Early Diagnostics Research Articles

Internet of Things-Based Induction Motor Diagnosis Using Convolutional Neural Network

We experimented analyzing motor vibration with aid of Raspberry Pi when, at that time, the engine vibration was abnormal. The Pi signal is transmitted to a relay by the motor supply disconnection. The control unit, nevertheless, monitors and sends the data to the storage system in good form with proper temperature. A FO-PID controller is utilized to analyze the effects of IM due to harmonic current, vibration, and noise. The induction motor’s response to harmonic and current fluctuations is stabilized by a FO-PID controller. The findings can be displayed on the mobile. The tests were carried out in a static state of vibration condition, and fast Fourier transformation is used to analyze the measured vibration data signals. The results of this model were based on the convolutional neural network (CNN), which considerably monitors early diagnostics of the vibration. With a maximum delay of around 1 s, the controller can forward cloud vibration data. Using the CNN model train to analyze the performance of the classification accuracy, the stored data are collected. This article offers a novel way of building tools for measuring vibration in real time based on the schematic architecture provided by the Python mode.

Expanding hyperspectral imaging applications to the clinical scene: non-invasive, label-free approaches for early diagnostics and precision medicine

Non-invasive, label-free hyperspectral imaging technologies are powerful tools that can provide critical insights into the spatiotemporal dynamics of evolving systems. They are already integrated into autonomous adaptive surveillance workflows for precision agriculture, remote sensing, environmental monitoring, and food analysis. However, these technologies are not yet routinely used in medicine. With these technologies applied to the biomedical sciences, we anticipate landmark advances in the physicochemical behavioral refinement of high signal-to-noise probes and in the rapid screening of patient exosome populations. To implement label-free spatiochemical imaging techniques while meeting the practical needs of clinicians, technology, workflow design and development must be tailored to the specific medical field while considering existing visualization modalities. This perspective merges basic, translational, and clinical views of label-free, non-invasive hyperspectral imaging. We explore its potential role in positively impacting cancer-related precision medicine and early diagnostics to support clinically implemented point-of-care technologies.

Longitudinal Three-Dimensional Follow-Up and Secondary Treatment Aspects after Endoscopic and Open Scaphocephaly Surgery.

This retrospective cohort study evaluated the longitudinal three-dimensional cranial shape developments and the secondary treatment aspects after endoscopically assisted craniosynostosis surgery (EACS) with helmet therapy and open cranial vault reconstruction (OCVR) for scaphocephaly. Longitudinally collected three-dimensional photographs from scaphocephaly patients and healthy infants were evaluated. Three-dimensional cranial shape measurements and growth maps were compared between the groups over time. Secondary treatment aspects were compared for the treatment groups. Both surgical techniques showed their strongest changes directly after surgery, with mean parietal three-dimensional growths up to 10 mm. At age 24 months, comparison of head shapes showed mean three-dimensional differences less than ±2 mm, with OCVR resulting in a lower vertex and longer cranial length when compared with EACS. At 48 months of age, no measurements were significantly different between treatment groups. Only the total head volume was somewhat larger in the male EACS group at age 48 months ( P = 0.046). Blood loss in EACS (mean, 18 mL; range, 0 to 160 mL) was lower than in OCVR (mean, 100 mL; range, 15 to 300 mL; P < 0.001). Median length of stay after surgery was shorter for EACS (mean, 2 days; range, 1 to 5 days) compared with OCVR (mean, 5 days; range, 3 to 8 days; P < 0.001). The authors conclude that EACS for scaphocephaly shows equal craniometric results at age 48 months and has a better surgery profile compared with OCVR. Early diagnostics and referral for suspected scaphocephaly to allow EACS is therefore recommended. Therapeutic, III.

Ensuring Explainability and Dimensionality Reduction in a Multidimensional HSI World for Early XAI-Diagnostics of Plant Stress.

