Diagnostic Analysis Research Articles

Diagnostic accuracy of cartridge-based nucleic acid amplification test and resistance pattern in new and previously treated tuberculosis cases: A prospective observational study

Background: Diagnostic methods, particularly sputum microscopy, are the standard method for diagnosing tuberculosis (TB) in many settings. The emergence of cartridge-based nucleic acid amplification test (CBNAAT) as a newer diagnostic tool for TB has shown promising results. CBNAAT is a rapid molecular test that detects the genetic material of Mycobacterium tuberculosis (MTB), the bacterium causing TB, in sputum samples. It offers higher sensitivity and faster results compared to sputum microscopy. Aim: The study aimed to 1) compare the diagnostic accuracy of CBNAAT in detecting smear-positive and smear-negative pulmonary TB cases, and 2) compare rifampicin resistance prevalence between newly diagnosed and previously treated pulmonary TB patients. Methodology: A hospital-based prospective study was conducted in the Respiratory Medicine Department of Guru Gobind Singh Government Hospital, Jamnagar, on PTB patients from August 2019 to December 2020. Data were collected through a self-structured questionnaire that included detailed clinical history, radiological, biochemical, and microbiological investigations. Descriptive statistical analyses were performed to present data as percentages and frequencies. Diagnostic accuracy analysis was conducted. A P-value <0.05 was considered significant. Results: Out of 150 cases, 104 (69.3 %) were male, while 46 (30.7%) were female. Sixty-one percent of new and 86% of previously treated cases were male, whereas 39% of new and 14% of previously treated cases were female. The sensitivity of sputum smear microscopy is 77.33% in cases of PTB, whereas sputum CBNAAT detected 94% of cases of PTB. The sensitivity of CBNAAT for MTB detection in smear microscopy–positive samples was 93.97%, whereas the sensitivity in smear microscopy–negative samples was 94.12%. Regarding rifampicin resistance, the prevalence was lower in newly diagnosed (3/100) compared to previously treated patients with rifampicin-resistant PTB (3/50). Conclusion: These findings suggest that CBNAAT can be a valuable tool for the detection of TB, particularly in cases where sputum smear microscopy results are negative. However, further research is needed to validate these results and evaluate the clinical implications of using CBNAAT in routine TB diagnostics.

Management of marketing activities in agricultural enterprises producing white sea buckthorn

Marketing management in a practical sense means management that uses marketing concepts, i.e. the management of an enterprise that has adopted and uses the marketing view or philosophical vision of marketing in its development process. The management of marketing activity of the enterprise in which there is the branch of production of white currant there must be organizational structures through which each employee, with different functions, level of training and duties, has the opportunity and obligation to act on the basis of marketing strategies, as well as responsibility centers. The concept of actively influencing market requirements also implies effective management of specialized marketing activity, i.e. activities related to product, pricing, placement and promotion policies. In order to establish appropriate management of marketing activity and to position it as effectively as possible in the organizational chart of an agricultural enterprise in which there is a white currant production branch, it is specific, first of all, to analyses the background parts of the constituent elements of the environment with which it operates in order to be able to establish strategic lines, which need to correspond to the appropriate form of organization. In the given article, the authors intend to identify and propose solutions to some problems, which, in essence, represent a diagnostic analysis of the enterprise, the results of which indicate one of the options for the organization of marketing activity and marketing department or specialist in agricultural enterprises.

Peripheral inflammation is associated with impaired sadness recognition in euthymic bipolar patients

BackgroundInflammation impairs cognitive function in healthy individuals and people with psychiatric disorders, such as bipolar disorder (BD). This effect may also impact emotion recognition, a fundamental element of social cognition. Our study aimed to investigate the relationships between pro-inflammatory cytokines and emotion recognition in euthymic BD patients and healthy controls (HCs). MethodsWe recruited forty-four euthymic BD patients and forty healthy controls (HCs) and measured their inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and TNF-α. We applied validated cognitive tasks, the Wisconsin Card-Sorting Test (WCST) and Continuous Performance Test (CPT), and a social cognitive task for emotion recognition, Diagnostic Analyses of Nonverbal Accuracy, Taiwanese Version (DANVA-2-TW). We analyzed the relationships between cytokines and cognition and then explored possible predictive factors of sadness recognition accuracy. ResultsRegarding pro-inflammatory cytokines, TNF-α was elevated in euthymic BD patients relative to HCs. In euthymic BD patients only, higher TNF-α levels were associated with lower accuracy of sadness recognition. Regression analysis revealed that TNF-α was an independent predictive factor of sadness recognition in patients with euthymic BD when neurocognition was controlled for.Conclusions: We demonstrated that enhanced inflammation, indicated by increased TNF-α, was an independent predictive factor of impaired sadness recognition in BD patients but not in HCs. Our findings suggested a direct influence of TNF-α on sadness recognition and indicated vulnerability to depression in euthymic BD patients with chronic inflammation.

