Significant Diagnostic Value Research Articles

A retinal vessel segmentation network approach based on rough sets and attention fusion module

The morphological changes of retinal vessels are of significant diagnostic value for early ophthalmic diseases and can aid in distinguishing other conditions such as diabetes and cardiovascular diseases. However, precise segmentation poses a challenge due to the complex structure of retinal vessels. To address these issues, we propose a Rough Attention Fusion Module (RAFM). This module employs max-pooling and average-pooling to define the upper and lower bounds of feature significance, introducing upper and lower weight matrices to obtain more reasonable attention coefficients. This enables the model to more accurately focus on important features in retinal images. Additionally, we integrate the RAFM into the GTS U-Net model, a simplified version of the GT U-Net model, which enhances the segmentation accuracy while reducing computational complexity. Ultimately, we construct a retinal vessel segmentation network based on the RAFM along with Group Transformer. Finally, the network structure is tested on the public DRIVE color fundus image dataset, achieving an Accuracy, F1 score, and AUC of 0.9641, 0.8506, and 0.9820, respectively. In contrast to prevalent retinal vessel segmentation networks in the mainstream, our proposed network demonstrates certain strengths.

Relationship of immature granulocytes with disease activity in rheumatoid arthritis.

To determine whether the IG count (#) and IG percentage (%) are associated with disease activity in rheumatoid arthritis (RA). This retrospective study included 65 RA patients and 65 healthy controls. Clinical and demographic characteristics of controls and RA patients (at active period and when the patients achieved remission) were obtained from medical records. Disease activity was defined by disease activity score 28 (DAS28). Furthermore, the clinical disease activity index (CDAI), and simple disease activity index (SDAI) were calculated. For the differential diagnosis of RA patients from healthy controls, the cut-off value was estimated by making receiver-operator curves (ROC). In active RA patients, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), IG#, and IG% levels were significantly higher compared to the healthy controls (p < .001, for all). When the patients achieved remission, DAS28, CDAI, SDAI, ESR, CRP, IG#, and IG% values were significantly decreased (p < .001, for all). IG# and IG% were significantly positively correlated with DAS28, CDAI, SDAI, ESR, and CRP (p = .024, p = .008, p = .003, p < .001, p < .001, respectively). According to ROC curve analysis, IG% and IG# were the biomarkers to have a significant diagnostic value for RA with the area under the curve of 0.853 and 0.865 (p < .001, for all). The present study demonstrated that two novel inflammatory markers, IG# and IG%, can be useful for monitoring RA patients' disease activity. Furthermore, IG# and IG% can also be used as fast, inexpensive, and easily available complementary diagnostic markers to diagnose RA patients.

Machine Learning Model for Predicting Axillary Lymph Node Metastasis in Clinically Node Positive Breast Cancer Based on Peritumoral Ultrasound Radiomics and SHAP Feature Analysis.

This study seeks to construct a machine learning model that merges clinical characteristics with ultrasound radiomic analysis-encompassing both the intratumoral and peritumoral-to predict the status of axillary lymph nodes in patients with early-stage breast cancer. The study employed retrospective methods, collecting clinical information, ultrasound data, and postoperative pathological results from 321 breast cancer patients (including 224 in the training group and 97 in the validation group). Through correlation analysis, univariate analysis, and Lasso regression analysis, independent risk factors related to axillary lymph node metastasis in breast cancer were identified from conventional ultrasound and immunohistochemical indicators, and a clinical feature model was constructed. Additionally, features were extracted from ultrasound images of the intratumoral and its 1-5 mm peritumoral to establish a radiomics feature formula. Furthermore, by combining clinical features and ultrasound radiomics features, six machine learning models (Logistic Regression, Decision Tree, Support Vector Machine, Extreme Gradient Boosting, Random Forest, and K-Nearest Neighbors) were compared for diagnostic efficacy, and constructing a joint prediction model based on the optimal ML algorithm. The use of Shapley Additive Explanations (SHAP) enhanced the visualization and interpretability of the model during the diagnostic process. Among the 321 breast cancer patients, 121 had axillary lymph node metastasis, and 200 did not. The clinical feature model had an AUC of 0.779 and 0.777 in the training and validation groups, respectively. Radiomics model analysis showed that the model including the Intratumor +3 mm peritumor area had the best diagnostic performance, with AUCs of 0.847 and 0.844 in the training and validation groups, respectively. The joint prediction model based on the XGBoost algorithm reached AUCs of 0.917 and 0.905 in the training and validation groups, respectively. SHAP analysis indicated that the Rad Score had the highest weight in the prediction model, playing a significant role in predicting axillary lymph node metastasis in breast cancer. The predictive model, which integrates clinical features and radiomic characteristics using the XGBoost algorithm, demonstrates significant diagnostic value for axillary lymph node metastasis in breast cancer. This model can provide significant references for preoperative surgical strategy selection and prognosis evaluation for breast cancer patients, helping to reduce postoperative complications and improve long-term survival rates. Additionally, the utilization of SHAP enhancing the global and local interpretability of the model.

