Table of Contents

Reduced oxygenation changes in the prefrontal cortex during cognitive tasks have been reported in major depressive disorder (MDD). However, prefrontal asymmetry during cognitive tasks and its relation to suicide ideations have been less frequently examined in patients with MDD. This study investigated prefrontal asymmetry and its moderating effect on the relationship between depression severity and suicidal ideation in MDD patients during cognitive tasks. Forty-two patients with MDD and 64 healthy controls (HCs) were assessed for changes in oxygenated and deoxygenated hemoglobin (Hb) in the prefrontal cortex using functional near-infrared spectroscopy (fNIRS) during the verbal fluency task (VFT), Stroop task, and two-back task. Depression, anxiety, and suicide ideation were measured through self-report questionnaires. Relatively smaller left oxy-Hb changes during VFT, but not during the Stroop or two-back tasks, were found in MDD patients compared with HCs. Furthermore, prefrontal asymmetry during VFT moderated the effect of depression severity on suicide ideation, and was significantly and positively correlated with suicide ideation in patients with MDD. Specifically, relatively greater left oxy-Hb changes were associated with greater suicide ideation. These findings suggest fNIRS-measured prefrontal asymmetry as a potential biomarker for MDD and for the assessment of suicidal risk in patients with MDD. Full article

Metabolic Syndrome (MetS) is a cluster of risk factors that increase the likelihood of heart disease and diabetes mellitus. It is crucial to get diagnosed with time to take preventive measures, especially for patients in locations without proper access to laboratories and medical consultations. This work presented a new methodology to diagnose diseases using data mining that documents all the phases thoroughly for further improvement of the resulting models. We used the methodology to create a new model to diagnose the syndrome without using biochemical variables. We compared similar classification models, using their reported variables and previously obtained data from a study in Colombia. We built a new model and compared it to previous models using the holdout, and random subsampling validation methods to get performance evaluation indicators between the models. Our resulting ANN model used three hidden layers and only Hip Circumference, dichotomous Waist Circumference, and dichotomous blood pressure variables. It gave an Area Under Curve (AUC) of 87.75% by the IDF and 85.12% by HMS MetS diagnosis criteria, higher than previous models. Thanks to our new methodology, diagnosis models can be thoroughly documented for appropriate future comparisons, thus benefiting the diagnosis of the studied diseases. Full article

The objective of this study was to investigate the development of a surface plasmon resonance (SPR) sensor platform equipped with multiple channels for the simultaneous determination of methicillin-resistant S. aureus (MRSA), methicillin-susceptible S. aureus (MSSA) and vancomycin-resistant Enterococcus (VRE), and vancomycin-susceptible Enterococcus (VSE). Drug resistance of S. aureus strains against cefoxitin and Enterococcus strains against vancomycin were investigated both using the minimum inhibitory concentration method (MIC) assay and the SPR system equipped with single and multiple channels. The MIC values of MRSA and MSSA ranged from 32 µg/mL to >128 µg/mL and from 1 µg/mL to 4 µg/mL, respectively. The MIC values of VRE and VSE were between 64 to >128 µg/mL and 2–4 µg/mL, respectively. With the multiple-channel system, the angle shifts of MRSA, MSSA, VRE and VSE were found to be −0.030° and −0.260°, −0.010° and −0.090° respectively. The antibiotic-resistant and susceptible strains were distinguished within 3 h for S. aureus strains and within 6 h for Enterococcus strains. Full article

Electronic Prescribing tools (e-prescribing) have shown several benefits in terms of prescribing process adequacy and health care quality in hospital settings. We hypothesize however, that an undesired effect of digitalisation, due to the easier and faster prescribing process allowing patients to skip face-to-face conversations with patients and nurses, is that it could facilitate the prescription of medications at high risk of overuse or abuse, such as benzodiazepines (BZDs). We conducted a panel data study to investigate, the impact of the introduction of an e-prescribing system on new BZD prescriptions in hospitalised patients in a network of five teaching hospitals. During the observation period 1 July 2014–30 April 2019, 43,320 admissions were analysed. A fixed-effects model was adopted to estimate the effect of e-prescribing on new BZD prescriptions. E-prescribing implementation was associated with a significant increase of new BZD prescriptions: absolute +1.5%, and relative +43% (p < 0.001). The effect was similar in males and females (respectively, absolute +2.3%, relative +65% (p < 0.001); absolute +1.8%, relative +58% (p = 0.01)) and in patients ≥70 years old (absolute +1.6%, relative +59% (p < 0.001)). After controlling for time-varying explanatory variables, the implementation of the e-prescribing tool showed similar significant effects. E-prescribing implementation was associated with a significant increase of new in-hospital BZD prescriptions. For classes of drugs at risk of overuse or abuse, e-prescribing should be used cautiously, to minimize the risk of over-prescriptions. Further research in other settings and countries is needed to analyse causal interactions between e-prescribing and BZD prescriptions in the hospital setting, and to promote the ultimate goal of high-value care. Full article

