Nuances of Interpreting X-ray Analysis by Deep Learning and Lessons for Reporting Experimental Findings

With the increase in the availability of annotated X-ray image data, there has been an accompanying and consequent increase in research on machine-learning-based, and ion particular deep-learning-based, X-ray image analysis. A major problem with this body of work lies in how newly proposed algorithms are evaluated. Usually, comparative analysis is reduced to the presentation of a single metric, often the area under the receiver operating characteristic curve (AUROC), which does not provide much clinical value or insight and thus fails to communicate the applicability of proposed models. In the present paper, we address this limitation of previous work by presenting a thorough analysis of a state-of-the-art learning approach and hence illuminate various weaknesses of similar algorithms in the literature, which have not yet been fully acknowledged and appreciated. Our analysis was performed on the ChestX-ray14 dataset, which has 14 lung disease labels and metainfo such as patient age, gender, and the relative X-ray direction. We examined the diagnostic significance of different metrics used in the literature including those proposed by the International Medical Device Regulators Forum, and present the qualitative assessment of the spatial information learned by the model. We show that models that have very similar AUROCs can exhibit widely differing clinical applicability. As a result, our work demonstrates the importance of detailed reporting and analysis of the performance of machine-learning approaches in this field, which is crucial both for progress in the field and the adoption of such models in practice.

Clinical Significance and Potential Role of LSM4 Overexpression in Hepatocellular Carcinoma: An Integrated Analysis Based on Multiple Databases

Background: Hepatocellular carcinoma (HCC) is a solid tumor with high recurrence rate and high mortality. It is crucial to discover available biomarkers to achieve early diagnosis and improve the prognosis. The effect of LSM4 in HCC still remains unrevealed. Our study is dedicated to exploring the expression of LSM4 in HCC, demonstrating its clinical significance and potential molecular mechanisms.Methods: Clinical information and LSM4 expression values of HCC were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Survival analysis and receiver operating characteristic (ROC) curve analysis were applied to evaluate the prognostic and diagnostic significance of LSM4. Calculating pooled standardized mean difference (SMD) and performing summary receiver operating characteristic (sROC) curve analysis to further determine its expression status and diagnostic significance. LSM4-related co-expressed genes (CEGs) were obtained and explored their clinical significance in HCC. LSM4-associated pathways were identified through Gene set enrichment analysis (GSEA).Results: Up-regulated LSM4 was detected in HCC tissues (SMD = 1.56, 95% CI: 1.29–1.84) and overexpressed LSM4 had excellent distinguishing ability (AUC = 0.91, 95% CI: 0.88–0.93). LSM4 was associated with clinical stage, tumor grade, and lymph node metastasis status (p < 0.05). Survival analysis showed that high LSM4 expression was related to poor overall survival (OS) of HCC patients. Cox regression analysis suggested that high LSM4 expression may be an independent risk factor for HCC. We obtained nine up-regulated CEGs of LSM4 in HCC tissues, and six CEGs had good prognostic and diagnostic significance. GSEA analysis showed that up-regulated LSM4 was closely related to the cell cycle, cell replication, focal adhesion, and several metabolism-associated pathways, including fatty acid metabolism.Conclusion: Overexpressed LSM4 may serve as a promising diagnostic and prognostic biomarker of HCC. Besides, LSM4 may play a synergistic effect with CEGs in promoting the growth and metastasis of HCC cells via regulating crucial pathways such as cell cycle, focal adhesion, and metabolism-associated pathways.

Diagnostic significance of reassessment of prostate biopsy specimens by experienced urological pathologists at a high-volume institution

In prostate cancer, accurate diagnosis and grade group (GG) decision based on biopsy findings are essential for determining treatment strategies. Diagnosis by experienced urological pathologists is recommended; however, their contribution to patient benefits remains unknown. Therefore, we analyzed clinicopathological information to determine the significance of reassessment by experienced urological pathologists at a high-volume institution to identify factors involved in the agreement or disagreement of biopsy and surgical GGs. In total, 1325 prostate adenocarcinomas were analyzed, and the GG was changed in 452/1325 (34.1%) cases (359 cases were upgraded, and 93 cases were downgraded). We compared the highest GG based on biopsy specimens, with the final GG based on surgical specimens of 210 cases. The agreement rate between the surgical GG performed and assessed in our institute and the highest biopsy GG assessed by an outside pathologist was 34.8% (73/210); the agreement rate increased significantly to 50% (105/210) when biopsy specimens were reevaluated in our institute (chi-square test, P < 0.01). Multivariate logistic regression analysis showed that only the length of the lesion in the positive core with the highest GG in the biopsy was a significant factor for determining the agreement between biopsy GG and surgical GG, with an odds ratio of 1.136 (95% confidence interval: 1.057–1.221; P < 0.01). Thus, reassessment by experienced urological pathologists at high-volume institutions improved the agreement rate. However, it should be noted there is a high probability of discordance between a small number of lesions or short lesions and surgical GG.