#3095 Pinpointing specific circulating microRNAs as putative biomarkers for chronic kidney disease and cardiovascular outcomes

Abstract Background and Aims Chronic kidney disease (CKD) affects over 10% of the worldwide population and entails a significant risk for cardiovascular disease (CVD), leading to an up to 500-fold increase in cardiovascular mortality in advanced stages. However, the pathophysiological mechanisms underlying kidney-heart intercommunication remain unknown. In recent years, microRNAs (miRNAs) emerged as critical regulators of gene expression and numerous miRNAs that have been implicated in both CKD and CVD pathogenesis. Still, so far, their role in kidney-heart crosstalk has not been addressed. In this study, we evaluated the expression of a panel of miRNAs in plasma from pre-dialysis CKD patients and explored their association with main comorbidities and significant outcomes in a 5-year follow up. Method The expression levels of miR-30c-5p, miR-132-3p, miR-199a-5p, and miR-324-3p was assessed by real time qRT-PCR in plasma samples from two cohorts of pre-dialysis CKD patients followed up at the Nephrology Department of Centro Hospitalar Universitário de São João (CHSJ, Porto, Portugal).The discovery cohort was established between November 2014 and August 2018 and comprises 52 CKD patients while the validation cohort comprises samples from 43 CKD patients who underwent a kidney biopsy for diagnostic purposes from November 2019 to December 2022. Patients with acute kidney injury, neoplasia diagnosis, recent infections (&amp;lt;1 week), or known psychiatric disorders were excluded from the study. Plasma samples from 38 healthy blood donors, recruited at the Immunohemotherapy Department of CHSJ, in which creatinine values were measured and considered normal were used as controls. Participants with a history of cancer, inflammatory, or infectious diseases and who were being treated with anti-inflammatory or anti-depressive drugs, were excluded. MiRs expression in comparison with the controls was validated in both cohorts and its expression in the Discovery cohort was correlated with the patients clinical data in a 5 year follow up. Results Results show that miR-30c-5p and miR-132-3p were downregulated in CKD patients compared with healthy controls, presenting a significant power to discriminate the disease condition. Still, considering the stratification of CKD in early/moderate (1-3) and advanced stages (4-5), only miR-30c-5p presented a decreased expression in the initial stages of the disease, showing a significant diagnostic value as an early biomarker for CKD, independently of eGFR. When analyzing the major disease outcomes in a 5 year time, miR-199a-5p was associated with increased frequency of CVD and mortality while miR-324-3p was downregulated in CKD patients that progressed to worse stages. Conclusion These findings highlight miR-30c-5p as a potential biomarker for the diagnosis of CKD in early stages of the disease and identify, for the first time, the enrollment of miR-199a-5p and miR-324-3p in kidney-heart pathophysiological crosstalk, paving the way for the putative establishment of new biomarkers and therapeutic targets for CKD and its outcomes.

Identification and validation of core genes associated with intracranial aneurysms through bioinformatics analysis and Mendelian randomization