This work is mostly devoted to the search for effective solutions to the problem of early diagnosis of plant stress (given an example of wheat and its drought stress), which would be based on explainable artificial intelligence (XAI). The main idea is to combine the benefits of two of the most popular agricultural data sources, hyperspectral images (HSI) and thermal infrared images (TIR), in a single XAI model. Our own dataset of a 25-day experiment was used, which was created via both (1) an HSI camera Specim IQ (400-1000 nm, 204, 512 × 512) and (2) a TIR camera Testo 885-2 (320 × 240, res. 0.1 °C). The HSI were a source of the k-dimensional high-level features of plants (k ≤ K, where K is the number of HSI channels) for the learning process. Such combination was implemented as a single-layer perceptron (SLP) regressor, which is the main feature of the XAI model and receives as input an HSI pixel-signature belonging to the plant mask, which then automatically through the mask receives a mark from the TIR. The correlation of HSI channels with the TIR image on the plant's mask on the days of the experiment was studied. It was established that HSI channel 143 (820 nm) was the most correlated with TIR. The problem of training the HSI signatures of plants with their corresponding temperature value via the XAI model was solved. The RMSE of plant temperature prediction is 0.2-0.3 °C, which is acceptable for early diagnostics. Each HSI pixel was represented in training by a number (k) of channels (k ≤ K = 204 in our case). The number of channels used for training was minimized by a factor of 25-30, from 204 to eight or seven, while maintaining the RMSE value. The model is computationally efficient in training; the average training time was much less than one minute (Intel Core i3-8130U, 2.2 GHz, 4 cores, 4 GB). This XAI model can be considered a research-aimed model (R-XAI), which allows the transfer of knowledge about plants from the TIR domain to the HSI domain, with their contrasting onto only a few from hundreds of HSI channels.

Ultrasensitive Terahertz Biodetection Enabled by Quasi-BIC-Based Metasensors.

Advanced sensing devices, highly sensitive, and reliable in detecting ultralow concentrations of circulating biomarkers, are extremely desirable and hold great promise for early diagnostics and real-time progression monitoring of diseases. Nowadays, the most commonly used clinical methods for diagnosing biomarkers suffer from complicated procedures and being time consumption. Here, a chip-based portable ultra-sensitive THz metasensor is reported by exploring quasi-bound states in the continuum (quasi-BICs) and demonstrate its capability for sensing low-concentration analytes. The designed metasensor is made of the designed split-ring resonator metasurface which supports magnetic dipole quasi-BIC combining functionalized gold nanoparticles (AuNPs) conjugated with the specific antibody. Attributed to the strong near-field enhancement near the surface of the microstructure enabled by the quasi-BICs, light-analyte interactions are greatly enhanced, and thus the device's sensitivity is boosted significantly. The system sensitivity slope is up to 674 GHz/RIU, allowing for repeatable resolving detecting ultralow concentration of C-reactive protein (CRP) and Serum Amyloid A (SAA), respectively, down to 1 pM. The results touch a range that cannot be achieved by ordinary immunological assays alone, offering a novel non-destructive and rapid trace measured approach for next-generation biomedical quantitative detectionsystems.

Correlational Extremal System for Controlling the Beginning of Faults in Oil Field Equipment by Analyzing their Wattmeter and Dynamometer Charts

The creation of technology for the analysis of wattmeter charts to control the main equipment of oil fields has always been of both theoretical and great practical interest. Numerous experiments have shown that the wattmeter chart of their electric motor is a highly noisy signal, and a significant part of the diagnostic information is contained in the estimates of the noise variance and the cross-correlation function between the noise and the useful signal. The lack of technologies for their analysis made it difficult and still makes it difficult to use the wattmeter chart to control the indicated equipment. The paper proposes a technology for controlling the onset of malfunctions and early diagnostics of the technical condition of sucker rod pumping units (SRPU), electric submersible pumps (ESPs), modular cluster pump stations (MCPS) of oil fields. It is shown that during operation, the wattmeter chart of the electric motors of these objects reflects information about the beginning of the latent period of change in their technical condition, which can be used as informative attributes in their diagnosis. A technology is proposed for determining the estimate of the cross-correlation function RXε(μ) between the useful signal X(iΔt) and the noise ε(iΔt) of the wattmeter chart and the technology for generating a set of reference wattmeter charts, in which the obtained informative attributes coincide with the informative attributes of the wattmeter charts of typical malfunctions. It is proposed to solve the problem of identifying faults in the equipment under consideration by the informative attributes of current and reference wattmeter charts of electric motors using correlation extremal systems. It is shown that using the proposed technology it is also possible to control the onset of similar malfunctions of SRPU by analyzing the dynamometer chart. The results of experiments showing the effectiveness and expediency of creating these control systems based on CES are presented.

Therapeutic targeting of Huntington's disease: Molecular and clinical approaches.