Protein linking fatty acids and its genetic regulation in children having food allergy

Objective: Study the effect of the Ala54Thr FABP gene polymorphism on the produce of the intestinal FABP fraction in blood serum. urine and coprofiltrate in children having food allergies.Methods: The content of the FABP intestinal fraction in urine, feces, and blood serum was determined using ELISA method. The study of FABP genes polymorphism (G163A, Ala54Thr) was carried out using PCR method.Results: Statistically significant increase of the FABP level in blood serum, urine and feces in children with FA was detected in various biological fluids. The distribution of FABP2 alleles and genotypes obeyed the Hardy-Weinberg law (χ 2 = 0; p = 1,000) and did not significantly differ from the distribution of genotypes in children having FA andin the control sample (p = 0.638).Conclusions: The study did not reveal an association of the pathological genotype FABP G163A, (Ala54Thr) with the hyperproduction of the FABP intestinal fraction in children having FA, confirming the diagnostic significance of this marker increase during exacerbation of the disease.

A practical case: features of the autoimmune insulin syndrome diagnosis

Autoimmune Insulin syndrome (AIS), also named Hirata disease, is a rare condition characterized by hypoglycemic episodes due to the presence of high titers of insulin autoantibodies (IAA). AIS is a form of immune-mediated hypoglycemia, which develops when a triggering factor (medication or a viral infection) acts on an underlying predisposing genetic background. The diagnosis of IAS is challenging, requiring a careful workup aimed at excluding other causes of hyperinsulinemic hypoglucemia. The article presents a case of Hirata disease diagnosing of a patient of the therapy department of the Multidisciplinary Medical Center of the Bank of Russia.Purpose: Determining of the features of the diagnosis of Autoimmune Insulin syndrome (Hirata disease)Materials and methods: the article presents a clinical case of the diagnosis of Autoimmune insulin syndrome (Hirata disease), focuses on the diagnostic significance of laboratory tests. The article is intended for general practitioners, endocrinologists, gastroenterologists.

Meta-analysis of synovial fluid polymerase chain reaction for diagnosing periprosthetic hip and knee infection

Background and objective The purpose of this study was to estimate the diagnostic performance of synovial fluid polymerase chain reaction (PCR) in periprosthetic hip and knee infection, and whether synovial fluid PCR has greater diagnostic significance than conventional methods. Methods The literature databases PubMed, Scopus, and the Web of Science were searched for English articles describing periprosthetic joint infection (PJI) diagnosis by synovial fluid PCR. Articles were limited to the period between January 1990 and December 2019. Subsequently, conventional methods that were used on at least two occasions were included for further analysis. Data analysis was performed using the Meta-DiSc and Stata software. Results Eleven studies with 1360 cases were included in the meta-analysis. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) of synovial fluid PCR were 0.70 (95% CI 0.66–0.74), 0.92 (95% CI 0.90–0.93), and 37.4 (95% CI 17.77–78.74), respectively. Conclusions Synovial fluid PCR provides an effective tool for rapid diagnosis of PJI, and also in the early stages of culture-negative bacterial infections.

DIAGNOSTIC SIGNIFICANCE OF MEASURING RETICULOCYTE MATURITY INDICES IN IRON DEFICIENCY ANAEMIA

Objective: To evaluate the diagnostic significance of reticulocyte maturity indices in iron deficiency anaemia. Study Design: Comparative cross-sectional study. Place and Duration of Study: Department of Hematology, Armed Forces Institute of Pathology, Rawalpindi, from Sep 2019 to Jun 2020. Methodology: A total of 340 children, ages between 1 and 5 years of either gender, were divided into two groups based on haemoglobin and ferritin level. Group A comprised of 203 children with haemoglobin >11 g/dL andferritin level >7 ng/ mL. Group B comprised of 137 children with haemoglobin <11g/dL and ferritin <7 ng/mL. Red blood cell and reticulocyte parameters were compared. Results: Iron deficiency anaemia was found to be 37.6% in the study population. Comparison revealed that the children in groups B had significantly higher mean red cell distribution width (17.1 ± 1.3% vs. 13.3 ± 1.3%) and significantly lower hemoglobin (9.5 ± 1.0 g/dL vs. 12.7 ± 1.0 g/dL), mean corpuscular hemoglobin (21.8 ± 2.5 pg vs. 28.6 ± 2.3 pg), mean corpuscular volume (69.4 ± 3.5 fL vs. 80.4 ± 3.3 fL), mean corpuscular hemoglobin concentration (31.5 ± 1.8 g/dL vs. 32.7 ± 1.6 g/dL) and serum ferritin level (4.5 ± 2.6 mg/mL vs. 55.9 ± 32.1 ng/mL). No significant differences in the mean total red blood cell count, hematocrit and reticulocytes between two groups were noted (p>0.05) and significant differences were noted in terms of low, medium & high fluorescence ratios in both groups (p<0.05). Conclusion: Our findings suggest that medium fluorescence ratio and high fluorescence ratio.......