Intracranial aneurysms (IAs) often go undetected until rupture, leading to significant morbidity and mortality. Identifying biomarkers for early detection of IAs is crucial. The current study attempted to identify core genes linked with IAs and determine their relevance through Mendelian randomization. Limma helped identify differentially expressed genes between IAs and control superficial temporal artery samples. WGCNA was utilized to find IA-related modules and associated genes, which were further evaluated using KEGG and GO analyses to ascertain their potential roles. Five highly associated genes were screened with the CytoHubba plugin of Cytoscape software. ROC curves assessed the diagnostic efficacy of these genes. A two-sample Mendelian randomization evaluated the causal relationship between the core gene PTRPC and IAs, along with its correlation with immune infiltration. WGCNA and differential expression analysis depicted 584 related genes involved in cellular metabolism and chemokine activity. PTPRC was among the top highly associated genes identified through Cytoscape. It showed significant diagnostic value for IAs. Moreover, mendelian randomization depicted that PTPRC in CD4+ T cells is related to IA risk, with an OR of 0.63538 (95 % CI = 0.41636–0.96959, p = 0.03545). No reverse causal relationship was observed between PTPRC and IAs, with an OR of 0.99947 (95 % CI = 0.99719–1.00176, p = 0.65022). Additionally, immune cell infiltration results indicated a positive correlation between PTPRC in IAs with neutrophils and unactivated dendritic cells and a negative association with regulatory T cells (Tregs). PTPRC was identified as a core gene linked with IAs, providing evidence for IA diagnosis and studying molecular mechanisms.

TPX2 upregulates MMP13 to promote the progression of lipopolysaccharide-induced osteoarthritis.

This study seeks to identify potential clinical biomarkers for osteoarthritis (OA) using bioinformatics and investigate OA mechanisms through cellular assays. Differentially Expressed Genes (DEGs) from GSE52042 (four OA samples, four control samples) were screened and analyzed with protein-protein interaction (PPI) analysis. Overlapping genes in GSE52042 and GSE206848 (seven OA samples, and seven control samples) were identified and evaluated using Gene Set Enrichment Analysis (GSEA) and clinical diagnostic value analysis to determine the hub gene. Finally, whether and how the hub gene impacts LPS-induced OA progression was explored by in vitro experiments, including Western blotting (WB), co-immunoprecipitation (Co-IP), flow cytometry, etc. Bioinformatics analysis of DEGs (142 up-regulated and 171 down-regulated) in GSE52042 identified two overlapping genes (U2AF2, TPX2) that exhibit significant clinical diagnostic value. These genes are up-regulated in OA samples from both GSE52042 and GSE206848 datasets. Notably, TPX2, which AUC = 0.873 was identified as the hub gene. In vitro experiments have demonstrated that silencing TPX2 can alleviate damage to chondrocytes induced by lipopolysaccharide (LPS). Furthermore, there is a protein interaction between TPX2 and MMP13 in OA. Excessive MMP13 can attenuate the effects of TPX2 knockdown on LPS-induced changes in OA protein expression, cell growth, and apoptosis. In conclusion, our findings shed light on the molecular mechanisms of OA and suggested TPX2 as a potential therapeutic target. TPX2 could promote the progression of LPS-induced OA by up-regulating the expression of MMP13, which provides some implications for clinical research.

MRI of shoulder girdle in polymyalgia rheumatica: inflammatory findings and their diagnostic value

BackgroundNon-synovial inflammation as detected by MRI is characteristic in polymyalgia rheumatica (PMR) with potentially high diagnostic value.ObjectiveThe objective is to describe inflammatory MRI findings in the shoulder girdle of patients...

Assessing the Diagnostic Efficacy of Handgrip Dynamometry and Diaphragmatic Ultrasound in Intensive Care Unit-Acquired Weakness.

The aim of this study is to examine the diagnostic significance of using handgrip dynamometry and diaphragmatic ultrasound in intensive care unit-acquired weakness (ICU-AW). This study included patients who received mechanical ventilation in the ICU at the Fourth Hospital of Hebei Medical University from July to December 2020. We collected comprehensive demographic data and selected conscious patients for muscle strength and ICU-AW assessments. The evaluation comprised grip strength measurement and bedside ultrasound for diaphragmatic excursion (DE) and thickening fraction (DTF). Results were documented for comparative analysis between patient groups, focusing on the diagnostic efficacy of grip strength, DE, DTF, and their combined application in diagnosing ICU-AW. A total of 95 patients were initially considered for inclusion in this study. Following the exclusion of 20 patients, a final cohort of 75 patients were enrolled, comprising of 32 patients (42.6%) diagnosed with ICU-AW and 43 patients (57.4%) classified as non-ICU-AW. Comparative analysis revealed that grip strength, DE, and DTF were significantly lower in the ICU-AW group (P < 0.05). Subgroup analysis specific to male patients demonstrated a noteworthy decrease in grip strength, DE, and DTF within the ICU-AW group (P < 0.05). Receiver operating characteristic curve analysis indicated statistically significant diagnostic value for ICU-AW with grip strength, DE, DTF, and grip strength and diaphragmatic ultrasound (P < 0.01). Furthermore, it was observed that the amalgamation of grip strength and diaphragmatic ultrasound significantly enhanced the diagnostic accuracy of ICU-AW in patients who are critically ill. Grip strength, DE, DTF, and the combined use of grip strength with diaphragm ultrasound demonstrated diagnostic efficacy in ICU-AW. Notably, the integration of grip strength with diaphragm ultrasound exhibited a heightened capacity to enhance the diagnostic value specifically in patients diagnosed who are critically ill with ICU-AW.