Background: Over the last two decades, many studies have investigated the association between interleukin 6 (IL-6) and pathogenesis and progression of coronary artery disease (CAD). Patients with CAD manifested at a young age are a particularly interesting group. They differ from older patients, not only in terms of the severity of coronary artery atherosclerosis, but also risk factor profiles, short- and long-term prognosis after myocardial infarction (MI). The role of IL-6 in younger patients with CAD is less well-known. Therefore, our study aimed to analyze the relationship between IL-6 level and other inflammations, atherosclerosis, and cardiac function parameters in early onset CAD patients. Methods: The study covered 100 patients with early onset CAD and a group of 50 healthy participants. Plasma levels of IL-6 and basic biochemical parameters, anthropometric, echocardiographic, and arteries Doppler ultrasound measurements were performed. Results: We did not observe a significant difference in IL-6 concentration in plasma between patients with early onset CAD and a control group, but IL-6 level was negatively correlated with echocardiographic measurements of ascending aorta diameter, left ventricular shortening fraction, and right ventricular end-diastolic diameter in our patients. Conclusions: In patients with early onset CAD, plasma IL-6 level is associated with other inflammation parameters and with cardiac function, potentially contributing to right ventricular remodeling and left ventricular systolic dysfunction. This suggests possible prognostic benefits of long-time observation of IL-6 level after the acute coronary syndrome. Full article

Introduction: Point-of-care ultrasound (POCUS) is a rapidly expanding discipline that has proven to be a valuable modality in the hospital setting. Recent evidence has demonstrated the utility of commercially available video conferencing technologies, namely, FaceTime (Apple Inc, Cupertino, CA, USA) and Google Glass (Google Inc, Mountain View, CA, USA), to allow an expert POCUS examiner to remotely guide a novice medical professional. However, few studies have evaluated the ability to use these teleultrasound technologies to guide a nonmedical novice to perform an acute care POCUS examination for cardiac, pulmonary, and abdominal assessments. Additionally, few studies have shown the ability of a POCUS-trained cardiac anesthesiologist to perform the role of an expert instructor. This study sought to evaluate the ability of a POCUS-trained anesthesiologist to remotely guide a nonmedically trained participant to perform an acute care POCUS examination. Methods: A total of 21 nonmedically trained undergraduate students who had no prior ultrasound experience were recruited to perform a three-part ultrasound examination on a standardized patient with the guidance of a remote expert who was a POCUS-trained cardiac anesthesiologist. The examination included the following acute care POCUS topics: (1) cardiac function via parasternal long/short axis views, (2) pneumothorax assessment via pleural sliding exam via anterior lung views, and (3) abdominal free fluid exam via right upper quadrant abdominal view. Each examiner was given a handout with static images of probe placement and actual ultrasound images for the three views. After a brief 8 min tutorial on the teleultrasound technologies, a connection was established with the expert, and they were guided through the acute care POCUS exam. Each view was deemed to be complete when the expert sonographer was satisfied with the obtained image or if the expert sonographer determined that the image could not be obtained after 5 min. Image quality was scored on a previously validated 0 to 4 grading scale. The entire session was recorded, and the image quality was scored during the exam by the remote expert instructor as well as by a separate POCUS-trained, blinded expert anesthesiologist. Results: A total of 21 subjects completed the study. The average total time for the exam was 8.5 min (standard deviation = 4.6). A comparison between the live expert examiner and the blinded postexam reviewer showed a 100% agreement between image interpretations. A review of the exams rated as three or higher demonstrated that 87% of abdominal, 90% of cardiac, and 95% of pulmonary exams achieved this level of image quality. A satisfaction survey of the novice users demonstrated higher ease of following commands for the cardiac and pulmonary exams compared to the abdominal exam. Conclusions: The results from this pilot study demonstrate that nonmedically trained individuals can be guided to complete a relevant ultrasound examination within a short period. Further evaluation of using telemedicine technologies to promote POCUS should be evaluated. Full article

