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AbstractBackgroundAimMethodsResultsConclusions and significanceUS guided sampling is a validated diagnostic approach for non-thyroid deep head and neck masses.To describe the setting of a clinician-driven Lump Clinic and analyze a monoinstitutional 7-year database of 849 patients undergoing US-guided sampling.FNA with Rapid OnSite Evalutation (ROSE) was the first diagnostic step. In the last years in selected cases, upon ROSE and discussion between clinician and histopathologist, a core biopsy was performed, usually in the same access. If cytology is non-diagnostic, and core biopsy have not been obtained, all available clinical and diagnostic data were re-examined by surgeons and cytopathologists to establish a multiparametric diagnosis (MD).Cytology and MD showed a sensitivity of 91.8% and 95.3% respectively and a specificity of 95.7% in diagnosing malignancy. Complication rate of US guided sampling was 0,12% (considering the number of patients: 1/849), without any serious adverse event.Present data confirm the great safety and utility of US guided procedures in the management of head and neck non-thryoid deep masses, while demonstrating the added value of a lump clinic built on the close cooperation between the head and neck surgeon and the histopathologists. [ABSTRACT FROM AUTHOR]

In this study, the authors carried out a multiparametric assessment of the influence of swirl patterns during aerosol flow on the shape of the interfacial area that forms the cone based on data obtained from experimental measurements using the PIV and LLS methods. The results were correlated with the disinfection process occurring in the near and far fields of the aerosol (direct surface disinfection and volume fogging). In this study, parameters such as turbulent kinetic energy (TKE), swirl strength (SS), pressure fields, and Sauter mean diameter (d32) are used to investigate the relationship between aerosol spray morphology and flow dynamics under different operating conditions. Three different geometrical settings of the aerosol-generating system and two different pressures corresponding to the air supply to the spray nozzle have been adopted. By evaluating the results obtained, the influence of each parameter on the formation of the aerosol displacement trajectory, the stabilization of the spray cone, and its degradation was identified. The shape of the boundary between the dynamically moving aerosol and the surrounding air was also evaluated. The conditions for swirling and straight-line flows within the aerosol cone, and, thus, the conditions for the volumetric development of swirling phenomena, were further clarified. [ABSTRACT FROM AUTHOR]

Abstract Academic data predictions are significantly important for improving the overall education system's effectiveness by providing early identification of weak students and personalized learning strategies. This paper proposes a deep learning model for the identification of weak and strong students using ensemble learning and multiparametric analysis. It combines several machine learning algorithms, including Naive Bayes, Support Vector Machines, Multi-Layer Perceptron, and Logistic Regression using an ensemble learning approach to enhance the model’s performance. Additionally, a custom 1D Convolutional Neural Network (CNN) is designed for classification. It utilizes multiparametric analysis to identify weak and strong students considering various parameters such as age, academic performance, location, and online learning behavior. The evaluation results indicate the performance of the proposed model has been improved in comparison to MLA FIS, SHMM, and DRL by 16.5%, 5.5%, and 2.4%, in terms of precision, 16.4%, 6.5%, and 3.5 % in terms of accuracy and 10.4%, 2.5% and 6.5% in terms of recall. These improvisations described that the model is efficient for multidomain feature extraction, ensemble classification, and high-variance feature selection, which result in a deeper understanding of student performance.

Academic data predictions are significantly important for improving the overall education system's effectiveness by providing early identification of weak students and personalized learning strategies. This paper proposes a deep learning model for the identification of weak and strong students using ensemble learning and multiparametric analysis. It combines several machine learning algorithms, including Naive Bayes, Support Vector Machines, Multi-Layer Perceptron, and Logistic Regression using an ensemble learning approach to enhance the model’s performance. Additionally, a custom 1D Convolutional Neural Network (CNN) is designed for classification. It utilizes multiparametric analysis to identify weak and strong students considering various parameters such as age, academic performance, location, and online learning behavior. The evaluation results indicate the performance of the proposed model has been improved in comparison to MLA FIS, SHMM, and DRL by 16.5%, 5.5%, and 2.4%, in terms of precision, 16.4%, 6.5%, and 3.5 % in terms of accuracy and 10.4%, 2.5% and 6.5% in terms of recall. These improvisations described that the model is efficient for multidomain feature extraction, ensemble classification, and high-variance feature selection, which result in a deeper understanding of student performance.Article Highlights: A deep learning model using ensemble learning and multiparametric analysis for identifying weak and strong students. The proposed deep learning model significantly improves identifying weak and strong students, boosting educational effectiveness. By combining various machine learning techniques with a custom CNN, the model enhances precision, accuracy, and recall. It offers a more detailed analysis of student performance, leveraging factors like age and online behavior for better personalized learning. [ABSTRACT FROM AUTHOR]

Neurodegenerative disorders, including Multiple Sclerosis (MS), are heterogenous disorders which affect the myelin sheath of the central nervous system (CNS). Magnetic Resonance Imaging (MRI) provides a non-invasive method for studying, diagnosing, and monitoring disease progression. As an emerging research area, many studies have attempted to connect MR metrics to underlying pathophysiological presentations of heterogenous neurodegeneration. Most commonly, small animal models are used, including Experimental Autoimmune Encephalomyelitis (EAE), Theiler's Murine Encephalomyelitis (TMEV), and toxin models including cuprizone (CPZ), lysolecithin, and ethidium bromide (EtBr). A contrast and comparison of these models is presented, with focus on the cuprizone model, followed by a review of literature studying neurodegeneration using MRI and the cuprizone model. Conventional MRI methods including T1 Weighted (T1W) and T2 Weighted (T2W) Imaging are mentioned. Quantitative MRI methods which are sensitive to diffusion, magnetization transfer, susceptibility, relaxation, and chemical composition are discussed in relation to studying the CPZ model. Overall, additional studies are needed to improve both the sensitivity and specificity of MRI metrics for underlying pathophysiology of neurodegeneration and the relationships in attempts to clear the clinico-radiological paradox. We therefore propose a multiparametric approach for the investigation of MR metrics for underlying pathophysiology. [ABSTRACT FROM AUTHOR]