Bioinformatics-based analysis of the relationship between plasminogen regulatory genes and photoaging.

Ultraviolet radiation causes skin photoaging by producing a variety of enzymes, which impact both skin health and hinder beauty. Currently, the early diagnosis and treatment of photoaging remain a challenge. Bioinformatics analysis has strong advantages in exploring core genes and the biological pathways of photoaging. To screen and validate key risk genes associated with plasminogen in photoaging and to identify potential target genes for photoaging. Two human transcriptome datasets were obtained by searching the Gene Expression Omnibus (GEO) database, and the mRNAs in the GSE131789 dataset were differentially analyzed, and then the weighted gene co-expression network analysis (WGCNA) was performed to find out the strongest correlations. Template genes, interaction analysis of differentially expressed genes (DEGs), modular genes with the most WGCNA correlations, and genecard database genes related to plasminogen were performed, and further Kyoto genes and Genome Encyclopedia (KEGG) pathway analysis. Two different algorithms, least absolute shrinkage and selection operator (LASSO) and support vector machines-recursive feature elimination (SVM-RFE), were used to find key genes. Then the data set (GSE206495) was validated and analyzed. Real-time PCR was performed to validate the expression of key genes through invitro cellular experiments. IFI6, IFI44L, HRSP12, and BMP4 were screened from datasets as key genes for photoaging and further analysis showed that these genes have significant diagnostic value for photoaging. IFI6, IFI44L, HRSP12, and BMP4 play a key role in the pathogenesis of photoaging, and serve as promising potential predictive biomarkers for photoaging.

Identification of shared potential diagnostic markers in asthma and depression through bioinformatics analysis and machine learning

BackgroundThere is mounting evidence that asthma might exacerbate depression. We sought to examine candidates for diagnostic genes in patients suffering from asthma and depression. MethodsMicroarray data were downloaded from the Gene Expression Omnibus(GEO) database and used to screen for differential expressed genes(DEGs) in the SA and MDD datasets. A weighted gene co-expression network analysis(WGCNA) was used to identify the co-expression modules of SA and MDD. The least absolute shrinkage and selection operatoes(LASSO) and support vector machine(SVM) were used to determine critical biomarkers. Immune cell infiltration analysis was used to investigate the correlation between immune cell infiltration and common biomarkers of SA and MDD. Finally, validation of these analytical results was accomplished via the use of both in vivo and in vitro studies. ResultsThe number of DEGs that were included in the MDD dataset was 5177, whereas the asthma dataset had 1634 DEGs. The intersection of DEGs for SA and MDD included 351 genes, the strongest positive modules of SA and MDD was 119 genes, which played a function in immunity. The intersection of DEGs and modular hub genes was 54, following the analysis using machine learning algorithms,three hub genes were identified and employed to formulate a nomogram and for the evaluation of diagnostic effectiveness, which demonstrated a significant diagnostic value (area under the curve from 0.646 to 0.979). Additionally, immunocyte disorder was identified by immune infiltration. In vitro studies have revealed that STK11IP deficiency aggravated the LPS/IFN-γinduced up-regulation in M1 macrophage activation. ConclusionAsthma and MDD pathophysiology may be associated with alterations in inflammatory processes and immune pathways. Additionally, STK11IP may serve as a diagnostic marker for individuals with the two conditions.

Abnormal expression of long non‑coding RNA LINC01270 in glioma and its correlation with X‑ray computed tomography signs.