Bioinformatics and system biology approach to identify the influences among COVID-19, influenza, and HIV on the regulation of gene expression.

Coronavirus disease (COVID-19), caused by SARS-CoV-2, has emerged as a infectious disease, coexisting with widespread seasonal and sporadic influenza epidemics globally. Individuals living with HIV, characterized by compromised immune systems, face an elevated risk of severe outcomes and increased mortality when affected by COVID-19. Despite this connection, the molecular intricacies linking COVID-19, influenza, and HIV remain unclear. Our research endeavors to elucidate the shared pathways and molecular markers in individuals with HIV concurrently infected with COVID-19 and influenza. Furthermore, we aim to identify potential medications that may prove beneficial in managing these three interconnected illnesses. Sequencing data for COVID-19 (GSE157103), influenza (GSE185576), and HIV (GSE195434) were retrieved from the GEO database. Commonly expressed differentially expressed genes (DEGs) were identified across the three datasets, followed by immune infiltration analysis and diagnostic ROC analysis on the DEGs. Functional enrichment analysis was performed using GO/KEGG and Gene Set Enrichment Analysis (GSEA). Hub genes were screened through a Protein-Protein Interaction networks (PPIs) analysis among DEGs. Analysis of miRNAs, transcription factors, drug chemicals, diseases, and RNA-binding proteins was conducted based on the identified hub genes. Finally, quantitative PCR (qPCR) expression verification was undertaken for selected hub genes. The analysis of the three datasets revealed a total of 22 shared DEGs, with the majority exhibiting an area under the curve value exceeding 0.7. Functional enrichment analysis with GO/KEGG and GSEA primarily highlighted signaling pathways associated with ribosomes and tumors. The ten identified hub genes included IFI44L, IFI44, RSAD2, ISG15, IFIT3, OAS1, EIF2AK2, IFI27, OASL, and EPSTI1. Additionally, five crucial miRNAs (hsa-miR-8060, hsa-miR-6890-5p, hsa-miR-5003-3p, hsa-miR-6893-3p, and hsa-miR-6069), five essential transcription factors (CREB1, CEBPB, EGR1, EP300, and IRF1), and the top ten significant drug chemicals (estradiol, progesterone, tretinoin, calcitriol, fluorouracil, methotrexate, lipopolysaccharide, valproic acid, silicon dioxide, cyclosporine) were identified. This research provides valuable insights into shared molecular targets, signaling pathways, drug chemicals, and potential biomarkers for individuals facing the complex intersection of COVID-19, influenza, and HIV. These findings hold promise for enhancing the precision of diagnosis and treatment for individuals with HIV co-infected with COVID-19 and influenza.

Evaluation of diagnostic value of Doppler ultrasound in the diagnosis of malignant breast masses.

Breast cancer is the leading cause of cancer mortality in women, and it is on the rise in Iran. Therefore, an early-stage diagnosis of breast cancer is of critical importance. Because ultrasound is one of the available, inexpensive, and minimally invasive techniques for distinguishing malignant from benign masses, a comparison of conventional ultrasound, color Doppler, and spectral Doppler findings can be useful. The purpose of this study was to determine the diagnostic value of sonographic indices, specifically Doppler parameters, in identifying the nature of breast masses. This is a cross-sectional study, with diagnostic value analysis. Before undergoing a biopsy, 80 patients with breast masses underwent B-mode and Doppler breast ultrasound. The ultrasound findings were then compared to pathologic results to determine which groups were malignant or benign. The resulting data were analyzed using statistical tests and diagnostic values with SPSS 22 software. B-mode grey-scale ultrasound indices such as mass shape, mass margin, mass orientation, and posterior features, as well as Doppler indices such as vascularity, RI (Resistive Index), PI (Pulsatility Index), and PSV (Peak Systolic Velocity), were found to be statistically significant with pathological findings. Color Doppler revealed vascularity in 65% of benign and 84% of malignant masses. The diagnostic value results revealed that mass shape, mass margin, mass orientation, and posterior features all play a significant role in predicting lesion malignancy, with a sensitivity of 92%, 58%, 64%, 56%, and specificity of 59%, 66%, 82%, and 84%, respectively. The RI, PI, and PSV indices were significantly higher in malignant masses, and all of them had remarkable diagnostic values in predicting malignancy, with a (Area Under The Curve) AUC of 0.863, 0.882, 0.702, a sensitivity of 84% and 84%, 68%, and a specificity of 83%, 86%, and 62%, respectively, at the optimal cut-off points (0.65, 1.32, 12.40) obtained from the Receiver Operating Characteristics (ROC) curves.

