These results highlight the potential of Sentinel-3 OLCI imagery in assessing ecological quality, contributing to our understanding of coastal water ecology. They also underscore the importance of merging remote sensing and machine learning in environmental monitoring and management. Future research should refine methodologies and expand datasets to enhance TRIX monitoring capabilities from space.Understanding and monitoring the ecological quality of coastal waters is crucial for preserving marine ecosystems. Eutrophication is one of the major problems affecting the ecological state of coastal marine waters. For this reason, the control of the trophic conditions of aquatic ecosystems is needed for the evaluation of their ecological quality. This study leverages space-based Sentinel-3 Ocean and Land Color Instrument imagery (OLCI) to assess the ecological quality of Mediterranean coastal waters using the Trophic Index (TRIX) key indicator. In particular, we explore the feasibility of coupling remote sensing and machine learning techniques to estimate the TRIX levels in the Ligurian, Tyrrhenian, and Ionian coastal regions of Italy. Our research reveals distinct geographical patterns in TRIX values across the study area, with some regions exhibiting eutrophic conditions near estuaries and others showing oligotrophic characteristics. We employ the Random Forest Regression algorithm, optimizing calibration parameters to predict TRIX levels. Feature importance analysis highlights the significance of latitude, longitude, and specific spectral bands in TRIX prediction. A final statistical assessment validates our model’s performance, demonstrating a moderate level of error (MAE of 0.51) and explanatory power (R Coastal ecosystems are vital components of our environment, providing numerous ecological, economic, and societal benefits. Water ecological quality refers to the health and sustainability of aquatic ecosystems. It underscores the interplay of biodiversity, nutrient cycling, and trophic dynamics, which collectively shape the overall health of aquatic ecosystems . EcologiWater ecological quality is, therefore, a fundamental concept within the European Union (EU) environmental framework, standing at the heart of environmental policies and regulations, with a focus on ensuring the health and sustainability of ecosystems. In particular, the EU Water Framework Directive   (WFD) plA plethora of parameters and tools are utilized to assess the health and functioning of coastal ecosystems . The conThe in situ monitoring of water quality is improving, for example, with the recent developments of instruments like multiparametric probes . While iEO techniques employ the relationships between water optical properties and surface concentrations of parameters linked to ecological quality, such as Chl-a, Suspended Particulate Matter (SPM), turbidity, Colored Dissolved Organic Matter (CDOM), etc. . At presSatellite remote sensing techniques, in particular, can provide information on coastal water quality over large areas and at high frequencies, which is difficult to achieve with in situ sampling alone . This caThese technological advancements could be particularly relevant for the estimation of an index like the TRIX, which is intrinsically dependent on the concentration of a major optically active seawater constituent, Chl-a. As the TRIX is normally computed by in situ data, with all the limits connected, in fact, the exciting possibility of obtaining it from a satellite ushers the potential to monitor, simultaneously, large sea areas with high temporal frequency. The exploration of this possibility is based on the pioneering work of Massi et al. (2019) , which sThese investigations suggest the feasibility of leveraging direct and indirect relationships between the TRIX and optically active seawater components to establish an alternative monitoring approach based on satellite observations. The same studies, however, also pointed out important issues needing further scientific and technological advancement. First, an optimal characterization of seawater TRIX values should be based on detailed spectral information, which can be currently obtained only from last-generation multispectral sensors. Second, the complex and irregular relationships between in situ TRIX values and spectral signatures should be addressed with the use of extremely efficient and flexible nonparametric estimation algorithms.Building on these premises, the current study endeavors to establish a remote sensing-based approach for monitoring and mapping the ecological conditions of marine coastal waters through the use of the TRIX. The achievement of this objective requires addressing the two mentioned issues, which is carried out by the application of advanced data processing methods to Sentinel 3 OLCI imagery. In particular, the study explores the application of machine learning techniques to OLCI and in situ data to obtain information about the TRIX levels of Italian coastal waters. In this way, our approach addresses the complex nonlinear relationships existing between spectral and in situ observations related to the TRIX.The exploitation of the latest generation high-resolution (300 m) OLCI images applied to TRIX estimation, highlighting the potential for water quality assessment as well as possible broader environmental applications.The pioneering use of machine learning algorithms to provide a novel framework for assessing ecological quality in coastal waters.A methodological advancement towards dealing with the complexities of coastal environments, overcoming the limitations of in situ monitoring and enabling more effective environmental management.Enhancing the versatility of the proposed methodology for application in coastal waters, where multiple environmental factors and stressors interact.The main novelty of the paper lies in the synergistic combination of data from state-of-the-art ocean color satellite sensors and machine learning to obtain information on the ecological quality of coastal waters. The scientific objectives of the paper are:The paper is organized as