Valuable Diagnostic Indicator Research Articles

Potential plasma biomarkers for the onset of heart and skeletal muscle inflammation from Piscine orthoreovirus-1 infection in Atlantic salmon (Salmo salar)

Biomarkers that give quantifiable information about disease development are valuable diagnostic indicators providing opportunities to thwart adverse outcomes through timely detection and initiation of countermeasures. Whereas human medicine already relies extensively on biomarker analysis, their application in the diagnostics of fish diseases is still at a tentative beginning. However, the increased utilisation of broad-range analytical approaches such as untargeted proteomics enhances the chances to discover changes in the levels of proteins, which are connected to fish health and could serve as novel biomarkers. In the present study, proteomic analysis accompanied by biostatistical data processing was employed with the aim of identifying plasma biomarker candidates for the onset of heart and skeletal muscle inflammation (HSMI) caused by Piscine orthoreovirus (PRV)-1 infection in Atlantic salmon. HSMI is a common viral disease and threat to fish welfare and productivity in Norwegian aquaculture, so that the early detection of HSMI development would allow a timely intervention to limit the damage. In the search for biomarker candidates, salmon plasma was sampled five and eight weeks after a PRV-1 cohabitation challenge experiment and from adequate control fish, and analysed by mass spectrometry-based proteomics. The proteome dataset contained 695 proteins with >90% probability of correct identification according to the set cut-off criteria for peptide quality. Time- and condition-related differences in protein abundance levels were revealed by multivariate analysis. Comparison of the proteins identified as significant using three different biostatistical models resulted in a short list of four potential biomarkers: galectin-3-binding protein (Gal-3BP), fucolectin-6, urokinase plasminogen activator surface receptor and ryanodine receptor 3. The physiological functions described for these proteins in mammals designate them as interesting indicators of inflammatory diseases also in other species, such as PRV-1 pathogenesis in salmon. In situ-hybridisation targeting Gal-3BP and PRV-1 mRNA in heart tissue sections from the same challenge trial showed a significant upregulation of Gal-3BP mRNA in infected salmon hearts as compared to controls, supporting the findings of the proteomic analysis and suggesting a role in the onset of heart- and skeletal muscle inflammation.

Clinical and Molecular Spectrum of Autosomal Recessive CA8-Related Cerebellar Ataxia.

Based on a limited number of reported families, biallelic CA8 variants have currently been associated with a recessive neurological disorder named, cerebellar ataxia, mental retardation, and dysequilibrium syndrome 3 (CAMRQ-3). We aim to comprehensively investigate CA8-related disorders (CA8-RD) by reviewing existing literature and exploring neurological, neuroradiological, and molecular observations in a cohort of newly identified patients. We analyzed the phenotype of 27 affected individuals from 14 families with biallelic CA8 variants (including data from 15 newly identified patients from eight families), ages 4 to 35 years. Clinical, genetic, and radiological assessments were performed, and zebrafish models with ca8 knockout were used for functional analysis. Patients exhibited varying degrees of neurodevelopmental disorders (NDD), along with predominantly progressive cerebellar ataxia and pyramidal signs and variable bradykinesia, dystonia, and sensory impairment. Quadrupedal gait was present in only 10 of 27 patients. Progressive selective cerebellar atrophy, predominantly affecting the superior vermis, was a key diagnostic finding in all patients. Seven novel homozygous CA8 variants were identified. Zebrafish models demonstrated impaired early neurodevelopment and motor behavior on ca8 knockout. Our comprehensive analysis of phenotypic features indicates that CA8-RD exhibits a wide range of clinical manifestations, setting it apart from other subtypes within the category of CAMRQ. CA8-RD is characterized by cerebellar atrophy and should be recognized as part of the autosomal-recessive cerebellar ataxias associated with NDD. Notably, the presence of progressive superior vermis atrophy serves as a valuable diagnostic indicator. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Sex hormone-binding globulin is a valuable diagnostic indicator of gestational diabetes mellitus