Clinical manifestation and imaging diagnostic analysis of fat embolism syndrome

To explore characteristics of clinical and imaging findings in patients with fat embolism syndrome. From January 2021 to October 2022,clinical manifestations of 13 patients with fat embolism due to fracture or orthopaedic surgery were retrospectively analyzed,including 11 males and 2 females,aged from 17 to 60 years old. Mental and respiratory abnormalities and changes in vital signs occurred after admission or after surgery,and patient's chest and brain imaging results were abnormal. The patient's mental and respiratory abnormalities,vital signs,chest and brain imaging results were continuously monitored. The main clinical manifestations of fat embolism syndrome were abnormal pulmonary respiration in 13 patients,abnormal central nervous function in 7 patients,and spotted rash in 2 patients. Chest CT showed diffuse distribution of ground glass shadows in 13 patients,and severe symptoms were "snowstorm". Nine patients with ground glass fusion consolidation,5 patients with multiple nodules and 4 patients accompanied by bilateral pleural effusion. Head CT findings of 5 patients were negative,and head MRI findings of 1 patient showed multiple T1WI low signal,T2WI high signal shadow,DWI high signal shadow,and "starry sky sign" in basal ganglia,radiative crown,hemioval center,thalamus,frontal parietal cortex and subcortex. Fat embolism syndrome has a high mortality rate. Clinical manifestations of respiratory system and nervous system are not specific,and the skin spot rash has a characteristic manifestation. The "blizzard" sign is the specific manifestation of chest X-ray and CT examination of fat embolism,and the "starry sky" sign is the typical manifestation of diffusion-weighted sequence of brain MRI examination of fat embolism.

Acute and Chronic Oak Decline in urban and forest ecosystems in Southern Italy

Abstract Since recently, a decline of holm oak (Quercus ilex L.) is observed in Salento (South Italy), this caused concern regarding the protection of native biodiversity and local forests. Symptomatic trees show browning of leaves, thinning of canopy, and loss of branches. The aim of this study was to understand the biotic factors involved in the observed decline. During the monitoring activity, the use of phenotypic descriptors highlighted the presence of two types of decline with distinct symptoms among oaks in rural and urban areas, which could be classified as Acute Oak Decline (AOD) and Chronic Oak Decline (COD), respectively. Following this, diagnostic analyses were carried out to assess the presence of various holm oak pathogens on twigs, trunk, and soil. These analyses revealed the presence of several Botryosphaeriaceae oak pathogens, present ubiquitously between the two environmental contexts, with Diplodia seriata being overall the most prevalent. Contrarily, bacteria associated with AOD were only present in the rural areas and included: Brenneria goodwinii, Gibbsiella quercinecans, and Rahnella victoriana. As far as known to the authors, this is the first time these pathogens have been found in the Mediterranean coastal regions. Lastly, soil analyses performed to detect the presence of Phytophthora cinnamomi were negative. Our results highlight the presence of several pathogens, which indicates that oak decline is a multifactorial phenomenon for which the predisposing, initial, and contributing factors are not yet known particularly for the recently described AOD and COD. Finally, the identification of AOD-related bacteria in Salento is a cause of concern for the need of urgent management actions aimed to contain their spread and to preserve the forest heritage of the region.

Cosmological constraints on f(Q)\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$f(Q)$$\\end{document} gravity with redshift space distortion data

In this paper, we explore one of Einstein’s alternative formulations which involves the non-metricity scalar, Q, within the framework of f(Q) theory. Our study focuses on solving the modified Friedmann equations for the case of dust matter, ρ=ρm\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\rho =\\rho _{m}$$\\end{document}, and a form of f(Q)=α+βQn\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$f(Q) = \\alpha + \\beta Q^n$$\\end{document}. We investigate the behavior of our model in both linear (n=1)\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$(n=1)$$\\end{document} and nonlinear (n≠1)\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$(n\ e 1)$$\\end{document} scenarios at the background and perturbation levels. By employing the Markov chain Monte Carlo (MCMC) method, we constrain our model using observational datasets including redshift space distortion, cosmic chronometers, and Pantheon+\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^+$$\\end{document}. Without using any parameterization of the growth rate index which quantifies the deviation from the Λ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\Lambda $$\\end{document}CDM model, both models exhibit good accuracy in describing the redshift space distortion. We further analyze the dynamics of the Universe using cosmography parameters, where our model exhibits a phase transition between deceleration and acceleration phases at z=0.789\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$z=0.789$$\\end{document}. Our findings reveal that our model exhibits a phantom-like behavior based on statefinder diagnostic analysis. Interestingly, the model demonstrates a rich variety of behaviors, resembling either a quintessence-like scenario for (n<1)\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$(n<1)$$\\end{document} or phantom-like scenario for (n≥1)\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$(n\\ge 1)$$\\end{document}. Using the MCMC best fit and parameterizing the growth index, the evolution of the growth index also depends on the parameter n, either remaining constant (in the linear case) or showing a decreasing trend (in the nonlinear case), indicating a weaker growth rate of density perturbations during earlier cosmic times. Finally, we compare our findings of the growth index with the values obtained in the literature.