follows. First, the TRIX is introduced, followed by a description of the study area and the dataset used: OLCI FR data and environmental parameters for TRIX estimation. The preprocessing and processing steps applied to in situ and satellite data are then illustrated, with a specific focus on the machine learning algorithm used. The TRIX index, a key indicator of trophic condition, is described . Then, tThe TRIX  is an esThe TRIX is useful to classify water bodies and is built on their nutrient enrichment and primary productivity, thereby distinguishing oligotrophic (low nutrient levels) from eutrophic (high nutrient levels) states; oxygen is included to indicate the ecosystem’s ability to support life at different trophic levels. The basis of this assessment lies in the trophic hierarchy, which includes primary producers like phytoplankton, primary consumers like zooplankton, and higher trophic levels, including fishes. The TRIX is typically defined through a linear combination of the logarithms of four environmental factors directly linked to productivity. These factors are the Chl-a concentration in µg/L, which indicates phytoplankton biomass; the absolute value of the percentage deviation from oxygen saturation (aDO%); and the total nitrogen (N) and total phosphorus (P) dissolved in water, which are both measured in µg/L.Consequently, the TRIX can be calculated using the following Equation (1):The scaling constants 1.5 and 1.2 in Equation (1) are derived from an extended dataset used to assess long-term trends and spatial trophic patterns in European coastal waters . The TRIAlthough first designed for lakes, the TRIX has been extended to coastal waters, initially for eutrophication assessment. In coastal environments, the TRIX assumes the role of assessing the effects of nutrient enrichment stemming from anthropogenic activities, such as agricultural practices and urban runoff.The coastal waters of the Ligurian, Tyrrhenian, and Ionian (around Sicily) Seas show distinct geographical, physical, biogeochemical, trophic, and optical characteristics that reflect their unique marine environments . GeograpThe coastal Ligurian Sea exhibits oligo-mesotrophic characteristics, which are primarily attributed to limited nutrient availability. These characteristics are the result of restricted nutrient inputs from internal areas and the influence of the Ligurian Current that, together with the geographical features of the region, hinder the transport of essential nutrients from land to sea.The trophic diversity of the coastal areas of the Tyrrhenian Sea results from physical and geographical characteristics that include the large estuary of the Tiber River. Along its coastlines, the Tyrrhenian Sea displays varying trophic states, encompassing oligotrophic to mesotrophic conditions. The coastal zone of the Tyrrhenian Sea is characterized by its proximity to the Italian peninsula, Sardinia, and Sicily, each of which contributes unique nutrient inputs to the sea. Additionally, the intricate interplay of multiple oceanic currents, including the inflow of Modified Atlantic Waters, shapes the physical dynamics of the coastal Tyrrhenian Sea. These currents play a pivotal role in determining nutrient availability and distribution, thereby exerting a direct impact on the trophic conditions observed in different coastal regions.The Ionian Sea exhibits distinct trophic conditions, which are shaped by a combination of geographical and physical factors specific to this region. The waters surrounding Sicily are characterized by their central location in the Mediterranean, diverse geography, and range of trophic conditions that sustain a dynamic marine ecosystem.http://www.db-strategiamarina.isprambiente.it/, accessed on 2 May 2023). The map includes Chl-a, a level 2 product obtained from OLCI FR via the OC4ME algorithm.The in situ data for the TRIX estimation were obtained from the Italian Institute for Environmental Protection and Research (ISPRA) in the framework of the monitoring activities established by the EU-MSFD . SpecifiThe EU-MSFD Module 1 is dedicated to the monitoring of the chemical–physical parameters of the water column, pelagic habitats, and the contaminants present in the water, including the ones used to estimate the TRIX. The areas are chosen along a coast-to-offshore transect in front of some of the stations identified for the implementation of the EU-WFD because they are characterized by different sources of pollution, both natural and anthropogenic: river mouths and/or nutrient inputs, upwelling  or downwelling (areas of accumulation and sinking of high-density and low-temperature water below lower-density and higher-temperature waters), and port areas. In this study, we selected all the monitoring points of the EU-MSFD located in the Ligurian and Tyrrhenian Seas. The transects include monitoring stations at a distance of 3, 6, and 12 NM from the coast for which OLCI Full Resolution (FR) data are available.For each sampling site, four environmental attributes were used to compute the TRIX: Chl-a, aDO%, total N, and total P. To estimate the TRIX using machine learning, the following environmental parameters of the ISPRA database were also included in the input dataset for machine learning: latitude, longitude, distance from the coast (ClosestCoast), sea depth, and mixing characteristics of the water column (Mixing) .OLCI is a high-resolution, multispectral imaging spectrometer onboard the Sentinel-3A and Sentinel-3B satellites. It provides 21 spectral bands in the visible and near-infrared (VNIR) range, with a spatial resolution of 300 meters at nadir. This makes OLCI a valuable tool for monitoring the coastal zone color features.OLCI scans the Earth’s surface using a push-broom method. The spatial resolution of OLCI FR is approximately 300 m at a sub-satellite point . Sentinehttps://doi.org/10.48670/moi-00299, accessed on 2 May 2023) provided by Copernicus Marine Service. Each OLCI L2 granule, before being merged with the others taken from the same sensor and from the same day, is quality checked via the application of the L2 flags provided by the