Objective: To assess the performance of the Sex Hormone-Binding Globulin (SHBG) assay as a diagnostic indicator of Gestational Diabetes Mellitus (GDM) in the study population.Design: Analytical cross-sectional studySetting: Hospital-based, Benue State University Teaching Hospital (BSUTH), Makurdi, Nigeria.Participants: Women with singleton pregnancies at 24 to 28 weeks gestational age attending Antenatal care at BSUTH, Makurdi.Intervention: Serum SHBG levels were assayed by ELISA during a diagnostic 75-gram Oral Glucose Tolerance Test (OGTT) for assessment of GDM in the cohort of consecutively selected participants who met the inclusion criteria.Main Outcome Measures: Serum levels of SHBG and presence of GDM in the participants.Result: Serum SHBG was significantly negatively correlated (rpb = - 0.534, p-value < 0.001) with the presence of GDM. It had an area under the ROC curve of 0.897 (95% Confidence Interval = 0.858–0.935; p-value < 0.001). A cut-off value of 452.0 nmol/L indicative of GDM had a diagnostic odds ratio of 21.4 in the study population.Conclusion: SHBG is a valuable diagnostic indicator for GDM in the study population.

Predictive value of the neutrophil-to-lymphocyte ratio in the prognosis and risk of death for adult sepsis patients: a meta-analysis.

The neutrophil-to-lymphocyte ratio (NLR) is a commonly used biomarker for acute inflammation that often rises during sepsis, making it a valuable diagnostic indicator for clinical practice. However, no consensus has been reached on the prognostic value of NLR for predicting the prognosis and mortality risk in adult sepsis patients. In light of this controversy, we conducted a meta-analysis to clarify the prognostic significance of NLR in adult sepsis patients. The meta-analysis was registered in the PROSPERO database (registration number CRD42023433143). We performed a comprehensive literature search in PubMed, Cochrane Library, Ovid, and Springer databases, using retrieval terms "sepsis" or "septic shock" and "prognosis" or "mortality" for studies published between January 1, 2000, and May 31, 2023. Children and neonates with sepsis were excluded from our research. Two independent researchers conducted the literature search and data extraction. Consensus was reached when discrepancies occurred, and in case of persistent discrepancies, the final decision was made by the research supervisor. The hazard ratio (HR) and its corresponding 95% confidence interval (95% CI) were extracted from each study included in the analysis. A random-effects model was used to synthesize all HRs and their 95% CIs. Sensitivity analysis was performed to investigate heterogeneity. Sensitivity analysis was conducted to identify studies that had a significant impact on the overall results of the meta-analysis. Subgroup analysis and meta-regression were performed to explore sources of heterogeneity. Egger's test was also used to investigate publication bias in this meta-analysis. After a comprehensive literature search and screening, we included 12 studies comprising 10,811 patients for the meta-analysis. The pooled results indicated that patients with a higher NLR level were associated with a poor prognosis (Random-effects model, HR: 1.6273, 95% CI: 1.3951-1.8981). Heterogeneity testing showed significant heterogeneity (I2 = 87.2%, 95% CI: 79.5-92, p<0.0001). Sensitivity analysis was performed to investigate the sources of heterogeneity, which revealed that the omission of one highly sensitive study significantly reduced the I2 value. After removing this study, a strong association was found between a higher NLR level and poor prognosis and risk of death in adult sepsis patients (Random-effects model, HR: 1.6884, 95% CI: 1.4338-1.9882). Both subgroup analysis and meta-regression indicated that the study design and testing time of NLR were sources of heterogeneity. Egger's test showed no obvious publication bias in this meta-analysis. NLR is a reliable and valuable biomarker for predicting prognosis and the risk of death in adult sepsis patients. [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023433143] PROSPERO, identifier [CRD42023433143].

Diagnostic value of measuring the talofibular space using stress sonography in chronic lateral ankle instability

ObjectivesTo investigate the diagnostic value of measuring the talofibular space using stress sonography for chronic lateral ankle instability (CLAI). Materials & methodsWe recruited patients who were clinically diagnosed with CLAI between October 2018 and December 2019 (CLAI group). A control group of healthy volunteers was also included for this study. Both groups underwent a preliminary stress sonographic examination. First, the ultrasonic characteristics of the anterior talofibular ligament (ATFL), including length, thickness, relaxation, calcification, and rupture, were observed using conventional sonography. Second, the talofibular space at the passive neutral position (D1) and maximum varus position (D2) was measured (by stress sonographic images), and the difference (ΔD = D1-D2) between them was determined. Third, the parameters of the two groups were statistically compared. Finally, receiver operating characteristic (ROC) curves and area under the curve (AUC) analyses were performed for parameters with significant differences. ResultsThe CLAI group comprised 60 patients, yielding data on 60 ankles, whereas the control group comprised 35 participants, yielding data for 70 ankles. Differences in D1, D2, and ΔD of the talofibular space between the two groups were significant, with ΔD proving to be the best diagnostic indicator (P < 0.001). Its AUC, optimal cutoff value, sensitivity, and specificity were 0.922, 0.11 cm, 73 %, and 94 %, respectively, followed by D2 (0.850, 0.47 cm, 67 %, and 94 %, respectively; P < 0.001) and D1 (0.635, 0.47 cm, 67 %, and 94 %, respectively; P = 0.006). ConclusionMeasurement of talofibular space in stress sonography is a valuable diagnostic indicator for CLAI, especially the ΔD between the neutral and stress position.