This study focused on the association of LINC01270 and computed tomography (CT) signs with glioma development, to evaluate their potential in the early detection of glioma. Serum LINC01270 was evaluated in glioma patients and healthy individuals using PCR. The involvement of LINC01270 in glioma onset and development was evaluated by ROC and chi‑square test. The association of LINC01270 with the CT signs and their combined effects in the diagnosis in glioma were also estimated. Serum LINC01270 was significantly elevated in glioma patients, which was closely associated with patients' advanced WHO grades and lower KPS. Both LINC01270 upregulation and CT findings showed significant potential in diagnosing glioma, and LINC01270 correlated significantly with the invasion risk and metastasis indicated on CT. The combination of LINC01270 expression and CT findings significantly improved the sensitivity and specificity of glioma diagnosis. Upregulated LINC01270 in glioma is associated with malignant and severe disease development and has significant diagnostic value. Combined detection of LINC01270 and CT findings could improve the diagnostic efficacy in glioma cases, thus optimizing clinical diagnosis.

The role of C-reactive protein:albumin ratio and Neutrophil:lymphocyte ratio in predicting coronary artery disease.

Acute coronary syndrome (ACS), one of the most common causes of death worldwide, is a condition characterised by ischaemia and/or infarction due to reduced coronary blood flow. The most prevalent cause of ACS is coronary artery disease. In this study, we aimed to investigate the relationship between blood parameters that we commonly use in the laboratory [C-reactive protein (CRP), albumin, neutrophils and lymphocytes] and coronary artery disease (CAD). This retrospective, single-centre study included 100 patients who underwent coronary angiography, with the diagnosis of acute coronary syndrome between January and June 2023, and 106 patients with high clinical suspicion and normal coronary arteries as a control group. The NLR was obtained from the ratio of neutrophils to lymphocytes and the CAR was obtained from the ratio of CRP to albumin. We analysed the relationship between CAD and NLR and CAR according to laboratory findings and demographic characteristics of the patients. The average age of the study group was 59 ± 10 years. NLR and CAR values were higher in the patient group than the control group (5.2 ± 3.3 vs 2.27 ± 1.2, p = 0.004 and 0.5 ± 0.1 vs 0.097 ± 0.095, respectively, p < 0.001). Albumin ratios were found to be statistically significantly lower in the patient group than the patient group (42.4 ± 4 vs 44 ± 3.3, respectively, p = 0.01). In addition, CAR and NLR showed a significant diagnostic value for CAD in receiver operating characteristic curve analysis (area under the curve: 0.68 ± 0.07, p = 0.003; 0.66 ± 0.09 p ≤ 0.001). NLR and CAR values, which are important indicators of inflammation, were found to be higher in the patient group. We believe it may be important to monitor these patients more frequently and follow them closely in terms of CAD, especially if the rate is higher in individuals without CAD who come for out-patient clinic check-ups.

Concurrent and Discriminant Validity of the Farsi Translation of the Social Responsiveness Scale-Second Edition (SRS-2) and Social Communication Questionnaire (SCQ).

Objective: Early detection of autism spectrum disorder (ASD) can lead to earlier intervention and greater improvement of children's quality of life and performance; hence, the use of screening tools is essential to facilitate the diagnosis process. The aim of the present study was to determine the clinical and differential validity of Social Responsiveness Scale-Second Edition (SRS-2) and Social Communication Questionnaire (SCQ) in a group of children and adolescents with autism spectrum disorder compared to a normal developmental group. Method : The study was conducted in Roozbeh Hospital involving 52 children with ASD and 53 typically developing (TD) children, aged between 4-12 years. Their parents completed the SRS-2 and SCQ. These children were also interviewed using the Childhood Autism Rating Scale, 2nd Edition (CARS-2) and Asperger Syndrome Diagnostic Scale (ASDS). After completion, the results were analyzed using the SPSS Version 18 software and a significant level of 0.05. Results: The average age of children in the autism group was 7.5 ± 2.7 years, while in the typically developing (TD) children group, it was 7.7 ± 2.3 years (P = 0.656). A positive correlation coefficient was observed between the CARS questionnaire score, the SRS questionnaire score, the SCQ questionnaire score, and the ASDS ‏(P < 0.01). In the SRS questionnaire, the area under the ROC curve was 0.976, and in the SCQ questionnaire it was 0.953, both of which had a good and significant diagnostic value (P < 0.001). A sensitivity of 0.942 and specificity of 0.811 for the cut-off point of 62.5 were obtained in the SRS questionnaire. Additionally, a sensitivity of 0.865 and specificity of 0.925 for the cut-off point of 15.5 were achieved in the SCQ questionnaire. Conclusion: The SRS-2 and the SCQ are sensitive and specific tools for identifying and discriminating children with autism spectrum disorder.