Abstract 909: Enhancing genomic analysis in cancer diagnostics: A machine learning approach for removing artifacts in FFPE specimens

Abstract Formalin-Fixed Paraffin-Embedded (FFPE) specimens, widely utilized in clinical cancer diagnostics, present significant challenges by introducing artifacts into genomic data. This study aimed to profile these FFPE-induced genomic alterations, with a particular focus on single-nucleotide variants (SNVs), small insertions and deletions (indels), and copy-number variations (CNVs), and to develop computational methods for filtering out such artifacts. Our primary focus was twofold: first, to comprehensively characterize the unique error profile of FFPE specimens observed through whole-genome sequencing (WGS), and second, to construct artifact classifiers and noise filters for SNV/indels and CNVs. We utilized machine learning (ML) and signal-processing techniques on a dataset of FFPE and matched fresh-frozen (FF) samples. The dataset of 52 FFPE-FF pairs were obtained from four different medical institutes and from various cancers including liver, breast, colon, stomach, and lung cancer, with varied FFPE archiving times. We also analyzed additional FFPE-only samples to refine our methods. Our methodology incorporated advanced computational approaches, including stacking ensemble, transfer learning, and wavelet transform, to enhance robustness and accuracy. The method's design was centered around the notion of not only achieving high performance in distinguishing true signals from FFPE-induced artifacts but also addressing the real-world challenges posed by the varying quality and conditions of clinical FFPE samples. In the analysis, we found peculiar patterns of FFPE-specific error profile, including well-known cytosine deamination and novel mutational signatures. The classifier, building on our findings, effectively differentiated true genomic variants from FFPE-induced artifacts for both SNVs and indels, demonstrating a sensitivity of 0.97, specificity of 0.87, and an F1 score of 0.94 for SNVs. For indels, it achieved a sensitivity of 0.91, specificity of 0.91, and an F1 score of 0.91. The CNV filter notably enhanced the signal-to-noise ratio (SNR) of CNV depth profiles, increasing it from 13dB to 17.5dB on average. Furthermore, we conducted evaluations on two critical measures in cancer and clinical genomics: homologous recombination deficiency (HRD) and tumor mutational burden (TMB), achieving post-filtering concordance rates of 0.99 for HRD—correctly identifying all 8 HRD-positive patients in our dataset—and 0.96 for SNV-based TMB and 0.87 for indel-based TMB. Additionally, a post hoc procedure for sensitive detection of cancer driver mutations resulted in concordance rates of 0.94 for SNVs, 0.91 for indels, and 0.95 for oncogene amplification. Taken together, our study advances FFPE WGS analysis in cancer diagnostics by effectively filtering artifacts and addressing challenges with older, degraded samples, enhancing clinical applicability. Citation Format: Joonoh Lim, Seongyeol Park, Won-Chul Lee, Ryul Kim, Sangmoon Lee, Jeong Seok Lee, Brian Baek-Lok Oh, Young Seok Ju. Enhancing genomic analysis in cancer diagnostics: A machine learning approach for removing artifacts in FFPE specimens [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 909.

Abstract 2938: Comprehensive genomic profiling of solid tumor patients with the OncoDEEP assay for broad analysis in clinical diagnostics

Abstract Somatic multi-gene analysis by Next Generation Sequencing (NGS) becomes standardly integrated in medical oncology for clinical decision making. However, with the fast-growing number of recommended and required genomic biomarkers, small panels have become vastly insufficient for most tumor types. Comprehensive Genomic Profiling (CGP) is amenable to screen for single nucleotide variants (SNVs) and subtle insertions and deletions (indels) in several hundreds of genes. Moreover, it provides information on copy number variations (CNVs) and gene fusions of the most relevant genes for optimal patient management. Currently, most comprehensive panels also allow for screening of tumor-agnostic genomic biomarkers, including microsatellite instability (MSI), tumor mutation burden (TMB) and homologous recombination deficiency (HRD), which are implemented as prognostic and therapeutic signatures in a wide variety of solid tumors. So far, only a handful of CGP assays have been validated for their diagnostic utility in routine laboratory practice for the care of cancer patients. In this study we report on an extensive multicentric analysis across multiple centers in Belgium and The Netherlands comparing the novel OncoDEEP CGP assay (OncoDNA) with the diagnostically validated TSO500 assay (Illumina). We describe the technical differences between both assays as well as their outcome and shortcomings. Detection of clinically relevant SNVs, indels and CNVs was very similar and differences were often due to assay-specific settings. Similarly, TMB, MSI and HRD data were concordant for most samples but those with scores close to the cut-offs could deviate. For fusion detection, concordance was found for the limited number of 11 clinically-actionable driver genes covered by the OncoDEEP kit. The uniformity of coverage was much higher with the OncoDEEP assay thereby allowing to pool 2- to 3-times more samples per NGS run. For the diagnostic implementation of the OncoDEEP assay we then performed an extensive validation with clinical samples representing a wide variety of solid tumor types, as well as reference samples. All performance metrics passed the validation criteria. In conclusion, the OncoDEEP kit can be used for reliable diagnostic comprehensive profiling of solid tumors, but currently, extensive fusion analysis requires an additional screening method. Citation Format: Ernst-Jan M. Speel, Pieter-Jan Volders, Joni Van der Meulen, Aaron De Cock, Stefanie Vermeire, Jacques Van Huysse, Marie De Barsy, Gabriela Beniuga, Wendy de Leng, Anne Jansen, Sharon Thijssen, Hendrikus Jan Dubbink, Zeliha Ozgur, Wilfred van Ijcken, Brigitte Maes, Guy Froyen. Comprehensive genomic profiling of solid tumor patients with the OncoDEEP assay for broad analysis in clinical diagnostics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2938.