European Space Agency (ESA) . All 10 sensor bands’ directional surface water reflectances, centered at 400, 412.5, 442.5, 490, 510, 560, 620, 665, 673.75, and 681.25 nanometers in the visible portion of the spectrum, were considered. Chl-a, in particular, an important component of the in situ TRIX estimation, is typically observed in spectral regions that are sensitive to the molecular absorption and scattering features: Band Ratios (BR) of green (510 nm) and blue wavelengths  are used here as a proxy for Chl-a concentrations [In this work, we used the Sentinel 3 OLCI FR products . The matchup pixel extraction was performed via SNAP PixEx operator 1.3 (Copyright (C) 2011 Brockmann Consult GmbH (info@brockmann-consult.de) on a 3 × 3 pixel window and averaged, via a dedicated procedure in Python. The investigation then focused on 105 OLCI scenes, from which the values of standard Level 2 products were extracted in correspondence with 340 in situ TRIX observations.The images collected within 1 day of the in situ matchup sampling were processed using the ESA Sentinel Application Platform (SNAP) v8.0 and -Sentinel-3 Toolbox (S3TBX) v8.0.6  was applied to systematically identify outliers in the dataset . It is cIt is important to note that not all the data points identified as outliers in the box plots were removed. Some of these outliers were retained because they fell within the expected data range before the dataset was narrowed down based on satellite matchup criteria. This methodical approach enhances the data quality and reliability, while also considering specific criteria related to the satellite matchup.The RFR was applied using the Python Scikit-Learn library (sklearn) ,45,46 toX, features) and one dependent variable , was subjected to design, calibrate, and evaluate the RFR predictive model. The data underwent meticulous preprocessing using sklearn’s extensive tools for data scaling, normalization, and organization into training and testing subsets. A critical step in the model optimization involved hyperparameter tuning, which was carried out through grid search and cross-validation techniques. In particular, grid search is a hyperparameter optimization technique used in machine learning. It systematically explores a predefined set of hyperparameter values to find the optimal configuration for a model. This process allows one to efficiently tune the model performance and select the best hyperparameters to achieve the highest predictive accuracy. Cross-validation techniques are used in machine learning to assess the performance and generalizability of a predictive model.n_estimator); (2) the maximum number of node levels (max_depth) from the root to the leaf of each tree; and (3) the maximum number of features (max_features) to be used as a random subset of the original parameters in the best-split construction of the trees. In order to find the optimal configuration of these parameters, the dataset underwent random splitting into training (70%) and testing (30%) subsets for model fitting and model test phases, respectively. The training data were used for both the model setup, including the definition of the set of parameters, and for the training process of the model. In particular, the best set of parameters was obtained by minimizing the Mean Square Error of the resulting output over the training dataset.Specifically, the hyperparameters to be set for the application of the RFR method were: (1) the number of trees to be used (2), the Root Mean Square Error (RMSE), and the Mean Absolute Error (MAE).The model was trained with the best hyperparameters on the training data, using a fit method, directly provided by sklearn. The testing set was used for accuracy assessment, which was summarized by means of standard statistics, i.e., the coefficient of determination .The TRIX distribution obtained from in situ measurements grouped in the seven administrative regions reveals distinct geographic patterns along the Italian coasts . A notabn_estimator (i.e. the number of trees of the forest), chosen is 100, coinciding with the default number of estimators of the software module. A value of 10 was chosen for the depth of the trees, max_depth, allowing the trees to capture complex data relationships without overfitting, resulting in a computationally efficient algorithm. The maximum number of features considered when a split decision is made, max_features, was tested up to 20 and set to 15, influencing the model comprehensiveness and training speed and preventing overfitting as well.The best set of parameters resulting from the RFR calibration is shown in bold in 2 of 0.91, an MAE of 0.19, and an RMSE of 0.24.Careful hyperparameter tuning ensured optimal performance of the RFR algorithm, effectively predicting the TRIX levels while preventing overfitting. When evaluated versus the training set, the calibrated RFR algorithm yields an RIn The relevance of the geographic patterns observed earlier, and the satellite bands used for Chl-a retrieval, is confirmed by the results of the RFR algorithm’s feature importance analysis . Latitud2) of 0.37 indicates a moderate and statistically significant level of explanatory power.The assessment of the RFR TRIX estimates versus the test observations indicates the moderate efficiency of the algorithm . As can In summary, our model provides valuable insights into TRIX levels in coastal waters while exhibiting a moderate level of error. The scatter plot and statistical analysis validate the model’s performance and contribute to our understanding of complex coastal water ecology dynamics.An example of the TRIX maps, which can be obtained through the described procedure, is displayed in Many satellites dedicated to ocean color have been active since the late seventies, and the technology has made strong improvements in terms of data quality, such as spatial resolution, in recent times. The current satellite sensors show that characteristics such as spatial resolution have improved with respect to the former generation of satellites, which increases the data quality, and, as a consequence, water quality