PARP9 affects myocardial function through TGF-β/Smad axis and pirfenidone.

Cardiac arrhythmias are often linked to the overactivity of cardiac fibroblasts (CFs). Investigating the impact of poly (ADP-ribose) polymerase 9 (PARP9) on Angiotensin II (Ang II)-induced fibroblast activation and the therapeutic effects of pirfenidone (PFD) offers valuable insights into cardiac arrhythmias. This study utilized weighted gene co-expression network analysis (WGCNA), differential gene expression (DEG) analysis, protein-protein interaction (PPI), and receiver operating characteristic (ROC) analysis on the GSE42955 dataset to identify the hub gene with a significant diagnostic value. The ImmuCellAI tool revealed an association between PARP9 and immune cell infiltration. Our in vitro assessments focused on the influence of PFD on myofibroblast differentiation, transforming growth factor-beta (TGF-β) expression, and Ang II-induced proliferation and migration in CFs. Additionally, we explored the impact on fibrosis markers and the TGF-β/Smad signaling pathway in the context of PARP9 overexpression. Analysis of the GSE42955 dataset revealed PARP9 as a central gene with high clinical diagnostic value, linked to seven types of immune cells. The in vitro studies demonstrated that PFD significantly mitigates Ang II-induced CF proliferation, migration, and fibrosis. It also reduces Ang II-induced PARP9 expression and decreases fibrosis markers, including TGF-β, collagen I, collagen III, and α-SMA. Notably, PARP9 overexpression can partially counteract PFD's inhibitory effects on CFs and modify the expression of fibronectin, CTGF, α-SMA, collagen I, collagen III, MMP2, MMP9, TGF-β, and p-Smad2/3 in the TGF-β/Smad signaling pathway. In summary, our findings suggest that PFD effectively counteracts the adverse effects of Ang II-induced CF proliferation and fibrosis, and modulates the TGF-β/Smad signaling pathway and PARP9 expression. This identifies a potential therapeutic approach for managing myocardial fibrosis.

Association between subclinical atherosclerosis burden and unrecognized myocardial infarction detected by cardiac magnetic resonance in middle-aged low-risk adults.

Evidence on the association between subclinical atherosclerosis (SA) and cardiovascular (CV) events in low-risk populations is scant. To study the association between SA burden and an ischaemic scar (IS), identified by cardiac magnetic resonance (CMR), as a surrogate of CV endpoint, in a low-risk population. A cohort of 712 asymptomatic middle-aged individuals from the Progression of Early SA (PESA-CNIC-Santander) study (median age 51 years, 84% male, median SCORE2 3.37) were evaluated on enrolment and at 3-year follow-up with 2D/3D vascular ultrasound (VUS) and coronary artery calcification scoring (CACS). A cardiac magnetic study (CMR) was subsequently performed and IS defined as the presence of subendocardial or transmural late gadolinium enhancement (LGE). On CMR, 132 (19.1%) participants had positive LGE, and IS was identified in 20 (2.9%) participants. Individuals with IS had significantly higher SCORE2 at baseline and higher CACS and peripheral SA burden (number of plaques by 2DVUS and plaque volume by 3DVUS) at both SA evaluations. High CACS and peripheral SA (number of plaques) burden were independently associated with the presence of IS, after adjusting for SCORE2 [OR for 3rd tertile, 8.31; 95% confidence interval (CI) 2.85-24.2; P < 0.001; and 2.77; 95% CI, 1.02-7.51; P = 0.045, respectively] and provided significant incremental diagnostic value over SCORE2. In a low-risk middle-aged population, SA burden (CAC and peripheral plaques) was independently associated with a higher prevalence of IS identified by CMR. These findings reinforce the value of SA evaluation to early implement preventive measures. Progression of Early Subclinical Atherosclerosis (PESA) Study Identifier: NCT01410318.