Mucopolysaccharidoses (MPS) are a group of inborn errors of metabolism with an aggressive and usually fatal course. Therefore, early treatment is essential because the involvement of head and neck structures is almost always present in MPS. Our study aimed to retrospectively assess—via a chart review and a survey of caregivers—the history of ear, nose and throat (ENT) symptoms, the number of otolaryngology visits prior to diagnosis, and whether otolaryngologists diagnosed the disease in a cohort of MPS patients followed at an academic medical center. Twenty-three patients were evaluated. Age at diagnosis ranged from 0.2 to 33.0 years (median, 3.2 years). Prior to being diagnosed with MPS, 20/23 (87%) patients presented with at least one episode of otalgia, airway disorder, sleep disturbance, speech delay or suspected hearing loss. One patient had an adenotonsillectomy with paracentesis of tympanic membranes. Ten of the 23 patients (43%) were seen by an otolaryngologist before the diagnosis of MPS, none of which had the disease suspected during these visits. Notwithstanding limitations, our results suggest that increased awareness of MPS among otolaryngologists may allow for earlier diagnosis and better management of these patients. Full article

The diagnosis of neck pain is challenging. Many visceral disorders are known to cause it, and clinical practice guidelines recommend to rule them out during neck pain diagnosis. However, the absence of suspicion of any cause impedes one from establishing that specific aetiology as the final diagnosis. To investigate the degree of consideration given to visceral aetiology, a systematic search of trials about neck pain was carried out to evaluate their selection criteria. The search yielded 309 eligible articles, which were screened by two independent reviewers. The PEDro scale score was used to assess the methodological quality of the studies. The following information was retrieved: number of authors affiliated to a clinical or non-clinical institution, number of citations in the Web of Science, study aims, characteristics of participants, and eligibility criteria. The top 15 most cited trials, and the 15 most recent studies about treatment efficacy in neck pain, published in first quartile journals of the Journal Citation Reports, were selected. Females represented 67.5% of participants. A single study was of poor methodological quality (4/10). Based on the eligibility criteria of the articles that were systematically reviewed, it would appear that visceral aetiology was not considered in eighty percent of the trials on neck pain, showing a low level of suspicion both in research and clinical settings. Full article

Autosomal recessive renal tubular dysgenesis (ARRTD) is a rare and lethal disorder that causes stillbirth or early neonatal death. Most of the reported cases are diagnosed postnatally by a histopathological hallmark of the absence or paucity of differentiated proximal tubules in kidneys. Prenatal diagnosis of ARRTD is challenging because only a few fetal features (e.g., oligohydramnios/anhydramnios, anuria) are associated with this condition. In this study, we report a fetus with ARRTD, which showed anhydramnios and invisible urinary bladder since the second trimester, followed by growth restriction and reversed end diastolic flow in the middle cerebral artery (MCA-REDF). No morphological anomaly was detected on the fetal kidneys during an ultrasound scan. The baby died of refractory hypotension the day after their birth. Genetic analysis of genes that are involved in the renin-angiotensin-aldosterone system (RAAS), which are the known genetic causes of ARRTD, identified a novel, biparental-origin homozygous c.857-619_1269+243delinsTTGCCTTGC mutation in the AGT gene. The mutation is considered as pathogenic because it is cosegregated with ARRTD and detected in other unrelated ARRTD families. Our findings link the fetal ultrasound manifestations to the ARRTD, highlighting clues that are useful for prenatal diagnosis, which warrants confirmatory genotyping of the RAAS genes including oligohydramnios/anhydramnios, anuria (absent filling of a fetal urinary bladder), MCA-REDF, and a morphologically normal kidney. Full article

Purpose: Carotid intraplaque hemorrhage (IPH) increases risk of territorial cerebral ischemic events, but different sequences or criteria have been used to diagnose or quantify carotid IPH. The purpose of this study was to compare manual segmentation and semi-automatic segmentation for quantification of carotid IPH on magnetization-prepared rapid acquisition with gradient-echo (MPRAGE) sequences. Methods: Forty patients with 16–79% carotid stenosis and IPH on MPRAGE sequences were reviewed by two trained radiologists with more than five years of specialized experience in carotid plaque characterization with carotid plaque MRI. Initially, the radiologists manually viewed the IPH based on the MPRAGE sequence. IPH volume was then measured by three different semi-automatic methods, with high signal intensity 150%, 175%, and 200%, respectively, above that of adjacent muscle on the MPRAGE sequence. Agreement on measurements between manual segmentation and semi-automatic segmentation was assessed using the intraclass correlation coefficient (ICC). Results: There was near-perfect agreement between manual segmentation and the 150% and 175% criteria for semi-automatic segmentation in quantification of IPH volume. The ICC of each semi-automatic segmentation were as follows: 150% criteria: 0.861, 175% criteria: 0.809, 200% criteria: 0.491. The ICC value of manual vs. 150% criteria and manual vs. 175% criteria were significantly better than the manual vs. 200% criteria (p < 0.001). Conclusions: The ICC of 150% and 175% criteria for semi-automatic segmentation are more reliable for quantification of IPH volume. Semi-automatic classification tools may be beneficial in large-scale multicenter studies by reducing image analysis time and avoiding bias between human reviewers. Full article