Abstract 6661: Profiling response to oncolytic adenovirus and immune checkpoint inhibitors by mass cytometry in a triple negative breast cancer mouse model

Abstract Immune checkpoint inhibitors (ICIs) based immunotherapy has found success in treating breast cancers but for more immunosuppressive cancer types, especially most of triple negative breast cancers (TNBCs), response rates generally are low. Also, combination immunotherapy with oncolytic adenoviruses (OAVs) has been shown to induce a more immune inflamed phenotype in many pre-clinical studies. Here, by using a 40-antibody panel for mass cytometry, we profiled comprehensive changes of cell phenotypes in a TNBC mouse model both systemically and in the tumor microenvironment in response to the treatment of ICIs and/or a new systemically delivered, TGFβ signaling inhibiting OAV, mHAdLyp.sT. The samples in this study were collected on day 16 of tumor cell inoculation, while mHAdLyp.sT were applied by tail vein on day 7 and 9, and anti-PD-1 and anti-CTLA-4 antibodies were injected Intraperitoneally on day 8, 10, 12, 14. After sample processing and data acquisition on Helios system, a standard workflow was applied for data preprocessing including normalization, compensation, transformation, diagnostic analysis, marker ranking, cell population identification, visual representation, differential analysis, and statistical analysis. In blood samples, for T cell clusters, percentages of effector CD8+ T cells, naïve CD8+ T cells, and CD44lowCD62Llow CD8+ T cells among total cells were increased by mHAdLyp.sT, anti-PD-1, and anti-CTLA-4 combination when compared to the buffer group but none of these significant changes were observed in groups treated with mHAdLyp.sT or ICI antibodies alone. Combination treatment also increased percentages of clusters of CD272highCD44high DCs, CD44highCD62Llow B cells, and CD44high macrophages significantly. In spleen, combination treatment significantly increased several T cell clusters, including TCRβhighCD38highRORγthigh T cells, TCRβhigh CD4+ T cells, effector CD8+ T cells, TCRβhighCD44lowCD62Llow CD8+ T cells, and CD11bhigh CD8+ T cells when compared to the buffer group. Interestingly, while ICIs treatment increased several macrophage clusters, such as CD44highLy-6G/Chigh macrophages, CD11blow macrophages, and CD44highCD11bhigh macrophages, they are not significantly increased in the combination treatment group. In the tumor, we did not detect any significant changes by the combination treatment in the clusters we identified now although the average percentages of several clusters were either increased or decreased. We will refine these algorithm-generated clusters from tumors once we obtain our data from day 24 sample collection point for advanced analysis. In short, our current results suggested that the combination therapy is more potent in generating cytotoxic T cells and other anti-tumor immune cell populations systemically in the early stage of the treatment and tumor progression. Citation Format: Weidong Xu, Qiaoshan Lin, Yan Li, Beniamin Filimon, Soon Cheon Shin, Michael Olson, Mengjie Chen. Profiling response to oncolytic adenovirus and immune checkpoint inhibitors by mass cytometry in a triple negative breast cancer mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6661.

Diagnosis of acute diverticulitis colon and its purulent – destructive complications

Aim. To determine the diagnostic effectiveness of clinical, laboratory and instrumental methods for detecting acute diverticulitis and its perforation complications. Materials and methods. Retrospective analysis of clinical, laboratory and instrumental diagnostics of 655 patients with a diagnosis of “acute diverticulitis”, and evaluation of its diagnostic accuracy. Results. Clinical and laboratory diagnosis of acute diverticulitis and its perforated forms allows to suspect this disease as the most likely among other acute inflammatory diseases of the abdomen; at the same time, the sensitivity of these methods for detecting complicated forms does not exceed 51.2 %. Abdominal ultrasound diagnostic has a high sensitivity of 95.3 % and specificity of 99.6 % in the diagnosis of acute diverticulitis and its complications: sensitivity of 88.7 %, specificity of 99.7 %, and could be a leading method verification of this disease. Abdominal CT, which has similar accuracy, could be used as a second-line method in cases of unclear ultrasound data and absence of a free peritonitis clinic. Conclusions. The sensitivity of clinical methods for detecting complicated forms of acute diverticulitis of the colon does not exceed 51.2 %. The sensitivity of ultrasound diagnosis of acute diverticulitis is 95.3 %, the specificity is 99.6 %, and its complicated forms are 88.7 % and 99.7 %, respectively, which makes this method essential in diagnosis and differential diagnosis. CT according to various indicators should be used as a method of the second line of diagnosis. Ultrasound and CT diagnostics allow monitoring the course of the pathological process and the effectiveness of treatment of acute diverticulitis complicated forms.