Objective: In the era of image-guided adaptive radiotherapy, definition of the clinical target volume (CTV) is a challenge in various solid tumors, including esophageal cancer (EC). Many tumor microenvironmental factors, e.g., tumor cell proliferation or cancer stem cells, are hypothesized to be involved in microscopic tumor extension (MTE). Therefore, this study assessed the expression of FAK, ILK, CD44, HIF-1α, and Ki67 in EC patients after neoadjuvant radiochemotherapy followed by tumor resection (NRCHT+R) and correlated these markers with the MTE. Methods: Formalin-fixed paraffin-embedded tumor resection specimens of ten EC patients were analyzed using multiplex immunofluorescence staining. Since gold fiducial markers had been endoscopically implanted at the proximal and distal tumor borders prior to NRCHT+R, correlation of the markers with the MTE was feasible. Results: In tumor resection specimens of EC patients, the overall percentages of FAK+, CD44+, HIF-1α+, and Ki67+ cells were higher in tumor nests than in the tumor stroma, with the outcome for Ki67+ cells reaching statistical significance (p < 0.001). Conversely, expression of ILK+ cells was higher in tumor stroma, albeit not statistically significantly. In three patients, MTE beyond the fiducial markers was found, reaching up to 31 mm. Conclusion: Our findings indicate that the overall expression of FAK, HIF-1α, Ki67, and CD44 was higher in tumor nests, whereas that of ILK was higher in tumor stroma. Differences in the TME between patients with residual tumor cells in the original CTV compared to those without were not found. Thus, there is insufficient evidence that the TME influences the required CTV margin on an individual patient basis. Trial registration number and date: BO-EK-148042017 and BO-EK-177042022 on 20.06.2022, DRKS00011886, https://drks.de/search/de/trial/DRKS00011886. [ABSTRACT FROM AUTHOR]

Objectives: Several ultrasound measures have shown promise for assessment of steatosis compared to traditional B-scan, however clinicians may be required to integrate information across the parameters. Here, we propose an integrated multiparametric approach, enabling simple clinical assessment of key information from combined ultrasound parameters. Methods: We have measured 13 parameters related to ultrasound and shear wave elastography. These were measured in 30 human subjects under a study of liver fat. The 13 individual measures are assessed for their predictive value using independent magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) measurements as a reference standard. In addition, a comprehensive and fine-grain analysis is made of all possible combinations of sub-sets of these parameters to determine if any subset can be efficiently combined to predict fat fraction. Results: We found that as few as four key parameters related to ultrasound propagation are sufficient to generate a linear multiparametric parameter with a correlation against MRI-PDFF values of greater than 0.93. This optimal combination was found to have a classification area under the curve (AUC) approaching 1.0 when applying a threshold for separating steatosis grade zero from higher classes. Furthermore, a strategy is developed for applying local estimates of fat content as a color overlay to produce a visual impression of the extent and distribution of fat within the liver. Conclusion: In principle, this approach can be applied to most clinical ultrasound systems to provide the clinician and patient with a rapid and inexpensive estimate of liver fat content.

Background: The prevalence of liver diseases, especially steatosis, requires a more convenient and noninvasive tool for liver diagnosis, which can be a surrogate for the gold standard biopsy. Magnetic resonance (MR) measurement offers potential, however ultrasound (US) has better accessibility than MR. Purpose: This study aims to suggest a multiparametric US approach which demonstrates better quantification and imaging performance than MR imaging‐based proton density fat fraction (MRI‐PDFF) for hepatic steatosis assessment. Methods: We investigated early‐stage steatosis to evaluate our approach. An in vivo (within the living) animal study was performed. Fat inclusions were accumulated in the animal livers by feeding a methionine and choline deficient (MCD) diet for 2 weeks. The animals (n = 19) underwent US and MR imaging, and then their livers were excised for histological staining. From the US, MR, and histology images, fat accumulation levels were measured and compared: multiple US parameters; MRI‐PDFF; histology fat percentages. Seven individual US parameters were extracted using B‐mode measurement, Burr distribution estimation, attenuation estimation, H‐scan analysis, and shear wave elastography. Feature selection was performed, and the selected US features were combined, providing quantification of fat accumulation. The combined parameter was used for visualizing the localized probability of fat accumulation level in the liver; This procedure is known as disease‐specific imaging (DSI). Results: The combined US parameter can sensitively assess fat accumulation levels, which is highly correlated with histology fat percentage (R = 0.93, p‐value < 0.05) and outperforms the correlation between MRI‐PDFF and histology (R = 0.89, p‐value < 0.05). Although the seven individual US parameters showed lower correlation with histology compared to MRI‐PDFF, the multiparametric analysis enabled US to outperform MR. Furthermore, this approach allowed DSI to detect and display gradual increases in fat accumulation. From the imaging output, we measured the color‐highlighted area representing fatty tissues, and the fat fraction obtained from DSI and histology showed strong agreement (R = 0.93, p‐value < 0.05). Conclusions: We demonstrated that fat quantification utilizing a combination of multiple US parameters achieved higher performance than MRI‐PDFF; therefore, our multiparametric analysis successfully combined selected features for hepatic steatosis characterization. We anticipate clinical use of our proposed multiparametric US analysis, which could be beneficial in assessing steatosis in humans. [ABSTRACT FROM AUTHOR]

We demonstrate a sensing scheme for liquid analytes that integrates multiple optical fiber sensors in a near-infrared spectrometer. With a simple optofluidic method, a broadband radiation is encoded in a time-domain interferogram and distributed to different sensing units that interrogate the sample simultaneously; the spectral readout of each unit is extracted from its output signal by a Fourier transform routine. The proposed method allows performing a multiparametric analysis of liquid samples in a compact setup where the radiation source, measurement units, and spectral readout are all integrated in a robust telecom optical fiber. An experimental validation is provided by combining a plasmonic nanostructured fiber probe and a transmission cuvette in the setup and demonstrating the simultaneous measurement of the absorption spectrum and the refractive index of water–methanol solutions. [ABSTRACT FROM AUTHOR]