Huntington's disease (HD) is an autosomal dominant ailment that affects a larger population. Due to its complex pathology operating at DNA, RNA, and protein levels, it is regarded as a protein-misfolding disease and an expansion repeat disorder. Despite the availability of early genetic diagnostics, disease-modifying treatments are still missing. Importantly, potential therapies are starting to make their way through clinical trials. Still, clinical trials are ongoing to discover potential drugs to relieve HD symptoms. However, now being aware of the root cause, the clinical studies are focused on molecular therapies to target it. The road to success has not been without bumps since a big phase III trial of tominersen was unexpectedly discontinued due to exceeding risks than drug's benefit to the patients. Although the trial's conclusion was disappointing, there is still cause to be optimistic about what this technique may achieve. We have reviewed the present disease-modifying therapies in clinical development for HD and examined the current landscape of developing clinical therapies. We further investigated the pharmaceutical development of Huntington's medicine in the pharma industries and addressed the existing challenges in their therapeutic success.

Liquid biopsy using cell-free DNA in the early diagnosis of hepatocellular carcinoma.

Hepatocellular carcinoma ranks fourth in cancer-related causes of death worldwide and second in China. Patients with hepatocellular carcinoma (HCC) at the early stage have a better prognosis compared to HCC patients at the late stage. Therefore, early screening for HCC is critical for clinical treatment decisions and improving the prognosis of patients. Ultrasound (US), computed tomography (CT), and serum alpha fetoprotein (AFP) have been used to screen HCC, but HCC is still difficult to be diagnosed in the early stage due to the low sensitivity of the above methods. It is urgent to find a method with high sensitivity and specificity for the early diagnosis of HCC. Liquid biopsy is a noninvasive detection method using blood or other bodily fluids. Cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) are important biomarkers for liquid biopsy. Recently, HCC screening methods using the application of cfDNA and ctDNA have become the hot spot of early HCC diagnostics. In this mini review, we summarize the latest research progress of liquid biopsy based on blood cfDNA in early screening of HCC.

Peroxisome Proliferator-Activated Receptor-γ as a Target and Regulator of Epigenetic Mechanisms in Nonalcoholic Fatty Liver Disease

Peroxisome proliferator-activated receptor-γ (PPARγ) belongs to the superfamily of nuclear receptors that control the transcription of multiple genes. Although it is found in many cells and tissues, PPARγ is mostly expressed in the liver and adipose tissue. Preclinical and clinical studies show that PPARγ targets several genes implicated in various forms of chronic liver disease, including nonalcoholic fatty liver disease (NAFLD). Clinical trials are currently underway to investigate the beneficial effects of PPARγ agonists on NAFLD/nonalcoholic steatohepatitis. Understanding PPARγ regulators may therefore aid in unraveling the mechanisms governing the development and progression of NAFLD. Recent advances in high-throughput biology and genome sequencing have greatly facilitated the identification of epigenetic modifiers, including DNA methylation, histone modifiers, and non-coding RNAs as key factors that regulate PPARγ in NAFLD. In contrast, little is still known about the particular molecular mechanisms underlying the intricate relationships between these events. The paper that follows outlines our current understanding of the crosstalk between PPARγ and epigenetic regulators in NAFLD. Advances in this field are likely to aid in the development of early noninvasive diagnostics and future NAFLD treatment strategies based on PPARγ epigenetic circuit modification.

SERS substrates based on rose petal replicas for the oxidative stress detection

Oxidative stress leads to multiple changes in properties of cells and of biological liquids that can cause various pathologies including cardiovascular and metabolic diseases. Modern test systems make it possible to assess the concentration of oxidized molecules in the blood plasma, but do not provide direct information about oxidation of cell membranes. In this work, we presented an effective, scalable, and inexpensive technique for manufacturing biomimetic SERS sensors for the detection of biomembrane oxidation. The main feature of this technique is the use of rose petals as templates for scalable manufacturing of SERS substrates with a cavity structure that promotes the capture and immobilization of blood cells on the grooved inner surfaces of microcavities. To obtain the SERS effect in these microcavities, the silicone replicas of rose petals were covered with an Au thin film (100 nm) and spherical Au nanoparticles by the sequential deposition and annealing processes. The application of SERS substrates with a cavity structure enables to perform studies on individual erythrocytes and detect first signs of their membrane oxidation, which can be used for early diagnostics of various blood and metabolic diseases.

Biophysical Changes of Leukocyte Activation (and NETosis) in the Cellular Host Response to Sepsis.