monitoring. The following water quality parameters are detectable by satellite remote sensing: Chl-a, CDOM, SPM, turbidity, and sea surface temperature (SST). These data can be used to understand the health of coastal ecosystems, track changes over time, and inform management decisions.With particular regard to water trophic conditions, previous investigations have indicated that high spatial resolution multispectral satellite imagery is informative on the TRIX levels of port and coastal seawaters ,26,27. TIn addition to the direct link with Chl-a, there is potential for multispectral data to contribute to the estimation of the TRIX through indirect relationships with other TRIX components, such as nitrogen and phosphorus. These components are influenced by the concentrations of other optically active seawater constituents, namely SPM and CDOM. Unfortunately, these relationships are also complex and variable, which makes the estimation of the TRIX particularly challenging.The approach currently applied to address such challenges is based on two major pillars. The first involves the use of multispectral imagery retrieved by an advanced sensor, the state-of-the-art Sentinel-3 OLCI, which is capable of accurately characterizing the optical properties of coastal seawater at a 300 m resolution. Owing to this property, the data taken by this sensor have been successfully used in several investigations. Su et al. , for exaThe second pillar centers on the application of an extremely flexible machine learning algorithm, the RFR. As previously noted, machine learning techniques can be used to combine in situ sampling data with satellite remotely sensed data to create more accurate and precise estimates of coastal water quality parameters. This is because machine learning algorithms can learn the complex relationships between different water quality parameters and the various factors that influence them. Among machine learning algorithms, the RFR demonstrates exceptional capability in adapting to complex and variable data patterns . ExtensiThe successful implementation of the current research strategy has required the collection and meticulous preprocessing of an extensive dataset, including in situ TRIX observations and OLCI images representative of the inhomogeneous coastal waters within the study area. A preliminary analysis of the in situ observations has provided relevant information on the trophic status of the area. Most of these observations, in fact, denote good to high ecological status; all the recorded TRIX values fall within concentration reference limits denoting ‘sufficient’ ecological status . These fThe developed and applied RFR model has been capable of utilizing both spatial and spectral information sources. In fact, the most important features identified by the algorithm above the threshold level of 0.05  are latiFollowing latitude and longitude, the RFR algorithm identified features connected to Chl-a retrieval: Rrs 708 and Rrs 778 nm, Rrs 400 nm, and MBR. This might be explained by the fact that these bands are used for the satellite retrieval of chlorophyll. In particular, Rrs 708 and Rrs 778 nm are within the NIR and red spectral bands, which are used for Chl-a estimation in coastal waters because they are less prone to interference from suspended sediments and CDOM. Their longer wavelengths and reduced sensitivity to scattering and absorption by these substances make them valuable for remote sensing in environments with variable water quality, such as coastal and nearshore areas . The relBased on the aforementioned strengths, our investigation has succeeded in predicting the TRIX levels of the examined coastal waters with a moderate level of accuracy. The TRIX estimates obtained show space and time patterns which are generally explainable through basic ecological considerations. The highest TRIX values found near the estuaries of the main rivers, for example, are driven by several interconnected factors. This is the case for the Tiber River, which is a significant freshwater source delivering nutrients and organic matter into the coastal zone. Urbanization and agriculture in the Latium region introduce pollutants and nutrients via river runoff. The shallowness of coastal waters allows for efficient nutrient uptake by phytoplankton and the formation of algal blooms. Limited water exchange between the estuary and the open sea can trap and accumulate nutrients. The interplay of these factors results in eutrophic conditions.The oligotrophic nature of Sardinia’s coastal waters can instead be attributed to limited nutrient inputs, geographical isolation, and relatively deep waters close to shore. The region experiences low levels of external nutrient sources, resulting in reduced nutrient availability for primary production. Clear waters and the absence of excessive phytoplankton growth are indicative of this oligotrophic state. Additionally, the island’s relatively low population density and limited industrial activity contribute to lower anthropogenic nutrient inputs, reinforcing its oligotrophic coastal conditions. More generally, the western seas in Italy, included in the study area, are known to exhibit increasing levels of phytoplankton biomass and primary production from south to north, thereby indicating a northward decreasing trend in oligotrophic characteristics. This trend is confirmed by the positive and significant correlation which was found between TRIX and latitude.The TRIX is suitable for monitoring the ecological quality of coastal seawaters, which is important for both scientific and practical purposes. Both theoretical considerations and previous investigations indicate that the TRIX is estimable through the use of multi/hyperspectral remotely sensed data.This subject was investigated by the application of an advanced machine learning algorithm, the RFR, to in situ TRIX observations and optical imagery collected by the OLCI sensor. The results obtained are encouraging, particularly for future operational monitoring activities. Our research, in fact, contributes to the advancement of TRIX assessment in challenging coastal