(1) Background: Warthin tumors account for about 20% of all benign salivary tumors, approaching 50% if we consider only the parotid gland. Wait and see is considered a reasonable option, but the diagnosis should be certain. Diagnosis can be based on morphological and cytological data, but the sensitivity of the fine needle aspiration cytology (FNAC) is not absolute, with a high rate of non-diagnostic findings in the event of a Warthin tumor, hindering the counseling and therapeutic decisions. The aim of the study is to evaluate the reliability of FNAC and its combination with anamnestic, clinical, and ultrasonographic data in diagnosing Warthin tumors. (2) Methods: A total of 413 patients affected by masses within the major salivary gland and managed between 2017 and 2022 at our institution have been included in the present retrospective study. Each patient underwent fine needle aspiration biopsy (FNAB) with a subsequent cytological diagnosis; successively, for each patient, the clinician (otolaryngologist) and the histopathologist discussed the combination of cytological (even non-diagnostic), clinical, and ultrasonographic data in order to make a "multiparametric" diagnosis. A total of 214 cases were subsequently submitted to surgical resection and had a final histopathology report, to which the cytological and the multiparametric diagnoses can be compared. We extracted all the patients with a cytological, multiparametric, and/or histological diagnosis of Warthin tumors in order to assess the sensitivity and specificity of FNAC and of multiparametric analysis in diagnosing Warthin tumors in case of a major salivary gland mass. (3) Results: One hundred thirty-two cases had a cytological, multiparametric, and/or histological diagnosis of Warthin tumors. FNAC displays a sensitivity of 68.4% and a specificity of 98.7% in diagnosing Warthin tumors. The multiparametric evaluation allowed a considerable improvement in sensitivity (92.9% vs. 68.4%), minimizing the number of non-diagnostic results and preserving at the same time a similar value of specificity (95.5% vs. 98.7%). Notably, none of the patients with a cytological or multiparametric diagnosis of Warthin were affected by a malignant lesion in the final histopathological report. (4) Conclusions: In the case of Warthin tumors, a multiparametric evaluation encompassing anamnestic, clinical, and cytological data is effective in reducing the number of non-diagnostic reports and can safely guide the management of a tumor (e.g., antibiotic treatment of infectious complications, assign a low priority to surgery, even consider observation avoiding surgery) which is absolutely benign and can be associated with no clinically relevant issues. [ABSTRACT FROM AUTHOR]

Nanoscale multipoint structure-function analysis is essential for deciphering the complexity of multiscale biological and physical systems. Atomic force microscopy (AFM) allows nanoscale structure-function imaging in various operating environments and can be integrated seamlessly with disparate probe-based sensing and manipulation technologies. Conventional AFMs only permit sequential single-point analysis; widespread adoption of array AFMs for simultaneous multipoint study is challenging owing to the intrinsic limitations of existing technological approaches. Here, we describe a prototype dispersive optics-based array AFM capable of simultaneously monitoring multiple probe-sample interactions. A single supercontinuum laser beam is utilized to spatially and spectrally map multiple cantilevers, to isolate and record beam deflection from individual cantilevers using distinct wavelength selection. This design provides a remarkably simplified yet effective solution to overcome the optical cross-talk while maintaining subnanometer sensitivity and compatibility with probe-based sensors. We demonstrate the versatility and robustness of our system on parallel multiparametric imaging at multiscale levels ranging from surface morphology to hydrophobicity and electric potential mapping in both air and liquid, mechanical wave propagation in polymeric films, and the dynamics of living cells. This multiparametric, multiscale approach provides opportunities for studying the emergent properties of atomic-scale mechanical and physicochemical interactions in a wide range of physical and biological networks.

The results presented in this article are an attempt to develop a methodology for predicting productivity and determining the contour of the object of the I category of negative impact on the environment. Using an empirically derived set of methods of analysis, a study of the state of oil and gas fields in the Samara region of different terms and stages of the life cycle of operation, productivity, etc. was carried out. The methodology is based on the evaluation of fields as a part of the license area for the purpose of further decision-making on the system of measures in the field of waste management, development of programs for improving environmental efficiency, taking into account the development of the fields. The basic principle of the developed methodology implies a comprehensive analysis of the balance schemes of material flows of technological cycles of raw materials and energy, as well as the formed types of chemical compounds in the composition of emissions, effluents and wastes. Application of multi-parameter method of assessment will allow not only to identify additional volumes of uncontrolled impact and to implement preventive measures, but also to maintain communication between the participants of the process of environmental management: public authorities, public, production.

A multiparametric liquid chromatography-tandem mass spectrometry method has been developed for the simultaneous quantification of 11 antifungal drugs and their metabolites in human plasma. This method addresses the critical need for therapeutic drug monitoring in the treatment of invasive fungal infections, which are increasingly prevalent among immunocompromised patients and those in intensive care units. The method quantifies flucytosin, fluconazole, itraconazole, hydroxy-itraconazole, posaconazole, isavuconazole, voriconazole, voriconazole-N-oxide, anidulafungin, caspofungin, and micafungin. Key challenges in method development included optimising mass spectrometer settings, chromatographic conditions, and sample preparation techniques to ensure accurate, sensitive, and specific detection. Validation of this method was conducted in accordance with the guidelines set by the USA Food and drug administration and the European Medicines Agency covering linearity, precision, accuracy, selectivity, matrix effect, and stability. The method exhibited robust performance with intra- and inter-assay precision under 10 % and average accuracy for intra- and inter-assay comparison of −2.35 % and 0.80 %, respectively. Limits of detection (0.002 to 0.110 mg/L) and a quantification range between 0.005 and 200 mg/L make this method suitable for clinical TDM applications. The ability to simultaneously analyse eleven antifungals and their metabolites within a single 5-minute run enhances its utility in clinical settings, particularly for critically ill patients who may experience significant pharmacokinetic variations. The method requires only 100 µL of plasma, demonstrating good analytical performances rendering it a valuable tool for optimising antifungal therapy and improving patient outcomes in ICU management. [Display omitted] • A first UHPLC-MS/MS method quantifying simultaneously eleven antifungal drugs in human plasma was developed and validated. • Flucytosin, seven azoles including two metabolites, anidulafungin, caspofungin, and micafungin were quantified. • Simple protein precipitation with acetonitrile was performed. • The validation was conducted according to international and EMA guidelines. • The assay method demonstrated good precision and accuracy within the dynamic range. [ABSTRACT FROM AUTHOR]