Sepsis, the leading cause of mortality in hospitals, currently lacks effective early diagnostics. A new cellular host response test, the IntelliSep test, may provide an indicator of the immune dysregulation characterizing sepsis. The objective of this study was to examine the correlation between the measurements performed using this test and biological markers and processes associated with sepsis. Phorbol myristate acetate (PMA), an agonist of neutrophils known to induce neutrophil extracellular trap (NET) formation, was added to whole blood of healthy volunteers at concentrations of 0, 200, and 400 nM and then evaluated using the IntelliSep test. Separately, plasma from a cohort of subjects was segregated into Control and Diseased populations and tested for levels of NET components (citrullinated histone (cit-H3) DNA and neutrophil elastase (NE) DNA) using customized ELISA assays and correlated with ISI scores from the same patient samples. Significant increases in IntelliSep Index (ISI) scores were observed with increasing concentrations of PMA in healthy blood (0 and 200: p < 10-10; 0 and 400: p < 10-10). Linear correlation was observed between the ISI and quantities of NE DNA and Cit-H3 DNA in patient samples. Together these experiments demonstrate that the IntelliSep test is associated with the biological processes of leukocyte activation and NETosis and may indicate changes consistent with sepsis.

Electrochemical Sweat Sensors

Sweat analysis by means of minimally invasive wearable sensors is considered a potentially disruptive method for assessing clinical parameters, with exciting applications in early medical diagnostics and high-performance sports. Electrochemical sensors and biosensors are especially attractive because of the possibility of the electronic integration of wearable devices. In this article, we review several aspects regarding the potentialities and present limitations of electrochemical sweat (bio)sensors, including: the main target analytes and their relationships with clinical conditions; most usual electrochemical techniques of transduction used according to the nature of the target analytes; issues connected to the collection of representative sweat samples; aspects regarding the associated, miniaturized electronic instrumentation used for signal processing and communication; and signal processing by machine learning.

Polymorphism in ADD1 Gly460Trp rs4961 gene in workers exposed to occupational chemical factors (exemplified by saturated hydrocarbons)

Introduction. Nowadays it has become especially vital to reveal basic regularities in workers’ health formation in order to provide early diagnostics and to reduce overall and occupational morbidity.&#x0D; The aim of the study was to examine polymorphism in ADD1 Gly460Trp rs4961 gene in workers exposed to chemical occupational factors at their workplaces (exemplified by saturated hydrocarbons).&#x0D; Materials and methods. We examined workplace air and biological media (urine and buccal epithelium) of exposed workers from the test group (n=162) and workers who didn’t deal with any technological processes at their workplaces (the reference group, n=83); both groups were employed at a potash flotation factory.&#x0D; To assess exposure to saturated hydrocarbons (hexane and heptane) in workplace air, we performed laboratory-instrumental tests of air inside workshops (11) and in administrative rooms with GANK-4 gas analyzer. Biological media (urine) were examined to determine contents of saturated hydrocarbons (hexane and heptane) in them by analyzing vapor phase in equilibrium on "Kristall-5000" gas chromatographer according to methodical Guidelines MUK 4.1.764-99.&#x0D; We analyzed polymorphism in ADD1 Gly460Trp rs4961 gene. Genetic typing was accomplished by polymerase chain reaction (PCR) in real time mode through allele discrimination with using TaqMan-probes on CFX96 (Bio-Rad) system as well as oligonucleotide primers and probes synthesized by "Sintol" company (Moscow).&#x0D; We applied Student’s t-test and Fischer’s Z-test to estimate authenticity of differences in obtained results. Pearson’s chi-square test (χ2) was used to check normalcy of quantitative data. We also assessed whether frequencies of candidate gene genotypes conformed to Hardy–Weinburg equilibrium.&#x0D; Results. Hexane was detected in workplace air in concentrations within 14–68 mg/m3 range (0.1MPCworkplace) during the observation period; heptane, 20–84 mg/m3 (0.1MPCworkplace). We assessed contamination of workers’ urine with hexane and heptane depending on their working experience that involved occupational contacts with saturated hydrocarbons, from 1 year and up to longer than 10 years. The assessment revealed that hexane contents were by 1.5 times higher and heptane contents by 1.22 times higher in workers with their working experience being longer than 10 years against workers with shorter working experience (less than 10 years).&#x0D; The results of a comparative analysis of the features of genetic polymorphism in the workers of the observation group in relation to the comparison group allowed us to establish significant differences between the frequencies of genotypes and alleles of the adducine gene ADD1 Gly460Trp rs4961, characterized by an increase in the frequency of the wild GG genotype of the gene. The assessment of the odds ratio (OR) of the presence in the observation group of the variation of the genotype GG of the gene ADD1 Gly460Trp rs4961 according to the multiplicative (for G allele inherited by dominant type OR=2.94; CI: 1.46–5.94; p&lt;0.005) and general (for GG genotype, OR=3.14; CI: 1.44–6.86; p&lt;0.005) inheritance models, as well as an assessment of the relative risk (for the G allele RR=1.38; CI: 1.23–1.53), allowed us to verify the reliable probability of the formation of genetically determined disorders associated with the development of arterial hypertension.&#x0D; Limitations. A limitation of the study is the study of the polymorphism of the ADD1 Gly460Trp rs4961 adducin gene only when exposed to two saturated hydrocarbons, hexane and heptane.&#x0D; Conclusion. Our research revealed that workers with basic production occupations and with working experience at the factory that was longer than 10 years had authentically higher hexane and heptane contents in their urine, by 1.5 (р&lt;0.01) and 1.22 (р&lt;0.048) times accordingly, than workers with their working experience at the factory being shorter than 10 years.&#x0D; We established that detection of hexane in concentrations equal to 0.006±0.002 mg/dm3 in urine of workers with basic production occupations who contacted saturated hydrocarbons vapors corresponded to 81% of the variation of the ADD1 Gly460Trp rs4961 gene in the form of a wild GG genotype (p&lt;0.05) corresponded, which in conditions of contamination with marginal hydrocarbons can form the risk of cardiovascular pathology.&#x0D; Ethics. The research was performed in full conformity with ethical principles for medical research involving human subjects stipulated by the Declaration of Helsinki issued by the World Medical Association (the latest edition); all the participants gave their informed voluntary consent to take part in the research.