environments, further highlighting the potential of remote sensing and machine learning in environmental monitoring and management.On the one hand, the availability of a limited dataset of only 340 in situ TRIX matchups impacts the general validity of the quantitative errors shown, and, on the other hand, it leaves room for improvement with an increase in available measurements. The research, in fact, has identified several critical issues that require further investigation. This should concern both the methodologies applied, with the consideration of other TRIX retrieval algorithms, and the observations analyzed, with the use of additional in situ and satellite datasets.Optically complex water quality assessment by satellite: the research has addressed the challenge of evaluating coastal water quality using remote sensing OLCI Sentinel-3 data (unprecedently used for this application), providing a valuable methodology for monitoring and managing these complex environments.Machine learning for TRIX estimation using Sentinel-3 OLCI Data: this paper has used machine learning techniques, specifically the RFR applied in a pioneering way to high spatial and spectral resolution Sentinel-3 OLCI data, to estimate the TRIX, a crucial indicator of ecological quality. This approach offers a novel way, which is efficient and cost-effective, to assess the water quality in coastal ecosystems.Advancement on TRIX assessment: the paper advances the field by demonstrating the feasibility of estimating the TRIX using remotely sensed data.The main scientific contributions brought by the current investigation can, therefore, be summarized as follows:Though we recognize the limitations of the available in situ dataset presented and emphasize the need for further investigation, this study opens the avenue for future advancements in satellite sensors in conjunction with machine learning applicability for coastal ecosystems and water quality assessment and management.


Recently, some studies based on analytical methods and the application of mass spectroscopic imaging technology have been published in some academic journals. These studies have shown that mass spectrometry imaging (MSI) is the dominant technology applied in spatial localization, through scanning slices of biological samples and generating charged ions, obtaining the spatial distribution characteristics of various molecules via ion detectors, and performing data dimensionality reduction, statistical calculation, and visual analysis. These articles promote the development of MSI technology, which helps to efficiently and accurately mine MSI data to identify important molecular signatures, promote the application of MSI in clinical diagnosis, drug research and other fields, and lay the foundation for screening biomarkers of related diseases and elucidating the pharmacodynamic mechanism of drugs in organ microregions.etc.  and non-negative matrix factorization (NNMF), are widely used in MSI data analysis. In recent years, the non-linear dimensionality reduction method T-distributed random neighbor embedding has been widely used in omics data analysis. By means of dimensionality reduction, redundant information and noise information in high-dimensional space can be effectively removed, and the accuracy of image recognition can be improved. PCA, as one of the commonly used linear dimension reduction methods, uses the projection method to compress the high dimensional space to the low dimension, and maintains the characteristics that contribute the most to the variance of the data set. Non-linear dimensionality reduction is widely used in image data recognition problems to obtain better recognition results. As an unsupervised learning algorithm, NNMF is mainly used to extract useful features in multi-dimensional data, and has gradually become a widely accepted method for data processing in research fields such as biomedicine and image recognition. Recently, The brain is the central target of central nervous system diseases, and most central nervous system (CNS) drugs will produce pharmacological effects by acting on the brain. Therefore, mining the spatial information of drugs and related endogenous metabolites in the brain is of great significance for evaluating the drug efficacy and elaborating the relevant mechanism of action. Brain imaging techniques are used for the analysis of brain tissue structure, which cannot be comprehensively analyzed at the molecular level, and the types of substances that can be monitored are also limited. To be precise, a single metabolomics method can only reflect the average level of metabolites in a sample and lacks spatial distribution information. etc.MSI is more suitable for the identification of proteins, activation peptides, lipids and small biomolecules in tissue samples. These articles continue to improve MSI technology in the areas of sample pretreatment, data processing and functional analysis. MSI technology was used to analyze the spatial distribution of biological samples and reveal the molecular distribution mechanism of biological molecules. By combining MSI technology with multi-omics technology, spatial information and accurate quantification can be effectively correlated, which is of great significance for early diagnosis and prognosis of diseases, biomarker discovery, Although MSI has been widely used in recent years, there are still some limitations. For example, the imaging analysis of compounds with low abundance, low ionization efficiency, and easy interference by matrix peaks is poor, and the method of dimensionality reduction and clustering analysis of high-dimensional MSI data is not immaculate. Future work should focus on developing powerful statistical and deep learning methods to rapidly extract comprehensive molecular information with diagnostic capabilities, and developing new strategies for various qualitative and quantitative MSI based on simulated tissue models or standard deposition. The development of MSI technology has broad application prospects in the fields of omics analysis, precision medicine, toxicology and drug metabolism.