On the differential diagnostic prospects of determining the profile of the lateral organization of the personality during assessment of the systematic alcohol abuse

The article is devoted to the question of the possible improvement of the psychological examination of persons previously examined in alcoholic intoxication (hereinafter—PEAI). The authors propose an original view on the definition of the target of «alcohol screening», the principles and methods of assessing psychological markers of the systematic substance abuse. Purpose of the study: to determine the differential diagnostic significance of identifying the profile of the lateral organization (hereinafter—PLO) when assessing of the systematic of alcohol abuse in those previously examined in a state of alcoholic intoxication. The researchers made an attempt to highlight the features of PLO of such a «risk group» as those previously examined in a state of alcoholic intoxication (based on data obtained during the study according to the typology of E.D. Khomskaya (with a combination of three types of asymmetries: manual, auditory-verbal and visual) of lateral preferences of 19 PEAI patients of the branch of the Moscow Research and Practical Center for Narcology). As a result, the tendency of those previously examined in the state of intoxication to the lack of a «leading ear» and «leading eye», significant differences in the distribution of the attribute «leading hand» among those previously examined in a state of alcoholic intoxication and in the population were revealed. Conclusion. According to the results of this study, it is difficult to assume the presence of a significant differential diagnostic significance of PLO detection during «alcohol screening» among those previously examined in a state of alcoholic intoxication. At the same time, it should be noted that taking into account lateral preferences can contribute to the improvement of preventive work programs in the narcological service, providing greater individualization of psychological support measures. Directly in the rehabilitation work with PEAI, it is advisable to actively apply social and psychological training (because of a significant part of the contingent among the main factors of relapse with a high degree of probability has social stressors). The creation of short-term (3-5 meetings) programs of group exercises of a preventive orientation, which have different targets depending on the «vulnerability factors» of the owners of certain lateral profiles, also seems justified.

Identification and Validation of Glomerulotubular Crosstalk Genes Mediating IgA Nephropathy by Integrated Bioinformatics

BackgroundIgA nephropathy (IgAN), which has been reported as the most prevalent glomerulonephritis globally, is the major contributor to end-stage renal illness. This bioinformatics study aimed to explore glomeruli-tubulointerstitial crosstalk genes and dysregulated pathways relating to the pathogenesis of IgAN. MethodsThe microarray datasets from the Gene Expression Omnibus (GEO) database were searched. Weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) of both glomeruli and tubulointerstitial were conducted individually. The co-expression gene modules of tubulointerstitial and glomeruli were compared via gene function enrichment analysis. Subsequently, the crosstalk co-expression network was constructed via the STRING database and key genes were mined from the crosstalk network. Results583 DEGs and eight modules were identified in glomeruli samples, while 272 DEGs and four modules were in tubulointerstitial samples. There were 119 overlapping DEGs of the two groups. Among the distinctive modules, four modules in glomeruli and one module in tubulointerstitial were positively associated with IgAN. While four modules in glomeruli and two modules in tubulointerstitial were negatively associated with IgAN. The top ten key genes screened by CytoHubba were ITGAM, ALB, TYROBP, ITGB2, CYBB, HCK, CSF1R, LAPTM5, FN1and CTSS. The above genes were all validated using another two datasets, and all of the key genes demonstrated possible diagnostic significance. Conclusionshe crosstalk genes confirmed in this study may provide novel insight into the pathogenesis of IgAN. Immune-related pathways are associated with both glomerular and tubulointerstitial injuries in IgAN. The glomerulotubular crosstalk might perform a role in the pathogenesis of IgAN.

ANOSMIA AND AGEUSIA IN PATIENTS WITH COVID-19

Objective: To evaluate the prevalence and diagnostic significance of anosmia and ageusia among COVID-19 positive patients of Karachi, Pakistan. Study Design: Cross-sectional study. Place and Duration of Study: Dr Ruth K. M. Pfau Civil Hospital, (Dow University of Health Sciences), Karachi Pakistan, from Jan 2021 to Feb 2021. Methodology: The data were collected prospectively from 265 COVID-19 positive patients. Some patients were interviewed over the telephone, while for patient's ease, an online Google form was also formed, facilitating the online data collection. The patient's demographics, comorbidities, allergies, and COVID-19 associated characteristics were inquired. The statistical analysis was performed on SPSS version 23. Results: The observed frequency of anosmia and ageusia in COVID-19 patients was 49.1% & 43.8% respectively. The median time to recovery was 8-8.5 days (median) for both symptoms. We found no significant difference for gender, BMI, marital status, residential area, comorbidities and reason for long-standing breathing difficulties between patients with or without both anosmia and ageusia (p>0.05). Furthermore, most of the cigarette smokers reported none of the two symptoms (anosmia and ageusia), 24% and 25.2% of COVID-19 positive cases with smoking history were presented without anosmia and ageusia, respectively (p<0.05). Conclusion: Loss of sense of smell and taste was reported in almost half of the studied population infected by the SARS-CoV-2 virus. Therefore, screening for anosmia and ageusia must be considered while COVID-19 suspicion as an important diagnostic clue.