The alarming increase in water pollution is driving research into novel, environmentally friendly treatment solutions such as hydrodynamic cavitation. This study is part of the research on the pin disc rotational generator of hydrodynamic cavitation, which utilises the low pressure wake behind the rotor pins to induce cavitation and the short gap between the rotor and stator pins to enhance cavitation cloud fluctuation. Due to the lack of understanding of the effects of cavitation treatment, a laboratory device was built to investigate the mechanisms of cavitation generation and the effects of various geometric features such as the diameter, number, and shape of the rotor pins and the gap size between the rotor and stator pins. Using simultaneously measured pressure fluctuations and high-speed visualisation, a method was developed to quantify the extent of cavitation, and it was found that throttling the high-pressure side had an order- of- magnitude smaller effect on cavitation than the number of rotor pins. It was found that a smaller number of rotor pins with large downstream area produced the most aggressive cavitation conditions. The weak spectral response and lower mean vapour cloud area, as well as the lower fluctuation in the case without stator, demonstrated the key role of the stator in the onset and aggressiveness of cavitation.

The purpose of this study is to describe a methodology for assessing the geotechnical stability of agricultural facilities, enabling prediction of the state of the geotechnical system, taking into account the influence of external factors and combinations of reactions of the geotechnical system under study. According to the methodology, the heterogeneous geotechnical monitoring data obtained are used in an adjusted geotechnical system model, allowing a bifurcation analysis to be carried out. The bifurcation analysis determines critical values of influencing factors, and the limits of stability of the geotechnical system studied parameters are adjusted. The developed methodology was used to assess and predict the geotechnical stability of agricultural facilities during the processing of geoelectric, resistive acoustic, accelerometric and strain-gauge control data obtained in the period from 2016 to 2021. A feature of the geotechnical system under study is the periodic flooding of the building basement caused by the processes of reclamation and irrigation, leading to changes in the groundwater level. The results show that the permissible calculated elastic limit of the foundation elements (32.2–35.1 MPa) before the loss of stability should be significantly reduced with a change in the water content coefficient (W) of the soil base: at W = 0.15 Eb = 30.7–32.0 MPa; at W = 0.35 Eb = 26.8–28.2 MPa; at W = 0.55 Eb = 24.9–25.3 MPa. [ABSTRACT FROM AUTHOR]

Background: Current blood-based diagnostic tools for TB are insufficient to properly characterize the distinct stages of TB, from the latent infection (LTBI) to its active form (aTB); nor can they assess treatment efficacy. Several immune cell biomarkers have been proposed as potential candidates for the development of improved diagnostic tools. Objective: To compare the capacity of CD27, HLA-DR, CD38 and Ki-67 markers to characterize LTBI, active TB and patients who ended treatment and resolved TB. Methods: Blood was collected from 45 patients defined according to clinical and microbiological criteria as: LTBI, aTB with less than 1 month of treatment and aTB after completing treatment. Peripheral blood mononuclear cells were stimulated with ESAT-6/CFP-10 or PPD antigens and acquired for flow cytometry after labelling with conjugated antibodies against CD3, CD4, CD8, CD27, IFN-γ, TNF-α, CD38, HLA-DR, and Ki-67. Conventional and multiparametric analyses were done with FlowJo and OMIQ, respectively. Results: The expression of CD27, CD38, HLA-DR and Ki-67 markers was analyzed in CD4+ T-cells producing IFN-γ and/or TNF-α cytokines after ESAT-6/CFP-10 or PPD stimulation. Within antigen-responsive CD4+ T-cells, CD27− and CD38+ (ESAT-6/CFP-10-specific), and HLA-DR+ and Ki-67+ (PPD- and ESAT-6/CFP-10-specific) populations were significantly increased in aTB compared to LTBI. Ki-67 demonstrated the best discriminative performance as evaluated by ROC analyses (AUC > 0.9 after PPD stimulation). Data also points to a significant change in the expression of CD38 (ESAT-6/CFP-10-specific) and Ki-67 (PPD- and ESAT-6/CFP-10-specific) after ending the anti-TB treatment regimen. Furthermore, ratio based on the CD27 median fluorescence intensity in CD4+ T-cells over Mtb-specific CD4+ T-cells showed a positive association with aTB over LTBI (ESAT-6/CFP-10-specific). Additionally, multiparametric FlowSOM analyses revealed an increase in CD27 cell clusters and a decrease in HLA-DR cell clusters within Mtb-specific populations after the end of treatment. Conclusion: Our study independently confirms that CD27−, CD38+, HLA-DR+ and Ki-67+ populations on Mtb-specific CD4+ T-cells are increased during active TB disease. Multiparametric analyses unbiasedly identify clusters based on CD27 or HLA-DR whose abundance can be related to treatment efficacy. Further studies are necessary to pinpoint the convergence between conventional and multiparametric approaches. [ABSTRACT FROM AUTHOR]