PI3K/AKT signaling activates HIF1α to modulate the biological effects of invasive breast cancer with microcalcification.

Microcalcification (MC) is a valuable diagnostic indicator of breast cancer, and it is reported to be associated with increased tumor aggressiveness and poor prognosis. Nevertheless, the exact potential molecular mechanism is not completely understood. Here, we find that the mineralized invasive breast cancer (IBC) cells not only increased their proliferation and migration, but also showed the characteristic of doxorubicin resistance. The PI3K/AKT signaling pathway is associated with the generation of calcification in IBC, and it activates the transcription and translation of its downstream hypoxia-inducible factor 1α (HIF1α). Knockdown of HIF1α protein significantly downregulated cell proliferation and migration while calcification persists. Meanwhile, calcified breast cancer cells restored sensitivity to doxorubicin because of suppressed HIF1α expression. In addition, we provide initial data on the underlying value of HIF1α as a biomarker of doxorubicin resistance. These findings provide a new direction for exploring microcalcifications in IBC.

The role and clinical relevance of long non-coding RNAs in glioma

Glioma represents a complex and heterogeneous disease, posing significant challenges to both clinicians and researchers. Despite notable advancements in glioma treatment, the overall survival rate for most glioma patients remains dishearteningly low. Hence, there is an urgent necessity to discover novel biomarkers and therapeutic targets specifically tailored for glioma. In recent years, long non-coding RNAs (lncRNAs) have emerged as pivotal regulators of gene expression and have garnered attention for their involvement in the development and progression of various cancers, including glioma. The dysregulation of lncRNAs plays a critical role in glioma pathogenesis and influences clinical outcomes. Consequently, there is growing interest in exploring the potential of lncRNAs as diagnostic and prognostic biomarkers, as well as therapeutic targets. By understanding the functions and dysregulation of lncRNAs in glioma, researchers aim to unlock new avenues for the development of innovative treatment strategies catered to glioma patients. The identification and thorough characterization of lncRNAs hold the promise of novel therapeutic approaches that could potentially improve patient outcomes and enhance the management of glioma, ultimately striving for better prospects and enhanced quality of life for those affected by this challenging disease. The primary objective of this paper is to comprehensively review the current state of knowledge regarding lncRNA biology and their intricate roles in glioma. It also delves into the potential of lncRNAs as valuable diagnostic and prognostic indicators and explores their feasibility as promising targets for therapeutic interventions.

Association of sexual dysfunction according to DSM-5 diagnostic criteria with avoidance of and discomfort during sex in a population-based sample.

