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Diagnostics, Volume 9, Issue 2 (June 2019)

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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
Diagnostics 2019, 9(2), 54; https://doi.org/10.3390/diagnostics9020054
Received: 7 March 2019 / Revised: 7 May 2019 / Accepted: 9 May 2019 / Published: 13 May 2019
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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)
Open AccessCase Report
Giant Hepatic Artery Aneurysm
Diagnostics 2019, 9(2), 53; https://doi.org/10.3390/diagnostics9020053
Received: 10 April 2019 / Revised: 7 May 2019 / Accepted: 10 May 2019 / Published: 13 May 2019
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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)
Open AccessArticle
Framework for the Development of Data-Driven Mamdani-Type Fuzzy Clinical Decision Support Systems
Diagnostics 2019, 9(2), 52; https://doi.org/10.3390/diagnostics9020052
Received: 20 March 2019 / Revised: 3 May 2019 / Accepted: 6 May 2019 / Published: 9 May 2019
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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 Novel Diagnostic Technologies and Devices)
Open AccessArticle
MACE for Diagnosis of Dementia and MCI: Examining Cut-Offs and Predictive Values
Diagnostics 2019, 9(2), 51; https://doi.org/10.3390/diagnostics9020051
Received: 28 March 2019 / Revised: 23 April 2019 / Accepted: 1 May 2019 / Published: 6 May 2019
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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)
Open AccessArticle
Four Virtual-Reality Simulators for Diagnostic Abdominal Ultrasound Training in Radiology
Diagnostics 2019, 9(2), 50; https://doi.org/10.3390/diagnostics9020050
Received: 27 March 2019 / Revised: 27 April 2019 / Accepted: 1 May 2019 / Published: 6 May 2019
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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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Open AccessReview
Current and Emerging Methods of Antibiotic Susceptibility Testing
Diagnostics 2019, 9(2), 49; https://doi.org/10.3390/diagnostics9020049
Received: 18 March 2019 / Revised: 28 April 2019 / Accepted: 28 April 2019 / Published: 3 May 2019
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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)
Open AccessArticle
HAMP Downregulation Contributes to Aggressive Hepatocellular Carcinoma via Mechanism Mediated by Cyclin4-Dependent Kinase-1/STAT3 Pathway
Diagnostics 2019, 9(2), 48; https://doi.org/10.3390/diagnostics9020048
Received: 24 April 2019 / Accepted: 28 April 2019 / Published: 30 April 2019
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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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Open AccessArticle
Health Predictors of Pain in Elderly—A Serbian Population-Based Study
Diagnostics 2019, 9(2), 47; https://doi.org/10.3390/diagnostics9020047
Received: 9 April 2019 / Revised: 24 April 2019 / Accepted: 25 April 2019 / Published: 26 April 2019
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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
Open AccessArticle
Prostate Artery Embolization for Lower Urinary Tract Symptoms in Men Unfit for Surgery
Diagnostics 2019, 9(2), 46; https://doi.org/10.3390/diagnostics9020046
Received: 21 March 2019 / Revised: 18 April 2019 / Accepted: 24 April 2019 / Published: 25 April 2019
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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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Open AccessTechnical Note
Enhancement of Chest Radiograph in Emergency Intensive Care Unit by Means of Reverse Anisotropic Diffusion-Based Unsharp Masking Model
Diagnostics 2019, 9(2), 45; https://doi.org/10.3390/diagnostics9020045
Received: 18 March 2019 / Revised: 16 April 2019 / Accepted: 20 April 2019 / Published: 24 April 2019
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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)
Open AccessArticle
Preimplantation Genetic Diagnosis of Neurodegenerative Diseases: Review of Methodologies and Report of Our Experience as a Regional Reference Laboratory
Diagnostics 2019, 9(2), 44; https://doi.org/10.3390/diagnostics9020044
Received: 1 March 2019 / Revised: 2 April 2019 / Accepted: 9 April 2019 / Published: 23 April 2019
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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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Open AccessArticle
Association of Non-Carious Cervical Lesions with Oral Hygiene Habits and Dynamic Occlusal Parameters
Diagnostics 2019, 9(2), 43; https://doi.org/10.3390/diagnostics9020043
Received: 23 March 2019 / Revised: 9 April 2019 / Accepted: 10 April 2019 / Published: 12 April 2019
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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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Open AccessCase Report
Complete and Durable Response to Combined Chemo/Radiation Therapy in EGFR Wild-Type Lung Adenocarcinoma with Diffuse Brain Metastases
Diagnostics 2019, 9(2), 42; https://doi.org/10.3390/diagnostics9020042
Received: 1 March 2019 / Revised: 2 April 2019 / Accepted: 9 April 2019 / Published: 11 April 2019
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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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Open AccessArticle
Evidence of Clinical Pathology Abnormalities in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) from an Analytic Cross-Sectional Study
Diagnostics 2019, 9(2), 41; https://doi.org/10.3390/diagnostics9020041
Received: 27 March 2019 / Accepted: 4 April 2019 / Published: 10 April 2019
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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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Open AccessArticle
Dual-Time-Point FDG Uptake Correlates with Prognostic Factors of Invasive Breast Cancer: Clinical Usefulness of Early Delayed Scanning
Diagnostics 2019, 9(2), 40; https://doi.org/10.3390/diagnostics9020040
Received: 5 March 2019 / Revised: 5 April 2019 / Accepted: 7 April 2019 / Published: 9 April 2019
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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)
Open AccessArticle
Mining Featured Biomarkers Linked with Epithelial Ovarian CancerBased on Bioinformatics
Diagnostics 2019, 9(2), 39; https://doi.org/10.3390/diagnostics9020039
Received: 24 January 2019 / Revised: 31 March 2019 / Accepted: 5 April 2019 / Published: 9 April 2019
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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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Open AccessArticle
Visual Interpretation of Convolutional Neural Network Predictions in Classifying Medical Image Modalities
Diagnostics 2019, 9(2), 38; https://doi.org/10.3390/diagnostics9020038
Received: 5 March 2019 / Revised: 29 March 2019 / Accepted: 1 April 2019 / Published: 3 April 2019
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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)
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Open AccessReview
The Basics and the Advancements in Diagnosis of Bacterial Lower Respiratory Tract Infections
Diagnostics 2019, 9(2), 37; https://doi.org/10.3390/diagnostics9020037
Received: 1 March 2019 / Revised: 26 March 2019 / Accepted: 30 March 2019 / Published: 3 April 2019
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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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Open AccessArticle
Development of Rapid Extraction Method of Mycobacterium avium Subspecies paratuberculosis DNA from Bovine Stool Samples
Diagnostics 2019, 9(2), 36; https://doi.org/10.3390/diagnostics9020036
Received: 29 January 2019 / Revised: 18 March 2019 / Accepted: 27 March 2019 / Published: 29 March 2019
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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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