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Serum metabolome analysis is essential for identifying disease biomarkers and predicting patient outcomes in precision medicine. Thus, this study aims to compare Ultra-High Performance Liquid Chromatography-High-Resolution Mass Spectrometry (UHPLC-HRMS) with Fourier Transform Infrared (FTIR) spectroscopy in acquiring the serum metabolome of critically ill patients, associated with invasive mechanical ventilation (IMV), and predicting death. Three groups of 8 patients were considered. Group A did not require IMV and survived hospitalization, while Groups B and C required IMV. Group C patients died a median of 5 days after sample harvest. Good prediction models were achieved when comparing groups A to B and B to C using both platforms' data, with UHPLC-HRMS showing 8-17 % higher accuracies (≥83 %). However, developing predictive models using metabolite sets was not feasible when comparing unbalanced populations, i.e., Groups A and B combined to Group C. Alternatively, FTIR-spectroscopy enabled the development of a model with 83 % accuracy. Overall, UHPLC-HRMS data yields more robust prediction models when comparing homogenous populations, potentially enhancing understanding of metabolic mechanisms and improving patient therapy adjustments. FTIR-spectroscopy is more suitable for unbalanced populations. Its simplicity, speed, cost-effectiveness, and high-throughput operation make it ideal for large-scale studies and clinical translation in complex populations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Identifying high-risk patients, particularly in intensive care units (ICUs), enhances treatment and reduces severe outcomes. Since the pandemic, numerous studies have examined COVID-19 patient profiles and factors linked to increased mortality. Despite six pandemic waves, to the best of our knowledge, there is no extensive comparative analysis of patients' characteristics across these waves in Portugal. Thus, we aimed to analyze the demographic and clinical features of 1041 COVID-19 patients admitted to an ICU and their relationship with the different SARS-Cov-2 variants in Portugal. Additionally, we conducted an in-depth examination of factors contributing to early and late mortality by analyzing clinical data and laboratory results from the first 72 h of ICU admission. Our findings revealed a notable decline in ICU admissions due to COVID-19, with the highest mortality rates observed during the second and third waves. Furthermore, immunization could have significantly contributed to the reduction in the median age of ICU-admitted patients and the severity of their conditions. The factors contributing to early and late mortality differed. Age, wave number, D-dimers, and procalcitonin were independently associated with the risk of early death. As a measure of discriminative power for the derived multivariable model, an AUC of 0.825 (p < 0.001; 95% CI, 0.719-0.931) was obtained. For late mortality, a model incorporating age, wave number, hematologic cancer, C-reactive protein, lactate dehydrogenase, and platelet counts resulted in an AUC of 0.795 (p < 0.001; 95% CI, 0.759-0.831). These findings underscore the importance of conducting comprehensive analyses across pandemic waves to better understand the dynamics of COVID-19., Competing Interests: Declarations Ethics approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the institutional Ethics Committee of Unidade Local de Saúde São José (ULSSJ), Lisbon, Portugal, specifically Comissão de Ética para a Saúde, on 20 May 2020 (number 1043/2021), in the scope of the Predictive Models of COVID-19 Outcomes for Higher Risk Patients Towards a Precision Medicine (PREMO) project. Consent to participate Informed consent was obtained from all subjects involved in the study and approval was obtained before collecting any data. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

To robustly discover and explore phytocompounds, it is necessary to evaluate the interrelationships between the plant species, plant tissue, and the extraction process on the extract composition and to predict its cytotoxicity. The present work evaluated how Fourier Transform InfraRed spectroscopy can acquire the molecular profile of aqueous and ethanol-based extracts obtained from leaves, seeds, and flowers of Cynara Cardunculus, and ethanol-based extracts from Matricaria chamomilla flowers, as well the impact of these extracts on the viability of mammalian cells. The extract molecular profile enabled to predict the extraction yield, and how the plant species, plant tissue, and extraction process affected the extract's relative composition. The molecular profile obtained from the culture media of cells exposed to extracts enabled to capture its impact on cells metabolism, at a higher sensitivity than the conventional assay used to determine the cell viability. Furthermore, it was possible to detect specific impacts on the cell's metabolism according to plant species, plant tissue, and extraction process. Since spectra were acquired on small volumes of samples (25 µL), after a simple dehydration step, and based on a plate with 96 wells, the method can be applied in a rapid, simple, high-throughput, and economic mode, consequently promoting the discovery of phytocompounds., (© 2024 Wiley Periodicals LLC.)

Delirium presents a significant clinical challenge, primarily due to its profound impact on patient outcomes and the limitations of the current diagnostic methods, which are largely subjective. During the COVID-19 pandemic, this challenge was intensified as the frequency of delirium assessments decreased in Intensive Care Units (ICUs), even as the prevalence of delirium among critically ill patients increased. The present study evaluated how the serum molecular fingerprint, as acquired by Fourier-Transform InfraRed (FTIR) spectroscopy, can enable the development of predictive models for delirium. A preliminary univariate analysis of serum FTIR spectra indicated significantly different bands between 26 ICU patients with delirium and 26 patients without, all of whom were admitted with COVID-19. However, these bands resulted in a poorly performing Naïve-Bayes predictive model. Considering the use of a Fast-Correlation-Based Filter for feature selection, it was possible to define a new set of spectral bands with a wider coverage of molecular functional groups. These bands ensured an excellent Naïve-Bayes predictive model, with an AUC, a sensitivity, and a specificity all exceeding 0.92. These spectral bands, acquired through a minimally invasive analysis and obtained rapidly, economically, and in a high-throughput mode, therefore offer significant potential for managing delirium in critically ill patients.