Sexual dysfunction frequencies and diagnostic indicators among older populations are relevant for public health measures, but evidence from large population-based studies is still scarce. To determine sexual dysfunction frequencies for women and men according to the Diagnostic and Statistical Manual of Mental Disorders (fifth edition; DSM-5) among 45- to 74-year-old participants of the population-based Hamburg City Health Study and the factors associated with sexual dysfunction diagnoses. We determined sexual dysfunction frequencies according to the DSM-5 and the factors associated with sexual dysfunction diagnoses (quality/avoidance of and discomfort during sex) among 45- to 74-year-olds from 7786 participants of the population-based Hamburg City Health Study. We analyzed cross-sectional self-report questionnaire data collected between 2016 and 2019 using descriptive statistics, comparative tests (Fisher test, Mann-Whitney U test), and logistic regression. Outcomes included sexual dysfunction frequencies - specifically, sexual difficulties experienced frequently or more often, over at least six months in the last year, causing severe or very severe distress, and not associated with physical health or relationship problems - and items on quality/avoidance of and discomfort during sex. Participants' median age was 62.0 years (IQR,14) and 51.1% were women. The frequency of sexual dysfunction according to the DSM-5 was 9.3% (95% CI, 8.3%-10.4%) in women and 6.2% (95% CI, 5.4%-7.1%) in men, with women's sexual interest/arousal and men's erectile disorder being most common. Sexual dysfunction rates increased with age: whereas complaints were more frequent among women than men in the younger groups, participants aged ≥65 years with a sexual dysfunction were more often men. Quality/avoidance of and discomfort during sex were significantly associated with a diagnosis of sexual dysfunction. Results suggest that sexual dysfunction caused by other than physical health or relationship factors is important to consider in this population. In addition, the avoidance of, perceived quality of, and discomfort during sex serve as valuable diagnostic indicators for the presence of sexual dysfunction. This study draws on robust data from a large sample to give valuable insight on the frequency of sexual difficulties and dysfunctions as defined by DSM-5 criteria. Limitations represent the restriction to self-report questionnaire data, the focus on participants living in a metropolitan area, and the lack of experience of sexual difficulties due to a lack of sexual activity not being taken into account. The study provides estimates for DSM-5 sexual dysfunction frequencies among Germans from a metropolitan area and points to the diagnostic value of age-related changes as well as the quality/avoidance of and discomfort during sex.

Clinical and pathological features analysis of invasive breast cancer with microcalcification.

Microcalcification (MC) is a valuable diagnostic indicator to detect invasive breast cancer (IBC). This study aimed to determine the clinicopathological features of IBC with MC and detect biomarkers related to the potential mechanism of the MC formation in IBC. Data from 364 patients with IBC were collected for the clinical characteristic analysis. The analysis of clinical data helped us to establish a predictive model of axillary node metastasis (ANM) before surgery. In addition, 49 tissue samples of IBC patients were collected to test the protein levels of osteocalcin (OCN) and hypoxia-inducible factor-1α (HIF-1α) by immunohistochemistry. Significant differences were observed in tumor size, age, ANM, HER2+ , TNM stage, and mutant P53 between samples from IBC patients with MC and samples from IBC patients without MC. Younger age, a larger tumor size, a higher number of childbirths, and MC were independent predictors for ANM in IBC. HIF-1α protein level was higher in tumor tissue than in normal tissue. High protein levels of OCN and HIF-1α are related to the complication of MC in IBC. Of the patients that exhibited high HIF-1α protein levels, the percentage of high OCN protein levels was larger in patients with ANM. Based on this study, we concluded that patients with MC had a comparatively poor prognosis. MC was an independent predictive factor associated with the risk of ANM. High protein levels of OCN and HIF-1α were associated with MC and ANM, which were also related to poor prognosis. OCN and HIF-1α had a positive correlation in IBC.

Stool Image Analysis for Digital Health Monitoring By Smart Toilets

Gastrointestinal (GI) conditions are widespread and significantly impact the quality of life and healthcare. Stool appearance is a valuable GI diagnostic indicator, and with the advent of the Internet of Things (IoT), daily monitoring of excreta from a toilet is emerging as a promising digital health tool. This article describes a stool image analysis approach that classifies two physiologically relevant stool characteristics: 1) form and 2) color for an IoT-based smart toilet. We constructed a stool image data set with 3275 images, spanning all seven types of the Bristol stool-form scale (BSFS), a widely used metric for stool consistency and a variety of colors. We used ground-truth data obtained through the annotation of our data set by two gastroenterologists and developed a stool-color card to standardize the labeling of stool colors. We addressed two limitations associated with the application of computer-vision techniques to a smart-toilet system: 1) uneven separability between different stool-form categories and 2) class imbalance in the data set. We present results on hierarchical convolutional neural network (CNN) architectures for training a stool-form classifier and on perceptual color quantization coupled with machine-learning techniques to optimize the color-feature space for the classification of stool color. We utilized an edge–cloud approach to pursue an optimal balance between accuracy and latency and for the classification of stool form, we achieved a balanced accuracy of 84.4% and 84.2% reduction in latency compared to a cloud-model only. For color classification, the logistic-regression (LR) classifier provided 80.8% balanced accuracy and 47.3% reduction in communication latency.

Multiple Machine Learning Approaches for Morphometric Parameters in Prediction of Hydrocephalus.