Role of TNF superfamily members lymphotoxin-α, sCD40L, and TNF-α in endometriosis-related infertility

Introduction: TNF-α, LT-α, and sCD40L belong to the TNF superfamily and play a pivotal role in chronic inflammatory disease. Yet, these soluble molecules are largely unexplored in endometriosis cases with infertility. The present study aimed to evaluate serum and peritoneal fluid levels of these molecules and correlate its level to the endometriosis severity. Methods: Peripheral blood and peritoneal fluid samples were obtained from 87 infertility cases who underwent laparoscopy, consisting of 44 endometriotic women and 43 non-endometriotic women. The levels of TNF-α, LT-α, and sCD40L were determined using ELISA. Results: Serum and peritoneal TNF-α levels were significantly elevated in the endometriosis group compared to the control group ( p = 0.028; p = 0.027), but not the sCD40L and LT-α level. Serum and peritoneal TNF-α levels were significantly different between late-endometriosis (stage III or IV) compared to the control group ( p = 0.026, p = 0.041, respectively). Moreover, the serum LT-α level was significantly higher in late-endometriosis cases compared to the early-endometriosis (stage I or II) cases ( p = 0.03) and showed a positive correlation with endometriosis rASRM score ( p = 0.001). ROC curve analysis showed a significant diagnostic value of serum LT-α in differentiating the late cases to the early endometriosis patients (AUC = 0.751, p = 0.007). A negative correlation between LT-α and total Endometriosis Fertility Index (EFI) score was also observed ( p = 0.012). Conclusion: Severe endometriosis and lower EFI score are associated with higher serum LT-α level. Serum LT-α is a potential staging biomarker among endometriosis cases. Serum and peritoneal TNF-α levels were elevated in women with severe endometriosis among infertility cases. Further study should address the role and predictive value of LT-α in endometriosis-related infertility.

Optimized fuzzy K-nearest neighbor approach for accurate lung cancer prediction based on radial endobronchial ultrasonography

Radial endobronchial ultrasonography (R-EBUS) has been a surge in the development of new ultrasonography for the diagnosis of pulmonary diseases beyond the central airway. However, it faces challenges in accurately pinpointing the location of abnormal lesions. Therefore, this study proposes an improved machine learning model aimed at distinguishing between malignant lung disease (MLD) from benign lung disease (BLD) through R-EBUS features. An enhanced manta ray foraging optimization based on elite perturbation search and cyclic mutation strategy (ECMRFO) is introduced at first. Experimental validation on 29 test functions from CEC 2017 demonstrates that ECMRFO exhibits superior optimization capabilities and robustness compared to other competing algorithms. Subsequently, it was combined with fuzzy k-nearest neighbor for the classification prediction of BLD and MLD. Experimental results indicate that the proposed modal achieves a remarkable prediction accuracy of up to 99.38%. Additionally, parameters such as R-EBUS1 Circle-dense sign, R-EBUS2 Hemi-dense sign, R-EBUS5 Onionskin sign and CCT5 mediastinum lymph node are identified as having significant clinical diagnostic value.

EVALUATION OF THE ROLE OF FINE NEEDLE ASPIRATION CYTOLOGY IN DIAGNOSIS OF BREAST LESIONS AND CORRELATION WITH HISTOPATHOLOGICAL EXAMINATION

Introduction : Breast carcinoma is one of the most common carcinomas among the women. FNAC is part of a TRIPLE APPROACH for the diagnosis of breast lumps:a) Clinical examination, b) Imaging and c) Biopsy (FNAC and Core biopsy).FNAC is considered as valuable diagnostic techniques because of its simplicity, reliability, cost- effectivity and with minimal complications.&#x0D; Aims and Objectives : The aim of this study is to assess the accuracy of FNAC in diagnosis of breast lesions in correlation with histopathological findings.&#x0D; Material and Methedology : This is retrospective study for a period of one year of all the cases of breast lesions that were referred to pathology department for FNAC and These patients were subjected to Excisional biopsy/Incisional biopsy/Mastectomy.&#x0D; &#x0D; Result : In duration of 1 year of study, we received total 76 cases with complaint of breast lump. The frequency of benign breast lesions were higher in the range of 20-40 years and the frequency of malignant lesions were higher among the age group of 41-60 years. Out of 76 cases, 40 (52.6%) cases were of Fibroadenoma, 2 (2.6%) cases were of Abscess, 2 (2.6%) cases were of Fibrocystic disease, 2 (2.6%) cases were of lactating adenoma and 30 (39.5%) cases were of malignant lesion. Among total of 76 cases, 46 cases were non-malingant and 30 cases were malignant on cytological examination. 46 non-malignant cases diagnosed on FNAC were correlated with histopathology examination. 2 false negative cases were reported which were diagnosed as benign breast lesions turned out be malignant on histopathological examination. Out of 30 diagnosed malignant lesions on FNAC, all were consistent with histopathology examination. In our study, Incidence of Benign breast lesions is 57.9% and Malignant breast lesions is 39.5% respectively.&#x0D; Conclusion : Our study states that reporting and findings of FNAC were closely correlated with the histopathological diagnosis in accordance to NCI guidelines. FNAC has significant diagnostic value in differentiating the breast lumps for further operative management.Awareness of breast cancer is must and much needed in developing country like India which can be achieved by proper education, prevention, early detection and proper management of breast lesions.&#x0D; &#x0D;