Abstract 3751: Diagnostic assessment of Filamin A (FLNA) as a serum biomarker for identification of benign prostatic hyperplasia vs aggressive prostate cancer in a prospective Mexican cohort

Abstract Prostate cancer (PCa) exhibits a significant health risk to aging men, in which effective diagnosis of high gleason (Gleason &amp;gt;7) cancers is of critical need. Currently, the main screening tool utilized for detection of prostate cancer is prostate specific antigen (PSA), however, PSA exhibits limited utility in men with benign prostatic hyperplasia (BPH) due to inherent elevated PSA as the result of an enlarged prostate, resulting in increasing unnecessary biopsies. In Mexico, there is currently a higher incidence of aggressive PCa due to the risk within the overall population as well as the need for increased screening tools. Since, there is a critical unmet need to evaluate novel PCa diagnostic test that could serve as a reflex test within the screening paradigm, we evaluated the recently developed test, pSTATEdx, which measures the cleaved portion of Filamin A (FLNA) via IP-MRM mass spectrometry in conjunction with the patients age, to determine the overall risk of aggressive prostate cancer. In the current study, we analyzed a prospective cohort from Mexico City and Guadalajara evaluating 34 BPH and 44 PCa in men exhibiting symptoms with PSA levels between 4-10 ng/mL, who were all referred for 12 core prostate biopsies due to suspicion of prostate cancer. Additionally, we assessed 41 non-diseased men as controls who had PSA below 1.5 ng/mL, who were not assessed further. Comparison of non-diseased controls with BPH/PCa men exhibited an AUC of 0.99, PPV 0.96, NPV 0.89, OR 118, and P value 2 e-20, thus demonstrating that pSTATEdx had significant utility in assessing prostate health independent of PSA. In comparison with previously published data, FLNA mean levels were 24 ng/mL in previously published American study cohort and 55 ng/mL in the Mexican BPH/PCa cohort with a P value of &amp;lt;0.001. Assessment of patient populations revealed that there was superior diagnostic performance of FLNA for patients between PSA 4-7, which represents an increased unmet need for biopsy decision support. Analysis of BPH compared to all PCa exhibited a sensitivity of 0.94 and specificity of 0.53, PPV 0.64, NPV of 0.91, and OR of 16.4. Diagnostic analysis of BPH compared to high gleason PCa exhibited a sensitivity of 1, specificity of 0.21, PPV 0.38, NPV of 1, and OR of inf in this pilot study. This assessment revealed promising insight that aggressive PCa was not missed using pSTATEdx. pSTATEdx demonstrated diagnostic utility in prevention of unnecessary biopsies in the Mexican population as a reflex test to those patients with PSA levels between 4-7 as well as demonstrated that aggressive prostate cancers were not missed with the risk score. Additional studies are planned in the future to expand the utility of pSTATEdx in Latin America. Citation Format: Arturo Rodriguez, Arturo Mendoza, Matthew Rosenburg, José de J. Castaneda, Alejandro A. Melgar, Bernardo Ciseros, Adrian G. Gangemi, Nischal M. Chand, Poornima Tekumalla, Greg Miller, Anjan Thakurta, Diego Banuelos, Juan J. Real, Diego A. Joya, Alejandro Romero, Juan D. Farias, Eduardo Cabeza, Hector H. Remess, Julio J. Delgado, Hector M. Sanchez, Ignacio Barragan, Mabel Rodriguez, Barbara Garcia, David A. Sanchez, Juan Izquierdo, Elizabeth M. Lopez, Juan Hanao, Jeronimo G. Frusch, Niven R. Narain, Michael A. Kiebish. Diagnostic assessment of Filamin A (FLNA) as a serum biomarker for identification of benign prostatic hyperplasia vs aggressive prostate cancer in a prospective Mexican cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3751.

A flat FLRW dark energy model in f(Q,C)-gravity theory with observational constraints

In the recently suggested modified non-metricity gravity theory with boundary term in a flat FLRW spacetime universe, dark energy scenarios of cosmological models are examined in this study. An arbitrary function, [Formula: see text], has been taken into consideration, where [Formula: see text] is the non-metricity scalar, [Formula: see text] is the boundary term denoted by [Formula: see text], and [Formula: see text] is the model parameter, for the action that is quadratic in [Formula: see text]. The Hubble function [Formula: see text], where [Formula: see text] is the current value of the Hubble constant and [Formula: see text] and [Formula: see text] are arbitrary parameters with [Formula: see text], has been used to examine the dark energy characteristics of the model. We discovered a transit phase expanding universe model that is both decelerated in the past and accelerated in the present, and we discovered that the dark energy equation of state (EoS) [Formula: see text] behaves as [Formula: see text]. The Om diagnostic analysis reveals the quintessence behavior in the present and the cosmological constant scenario in the late-time universe. Finally, we calculated the universe’s current age, which was found to be quite similar to recent data.