Targeted MRM Quantification of Urinary Proteins in Chronic Kidney Disease Caused by Glomerulopathies.

Glomerulopathies with nephrotic syndrome that are resistant to therapy often progress to end-stage chronic kidney disease (CKD) and require timely and accurate diagnosis. Targeted quantitative urine proteome analysis by mass spectrometry (MS) with multiple-reaction monitoring (MRM) is a promising tool for early CKD diagnostics that could replace the invasive biopsy procedure. However, there are few studies regarding the development of highly multiplexed MRM assays for urine proteome analysis, and the two MRM assays for urine proteomics described so far demonstrate very low consistency. Thus, the further development of targeted urine proteome assays for CKD is actual task. Herein, a BAK270 MRM assay previously validated for blood plasma protein analysis was adapted for urine-targeted proteomics. Because proteinuria associated with renal impairment is usually associated with an increased diversity of plasma proteins being present in urine, the use of this panel was appropriate. Another advantage of the BAK270 MRM assay is that it includes 35 potential CKD markers described previously. Targeted LC-MRM MS analysis was performed for 69 urine samples from 46 CKD patients and 23 healthy controls, revealing 138 proteins that were found in ≥2/3 of the samples from at least one of the groups. The results obtained confirm 31 previously proposed CKD markers. Combination of MRM analysis with machine learning for data processing was performed. As a result, a highly accurate classifier was developed (AUC = 0.99) that enables distinguishing between mild and severe glomerulopathies based on the assessment of only three urine proteins (GPX3, PLMN, and A1AT or SHBG).

Feasibility for early cancer diagnostics by machine learning enabled synchrotron radiation based micro X-ray fluorescence imaging of trace biometals as cancer biomarkers