Intestinal mRNA expression analysis of polarity-related genes identified the discriminatory ability of CRB3 as a diagnostic marker for celiac disease.

Celiac disease (CD) is a chronic autoimmune disorder characterized by an abnormal immune response to gluten, a protein found in wheat, barley, and rye. It is well established that the integrity of epithelial tight junctions (TJs) and adherens junctions (AJs) plays a crucial role in the pathogenesis of CD. These junctional complexes contribute to the apical-basal polarity of the intestinal epithelial cells, which is crucial for their proper functioning. Sixty CD subjects, and 50 controls were enrolled in the current study. Mucosal samples were obtained from the distal duodenum, total RNA was extracted and complementary DNA was synthesized. The relative expression levels of the desired genes were evaluated by quantitative real-time polymerase chain reaction based on ΔΔCt method. The gene-gene interaction network was also constructed using GeneMANIA. CRB3 (p = .0005), LKB1 (p < .0001), and SCRIB (p = .0005) had lower expression in CD patients compared to controls, while PRKCZ expression did not differ between groups (p > .05). CRB3 represented a significant diagnostic value for differentiating CD patients from the control group (p = .02). The aim of the current study was to evaluate the changes in the mRNA expression levels of SCRIB, PRKCZ, LKB1, and CRB3 genes in the small intestinal biopsy samples of CD patients in comparison to the healthy control subjects. Our data uncover the importance of polarity-related genes (especially CRB3) in CD pahtomechanism, that may facilitate the planning of the future studies looking for finding innovative diagnostic and therapeutic strategies for CD.

FFAR4 activation inhibits lung adenocarcinoma via blocking respiratory chain complex assembly associated mitochondrial metabolism

Despite notable advancements in the investigation and management of lung adenocarcinoma (LUAD), the mortality rate for individuals afflicted with LUAD remains elevated, and attaining an accurate prognosis is challenging. LUAD exhibits intricate genetic and environmental components, and it is plausible that free fatty acid receptors (FFARs) may bridge the genetic and dietary aspects. The objective of this study is to ascertain whether a correlation exists between FFAR4, which functions as the primary receptor for dietary fatty acids, and various characteristics of LUAD, while also delving into the potential underlying mechanism. The findings of this study indicate a decrease in FFAR4 expression in LUAD, with a positive correlation (P < 0.01) between FFAR4 levels and overall patient survival (OS). Receiver operating characteristic (ROC) curve analysis demonstrated a significant diagnostic value [area under the curve (AUC) of 0.933] associated with FFAR4 expression. Functional investigations revealed that the FFAR4-specific agonist (TUG891) effectively suppressed cell proliferation and induced cell cycle arrest. Furthermore, FFAR4 activation resulted in significant metabolic shifts, including a decrease in oxygen consumption rate (OCR) and an increase in extracellular acidification rate (ECAR) in A549 cells. In detail, the activation of FFAR4 has been observed to impact the assembly process of the mitochondrial respiratory chain complex and the malate–aspartate shuttle process, resulting in a decrease in the transition of NAD+ to NADH and the inhibition of LUAD. These discoveries reveal a previously unrecognized function of FFAR4 in the negative regulation of mitochondrial metabolism and the inhibition of LUAD, indicating its potential as a promising therapeutic target for the treatment and diagnosis of LUAD.