and p53; and the Ki-67 labeling index (LI)) were evaluated from the surgical specimens. PET2 scans were conducted 17.7 ± 1.5 min after PET1. RI values gradually increased as the histologic grade increased (p = 0.016), and were significantly higher when ER expression was absent (p = 0.023) and Ki-67 LI was high (p < 0.001). RI values also showed a moderately positive correlation with Ki-67 LI (r = 0.629; p < 0.001). RI correlated with well-known biologic prognostic factors of iBC and mDTP scanning, which could be used as a substitute for conventional DTP PET. Full article

(This article belongs to the Section Medical Imaging and Theranostics)

26 pages, 8975 KiB

Open AccessArticle

Mining Featured Biomarkers Linked with Epithelial Ovarian CancerBased on Bioinformatics

by Varun Chandra Alur, Varshita Raju, Basavaraj Vastrad and Chanabasayya Vastrad

Diagnostics 2019, 9(2), 39; https://doi.org/10.3390/diagnostics9020039 - 09 Apr 2019

Cited by 5 | Viewed by 5253

Abstract

Epithelial ovarian cancer (EOC) is the18th most common cancer worldwide and the 8th most common in women. The aim of this study was to diagnose the potential importance of, as well as novel genes linked with, EOC and to provide valid biological information [...] Read more.

Epithelial ovarian cancer (EOC) is the18th most common cancer worldwide and the 8th most common in women. The aim of this study was to diagnose the potential importance of, as well as novel genes linked with, EOC and to provide valid biological information for further research. The gene expression profiles of E-MTAB-3706 which contained four high-grade ovarian epithelial cancer samples, four normal fallopian tube samples and four normal ovarian epithelium samples were downloaded from the ArrayExpress database. Pathway enrichment and Gene Ontology (GO) enrichment analysis of differentially expressed genes (DEGs) were performed, and protein-protein interaction (PPI) network, microRNA-target gene regulatory network and TFs (transcription factors) -target gene regulatory network for up- and down-regulated were analyzed using Cytoscape. In total, 552 DEGs were found, including 276 up-regulated and 276 down-regulated DEGs. Pathway enrichment analysis demonstrated that most DEGs were significantly enriched in chemical carcinogenesis, urea cycle, cell adhesion molecules and creatine biosynthesis. GO enrichment analysis showed that most DEGs were significantly enriched in translation, nucleosome, extracellular matrix organization and extracellular matrix. From protein-protein interaction network (PPI) analysis, modules, microRNA-target gene regulatory network and TFs-target gene regulatory network for up- and down-regulated, and the top hub genes such as E2F4, SRPK2, A2M, CDH1, MAP1LC3A, UCHL1, HLA-C (major histocompatibility complex, class I, C), VAT1, ECM1 and SNRPN (small nuclear ribonucleoprotein polypeptide N) were associated in pathogenesis of EOC. The high expression levels of the hub genes such as CEBPD (CCAAT enhancer binding protein delta) and MID2 in stages 3 and 4 were validated in the TCGA (The Cancer Genome Atlas) database. CEBPD andMID2 were associated with the worst overall survival rates in EOC. In conclusion, the current study diagnosed DEGs between normal and EOC samples, which could improve our understanding of the molecular mechanisms in the progression of EOC. These new key biomarkers might be used as therapeutic targets for EOC. Full article

(This article belongs to the Special Issue Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment)

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15 pages, 22584 KiB

Open AccessArticle

Visual Interpretation of Convolutional Neural Network Predictions in Classifying Medical Image Modalities

by Incheol Kim, Sivaramakrishnan Rajaraman and Sameer Antani

Diagnostics 2019, 9(2), 38; https://doi.org/10.3390/diagnostics9020038 - 03 Apr 2019

Cited by 50 | Viewed by 9910

Abstract

Deep learning (DL) methods are increasingly being applied for developing reliable computer-aided detection (CADe), diagnosis (CADx), and information retrieval algorithms. However, challenges in interpreting and explaining the learned behavior of the DL models hinders their adoption and use in real-world systems. In this [...] Read more.