Trace quantitative spectroscopic imaging has the potential to provide the location and distribution of trace biometals in a biological sample for disease (cancer) diagnostics. However, spatial qualitative analysis of the trace biometals for cancer diagnostics remains a challenge due to the complex biological matrices that result in weak analyte signals and intricate multivariate relationships between the analyte spatial distribution and disease (cancer) state. In this study, principal component analysis (PCA)-enabled artificial neural networks (ANN) for micro X-ray fluorescence for simultaneous determination of biometal (Mn, Fe, Cu and Se) spatial profiles as biomarkers for cancer diagnosis in model human cell cultures (DU145 and Vero). The cell lines were cultured on silicon nitride membranes and micro XRF analysis carried out at TwinMic beamline, Elletra synchrotron source at beam excitation energy of 1.7 keV. These enabled 2D mapping of Mn, Fe, Cu and Se using cylindrical beam dimensions of Æ690 nm in stepper motor-controlled step sizes of 0.6μm with dwell times of 10s per pixel. Python multichannel analyzer (PyMca) software was used for spectral deconvolution and determination of 2D maps of the trace biometals. Principal component analysis (PCA) reduced the data dimensions for optimal artificial neural networks (ANN) exploratory modelling of cancer pathogenesis stages utilizing the pixel spectral profile of the trace biometals (Mn, Fe, Cu, Se). The 2D spatial distribution maps of the trace biometals revealed high spatial correlations between Cu and Fe ((0.941) and (0.923)) in DU_D3 and DU_D4 in cancerous compared to normal cell culture stages (V_D3 and V_D4) at 0.661 and 0.203 respectively. Utilizing PC1 and PC2 scores from selected fluorescence L (Lα and Lβ) lines of Fe and Cu, ANN distinctively classified the cell cultures into cancerous and healthy groups. Further, the selected fluorescence L-lines of Fe, Cu and Compton scatter spectral profiles enabled ANN classification of cancerous cultured cells into early, intermediate and advanced stages. The study has provided proof of concept for early diagnosis of cancer based on the multivariate alterations and spatial distribution of the trace biometals as cancer biomarkers.

Method of Failure Diagnostics to Linear Rolling Guides in Handling Machines.

Linear rolling guides, used in production machines for the realisation of linear motion, demand in industrial practice early damage identification to prevent production outages and losses. Therefore, the article aims for early damage diagnostics that use the principle of a load-free diagnostic part integrated into the carriage of the linear rolling guide. This principle was employed for developing an innovative method of damage identification to a guiding profile or rolling elements. The proposed innovative method is based on analysing vibration acceleration measured on the diagnostic part in the context of carriage position. In addition, a unique connection of an acceleration sensor to the diagnostic part through a mechanical component with defined parameters of stiffness and mass was designed. The innovative method was verified by laboratory testing on a designed functional sample of the diagnostic system. The computed reliability of the proposed diagnostic method reached 98%.

Abstract 4600: Phenotypic &amp; functional diversity of tumor associated neutrophils in murine breast tumor models

Abstract Despite the advances in early diagnostics and therapeutics, women with metastatic breast cancer have limited treatment options. Women with TNBC, who constitute 15-20% of breast cancer patients, are often diagnosed with aggressive/metastatic disease. Advanced studies implicated immunosuppressive tumor microenvironment (TME) in aggressive/metastatic properties of TNBC subtype. Alternatively activated immature myeloid cells including tumor-associated macrophages (TAM), tumor-associated neutrophils (TAN), tumor-associated dendritic cells (TADC) and myeloid derived suppressor cells (MDSC) constitute a major component of TME. However, anti-tumorigenic microenvironment is also reported and that may have clinical relevance in early TNBC patients. Therefore, our hypothesis is that myeloid cells polarize to become immunosuppressive and infiltrate tumors and pre-metastatic niches in patients with advanced disease, while patients with early TNBCs may elicit anti-tumor immune response eliminating disseminated tumor cells (DTC). The utilization of syngeneic immunocompetent mouse models has contributed to our current understanding of immunosuppressive or immunomodulatory TME. Using these models, we have demonstrated that tumor dissemination and growth at metastatic sites is facilitated by MDSC’s. Emerging technologies; single cell RNA sequencing (scRNA-Seq), mass cytometry (CyTOF) or cellular indexing of transcriptomes and epitopes sequencing (CITE-Seq) has been powerful platforms for detailed characterization of tumors and TME compartments. We performed scRNA-Seq and CyTOF analyses of the myeloid cell populations of tumors and spleens from metastatic 4T1 and non-invasive EMT6 tumor-bearing mice. Tumors and spleens from 4T1 tumor-bearing mice exhibited a marked expansion of myeloid cell subsets that are characterized by the expression of immunosuppressive as well as progenitor markers. On the contrary, indicated tissues from EMT6 mice were enriched in NK cells, T and B lymphocytes and they were lacking immunosuppressive myeloid cell subsets. Furthermore, we identified a distinct differentiation pattern of immature myeloid cell subsets from neutrophil progenitors (NP) in 4T1 tumor-bearing mice. Using the murine TNBC models in syngeneic mice, we provide evidence that early TNBC tumors may elicit anti-tumor immune responses and thus the survival outcome in those patients is substantially increased after complete surgical resection of the primary tumors. Whereas immunosuppressive tumor microenvironment contributes to the poor overall survival in patients with advanced TNBCs. Therefore, identifying an anti-tumor immune signature in early TNBC patients may be utilized as a clinical biomarker before surgical intervention as well as improve the survival outcome. Citation Format: Hasan Korkaya, Elayne Benson, Fulya Koksalar Alkan, Justin Wilson, Tulshi Patel, Hilmi K. Alkan, Virginia McEvoy, Nika Shekastehband, Nate Francois, Huidong Shi, Catherine C. Hedrick. Phenotypic &amp; functional diversity of tumor associated neutrophils in murine breast tumor models. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4600.