Feasibility and clinical value of linear endoscopic ultrasonography imaging in the lower gastrointestinal subepithelial lesions.

Linear endoscopic ultrasonography (EUS) has been extensively utilized as a novel diagnostic and therapeutic modality across various fields. However, there have been relatively few studies focusing on lower gastrointestinal lesions. The aim of our study was to investigate the feasibility, safety and clinical value of linear EUS in the lower gastrointestinal subepithelial lesions. This was a retrospective study involving patients with lower gastrointestinal subepithelial lesions diagnosed by linear EUS from August 2019 to April 2023 at the Second Affiliated Hospital of Anhui Medical University. The data, including basic clinical information, linear EUS features, technical success rate, complications, and follow-up, were retrospectively collected and analyzed. A total of 69 patients with lower gastrointestinal subepithelial lesions underwent examination by linear EUS. Excluding the rectum, the technical success rate of linear EUS was 90.6% (29/32). Apart from the 7 patients whose diagnosis remained unknown, 3 patients with no abnormal EUS findings, and 3 patients failed the procedure, 56 patients were included in the final diagnostic performance analysis. The most common locations of the lesions were the rectum (37/56, 66.1%) and sigmoid colon (7/56, 12.5%). Based on endoscopy findings and pathological results, the most prevalent types of subepithelial lesions in the lower gastrointestinal tract were neuroendocrine tumor (NET) (12/56, 20.3%), lipoma (8/56, 13.6%) and extraluminal compression (8/56, 13.6%). The majority of lesions ranged in diameter from 1 to 3cm (χ2 = 18.750, p < 0.001). After undergoing linear EUS examination, 36 patients received EUS-FNA (3/36), biopsy (5/36), endoscopic resection (25/36), or surgical excision (3/36) respectively. The pathological results of 29 patients were entirely consistent with the diagnosis made using linear EUS, with an 80.6% (29/36) diagnostic accuracy rate. Follow-up indicated that the lesions remained unchanged within 6-36months. All patients tolerated the procedure well without any complications. In conclusion, linear EUS demonstrates technical feasibility, safety, and a high diagnostic accuracy for subepithelial lesions in the lower gastrointestinal tract.

Advancing instance segmentation and WBC classification in peripheral blood smear through domain adaptation: A study on PBC and the novel RV-PBS datasets

Automating blood cell counting and detection from smear slides holds significant potential for aiding doctors in disease diagnosis through blood tests. However, existing literature has not adequately addressed using whole slide data in this context. This study introduces the novel RV-PBS dataset, comprising ten distinct peripheral blood smear classes, each featuring multiple multi-class White Blood Cells per slide, specifically designed, for instance segmentation benchmarks. While conventional instance segmentation models like Mask R-CNN exhibit promising results in segmenting medical artifact instances, they face challenges in scenarios with limited samples and class imbalances within the dataset. This challenge prompted us to explore innovative techniques such as domain adaptation using a similar dataset to enhance the classification accuracy of Mask R-CNN, a novel approach in the domain of medical image analysis. Our study has successfully established a comprehensive pipeline capable of segmenting, detecting, and classifying blood samples from slides, striking an optimal balance between computational complexity and accurate classification of medical artifacts. This advancement enables precise cell counting and classification, facilitating doctors in refining their diagnostic analyses.

Current diagnostics and biomarkers for arboviral infections (a review on Dengue, Zika, West Nile and Chikungunya viruses)

Arboviral infections, transmitted to humans primarily through arthropod vectors, constitute a significant global health threat. Arboviruses, such as Dengue, Zika, Chikungunya, and West Nile viruses, continue to cause widespread outbreaks, necessitating advanced diagnostic tools. Emerging technologies including Lab On A Chip (LOC), Lab On A Disc (LOAD), Microfluidic Paper-Based Analytical Devices (µPADS), Lateral Flow Devices, CRISPR-CAS 12/13, Quartz crystal microbalance (QCM), and Nano-Technology are evaluated for their potential to enhance arboviral diagnosis, offering rapid, accurate, and point-of-care solutions. Furthermore, the identification of robust biomarkers, including Inflammatory Cytokines, Antibodies, Endothelial Activation Products and Indicators of Tissue or Organ Damage, is crucial for improving the understanding of disease pathogenesis, prognosis, and treatment response. A comprehensive analysis of potential diagnostics and biomarkers for arboviral infections sheds light on the evolving strategies to combat these medically significant diseases, ultimately contributing to more effective surveillance, diagnosis and management worldwide.

Validation of FIB-6 score in assessment of liver fibrosis in chronic hepatitis B.