Ovarian cancer is often diagnosed at late stages due to current inadequate detection. Therefore, the development of new detection methods of ovarian cancer is needed. This may be achieved by phage nanoparticles that display targeting peptides for optical imaging. Here, two such phage clones are reported. Ovarian cancer binding and specificity of phage clones (pJ18, pJ24) and peptides (J18, J24) were investigated using fluorescent microscopy and modified ELISA. Further, AF680-labeled phage particles were subjected to biodistribution and optical imaging studies in SKOV-3 xenografted mice. Fluorescent microscopy and ELISA of phage and peptides showed significantly increased binding to SKOV-3 cells compared to controls. Additionally, these studies revealed that J18 exhibits specificity for ovarian cancer SKOV-3 and OVCAR-3 cell lines. Further, peptides displayed increased SKOV-3 binding compared to N35 (non-relevant peptide) with EC₅₀ values of 22.2 ± 10.6 μM and 29.0 ± 6.9 (mean ± SE), respectively. Biodistribution studies of AF680-labeled phage particles showed tumor uptake after 4 h and excretion through the reticuloendothelial system. Importantly, SKOV-3 tumors were easily localized by optical imaging after 2 h and 4 h and displayed good tumor-to-background contrast. The fluorescent tumor signal intensity was significantly higher for pJ18 compared to wild type (WT) after 2 h. Full article

Breast cancer is one of the most common cancers among women worldwide. Ultrasound imaging has been widely used in the detection and diagnosis of breast tumors. However, due to factors such as limited spatial resolution and speckle noise, classification of benign and malignant breast tumors using conventional B-mode ultrasound still remains a challenging task. H-scan is a new ultrasound technique that images the relative size of acoustic scatterers. However, the feasibility of H-scan ultrasound imaging in the classification of benign and malignant breast tumors has not been investigated. In this paper, we proposed a new method based on H-scan ultrasound imaging to classify benign and malignant breast tumors. Backscattered ultrasound radiofrequency signals of 100 breast tumors were used (48 benign and 52 malignant cases). H-scan ultrasound images were constructed with the radiofrequency signals by matched filtering using Gaussian-weighted Hermite polynomials. Experimental results showed that benign breast tumors had more red components, while malignant breast tumors had more blue components in H-scan ultrasound images. There were significant differences between the RGB channels of H-scan ultrasound images of benign and malignant breast tumors. We conclude H-scan ultrasound imaging can be used as a new method for classifying benign and malignant breast tumors. Full article

In this special issue of Diagnostics, expert contributors have produced up-to-date research studies and reviews on various topics related to the diagnosis of dementia and cognitive impairment. The methods of the assessments discussed extend from simple neurological signs, which may be elicited in the clinical encounter, through cognitive screening instruments, to sophisticated analyses of neuroimaging and cerebrospinal fluid biomarkers of disease. It is hoped that these various methods may facilitate earlier diagnosis of dementia and its subtypes, and provide differential diagnosis of depression and functional cognitive disorders, as a prelude to meaningful interventions. Full article

Ηepatic involvement in multiple myeloma is not common; nevertheless, it is associated with poorer outcome. Heterogeneous features have been described in few published reports so far. We present the imaging findings of PET/CT in comparison to those of MRI for two multiple myeloma (MM) patients, one with a liver lesion suspicious for myeloma metastasis on PET and one with multiple liver lesions suspicious for myeloma metastases on MRΙ. The subsequent ultrasound-guided needle biopsies confirmed the extramedullary spread of the disease in both patients. The first case exhibited a match in both functional imaging modalities (PET and MRI) but a mismatch of intense metabolic activity on ¹⁸F-fluorodeoxyglucose (18F-FDG) PET/CT and iso-attenuating liver parenchyma on contrast-enhanced CT. The second case showed a mismatch of signal elevation persistence on diffusion-weighted imaging (DWI) and physiologic 18F-FDG distribution in the liver parenchyma. These cases present different imaging features in MM lesions of the liver using PET/CT and MRI, reflecting the high disease heterogeneity in patients with MM and demonstrating that the use of both PET/CT and MRI may offer complementary information. Full article