With the progression of diseases, modified cell–matrix interactions have major effects not only upon key cellular functions but also upon the structure of extracellular matrix and vasculature, which are two of the most prevalent fiber‐like structures in biological tissues. Unfortunately, quantitative approaches to assessing these structural changes are lacking. Herein, a multiparametric imaging system is established to resolve subtle organizational changes of collagen fibers and vasculature in disease progression. The pixel‐wise, automated waviness (paWav) is developed as a novel biomarker, and a multimodal analysis system combining paWav with orientation and alignment assessments is constructed. Aggregation‐induced emission luminogens (AIEgens) with second near‐infrared excitation or emission are developed for in vivo deep‐penetration vasculature imaging. The organization remodeling of cortical blood vessels in stroke in marmosets is quantitatively characterized using biologically excretable AIE dots that highlight the clinical translation potential, and a distance dependence law in vessel morphological remodeling is identified. Finally, the multiparametric analysis relying completely on collagen fiber signatures successfully differentiates cancerous from normal pancreatic tissues using a predictive classification approach. Collectively, the combined use of these structural changes in fibrillar tissue components may enable a better understanding of cell–matrix interactions in pathogenesis and identification of new potential treatment targets. [ABSTRACT FROM AUTHOR]

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Lung cancer is the leading cause of cancer mortality worldwide, with non-small cell lung cancer (NSCLC) being the most prevalent histology. While immunotherapy with checkpoint inhibitors has shown outstanding results in NSCLC, the precise identification of responders remains a major challenge. Most studies attempting to overcome this handicap have focused on adenocarcinomas or squamous cell carcinomas. Among NSCLC subtypes, the molecular and immune characteristics of lung large cell carcinoma (LCC), which represents 10% of NSCLC cases, are not well defined. We hypothesized that specific molecular aberrations may impact the immune microenvironment in LCC and, consequently, the response to immunotherapy. To that end, it is particularly relevant to thoroughly describe the molecular genotype–immunophenotype association in LCC–to identify robust predictive biomarkers and improve potential benefits from immunotherapy. We established a cohort of 18 early-stage, clinically annotated, LCC cases. Their molecular and immune features were comprehensively characterized by genomic and immune-targeted sequencing panels along with immunohistochemistry of immune cell populations. Unbiased clustering defined two novel subgroups of LCC. Pro-immunogenic tumors accumulated certain molecular alterations, showed higher immune infiltration and upregulated genes involved in potentiating immune responses when compared to pro-tumorigenic samples, which favored tumoral progression. This classification identified a set of biomarkers that could potentially predict response to immunotherapy. These results could improve patient selection and expand potential benefits from immunotherapy. [ABSTRACT FROM AUTHOR]

In medical imaging, quantitative measurements have shown promise in identifying diseases by classifying normal versus pathological parameters from tissues. The support vector machine (SVM) has shown promise as a supervised classification algorithm and has been widely used. However, the classification results typically identify a category of abnormal tissues but do not necessarily differentiate progressive stages of a disease. Moreover, the classification result is typically provided independently as a supplement to medical images, which contributes to an overload of information sources in the clinic. Hence, we propose a new imaging method utilizing the SVM to integrate classification results into medical images. This framework is called disease-specific imaging (DSI) that produces a color overlaid highlight on B-mode ultrasound images indicating the type, location, and severity of pathology from different conditions. In this article, the SVM training was performed to construct hyperplanes that can differentiate normal, fibrosis, steatosis, and pancreatic ductal adenocarcinoma (PDAC) metastases in livers based on ultrasound echoes. Also, cluster centroids for specific diseases define unique disease axes, and the inner product between measured features and any disease axis selected by the SVM quantifies the disease progression. The features were measured from 2794 ultrasound frames using the H-scan analysis, attenuation estimation, and B-mode image analysis. The performance of our proposed DSI method was evaluated for a preclinical model of steatosis (${n} =400$ frames). The contribution of each feature was assessed, and the results were compared with ground truth from histology. Moreover, the images generated by our DSI were compared with earlier imaging methods of B-mode, H-scan, and histology. The comparisons demonstrate that DSI images yield higher sensitivity to monitor progressive steatosis than B-mode and H-scan and provide a comparable performance with the histology. For the parameter comparison, DSI and H-scan resulted in similar correlation with histology (${r}_{s} =0.83$) but higher than attenuation (${r}_{s} =0.73$) and B-mode (${r}_{s} =0.47$). Therefore, we conclude that DSI utilizing the SVM applied to steatosis can visually represent the classification results with color highlighting, which can simplify the interpretation of classification compared to the traditional SVM result. We expect that the proposed DSI can be used for any medical imaging modality that can estimate multiple quantitative parameters at high resolution. [ABSTRACT FROM AUTHOR]

The purpose of this study is to describe a methodology for assessing the geotechnical stability of agricultural facilities, enabling prediction of the state of the geotechnical system, taking into account the influence of external factors and combinations of reactions of the geotechnical system under study. According to the methodology, the heterogeneous geotechnical monitoring data obtained are used in an adjusted geotechnical system model, allowing a bifurcation analysis to be carried out. The bifurcation analysis determines critical values of influencing factors, and the limits of stability of the geotechnical system studied parameters are adjusted. The developed methodology was used to assess and predict the geotechnical stability of agricultural facilities during the processing of geoelectric, resistive acoustic, accelerometric and strain-gauge control data obtained in the period from 2016 to 2021. A feature of the geotechnical system under study is the periodic flooding of the building basement caused by the processes of reclamation and irrigation, leading to changes in the groundwater level. The results show that the permissible calculated elastic limit of the foundation elements (32.2–35.1 MPa) before the loss of stability should be significantly reduced with a change in the water content coefficient (W) of the soil base: at W = 0.15 Eb = 30.7–32.0 MPa; at W = 0.35 Eb = 26.8–28.2 MPa; at W = 0.55 Eb = 24.9–25.3 MPa.