Robust data normalization and analysis are pivotal in biomedical research to ensure that observed differences in populations are directly attributable to the target variable, rather than disparities between control and study groups. ArsHive addresses this challenge using advanced algorithms to normalize populations (e.g., control and study groups) and perform statistical evaluations between demographic, clinical, and other variables within biomedical datasets, resulting in more balanced and unbiased analyses. The tool's functionality extends to comprehensive data reporting, which elucidates the effects of data processing, while maintaining dataset integrity. Additionally, ArsHive is complemented by A.D.A. (Autonomous Digital Assistant), which employs OpenAI's GPT-4 model to assist researchers with inquiries, enhancing the decision-making process. In this proof-of-concept study, we tested ArsHive on three different datasets derived from proprietary data, demonstrating its effectiveness in managing complex clinical and therapeutic information and highlighting its versatility for diverse research fields.

Background and Objectives : Given the wide spectrum of clinical and laboratory manifestations of the coronavirus disease 2019 (COVID-19), it is imperative to identify potential contributing factors to patients' outcomes. However, a limited number of studies have assessed how the different waves affected the progression of the disease, more so in Portugal. Therefore, our main purpose was to study the clinical and laboratory patterns of COVID-19 in an unvaccinated population admitted to the intensive care unit, identifying characteristics associated with death, in each of the first three waves of the pandemic. Materials and Methods : This study included 337 COVID-19 patients admitted to the intensive care unit of a single-center hospital in Lisbon, Portugal, between March 2020 and March 2021. Comparisons were made between three COVID-19 waves, in the second ( n = 325) and seventh ( n = 216) days after admission, and between discharged and deceased patients. Results : Deceased patients were considerably older ( p = 0.021) and needed greater ventilatory assistance ( p = 0.023), especially in the first wave. Differences between discharged and deceased patients' biomarkers were minimal in the first wave, on both analyzed days. In the second wave significant differences emerged in troponins, lactate dehydrogenase, procalcitonin, C-reactive protein, and white blood cell subpopulations, as well as platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios (all p < 0.05). Furthermore, in the third wave, platelets and D-dimers were also significantly different between patients' groups (all p < 0.05). From the second to the seventh days, troponins and lactate dehydrogenase showed significant decreases, mainly for discharged patients, while platelet counts increased (all p < 0.01). Lymphocytes significantly increased in discharged patients (all p < 0.05), while white blood cells rose in the second (all p < 0.001) and third (all p < 0.05) waves among deceased patients. Conclusions : This study yields insights into COVID-19 patients' characteristics and mortality-associated biomarkers during Portugal's first three COVID-19 waves, highlighting the importance of considering wave variations in future research due to potential significant outcome differences.

Biofluid metabolomics is a very appealing tool to increase the knowledge associated with pathophysiological mechanisms leading to better and new therapies and biomarkers for disease diagnosis and prognosis. However, due to the complex process of metabolome analysis, including the metabolome isolation method and the platform used to analyze it, there are diverse factors that affect metabolomics output. In the present work, the impact of two protocols to extract the serum metabolome, one using methanol and another using a mixture of methanol, acetonitrile, and water, was evaluated. The metabolome was analyzed by ultraperformance liquid chromatography associated with tandem mass spectrometry (UPLC-MS/MS), based on reverse-phase and hydrophobic chromatographic separations, and Fourier transform infrared (FTIR) spectroscopy. The two extraction protocols of the metabolome were compared over the analytical platforms (UPLC-MS/MS and FTIR spectroscopy) concerning the number of features, the type of features, common features, and the reproducibility of extraction replicas and analytical replicas. The ability of the extraction protocols to predict the survivability of critically ill patients hospitalized at an intensive care unit was also evaluated. The FTIR spectroscopy platform was compared to the UPLC-MS/MS platform and, despite not identifying metabolites and consequently not contributing as much as UPLC-MS/MS in terms of information concerning metabolic information, it enabled the comparison of the two extraction protocols as well as the development of very good predictive models of patient's survivability, such as the UPLC-MS/MS platform. Furthermore, FTIR spectroscopy is based on much simpler procedures and is rapid, economic, and applicable in the high-throughput mode, i.e., enabling the simultaneous analysis of hundreds of samples in the microliter range in a couple of hours. Therefore, FTIR spectroscopy represents a very interesting complementary technique not only to optimize processes as the metabolome isolation but also for obtaining biomarkers such as those for disease prognosis., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Current infection biomarkers are highly limited since they have low capability to predict infection in the presence of confounding processes such as in non-infectious inflammatory processes, low capability to predict disease outcomes and have limited applications to guide and evaluate therapeutic regimes. Therefore, it is critical to discover and develop new and effective clinical infection biomarkers, especially applicable in patients at risk of developing severe illness and critically ill patients. Ideal biomarkers would effectively help physicians with better patient management, leading to a decrease of severe outcomes, personalize therapies, minimize antibiotics overuse and hospitalization time, and significantly improve patient survival. Metabolomics, by providing a direct insight into the functional metabolic outcome of an organism, presents a highly appealing strategy to discover these biomarkers. The present work reviews the desired main characteristics of infection biomarkers, the main metabolomics strategies to discover these biomarkers and the next steps for developing the area towards effective clinical biomarkers.