Lysine Acetylome of Breast Cancer-Derived Small Extracellular Vesicles Reveals Specific Acetylation Patterns for Metabolic Enzymes

Cancer-derived small extracellular vesicles have been proposed as promising potential biomarkers for diagnosis and prognosis of breast cancer (BC). We performed a proteomic study of lysine acetylation of breast cancer-derived small extracellular vesicles (sEVs) to understand the potential role of the aberrant acetylated proteins in the biology of invasive ductal carcinoma and triple-negative BC. Three cell lines were used as models for this study: MCF10A (non-metastatic), MCF7 (estrogen and progesterone receptor-positive, metastatic) and MDA-MB-231 (triple-negative, highly metastatic). For a comprehensive protein acetylation analysis of the sEVs derived from each cell line, acetylated peptides were enriched using the anti-acetyl-lysine antibody, followed by LC-MS/MS analysis. In total, there were 118 lysine-acetylated peptides, of which 22, 58 and 82 have been identified in MCF10A, MCF7 and MDA-MB-231 cell lines, respectively. These acetylated peptides were mapped to 60 distinct proteins and mainly identified proteins involved in metabolic pathways. Among the acetylated proteins identified in cancer-derived sEVs from MCF7 and MDA-MB-231 cell lines are proteins associated with the glycolysis pathway, annexins and histones. Five acetylated enzymes from the glycolytic pathway, present only in cancer-derived sEVs, were validated. These include aldolase (ALDOA), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase (PGK1), enolase (ENO) and pyruvate kinase M1/2 (PKM). For three of these enzymes (ALDOA, PGK1 and ENO) the specific enzymatic activity was significantly higher in MDA-MB-231 when compared with MCF10A-derived sEVs. This study reveals that sEVs contain acetylated glycolytic metabolic enzymes that could be interesting potential candidates for early BC diagnostics.

Cheap and Mass-Producible Electrochemical Sensor of Hydrogen Peroxide

Abstract Hydrogen peroxide is present naturally in any living cell. Although hydrogen peroxide concentration in cell is strictly regulated during normal metabolism, several human diseases lead to increased hydrogen peroxide concentration in body fluids. It is beneficial to monitor hydrogen peroxide levels in human body for early disease diagnostics. This can be done by creation of electronic device, which will use electrochemical sensor in order to perform automated hydrogen peroxide concentration measurement in a sample. The aim of the research is to use printed circuit board (PCB) technology in order to create a replaceable electrochemical hydrogen peroxide sensor that could be cheaply mass-produced to enable further development of automated health diagnostics device.

Management of the Bone Deformity Caused by Congenital Cyst of the Periorbital Area: Analysis of the Surgical Technique and a Short-term Outcome

The congenital periorbital cysts like dermoids/epidermoids, in rare cases, can require not only its’ excision but also correction/camouflage of the caused bone deformity. This management can require virtual surgical planning, osteotomy, and placement of the custom-made patient implant. In this report, the ultrasonography (USG) was proved as a highly effective imaging for the presurgical verification of the mass’s structure and establishment of the clinical diagnosis. The multi-slice computed tomography (MSCT), even on a two-slice MSCT machine, provided high-quality three-dimensional reconstruction of the area of bone deformation caused by the cyst and allowed for accurate surgical planning. A 20-year-old male patient with a congenital periorbital epidermoid cyst that led to the deformation of the lateral orbital rim was treated using the soft tissue volume-increasing technique for the correction of bone deformation following cyst removal. Analysis of the terminological diversity related with dermoid/epidermoid cysts is presented. Early diagnostics and management of congenital periorbital cysts can decrease the visual, orbital, and esthetic complications, as well as the need to perform bone reconstructive surgeries or other corrective surgical procedures.