The outcomes of hypertension refer to the death or serious complications (such as myocardial infarction or stroke) that may occur in patients with hypertension. The outcomes of hypertension are very concerning for patients and doctors, and are ideally avoided. However, there is no satisfactory method for predicting the outcomes of hypertension. Therefore, this paper proposes a prediction method for outcomes based on physical examination indicators of hypertension patients. In this work, we divide the patients’ outcome prediction into two steps. The first step is to extract the key features from the patients’ many physical examination indicators. The second step is to use the key features extracted from the first step to predict the patients’ outcomes. To this end, we propose a model combining recursive feature elimination with a cross-validation method and classification algorithm. In the first step, we use the recursive feature elimination algorithm to rank the importance of all features, and then extract the optimal features subset using cross-validation. In the second step, we use four classification algorithms (support vector machine (SVM), C4.5 decision tree, random forest (RF), and extreme gradient boosting (XGBoost)) to accurately predict patient outcomes by using their optimal features subset. The selected model prediction performance evaluation metrics are accuracy, F1 measure, and area under receiver operating characteristic curve. The 10-fold cross-validation shows that C4.5, RF, and XGBoost can achieve very good prediction results with a small number of features, and the classifier after recursive feature elimination with cross-validation feature selection has better prediction performance. Among the four classifiers, XGBoost has the best prediction performance, and its accuracy, F1, and area under receiver operating characteristic curve (AUC) values are 94.36%, 0.875, and 0.927, respectively, using the optimal features subset. This article’s prediction of hypertension outcomes contributes to the in-depth study of hypertension complications and has strong practical significance. Full article

Background: To study the changes in protein composition of atherosclerotic plaques at different stages of their development in coronary atherosclerosis using proteomics. Methods: The object of research consisted of homogenates of atherosclerotic plaques from coronary arteries at different stages of development, obtained from 15 patients. Plaque proteins were separated by two-dimensional electrophoresis. The resultant protein spots were identified by the matrix-assisted laser desorption ionization method with peptide mass mapping. Results: Groups of differentially expressed proteins, in which the amounts of proteins differed more than twofold (p < 0.05), were identified in pools of homogenates of atherosclerotic plaques at three stages of development. The amounts of the following proteins were increased in stable atherosclerotic plaques at the stage of lipidosis and fibrosis: vimentin, tropomyosin β-chain, actin, keratin, tubulin β-chain, microfibril-associated glycoprotein 4, serum amyloid P-component, and annexin 5. In plaques at the stage of fibrosis and calcification, the amounts of mimecan and fibrinogen were increased. In unstable atherosclerotic plaque of the necrotic–dystrophic type, the amounts of human serum albumin, mimecan, fibrinogen, serum amyloid P-component and annexin were increased. Conclusion: This proteomic study identifies the proteins present in atherosclerotic plaques of coronary arteries by comparing their proteomes at three different stages of plaque development during coronary atherosclerosis. Full article

Deep convolutional generative adversarial networks (DCGANs) are newly developed tools for generating synthesized images. To determine the clinical utility of synthesized images, we generated breast ultrasound images and assessed their quality and clinical value. After retrospectively collecting 528 images of 144 benign masses and 529 images of 216 malignant masses in the breasts, synthesized images were generated using a DCGAN with 50, 100, 200, 500, and 1000 epochs. The synthesized (n = 20) and original (n = 40) images were evaluated by two radiologists, who scored them for overall quality, definition of anatomic structures, and visualization of the masses on a five-point scale. They also scored the possibility of images being original. Although there was no significant difference between the images synthesized with 1000 and 500 epochs, the latter were evaluated as being of higher quality than all other images. Moreover, 2.5%, 0%, 12.5%, 37.5%, and 22.5% of the images synthesized with 50, 100, 200, 500, and 1000 epochs, respectively, and 14% of the original images were indistinguishable from one another. Interobserver agreement was very good (|r| = 0.708–0.825, p < 0.001). Therefore, DCGAN can generate high-quality and realistic synthesized breast ultrasound images that are indistinguishable from the original images. Full article