The diagnosis of hydrocephalus is mainly based on imaging findings. However, the significance of many imaging indicators may change, especially in some degenerative diseases, and even lead to misdiagnosis. This study explored the effectiveness of commonly used morphological parameters and typical radiographic findings in hydrocephalus diagnosis. The patients' imaging data were divided into three groups, including the hydrocephalus group, the symptomatic group, and the normal control group. The diagnostic validity and weight of various parameters were compared between groups by multiple machine learning methods. Our results demonstrated that Evans' ratio is the most valuable diagnostic indicator compared to the hydrocephalus group and the normal control group. But frontal horns' ratio is more useful in diagnosing patients with symptoms. Meanwhile, the sign of disproportionately enlarged subarachnoid space and third ventricle enlargement could be effective diagnostic indicators in all situations. Both morphometric parameters and radiological features were essential in diagnosing hydrocephalus, but the weights are different in different situations. The machine learning approaches can be applied to optimize the diagnosis of other diseases and consistently update the clinical diagnostic criteria.

Crop Diversification Effects on Soil Aggregation and Aggregate-Associated Carbon and Nitrogen in Short-Term Rainfed Olive Groves under Semiarid Mediterranean Conditions

Soil particle aggregation and their associated carbon (C) and nitrogen (N) content can provide valuable diagnostic indicators of changes in soil properties in response to the implementation of different agricultural management practices. In this sense, there is limited knowledge regarding the impact of intercropping on soil organic carbon (SOC) and total nitrogen (TN) pools in aggregates. This study aimed to evaluate the short-term effect (4 years) of three crop diversifications in rainfed olive orchards on soil aggregation, SOC and TN concentration and SOC stocks (SOC-S) under semi-arid Mediterranean conditions. Olive orchards were diversified with Crocus sativus (D-S), Vicia sativa and Avena sativa in rotation (D-O) and Lavandula x intermedia (D-L) and compared with monocropping system (CT). Soil samples were collected at two depths (0–10 and 10–30 cm) and analysed for soil aggregate mass, SOC and TN content in aggregate-size fractions obtained by the wet-sieving method. Changes caused by crop diversifications on SOC-S were also determined. Overall, after 4 years, a reduction in aggregation values was observed. However, D-S increased the macroaggregates (&gt;250 μm) percentage, Mean Weigh Diameter values, and Geometric Mean Value in the 0–10 cm. Across treatments, aggregate-associated C in 0–10 cm was higher in the D-S treatment, while in the 10–30 cm soil layer, the greatest values were found in CT. Regarding the SOC-S, after 4 years, significant losses were recorded under CT management in 0–10 cm (−1.21 Mg ha−1) and 10–30 cm (−0.84 Mg ha−1), while D-O and D-L showed similar values to those obtained at the beginning of the study. The highest increases in SOC-S were found in D-S, with an increase of 5.88% in the 0–10 cm and 14.47% in the 10–30 cm. Our results showed the high potential of the diversified cropping system to increase soil stability and SOC sequestration.

Establishing Classification Tree Models in Rheumatoid Arthritis Using Combination of Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry and Magnetic Beads.