Deep learning (DL) methods are increasingly being applied for developing reliable computer-aided detection (CADe), diagnosis (CADx), and information retrieval algorithms. However, challenges in interpreting and explaining the learned behavior of the DL models hinders their adoption and use in real-world systems. In this study, we propose a novel method called “Class-selective Relevance Mapping” (CRM) for localizing and visualizing discriminative regions of interest (ROI) within a medical image. Such visualizations offer improved explanation of the convolutional neural network (CNN)-based DL model predictions. We demonstrate CRM effectiveness in classifying medical imaging modalities toward automatically labeling them for visual information retrieval applications. The CRM is based on linear sum of incremental mean squared errors (MSE) calculated at the output layer of the CNN model. It measures both positive and negative contributions of each spatial element in the feature maps produced from the last convolution layer leading to correct classification of an input image. A series of experiments on a “multi-modality” CNN model designed for classifying seven different types of image modalities shows that the proposed method is significantly better in detecting and localizing the discriminative ROIs than other state of the art class-activation methods. Further, to visualize its effectiveness we generate “class-specific” ROI maps by averaging the CRM scores of images in each modality class, and characterize the visual explanation through their different size, shape, and location for our multi-modality CNN model that achieved over 98% performance on a dataset constructed from publicly available images. Full article

(This article belongs to the Section Medical Imaging and Theranostics)

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12 pages, 611 KiB

Open AccessReview

The Basics and the Advancements in Diagnosis of Bacterial Lower Respiratory Tract Infections

by Stephanie Noviello and David B. Huang

Diagnostics 2019, 9(2), 37; https://doi.org/10.3390/diagnostics9020037 - 03 Apr 2019

Cited by 22 | Viewed by 8619

Abstract

Lower respiratory tract infections (LRTIs) are the leading infectious cause of death and the sixth-leading cause of death overall worldwide. Streptococcus pneumoniae, with more than 90 serotypes, remains the most common identified cause of community-acquired acute bacterial pneumonia. Antibiotics treat LRTIs with [...] Read more.

Lower respiratory tract infections (LRTIs) are the leading infectious cause of death and the sixth-leading cause of death overall worldwide. Streptococcus pneumoniae, with more than 90 serotypes, remains the most common identified cause of community-acquired acute bacterial pneumonia. Antibiotics treat LRTIs with a bacterial etiology. With the potential for antibiotic-resistant bacteria, defining the etiology of the LRTI is imperative for appropriate patient treatment. C-reactive protein and procalcitonin are point-of-care tests that may differentiate bacterial versus viral etiologies of LRTIs. Major advancements are currently advancing the ability to make rapid diagnoses and identification of the bacterial etiology of LRTIs, which will continue to support antimicrobial stewardship, and is the focus of this review. Full article

(This article belongs to the Special Issue Diagnosis of Bacterial Pathogens)

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9 pages, 2316 KiB

Open AccessArticle

Development of Rapid Extraction Method of Mycobacterium avium Subspecies paratuberculosis DNA from Bovine Stool Samples

by Sören Hansen, Marco Roller, Lamia M. A. Alslim, Susanne Böhlken-Fascher, Kim Fechner, Claus-Peter Czerny and Ahmed Abd El Wahed

Diagnostics 2019, 9(2), 36; https://doi.org/10.3390/diagnostics9020036 - 29 Mar 2019

Cited by 10 | Viewed by 8572

Abstract

The rapid identification of Mycobacterium avium subspecies paratuberculosis (MAP) infected animals within the herd is essential for preventing the spread of the disease as well as avoiding human exposure. Although culture is seen as the gold standard, there are various molecular assays available [...] Read more.

The rapid identification of Mycobacterium avium subspecies paratuberculosis (MAP) infected animals within the herd is essential for preventing the spread of the disease as well as avoiding human exposure. Although culture is seen as the gold standard, there are various molecular assays available i.e., polymerase chain reaction (PCR) or isothermal amplification technique (recombinase polymerase amplification (RPA)) for the detection of MAP. The accuracy of the molecular assays is highly dependent on the DNA extraction method. In order to establish a rapid point of need system for the detection of MAP DNA from stool samples, we developed a rapid DNA extraction protocol (MAP DNA SpeedXtract) specified for use in combination with the RPA. The whole procedure from “sample in” to “result out” was conducted in a mobile suitcase laboratory. The DNA extraction is based on reverse purification by magnetic beads, which reduces the required technical demand. The MAP DNA SpeedXtract was performed within 25 min and only three pipetting steps were needed. The amplification and detection time were 20 min in RPA. The sensitivity and specificity of the developed protocol in comparison with the lab-based silica membrane column extraction and real-time PCR were 90.9% (n = 22) and 100% (n = 23), respectively. In conclusion, we established a rapid and reliable protocol for the extraction and detection of MAP DNA. All reagents are cold chain independent. The entire setup is ideal for point of need identification of MAP infected cases. Full article

(This article belongs to the Special Issue Diagnosis of Bacterial Pathogens)

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