We recently developed a simple novel index called fibrosis 6 (FIB-6) using machine learning data analysis. We aimed to evaluate its performance in the diagnosis of liver fibrosis and cirrhosis in chronic hepatitis B (CHB). A retrospective observational analysis of data was obtained from seven countries (Egypt, Kingdom of Saudi Arabia (KSA), Turkey, Greece, Oman, Qatar, and Jordan) of CHB patients. The inclusion criteria were receiving an adequate liver biopsy and a complete biochemical and hematological data. The diagnostic performance analysis of the FIB-6 index was conducted and compared with other non-invasive scores. A total of 603 patients were included for the analysis; the area under the receiver operating characteristic curve (AUROC) of FIB-6 for the discrimination of patients with cirrhosis (F4), compensated advanced chronic liver disease (cACLD) (F3 and F4), and significant fibrosis (F2-F4) was 0.854, 0.812, and 0.745, respectively. The analysis using the optimal cut-offs of FIB-6 showed a sensitivity of 70.9%, specificity of 84.1%, positive predictive value (PPV) of 40.3%, and negative predictive value (NPV) of 95.0% for the diagnosis of cirrhosis. For the diagnosis of cACLD, the results were 71.5%, 69.3%, 40.8%, and 89.2%, respectively, while for the diagnosis of significant fibrosis, the results were 68.3%, 67.5%, 59.9%, and 75.0%, respectively. When compared to those of fibrosis 4 (FIB-4) index, aspartate aminotransferase (AST)-to-platelet ratio index (APRI), and AST-to-alanine aminotransferase (ALT) ratio (AAR), the AUROC for the performance of FIB-6 was higher than that of FIB-4, APRI, and AAR in all fibrosis stages. FIB-6 gave the highest sensitivity and NPV (89.1% and 92.4%) in ruling out cACLD and cirrhosis, as compared to FIB-4 (63.8% and 83.0%), APRI (53.9% and 86.6%), and AAR (47.5% and 82.3%), respectively. The FIB-6 index could be used in ruling out cACLD, fibrosis, and cirrhosis with good reliability.

Orbital CT scan parameters in dysthyroid optic neuropathy: a systematic review and meta-analysis.

Addressing Dysthyroid Optic Neuropathy (DON) is crucial due to its debilitating impact in thyroid eye disease (TED). Prompt treatment can preserve vision. Despite lacking definitive diagnostic criteria, computed tomography's (CT) parameters are commonly used for diagnosis. However, these parameters exist without consensus on their diagnostic performance. Systematic review and meta-analysis. We conducted a meta-analysis of studies assessing orbital CT diagnostic performance for DON in adults with TED. We searched various databases including Medline, PubMed, Scopus, and EMBASE, and others electronic databases, until July 2023. Evaluated CT parameters includes Barrett index (BI), fat prolapse via superior-orbital-fissure (SOF), superior-ophthalmic-vein-dilatation (SOVD), and the Nugent score. Diagnostic Test Accuracy analysis (DTA) was performed using R. A total of 9 articles with documented target parameters, collectively analysed 212 orbits with DON. Nugent score exhibited highest diagnostic ability with a log diagnostic odd ratio (logDOR) of 2.64 (95% CI, 2.02, 3.25). Another significant DON indicator was a BI ≥ 50%, with a logDOR of 1.97 (95% CI, 1.17; 2.77). Conversely, fat prolapse via SOF and SOVD proved less sensitive, with a logDOR of 1.42 and 1.09 respectively. Regarding the SROC curve, Nugent score and the BI have the greatest AUC. Variations in study locale, participant demographics, and measurement methods accounted for heterogeneity in meta-analysis. Nugent score and a BI ≥ 50% prove to be significant diagnostic parameters for DON, distinguishing them from fat prolapse via SOF and SOVD. Prioritizing these parameters can lead to prompt treatment and thus enhanced visual outcomes. CRD42023446376.

Regional differences in the biological variability of plantar pressure as a basis for refining diagnostic gait analysis.

The variability of movement plays a crucial role in shaping individual's gait pattern and could, therefore, potentially serve diagnostic purposes. Nevertheless, existing concepts for the use of variability in diagnosing gait present a challenge due to the lack of adequate benchmarks and methods for comparison. We assessed the individuality of contribution of foot parts that directly mediate the transmission of forces between the foot and the ground in body weight shifting during walking based on 200 pedobarometric measurements corresponding to the analysed foot parts for each of 19 individuals in a homogeneous study group. Our results show a degree of individualisation of the contribution of particular foot parts in the weight-shift high enough to justify the need to consider it in the diagnostic analysis. Furthermore they reveal noticeable, functionally driven differences between plantar areas most apparent between the lowest individuality for the first foot ray and the highest for second one and metatarsus. The diagnostic reference standard in pedobarometry should describe the contribution in the shift of body weight during walking for each area of the foot separately and include information on the intra-individual variation and individualisation of descriptors of the contribution. Such a comprehensive standard has the potential to increase the diagnostic value of pedobarometry through enrichment of the assessment description.