Background: There is no simple method for early diagnosis and evaluation of rheumatoid arthritis (RA). This study aimed to determine potential biomarkers and establish diagnostic patterns for RA using proteomic fingerprint technology combined with magnetic beads.Methods: The serum protein profiles of 97 RA patients and 76 healthy controls (HCs) were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) with weak cationic exchange (WCX) magnetic beads. Samples were randomly divided into training (83 RA patients and 56 HCs) and test sets (14 RA patients and 20 HCs). Patients were classified according to their Disease Activity Score: in remission, n = 28; with low disease activity, n = 17; with moderate disease activity, n = 21; with high disease activity, n = 31. There are 44 RA patients alone, 22 RA patients with interstitial lung disease (RA-ILD), 18 RA patients with secondary Sjögren's syndrome (RA-sSS), 6 RA patients with osteonecrosis of the femoral head (RA-ONFH), and 7 RA patients with other complications. Eleven patients were treated with etanercept only for half a year, after which their serum protein profiles were detected. The proteomic pattern was identified by Biomarker Patterns Software, and the potential biomarkers for RA diagnosis were further identified and quantified by enzyme-linked immunosorbent assay.Results: The diagnostic pattern with four potential protein biomarkers, mass-to-charge (m/z) 3,448.85, 4,716.71, 8,214.29, and 10,645.10, could accurately recognize RA patients from HCs (specificity, 91.57%; sensitivity, 92.86%). The test set were correctly classified by this model (sensitivity, 95%; specificity, 100%). The components containing the four biomarkers were preliminarily retrieved through the ExPasy database, including the C-C motif chemokine 24 (CCL24), putative metallothionein (MT1DP), sarcolipin (SLN), and C-X-C motif chemokine 11 (CCXL11). Only the CCL24 level was detected to have a significant decrease in the serum of RA patients as compared with HCs (p < 0.05). No significant difference was found in others, but a decreasing trend consistent with the down-regulation of the four biomarkers detected by MALDI-TOF-MS was observed. The diagnostic models could effectively discriminate between RA alone and RA with complications (RA-ILD: m/z 10,645.10 and 12,595.86; RA-sSS: m/z 6,635.62 and 33,897.72; RA-ONFH: m/z 2,071.689). The classification model, including m/z 1,130.776, 1,501.065, 2,091.198, and 11,381.87, could distinguish between RA patients with disease activity and those in remission. RA with low disease activity could be efficiently discriminated from other disease activity patients by specific protein biomarkers (m/z 2,032.31, 2,506.214, and Z9286.495). Two biomarkers (m/z 2,032.31 and 4,716.71) were applied to build the classification model for RA patients with moderate and high disease activities. Biological markers for etanercept (m/z 2,671.604064, 5,801.840579, 8,130.195641, and 9,286.49499) were observed between the responder (n = 7) and non-responder groups (n = 4) (p < 0.05).Conclusion: We successfully established a series of diagnostic models involving RA and RA with complications as well as assessed disease activity. Furthermore, we found that CCL24 may be a valuable auxiliary diagnostic indicator for RA. These results provide reference values for clinical practice in the future.

Pleural Fluid Cholesterol Level in Differentiating Exudate from Trasudate Pleural Effusion

Correlation of pleural fluid cholesterol level with light’s criteria to differentiate exudate from transudate pleural effusion. Classification of transudate and exudate clinically was done independently based on the light's criteria. Pleural fluid cholesterol levels of 100 selected patients were obtained. The cholesterol levels were compared with the earlier obtained data to study its specificity and sensitivity in differentiating exudate from transudate effusion. It was found that pleural fluid cholesterol in comparison to protein values in differentiating exudate from transudate showed a sensitivity of 79.55%, specificity of 91.07%, the positive predictive value of 87.50%, the negative predictive value of 85.00%, with a P-value of &lt;0.001. Comparison of pleural fluid cholesterol with LDH values showed a sensitivity of 86.36% specificity of 94.64%, the positive predictive value of 92.68%, the negative predictive value of 89.83%, with a P-value of &lt;0.001. Also, a comparison of pleural fluid cholesterol to light's criteria showed a sensitivity of 100% and 86.4% in the transudative group and sensitivity of 100% and 91.1 % in the exudative group, respectively. Routine measurement of pleural fluid cholesterol may serve as a valuable diagnostic indicator for differentiating exudate from transudate effusion.

Role of ascitic endocan levels in the diagnosis of spontaneous bacterial peritonitis in decompensated cirrhosis

Objective: To assess the role of ascitic endocan levels in the diagnosis of spontaneous bacterial peritonitis (SBP) in decompensated cirrhosis.Methods: Ascites samples, as well as demographic and laboratory data, were collected at admission from patients with decompensated cirrhosis. Ascitic endocan, tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were measured by ELISA. The influencing factors of SBP, the correlation of ascitic endocan with other inflammatory indicators, and the diagnostic value of ascitic endocan for SBP were analyzed.Results: A total of 167 patients were enrolled, 39 with the SBP group and 128 in the non-SBP group. Ascitic endocan, TNF-α, and IL-6 levels were significantly higher in the SBP group than in the non-SBP group (p < 0.001). Multivariate analysis demonstrated that ascitic endocan was an independent risk factor for SBP [OR = 1.006 (95% CI: 1.002–1.011); p < 0.001]. Endocan was positively correlated with ascites polymorphonuclear leukocytes, TNF-α, and IL-6. ROC curve analysis showed that ascitic endocan had an AUC of 0.805 for the diagnosis of SBP (p < 0.001) and had a sensitivity of 82.1% and specificity of 73.4% when the cut-off value was 295.011 pg/ml.Conclusions: Ascitic endocan level is an independent risk factor and a valuable diagnostic indicator for SBP in decompensated cirrhosis.