Background: In Ghana, a blood group and rhesus type test is one of the essential recommended screening tests for women during antenatal care since blood transfusion is a key intervention for haemorrhage. We estimated the spatial accessibility to health facilities for blood group and type point-of-care (POC) testing in the Upper East Region (UER), Ghana. Methods: We assembled the attributes and spatial data of hospitals, clinics, and medical laboratories providing blood group and rhesus type POC testing in the UER. We also obtained the spatial data of all the 131 towns, and 94 health centres and community-based health planning and services (CHPS) compounds providing maternal healthcare in the region. We further obtained the topographical data of the region, and travel time estimated using an assumed tricycle speed of 20 km/h. We employed ArcGIS 10.5 to estimate the distance and travel time and locations with poor spatial access identified for priority improvement. Findings: In all, blood group and rhesus type POC testing was available in 18 health facilities comprising eight public hospitals and six health centres, one private hospital, and three medical laboratories used as referral points by neighbouring health centres and CHPS compounds without the service. Of the 94 health centres and CHPS compounds, 51.1% (48/94) and 66.4% (87/131) of the towns were within a 10 km range to a facility providing blood group and rhesus type testing service. The estimated mean distance to a health facility for blood group and rhesus POC testing was 8.9 ± 4.1 km, whilst the mean travel time was 17.8 ± 8.3 min. Builsa South district recorded the longest mean distance (25.6 ± 7.4 km), whilst Bongo district recorded the shortest (3.1 ± 1.9 km). The spatial autocorrelation results showed the health facilities providing blood group and rhesus type POC testing were randomly distributed in the region (Moran Index = 0.29; z-score = 1.37; p = 0.17). Conclusion: This study enabled the identification of district variations in spatial accessibility to blood group and rhesus type POC testing in the region for policy decisions. We urge the health authorities in Ghana to evaluate and implement recommended POC tests such as slide agglutination tests for blood group and rhesus type testing in resource-limited settings. Full article

Nasal polyposis is characterized by benign, non-cancerous and painless growths originating in the tissue of the nasal cavities and paranasal sinuses. Polyps arise from chronic inflammation due to asthma, recurrent infections, allergies, drug sensitivity or immune disorders. They can obstruct the nasal cavities and thus cause respiratory problems, a reduction in the sense of smell and susceptibility to infections. Furthermore, nasal polyps can recur. Hence the importance of using valid diagnostic methods. In this work, the diagnostic investigation carried out by scanning electron microscopy (SEM) and nasal cytology led, for the first time, to the identification of a mycoplasma superinfection on nasal polyposis. Full article

There is growing interest in anal cancer screening strategies. However, cytological/molecular evaluation of anal samples is challenging. We aimed to determine the feasibility of detecting, in anal liquid-based cytologies, the expression of biomarkers involved in the cell cycle disturbance elicited by human papillomavirus (HPV). The accuracy of this approach in the identification of high-grade squamous intraepithelial lesions/anal intraepithelial neoplasia grade2–3 (HSIL/AIN2–3) was also evaluated. 215 anal cytologies from men having sex with men living with human immunodeficiency virus were evaluated. Patients showing concordant cytological and anoscopy-directed biopsy diagnosis were selected: 70 with negative cytology and HPV test, 70 with low-grade SIL (LSIL/AIN1) cytology and biopsy, and 75 with cytology and biopsy of HSIL/AIN2–3. CDKN2A/p16, MKI67 and TOP2A mRNA expression was analyzed. HPV detection was performed with Xpert HPV Assay (Cepheid, Sunnyvale, CA, USA). HSIL/AIN2–3 showed higher expression for the biomarkers than LSIL/AIN1 or negative samples. The specificity for HSIL/AIN2–3 detection for a sensitivity established at 70% was 44.7% (95%confidence interval [CI] 36.5–53.2) for TOP2A and MKI67 and 54.5% (95%CI 46.0–62.8%) for CDKN2A/p16. mRNA detection of cell biomarkers in anal liquid-based cytology is feasible. Further studies are warranted to confirm if strategies based on mRNA detection have any role in anal cancer screening. Full article

Introduction: Viral bronchiolitis is a common cause of lower respiratory tract infection in the first year of life, considered a health burden because of its morbidity and costs. Its diagnosis is based on history and physical examination and the role of radiographic examination is limited to atypical cases. Thus far, Lung Ultrasound (LUS) is not considered in the diagnostic algorithm for bronchiolitis. Methods: PubMed database was searched for trials reporting on lung ultrasound examination and involving infants with a diagnosis of bronchiolitis. Results: Eight studies were suitable. Conclusions: This review analyzed the current evidence about the potential usefulness of LUS in the clinical management of bronchiolitis. Literature supports a peculiar role of LUS in the evaluation of the affected children, considering it as a reliable imaging test that could benefit the clinical management of bronchiolitis. Full article