Infection with SARS-CoV-2, the virus responsible for COVID-19 diseases, can impact different tissues and induce significant cellular alterations. The production of extracellular vesicles (EVs), which are physiologically involved in cell communication, is also altered during COVID-19, along with the dysfunction of cytoplasmic organelles. Since circulating EVs reflect the state of their cells of origin, they represent valuable tools for monitoring pathological conditions. Despite challenges in detecting EVs due to their size and specific cellular compartment origin using different methodologies, flow cytometry has proven to be an effective method for assessing the role of EVs in COVID-19. This review summarizes the involvement of plasmatic EVs in COVID-19 patients and individuals with Long COVID (LC) affected by post-acute sequelae of SARS-CoV-2 infection (PASC), highlighting their dual role in exerting both pro- and antiviral effects. We also emphasize how flow cytometry, with its multiparametric approach, can be employed to characterize circulating EVs, particularly in infectious diseases such as COVID-19, and suggest their potential role in chronic impairments during post-infection., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fanelli M and Petrone V reported that financial support was provided by HERVCOV project funded by the HORIZONHLTH-2021-DISEASE G.A.101057302. The other authors declared that there are no conflicts of interest., (© The Author(s) 2024.)

In this work, an innovative screening platform based on MicroNIR and chemometrics is proposed for the on-site and contactless monitoring of the quality of milk using simultaneous multicomponent analysis. The novelty of this completely automated tool consists of a miniaturized NIR spectrometer operating in a wireless mode that allows samples to be processed in a rapid and accurate way and to obtain in a single click a comprehensive characterization of the chemical composition of milk. To optimize the platform, milk specimens with different origins and compositions were considered and prediction models were developed by chemometric analysis of the NIR spectra using Partial Least Square regression algorithms. Once calibrated, the platform was used to predict samples acquired in the market and validation was performed by comparing results of the novel platform with those obtained from the chromatographic analysis. Results demonstrated the ability of the platform to differentiate milk as a function of the distribution of fatty acids, providing a rapid and non-destructive method to assess the quality of milk and to avoid food adulteration.

In mice, monocytes (Mo) are conventionally described as CX3CR1low classical Mo (CMo) and CX3CR1high non-classical Mo (NCMo) based on the expression of EGFP in Cx3cr1+/EGFP mice and by analogy with human CX3CR1 expression. Although this terminology is widely used, it may not reflect the expression of CX3CR1 on Mo subsets. Using an unsupervised multiparametric analysis of blood Mo in steady state and after sterile peritonitis, we observed that CX3CR1 expression did not discriminate the CMo from the NCMo subsets. Our results highlight that despite being a reliable reporter to discriminate Mo subpopulations, EGFP level in Cx3cr1+/EGFP mice does not reflect CX3CR1 expression measured by a fluorescently-labeled CX3CL1 chemokine and a CX3CR1 specific antibody. In conclusion, authors should be cautious not to identify murine classical and non-classical Mo as CX3CR1low and CX3CR1high but rather use alternative markers such as the combination of Ly6C and CD43.

Structural integrity is a major concern for both manufacturers and consumers, thus health monitoring is mandatory for a proper quality control. The use of more reliable and widespread techniques is urged. In this context, this work developed a nondestructive procedure for microstructural characterization of age-hardened aluminum alloys. By the combination of ultrasonic inspection parameters, we developed two highly sensitive methods of hardness evaluation. The results proved the versatility of ultrasonic waves for materials inspection and characterization, expanding the onsite evaluations range. [ABSTRACT FROM AUTHOR]

Fifty years of research on the nature of backscatter from tissues has resulted in a number of promising diagnostic parameters. We recently introduced two analyses tied directly to the biophysics of ultrasound scattering: the H-scan, based on a matched filter approach to distinguishing scattering transfer functions, and the Burr distribution for quantification of speckle patterns. Together, these analyses can produce at least five parameters that are directly linked to the mathematics of ultrasound in tissue. These have been measured in vivo in 35 rat livers under normal conditions and after exposure to compounds that induce inflammation, fibrosis, and steatosis in varying combinations. A classification technique, the support vector machine, is employed to determine clusters of the five parameters that are signatures of the different liver conditions. With the multiparametric measurement approach and determination of clusters, the different types of liver pathology can be discriminated with 94.6% accuracy. [ABSTRACT FROM AUTHOR]

Potential under- or overdose of antibiotics may occur in intensive care units due to high variability in plasma concentrations. The risk is either treatment failure or toxicity. Thus, therapeutic drug monitoring of antibiotics may guide dosing adjustment, maximising antibacterial efficacy and minimising toxicity. The aim of this study was to develop and validate a method for the analysis of 15 antibiotics including beta-lactams, linezolid, fluoroquinolones, daptomycin, and clindamycin to have a complete panel in the management of infections. We proposed to develop a fast, sensitive, and quantitative method for the analysis of 15 antibiotics using ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometer (UPLC-MS/MS) technology. this method required only 100 µL of plasma and consisted of a rapid liquid–liquid deproteinisation using methanol. Calibration curves ranged from 0.078 to 500 mg/L depending on the molecules, and were defined according to a therapeutic range. Inter- and intra-assay precisions values were less than 15%. This work described the development and the full validation of a precise, sensitive and accurate assay using UPLC-MS/MS technology. After validation, this new assay was successfully applied to routine therapeutic drug monitoring.

This paper presents the results of the comparative multiparametric analysis of the efficiency of the economic activity of the water and sewerage operators in Bulgaria in the period 2000-2015. It is part of a comprehensive study of a scientific project, according to the Ordinance No.9 of the Ministry of Education and Science of 08.08.2013, with No.НПИ-130/2014, on the topic: „The concession as a factor for development of the Water Supply and Sanitation sector in the Republic of Bulgaria“. Conclusions and recommendations concerning the efficiency of revenues, financial results and management of the WSS operators in the statistical regions of the country are made. The possibilities for restructuring the water sector have been examined in order to improve its economic activity and the quality of the WSS services provided to the population.