Screening and identification of serum biomarkers of osteoarticular tuberculosis based on mass spectrometry.

BackgroundIn view of the current difficulty of clinically diagnosing osteoarticular tuberculosis, our aim was to use mass spectrometry to establish diagnostic models and to screen and identify serum proteins which could serve as potential diagnostic biomarkers for early detection of osteoarticular tuberculosis.MethodsMatrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS) was used to select an osteoarticular tuberculosis‐specific serum peptide profile and establish diagnostic models. Further, liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) was used to identify potential serum biomarkers that could be used for auxiliary diagnosis of osteoarticular tuberculosis, and then clinical serum samples were used to verify these biomarkers by enzyme‐linked immunosorbent assay (ELISA).ResultsWe established four diagnostic models that can distinguish osteoarticular tuberculosis from rheumatoid arthritis, ankylosing spondylitis, osteoarticular infections, and healthy adults. The models were osteoarticular tuberculosis‐rheumatoid arthritis, osteoarticular tuberculosis‐ankylosing spondylitis, osteoarticular tuberculosis‐osteoarticular infections, and osteoarticular tuberculosis‐healthy adult, and their accuracy was 76.78%, 79.02%, 83.77%, and 88.16%, respectively. Next, we selected and identified 18 proteins, including complement factor H‐related protein 1 (CFHR1) and complement factor H‐related protein 2 (CFHR2), which were upregulated in the tuberculosis group only.ConclusionsWe successfully established four diagnostic models involving osteoarticular tuberculosis, rheumatoid arthritis, ankylosing spondylitis, osteoarticular infections, and healthy adults. Furthermore, we found that CFHR1 and CFHR2 may be two valuable auxiliary diagnostic indicators for osteoarticular tuberculosis. These results provide reference values for rapid and accurate diagnosis of osteoarticular tuberculosis.

Determination of 27 amino acids’ levels in seminal plasma of asthenospermia and oligospermia patients and diagnostic value analysis

•Amino acids (AAs) are abundant in seminal fluid and play an important role in the reproduction process. However, the functional significance of AAs in seminal is not clear. This study was designed to profile the AAs in seminal fluid of asthenozoospermia (AS) and oligospermia (OL) patients and evaluate its potential diagnostic value. To determine the true function of AAs in seminal fluid, an ultra high performance liquid chromatography-mass spectrometry (UPLC-MS/MS) was developed and validated. The seminal fluid samples collected from 76 AS patients, 58 OL patients, and 76 healthy subjects were determined by UPLC-MS/MS and analyzed by fisher discriminant and receiver operating characteristic (ROC). The results showed that, the AAs levels were dramatically decreased in AS and OL patients compared with healthy subjects. What’s more there were significant variation in the AAs profile of AS and OL patients. Specifically, some polar AAs decreased, while nonpolar AAs increased in OL patients. Based on the level of AAs, 93.4 % of original and 90.9 % of cross-validated grouped cases were correctly classified between AS patients, OL patients, and healthy subjects. The further ROC analysis shows that glutamic acid, tyrosine, aspartic acid, proline, and tryptophan have the diagnostic value (P < 0.01) in the three groups. Moreover, aspartic acid and glutamic acid exhibit a high correlation (Correlation Coefficient >0.9) in AS, OL, and healthy subjects. In conclusion, there are significant variation in AAs profile in seminal plasma of AS and OL patients with high accuracy in fisher classification. The associations between the levels of AAs in seminal fluid of AS, OL, and healthy subjects may have clinical applications in providing valuable diagnostic indicator.

Liver contrast-enhanced sonography: computer-assisted differentiation between focal nodular hyperplasia and inflammatory hepatocellular adenoma by reference to microbubble transport patterns