The nasal septal cartilage plays an important role in preventing the collapse of the nasal bones and maintaining the appearance of the nose. In the context of inherent difficulties regarding septal cartilage repair and the shortage of cartilage graft resources for regeneration, tissue engineering, especially the in situ strategy based on scaffolds, has become a new prospect and become one of the most promising approaches. Given that it is difficult for chondrocytes to achieve directional migration and secrete matrix components to participate in tissue repair after cartilage injury, cartilage progenitor cells (CPCs), with great migratory ability and stem cell characteristics, have caught the attention of researchers and brought hope for nasal septal cartilage in situ regeneration. In this review, we first summarized the distribution, characteristics, isolation, and culture methods of nasal septal CPCs. Subsequently, we described the roles of migratory CPCs in cartilage regeneration. Finally, we reviewed the existing studies on CPCs-based cartilage tissue engineering and summarized the strategies for promoting the migration and chondrogenesis of CPCs so as to provide ideas for achieving nasal septal cartilage in situ regeneration. The nasal septal cartilage plays an important role in preventing the collapse of the nasal bones and maintaining the appearance of the nose. Clinically, trauma, surgery, tumor, infection, and congenital factors may cause nasal septal deformity and defect, which affects the respiratory function of the patient’s nose and results in morphological deformity, impacting the patient’s daily life . TherefoIn the context of the inherent difficulties for septal cartilage self-repair and the shortage of cartilage graft resources for transplant surgery, tissue engineering strategies have revealed a new prospect and become one of the most promising approaches. In the study by Bermueller et al. , an orthIn situ regeneration is one of the most sought-after tissue engineering methods, requiring only the implantation of a scaffold and the recruitment of autologous in situ cells to achieve tissue regeneration. The absence of additional seed cells ensures biosafety and reduces the number of pre-implantation procedures, which facilitates clinical translation. The successful recruitment of autologous in situ cells is the key to in situ regeneration. However, it is difficult for chondrocytes harbored in the pyknotic cartilage matrix to achieve directed migration and secrete matrix components to achieve satisfying tissue repair after cartilage injury.Cartilage progenitor cells (CPCs) were first reported to be found in bovine joints , and subThis review is aimed at summarizing the existing basic information on NCPCs and existing CPC-related tissue engineering designs to provide support and references for the in situ regeneration of nasal septal cartilage . SpecifiNasal cartilage mainly includes the central septal cartilage, two upper lateral cartilages, and two lower lateral cartilages. These cartilaginous structures are made up of hyaline cartilage, consisting of an extracellular matrix (ECM) and chondrocytes, and which was formerly considered to be the only existing cell component . With thEarly in 1995, in the study of Pirsig et al. , an implSimilar flat cells are also distributed on the surface of articular cartilage and other cartilage tissues. In early studies, researchers only speculated that there were progenitor cell subsets on the surface of the cartilage . In 2004Like CPCs from other sites, NCPCs possessed properties of adult stem cells, such as self-renewal capacity, multilineage differentiation potential, and MSC-related surface markers  25]. NC. NC25]. Summarizing the existing studies on NCPCs, these cells were positive for the surface markers CD44, CD49d/e/f, CD54, CD73, CD90, CD105, CD106, CD146 and CD166, and were negative for CD14, C19, CD31, CD34, and CD45 . In the 2 pieces. The most commonly used fibronectin adhesion assay protocol is based on the strong adhesion to fibronectin of the CPCs, with fibronectin receptors, integrin-α5 and integrin-β1, on their surface [Different methods could be used to isolate CPCs, including fibronectin adhesion assay, method of migration, cell sorting, enzymatic digestion, and colony screening . Before  surface . The cel surface ,26. Alte surface ,29,30,31 surface ,22. In t surface ; thus, t surface .However, CPCs isolated in different ways may possess different characteristics. In the study of Elizabeth et al. , CPCs isCPCs have been shown to play an important role in the process of chondrogenesis and regeneration. When we talk about the physiological and pathological functions of CPCs, their migration is often the focus of our attention.After injury in the bovine osteochondral explant, CPCs migrated to the injury site in 7–14 days, via the increase in high mobility group box chromosomal protein 1 (HMGB-1) and the receptor for advanced glycation end products (RAGE)-mediated chemotaxis, and promoted the repair of chondral damage . In the Danger/damage-associated molecular patterns (DAMPs) not only triggered the chemotaxis, but also elicited the immunomodulatory response of CPCs, showing a significant increase in pro- and anti-inflammatory gene expression . MoreoveWith the increased frequency and MSC surface markers in osteoarthritic cartilage, CPCs are recognized to be involved in the pathogenesis of osteoarthritis (OA) . CPCs weIn the OA articular cartilage, the phenotype of CSPCs correlating with the degree of ECM degeneration is likely to be different at different stages of OA. Tong et al. disclosed that CPCs were activated and exhibited a transient proliferative response in early OA as an initial attempt for self-repair, gradually quieting as the OA process was mediated by IL-1β via the NF-κB pathway . In the The migration of CPCs is undoubtedly an objective pathological manifestation. When we design a treatment plan, whether to promote the migration of CPCs to achieve better cartilage regeneration or to inhibit migration to restore disturbed tissue architecture is a vital question whose answer depends, at least in part, on the stage of OA. At present, the roles of CSPCs in the onset and progression of OA have not been clarified. More research and evidence are urgently needed to determine the related mechanisms