The critically ill polytrauma patient is characterized by a series of metabolic changes induced by inflammation, oxidative stress, sepsis, and primary trauma, as well as associated secondary injuries associated. Metabolic and nutritional dysfunction in the critically ill patient is a complex series of imbalances of biochemical and genetic pathways, as well as the interconnection between them. Therefore, the equation changes in comparison to other critical patients or to healthy individuals, in which cases, mathematical equations can be successfully used to predict the energy requirements. Recent studies have shown that indirect calorimetry is one of the most accurate methods for determining the energy requirements in intubated and mechanically ventilated patients. Current research is oriented towards an individualized therapy depending on the energy consumption (kcal/day) of each patient that also takes into account the clinical dynamics. By using indirect calorimetry, one can measure, in real time, both oxygen consumption and carbon dioxide production. Energy requirements (kcal/day) and the respiratory quotient (RQ) can be determined in real time by integrating these dynamic parameters into electronic algorithms. In this manner, nutritional therapy becomes personalized and caters to the patients’ individual needs, helping patients receive the energy substrates they need at each clinically specific time of treatment. Full article

Advanced heart failure (AdHF) represents a challenging aspect of heart failure patients. Because of worsening clinical symptoms, high rates of re-hospitalization and mortality, AdHF represents an unstable condition where standard treatments are inadequate and additional interventions must be applied. A heart transplant is considered the optimal therapy for AdHF, but the great problem linked to the scarcity of organs and long waiting lists have led to the use of mechanical circulatory support with ventricular-assist device (VAD) as a destination therapy. VAD placement improves the prognosis, functional status, and quality of life of AdHF patients, with high rates of survival at 1 year, similar to transplant. However, the key element is to select the right patient at the right moment. The complete assessment must include a careful clinical evaluation, but also take into account psychosocial factors that are of crucial importance in the out-of-hospital management. It is important to distinguish between AdHF and end-stage HF, for which advanced therapy interventions would be unreasonable due to severe and irreversible organ damage and, instead, palliative care should be preferred to improve quality of life and relief of suffering. The correct selection of patients represents a great issue to solve, both ethically and economically. Full article

A family history of pancreatic cancer (PC) is a risk factor of PC, and risk levels increase as affected families grow in number and/or develop PC at younger ages. Familial pancreatic cancer (FPC) is defined as a client having at least two PC cases in a first degree relatives. In the narrow sense, FPC does not include some inherited cancer syndromes that are known to increase the risks of PC, such as Peutz–Jeghers syndrome (PJS), hereditary pancreatitis (HP), hereditary breast ovarian cancer syndrome (HBOC), and so on. FPC accounts for 5%–10% of total PC diagnoses and is marked by several features in genetic, epidemiological, and clinicopathological findings that are similar to or distinct from conventional PC. Recent advances in genetic medicine have led to an increased ability to identify germline variants of cancer-associated genes. To date, high-risk individuals (HRIs) in many developed countries, including FPC kindreds and inherited cancer syndromes, are screened clinically to detect and treat early-stage PC. This article highlights the concept of FPC and the most recent data on its detection. Full article

Early diagnosis of malaria reduces disease, prevents deaths, and contributes to decreased malaria transmission. The use of specific and sensitive antigens in the execution of serological diagnostics may have an impact on the transmission of the disease. However, many individuals cannot be easily diagnosed by serological tests due to low levels of antibodies in the serum. Using two different Enzyme-Linked Immunosorbent Assay (ELISA) tests (a commercial and an in-house ELISA), a total of 365 serum samples from individuals with a clinical history of malaria were analyzed. From the serum samples analyzed, 192 (53%) samples from the commercial ELISA and 219 (60%) samples from the in-house ELISA presented positive serological reactivity to malaria. The concordance of the samples tested (n = 365) between both ELISAs was of 67% (n = 242), and with the negative control was 100% (n = 17). We demonstrated that the in-house ELISA showed high antigenic reactivity to Plasmodium falciparum antigens when compared with the commercial ELISA. The degree of concordance of both ELISAs suggested the possibility of existence of other P. falciparum antigens present in the crude extract of P. falciparum that are important in the serological response during malaria infection. Full article

Background: Hepatocellular carcinoma (HCC) pathogenesis involves the alteration of multiple liver-specific metabolic pathways. We systematically profiled cancer- and liver-related classes of metabolites in HCC and adjacent liver tissues and applied supervised machine learning to compare their potential yield for HCC biomarkers. Methods: Tumor and corresponding liver tissue samples were profiled as follows: Bile acids by ultra-performance liquid chromatography (LC) coupled to tandem mass spectrometry (MS), phospholipids by LC-MS/MS, and other small molecules including free fatty acids by gas chromatography—time of flight MS. The overall classification performance of metabolomic signatures derived by support vector machine (SVM) and random forests machine learning algorithms was then compared across classes of metabolite. Results: For each metabolite class, there was a plateau in classification performance with signatures of 10 metabolites. Phospholipid signatures consistently showed the highest discrimination for HCC followed by signatures derived from small molecules, free fatty acids, and bile acids with area under the receiver operating characteristic curve (AUC) values of 0.963, 0.934, 0.895, 0.695, respectively, for SVM-generated signatures comprised of 10 metabolites. Similar classification performance patterns were observed with signatures derived by random forests. Conclusion: Membrane phospholipids are a promising source of tissue biomarkers for discriminating between HCC tumor and liver tissue. Full article