A new computer tool is proposed to distinguish between focal nodular hyperplasia (FNH) and an inflammatory hepatocellular adenoma (I-HCA) using contrast-enhanced ultrasound (CEUS). The new method was compared with the usual qualitative analysis. The proposed tool embeds an "optical flow" algorithm, designed to mimic the human visual perception of object transport in image series, to quantitatively analyse apparent microbubble transport parameters visible on CEUS. Qualitative (visual) and quantitative (computer-assisted) CEUS data were compared in a cohort of adult patients with either FNH or I-HCA based on pathological and radiological results. For quantitative analysis, several computer-assisted classification models were tested and subjected to cross-validation. The accuracies, area under the receiver-operating characteristic curve (AUROC), sensitivity and specificity, positive predictive values (PPVs), negative predictive values (NPVs), false predictive rate (FPRs) and false negative rate (FNRs) were recorded. Forty-six patients with FNH (n = 29) or I-HCA (n = 17) with 47 tumours (one patient with 2 I-HCA) were analysed. The qualitative diagnostic parameters were accuracy = 93.6%, AUROC = 0.94, sensitivity = 94.4%, specificity = 93.1%, PPV = 89.5%, NPV = 96.4%, FPR = 6.9% and FNR = 5.6%. The quantitative diagnostic parameters were accuracy = 95.9%, AUROC = 0.97, sensitivity = 93.4%, specificity = 97.6%, PPV = 95.3%, NPV = 96.7%, FPR = 2.4% and FNR = 6.6%. Microbubble transport patterns evident on CEUS are valuable diagnostic indicators. Machine-learning algorithms analysing such data facilitate the diagnosis of FNH and I-HCA tumours. • Distinguishing between focal nodular hyperplasia and an inflammatory hepatocellular adenoma using dynamic contrast-enhanced ultrasound is sometimes difficult. • Microbubble transport patterns evident on contrast-enhanced sonography are valuable diagnostic indicators. • Machine-learning algorithms analysing microbubble transport patterns facilitate the diagnosis of FNH and I-HCA.

Diagnostic indicators for adult-onset neuronal intranuclear inclusion disease.

Adult-onset neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder. Abnormally high signals of diffusion-weighted image (DWI) along the corticomedullary junction are a useful diagnostic indicator for patients with adult-onset NIID. However, the DWI abnormalities usually were observed in the late stage of disease; further study might be helpful to elucidate some clinical indicators regarding the early awareness of NIID. In this study, we summarized 9 patients with NIID from multiple centers. The mean age was 60.0 ± 6.2 years. The mean duration of disease was 4.4 ± 3.2 years. The most common symptoms included cognitive impairment, episodic encephalopathy, and bladder dysfunction. Among the 6 patients with bladder dysfunction, 3 patients had the symptom prior to the development of other neurological symptoms; 5 patients needed permanent cystostomy. Isolated high DWI signals on the splenium of corpus callosum were observed in 2 patients at the early stage. The characteristic intranuclear inclusions in the skin were identified in all patients and confirmed by electron microscopy. Episodic encephalopathy or bladder dysfunction prior to other neurological symptoms were valuable diagnostic indicators for adult-onset NIID. High DWI signals on the splenium of corpus callosum might be an early indicator for the diagnosis of NIID. The immunostain of anti-ubiquitin or anti-p62 antibody was a convenient and sensitive biomarker for NIID with the background of typical phenotype with cognitive impairment and autonomic dysfunctions.

A New Risk Index Combining d-Dimer, Fibrinogen, HE4, and CA199 Differentiates Suspecting Endometrial Cancer From Patients With Abnormal Vaginal Bleeding or Discharge.

Purpose:To establish an efficient new risk index for screening patients with endometrial cancer from patients with abnormal vaginal bleeding or discharge.Method:A total of 254 patients with abnormal vaginal bleeding or discharge were included in this study. Several candidate markers, including HE4, CA125, CA199, CA153, AFP, CEA, d-dimer, and fibrinogen, were employed. A new risk index for endometrial cancer screening was established by binary logistic regression. The diagnostic value of the candidate markers and the new risk index were assessed by a receiver operating characteristic curve, sensitivity, and specificity.Results:The most valuable diagnostic indicator for endometrial cancer was HE4, followed by d-dimer and then fibrinogen (area under the receiver operating characteristic curve: HE4 = 0.794, d-dimer = 0.717, fibrinogen = 0.690). The new risk index was superior to a single application of markers and a widely used combination (HE4 and CA125). At the ideal cutoff level, the sensitivity and specificity were 91.34% and 70.08%, respectively. In addition, only patients without organic disease served as controls, which further increase its performance (area under the receiver operating characteristic curve = 0.932, sensitivity = 94.49%, and specificity = 77.42%).Conclusions:The new risk index combining HE4, d-dimer, fibrinogen, and CA199 was the ideal combination for the screening of endometrial cancer. As a simple, rapid, nondestructive detection method, the new risk index is worth promotion in clinical practice, especially in primary medical institutions.