Although the widespread introduction of numerical tools and the CFD models have improved the design methodology of thermoacoustic coolers and eased optimization of such units, high computational costs vitally limit their application in parametric analyses of thermoacoustic devices. Thus, experimental investigation remains essential field of research, considering design of such units. In the paper, the design and construction of an experimental setup, dedicated to perform an extensive multiparametric analyses on compact thermoacoustic devices with varying characteristic parameters, is discussed in detail. A complete design path, beginning with general consideration, with further detailed dimensioning and selection of market-available parts, ending with installation of control and data acquisition equipment, is described. Initial testing of the device, performed both computationally at the design stage and experimentally after the final setup assembling, is discussed as well. The results of the tests demonstrated ability to observe the variability in the operational parameters of the cooler following change in number of environmental and constructional parameters. The data acquired indicated vital importance of the stack porosity and frequency of the acoustic wave on performance of the thermoacoustic device, which corresponds to the data presented in the literature. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: The aim of this study was to assess variability in quantitative air trapping (QAT) measurements derived from spatially aligned expiration CT scans.Materials and Methods: Sixty-four paired CT examinations, from 16 school-age cystic fibrosis subjects examined at four separate time intervals, were used in this study. For each pair, visually inspected lobe segmentation maps were generated and expiration CT data were registered to the inspiration CT frame. Measurements of QAT, the percentage of voxels on the expiration CT scan below a set threshold were calculated for each lobe and whole-lung from the registered expiration CT and compared to the true values from the unregistered data.Results: A mathematical model, which simulates the effect of variable regions of lung deformation on QAT values calculated from aligned to those from unaligned data, showed the potential for large bias. Assessment of experimental QAT measurements using Bland-Altman plots corroborated the model simulations, demonstrating biases greater than 5% when QAT was approximately 40% of lung volume. These biases were removed when calculating QAT from aligned expiration CT data using the determinant of the Jacobian matrix. We found, by Dice coefficient analysis, good agreement between aligned expiration and inspiration segmentation maps for the whole-lung and all but one lobe (Dice coefficient > 0.9), with only the lingula generating a value below 0.9 (mean and standard deviation of 0.85 ± 0.06).Conclusion: The subtle and predictable variability in corrected QAT observed in this study suggests that image registration is reliable in preserving the accuracy of the quantitative metrics. [ABSTRACT FROM AUTHOR]

Nanoscale multipoint structure-function analysis is essential for deciphering the complexity of multiscale biological and physical systems. Atomic force microscopy (AFM) allows nanoscale structure-function imaging in various operating environments and can be integrated seamlessly with disparate probe-based sensing and manipulation technologies. Conventional AFMs only permit sequential single-point analysis; widespread adoption of array AFMs for simultaneous multipoint study is challenging owing to the intrinsic limitations of existing technological approaches. Here, we describe a prototype dispersive optics-based array AFM capable of simultaneously monitoring multiple probe-sample interactions. A single supercontinuum laser beam is utilized to spatially and spectrally map multiple cantilevers, to isolate and record beam deflection from individual cantilevers using distinct wavelength selection. This design provides a remarkably simplified yet effective solution to overcome the optical cross-talk while maintaining subnanometer sensitivity and compatibility with probe-based sensors. We demonstrate the versatility and robustness of our system on parallel multiparametric imaging at multiscale levels ranging from surface morphology to hydrophobicity and electric potential mapping in both air and liquid, mechanical wave propagation in polymeric films, and the dynamics of living cells. This multiparametric, multiscale approach provides opportunities for studying the emergent properties of atomic-scale mechanical and physicochemical interactions in a wide range of physical and biological networks. [ABSTRACT FROM AUTHOR]

Abstract In this work we tuned the surface chemistry of distinctly-sized CdTe quantum dots (QDs), by using a variety of capping ligands with distinctive functional moieties, and combined them in multi-QDs probing solutions for Hg2+, Cu2+ and Ag+. Upon the individual interaction of the distinctly-capped QDs with each of the abovementioned metal ions, several parameters such as Stern-Volmer constants, equilibrium binding constants, the red-shift magnitude and photoluminescence (PL) lifetime values were thoroughly evaluated. Due to their great reactivity, selectivity could become a major issue in the application of semiconductor quantum dots in chemical analysis. Therefore, the combination in the same analysis of multiple QDs, capped with distinct ligands and emitting at different wavelengths, was exploited to guarantee a specific analyte-response profile. When coupled with chemometrics, for data analysis and processing, the developed approach provided enhanced selectivity and accuracy. In fact, the obtained results of all the partial least squares (PLS) models coefficient of determination of cross-validation (R2 CV) close to 1, root mean square error of calibration (RMSEC) and root mean square error of cross-validation (RMSECV) values ranging 0.0094–0.15 and 0.013–0.19 mg L−1, respectively. demonstrated the possibility to perform accurate predictions of Hg2+ and Cu2+. Additionally, the sensitivity of the developed models was also calculated and allowed us to conclude which combination of distinctly-capped QDs assured a more sensitive quantification of Cu2+ (sensitivity = 653 L−1 mg for 3-mercaptopropionic acid (MPA)/MPA conjugated probe) and Hg2+ (sensitivity = 14,017 L−1 mg for reduced glutathione (GSH)/MPA-conjugated probe). Graphical abstract fx1 Highlights • Tuning of QDs surface with distinct ligands and functional groups to adjust reactivity. • Combination of multiple QDs provided multipoint detection improving selectivity. • Chemometrics facilitated data analysis and processing and enhanced accuracy and reproducibility. [ABSTRACT FROM AUTHOR]