The ability to accurately measure multiple proteins simultaneously in a single assay has the potential to markedly improve the efficiency of clinical tests composed of multiple biomarkers. We investigated the diagnostic accuracy of the two multiplex protein array platforms for detecting a bladder-cancer-associated diagnostic signature in samples from a cohort of 80 subjects (40 with bladder cancer). Banked urine samples collected from Kyoto and Nara Universities were compared to histologically determined bladder cancer. The concentrations of the 10 proteins (A1AT; apolipoprotein E—APOE; angiogenin—ANG; carbonic anhydrase 9—CA9; interleukin 8—IL-8; matrix metalloproteinase 9—MMP-9; matrix metalloproteinase 10—MMP10; plasminogen activator inhibitor 1—PAI-1; syndecan—SDC1; and vascular endothelial growth factor—VEGF) were monitored using two prototype multiplex array platforms and an enzyme-linked immunosorbent assay (ELISA) according to the manufacturer’s technical specifications. The range for detecting each biomarker was improved in the multiplex assays, even though the lower limit of quantification (LLOQ) was typically lower in the commercial ELISA kits. The area under the receiver operating characteristics (AUROC) of the prototype multiplex assays was reported to be 0.97 for the multiplex bead-based immunoassay (MBA) and 0.86 for the multiplex electrochemoluminescent assay (MEA). The sensitivities and specificities for MBA were 0.93 and 0.95, respectively, and for MEA were 0.85 and 0.80, respectively. Accuracy, positive predictive values (PPV), and negative predictive values (NPV) for MBA were 0.94, 0.95, and 0.93, respectively, and for MEA were 0.83, 0.81, and 0.84, respectively. Based on these encouraging preliminary data, we believe that a multiplex protein array is a viable platform that can be utilized as an efficient and highly accurate tool to quantitate multiple proteins within biologic specimens. Full article

Breast cancer is one of the major health issues across the world. In this study, a new computer-aided detection (CAD) system is introduced. First, the mammogram images were enhanced to increase the contrast. Second, the pectoral muscle was eliminated and the breast was suppressed from the mammogram. Afterward, some statistical features were extracted. Next, k-nearest neighbor (k-NN) and decision trees classifiers were used to classify the normal and abnormal lesions. Moreover, multiple classifier systems (MCS) was constructed as it usually improves the classification results. The MCS has two structures, cascaded and parallel structures. Finally, two wrapper feature selection (FS) approaches were applied to identify those features, which influence classification accuracy. The two data sets (1) the mammographic image analysis society digital mammogram database (MIAS) and (2) the digital mammography dream challenge were combined together to test the CAD system proposed. The highest accuracy achieved with the proposed CAD system before FS was 99.7% using the Adaboosting of the J48 decision tree classifiers. The highest accuracy after FS was 100%, which was achieved with k-NN classifier. Moreover, the area under the curve (AUC) of the receiver operating characteristic (ROC) curve was equal to 1.0. The results showed that the proposed CAD system was able to accurately classify normal and abnormal lesions in mammogram samples. Full article

A magnetic resonance imaging (MRI) system is a complex, high cost, and long-life product. It is a widely known fact that performing a system reliability test of a MRI system during the development phase is a challenging task. The major challenges include sample size, high test cost, and long test duration. This paper introduces a novel approach to perform a MRI system reliability test in a reasonably acceptable time with one sample size. Our approach is based on an accelerated reliability growth test, which consists of test cycle made of a very high-energy time-of-flight three-dimensional (TOF3D) pulse sequence representing an actual hospital usage scenario. First, we construct a nominal day usage scenario based on actual data collected from an MRI system used inside the hospital. Then, we calculate the life-time stress based on a usage scenario. Finally, we develop an accelerated reliability growth test cycle based on a TOF3D pulse sequence that exerts highest vibration energy on the gradient coil and MRI system. We use a vibration energy model to map the life-time stress and reduce the test duration from 537 to 55 days. We use a Crow AMSAA plot to demonstrate that system design reaches its useful life after crossing the infant mortality phase. Full article