and devise CPC-targeted therapies.The stronger migration ability is shared by CPCs obtained via different methods and is an essential characteristic that distinguishes CPCs from MSCs. Migratory CPCs (MCPCs), which are defined by the isolation method (method of migration) with outstanding migration capacity, are of particular interest for research. To determine what role they play in cartilage regeneration and to achieve better cartilage repair, many researchers have targeted MCPCs for study .MCPCs were first isolated and identified from human OA-articular cartilage by Keoling et al. . Most ofOther researchers constructed cartilage injury models  and isolated MCPCs that migrated after stimulation. In the study by Seol et al. , blunt iBased on CPCs, many researchers have constructed tissue-engineered cartilage using a variety of scaffold materials, conducting in vivo experiments . With thIn CPCs-based cartilage tissue engineering, natural hydrogel materials  (PLLA)/Polycaprolactone (PCL) hybrid scaffolds, and the proliferation and chondrogenic differentiation of NCPCs were significantly enhanced compared to those obtained from samples seeded on random scaffolds . In the In order to achieve in situ regeneration, the migration of cells around the defective tissue is the most important link. CPCs have a strong ability for basic migration, and could respond to inflammatory factors and migrate to the injured site, which was fully discussed in the previous section. However, despite possessing resident progenitors committed to chondrogenesis, cartilage does not show strong intrinsic self-repair ability, indicating that migration and regeneration of the natural physiological/pathological levels is insufficient to repair cartilage defects . TherefoStromal cell-derived factor 1 (SDF-1) is a key chemokine regulating stem cell migration and homing to sites of tissue damage through binding to the cell surface receptor CXCR4. In the study by Jayasuriya et al. , treatinNatural combinations of growth factors, including platelet lysate (PL), platelet-rich plasma (PRP), and extracellular vesicles (EVs), could also promote CPCs migration, and at the same time, they have a prominent effect of promoting the chondrogenesis of CPCs. The platelet membrane is always ruptured in the PRP suspension to obtain the PL . As prodIn addition, some mechanical stimulation can also promote the migration of CPCs. Low-intensity pulsed ultrasound (LIPUS) promoted the migration of CPCs to the injured site via the focal adhesion kinase pathway . Under tSimilarly, the promotion of migration of chondrocytes, which had not yet been identified to be CPCs, was explored in some studies ,99,100. Compared to the promotion of chondrogenic progenitor cell migration, the promotion of chondrogenesis seems to be easier, as the previous systems of research on the induction of chondrogenic differentiation of stem cells and the promotion of chondrocyte secretion of cartilage matrix are more fully developed. In the study by Padmaja et al. , bone moIn addition to factors that have been shown to promote CPCs chondrogenesis, other factors that could promote the chondrogenic differentiation of BMSCs and the proliferation of chondrocytes may also be considered as potentially effective additions ,105,106.Increasing evidence has shown that CPCs are promising seed cells for cartilage tissue engineering and have superior migration ability and in situ distribution compared to other seed cells, which have been fully discussed in the previous section. Therefore, the use of CPCs is expected to achieve in situ regeneration, which has great potential for clinical application and brings hope for the treatment of cartilage injury-related diseases. Currently, studies on articular cartilage progenitor cells are more comprehensive, while studies on nasal CPCs are yet to be further developed. The easier availability and larger surface layer in which CPCs are mainly distributed both illustrate the advantages of using NCPCs for in situ regeneration of nasal cartilage compared to those using articular cartilage. Moreover, with perichondrium on the surface, it is not clear whether perichondrium-derived progenitor cells or superficial cartilage-derived progenitor cells are the main force in nasal cartilage regeneration. Moreover, given that CPCs from the deep zone of articular cartilage possess greater chondrogenic and osteogenic potential , the difAt the same time, nasal septal cartilage is often used as a source of cartilage autograft due to its easy accessibility and superior mechanical properties. Therefore, if regeneration of nasal septal cartilage can be achieved, it can not only solve the problem of the nasal septal defect, but also serve as a regenerable cartilage donor area, indirectly solving the problem of insufficient cartilage sources faced when diseases in other parts of the body require treatment with cartilage grafts, such as contracted nose deformity, cleft lip nasal deformity, microtia, osteoarthritis, etc.However, studies on NCPCs and even CPCs are still insufficient in terms of the overall perspective. The study of different functional subpopulations of CPCs is still at a preliminary stage, and the mechanisms of the migration and participation of CPCs in tissue repair and the interaction and transformation of CPCs with mature chondrocytes are still unclear. More systematic and in-depth studies need to be completed to further elucidate the mechanisms involved, with subsequent improvement of the cartilage scaffold  to increase its ability to recruit CPCs. The unresolved status of these issues not only affects the judgment of CPCs-based strategy security, but also limits the development of new strategies. Moreover, as one of the most important aspects of achieving in situ cartilage regeneration, the efficacy of CPCs recruitment requires further improvement. New strategies for improving the cartilage scaffold , as well as new additives, are constantly emerging. However, none of these has yet showed absolute superiority. In addition, whether these strategies have other side effects is also an important issue to be determined. Additional in vivo and in situ animal experiments need to be completed, which would lay a foundation for clinical application and ultimately provide help for patients with nasal cartilage defects in the future.