Therapeutic drug monitoring is strongly recommended for psychotropic drugs, which present a strong inter- and intra-individual variability due to multiple factors like inflammatory state, smoking, diet, drug interactions due to polypharmacy, and genetic profile. The aim of this study was to develop and validate a fast, simple, and sensitive method allowing the simultaneous quantification of a large number of psychotropic drugs. After a simple sample preparation with a one-step protein precipitation, a total of 55 compounds, including 22 antidepressants, 18 antipsychotics, 2 other psychotropic drugs (bupropion and nefopam), and their metabolites, was separated on a Waters Acquity HSS T3 ultra-performance liquid chromatography column, and subsequently detected and quantified by a triple quadrupole Quantis mass spectrometer with electrospray ionization operated in positive mode. Total run time was only 5.7 min. Limits of detection ranged from 0.01 to 0.18 µg/L depending on compound. Measuring ranges were from 0.195 to 1000 µg/L depending on compound, and were defined according to therapeutic ranges. Inter- and intra-assay precisions values were less than 15 %. After validation, this method was successfully applied in daily practice for therapeutic drug monitoring of polymedicated psychiatric patients. We developed and validated one of the most sensitive and complete UPLC-MS/MS methods in psychopharmacology, allowing the simultaneous determination of 55 psychotropic drugs in only 5.7 min after a simple sample preparation. This method has been successfully used in daily practice for therapeutic drug monitoring of psychiatric patients and is especially useful in polymedicated patients. [Display omitted] • We developed and validated a fast, simple, and sensitive method allowing the simultaneous quantification of psychotropic drugs. • The simplicity and robustness of the method should make it easy to implement. • Thanks to this method, therapeutic drug monitoring in psychopharmacology has been applied in the clinical setting. [ABSTRACT FROM AUTHOR]

Purpose To assess the response to initial treatment strategies of cervical cancer using multiparametric-PET/MRI. Material and methods PET/MR-derived morphological (tumor size), functional (DWI, DCE-MRI) and metabolic (18F-FDG PET) parameters were acquired in pre- and posttreatment examinations of 8 patients. Besides RECIST- and PERCIST-criteria, functional quantitative parameters were used to assess therapeutic response. Results RECIST- and PERCIST-response criteria demonstrated high correlations for the differentiation between therapy-responders and non-responders, which was additionally reflected by functional (DWI, DCE-MRI) quantitative imaging parameters. Conclusion Multiparametric-PET/MRI bears the potential of a more comprehensive response assessment of initial treatment strategies in cervical cancer patients. [ABSTRACT FROM AUTHOR]

A method of identifying the basic parameters of airplane components is proposed on the basis of correlation and factorial analysis, with the subsequent derivation of polynomials by the least-squares method and by Brandon’s method. A multiparametric approach to design analysis and synthesis is formulated on the basis of a formalized process. This approach permits clear decisions for individual aircraft components at the preliminary design stage, as demonstrated here for the example of a wing. [ABSTRACT FROM AUTHOR]

The work presents a heat transfer analysis carried out with the use of COMSOL Multiphysics software applied to a new solar concentrator, defined as the Compound Parabolic Concentrator (CPC) system. The experimental measures have been conducted for a truncated CPC prototype system with a half-acceptance angle of 60°, parabola coefficient of 4 m−1 and four solar cells in both covered and uncovered configurations. These data are used to validate the numerical scenario, to be able to use the simulations for different future systems and works. The second challenge has been to change the reflector geometry, the half-acceptance angle (60° ÷ 75°) and the parabola coefficient (3 m−1 ÷ 6 m−1) to enhance the concentration of sun rays on the solar cells. The results show that the discrepancy between experimental data and COMSOL Multiphysics (CM) have led to validate the scenarios considering the average temperature on the solar cells. These scenarios are used for the parametric analysis, observing that the optimal geometry for the higher power and efficiency of the whole system is reached with a lower half-acceptance angle and parabola coefficient.

Abstract. The purpose of this article was to make a broad audience of experts familiar to new developments in the method of flow cytometry that have found applications in medical and biologic studies, in order of their further implementation into everyday practice. These applications include the following approcahes: detection of antigen-specific T-cells by using of tetramer technology, flow cytometric determination of cytokines in biological liquids, determination of in vitro sensitivity of basophilic granulocytes to allergen effects, detection of Th1 and Т-reg cells by their cell surface markers. When using multiparametric analysis, a multi-step gating and other new technologies, the flow cytometry technique allows of location and tracing the majority of processes occurring in development of immune response. When studying these dynamic events, we get an opportunity to react adequately to apropriate changes, and to develop new approaches to correct altered cellular activities, that they should determinate.

Abstract. Temporary immunodeficiency is often associated with various pathological conditions, such as myocardial infarction, severe trauma, or major surgery. However, there are no clinical criterions indicative for presence or absence of such immune deficiency. Meanwhile, clinical signs of infectious complications may be absent because of deficient immune response.A technique for monitoring septic conditions in the patients with open traumas and during postsurgical period has been proposed, employing a flow-cytometric approach. The evaluation principle for septic conditions consists of measuring expression of HLA-DR antigens at the surface of peripheral blood monocytes.As a criterion of patient evaluation in septic state, a relative amount of monocytes expressing HLA-DR may be applied, and the disease prognosis is considered as favorable, if the amounts of positive cells exceed 40% by day 5 after the patient was admitted to the hospital, and an adequate treatment was carried out. This technique may find wide application for estimation and monitoring of septic conditions in the patients. (Med. Immunol., vol. 10, N 4-5, pp 379-388).

Abstract. Flow cytometry is considered as a modern technology for fast measurements of cellular characteristics, their organelles, and processes occurring within them. It is regarded as an efficient solution in many important areas of cell biology, immunology and cellular engineering. Present article bears on main developments in flow cytometry and their applications in medical and biological practice. Usage of modern achievements in fluorescent dyes, progress in laser and computer technologies, as well as potent software, resulted in wide application of this technique in medical practice. Accordingly, usage of monoclonal antibodies conjugated to different fluorochromes has led to elaboration of multiparametric analysis and did sufficiently simplify specialized works aimed for diagnostics of various immune disorders. The new directions in flow cytometry, e.g., flow cytoenzymology, provide wide opportunities for detailed identification of damaged or altered cells, and taking adequate decisions in treatment of detected pathological changes. The authors suggest that this article could initiate a series of publications concerning usage of this technology and its modern applications in broad laboratory practice.