Fusobacterium nucleatum surface protein in tumor immune evasion. Other top-cited articles investigated the correlation between the oral bacteriome and cancer using 16S rRNA amplicon sequencing, showing microbial shifts associated with oral cancer development. The functional prediction analysis used by recent studies has further revealed an inflammatory bacteriome associated with carcinogenesis. Furthermore, a keyword analysis reveals four distinct research themes: cancer mechanisms, periodontitis and microbiome, inflammation and Fusobacterium, and risk factors. This analysis provides an objective assessment of the research landscape, offers valuable information, and serves as a resource for researchers to advance knowledge and collaboration in the search for the influence of bacteria on the prevention, diagnosis, and treatment of oral cancer.The research domain investigating bacterial factors in the development of oral cancer from January 2013 to December 2022 was examined with a bibliometric analysis. A bibliometric analysis is a mathematical and statistical method used to examine extensive datasets. It assesses the connections between prolific authors, journals, institutions, and countries while also identifying commonly used keywords. A comprehensive search strategy identified 167 relevant articles, revealing a progressive increase in publications and citations over time. China and the United States were the leading countries in research productivity, while Harvard University and the University of Helsinki were prominent affiliations. Prolific authors such as Nezar Al-Hebshi, Tsute Chen, and Yaping Pan were identified. The analysis also highlights the contributions of different journals and identifies the top 10 most cited articles in the field, all of which focus primarily on molecular research. The article of the highest citation explored the role of a  Oral cancer has a significant impact on public health, including morbidity and mortality rates, as well as socioeconomic burdens . The latFusobacterium, Prevotella, Porphyromonas, and Lactobacillus, within tumor tissues, suggesting its potential involvement in cancer progression [Oral carcinogenesis is a multifactorial process that involves many risk factors , such asgression ,11.Early detection of oral cancer is crucial to achieving favorable clinical outcomes and, therefore, higher survival rates . The assBibliometric analysis  objectivResearch on oral cancer and bacteria from January 2013 to December 2022 was carried out using the Thomson Reuters Web of Science database (WoS). This database was chosen due to its extensive collection of medical literature and comprehensive citation analysis [Only original articles written in English and published between 2013 and 2022 were included in this study . Since oThe WoS covers extensive biomedical research and contains tools for citation analysis. The H-index , which eBetween 2013 and 2022, a total of 167 articles on the topic of oral cancer and bacteria met the search criteria and were included in the evaluation. The number of publications showed a progressive increase over time, with the highest number of publications observed in 2022, reaching 35 articles . The citThe authorship productivity and citation counts were assessed to identify the most prolific authors . NotableIn terms of affiliations, Harvard University demonstrated the highest level of contribution with 12 publications . The UniA country’s productivity in the field of oral cancer and bacteria was assessed . AnalysiThe co-authorship network of countries is depicted in Frontiers in Cellular and Infection Microbiology, with an impact factor (IF) of 6.073, published the highest number of studies, accounting for 10 publications (5.99%). Scientific Reports ranked second with nine publications (5.39%), and Frontiers in Microbiology ranked third with seven publications (4.19%). It is worth noting that three of the top 10 journals, Frontiers in Cellular and Infection Microbiology, Frontiers in Microbiology, and Frontiers in Oncology, were published by the same publisher, Frontiers Media SA. This highlights the significant contribution of this publisher to this field of research.The contributions of different journals to the field of interest were examined . FrontieImmunity, investigated the role of the Fap2 protein in tumor immune evasion. The study shows how Fusobacterium nucleatum binds to tumor cell surfaces, facilitating its interaction with the inhibitory receptor TIGIT of NK cells through its Fap2 protein. This interaction shields tumor cells from immune cell attacks, contributing to cancer progression. The findings shed light on the potential mechanisms employed by periodontal pathogens to protect tumors from immune cell attack.In terms of citation impact, the top 10 most cited articles in the field of oral cancer and bacteria are listed in The articles ranked 2 and 4 to 10 explored the correlation between the oral bacteriome and cancer using molecular techniques, particularly 16S rRNA amplicon sequencing. However, these studies show inconsistent results regarding specific species or microbial shifts associated with oral cancer. The limitation of these investigations lies in their narrow focus on compositional analysis. To overcome this limitation, some of the more recent studies ,28 used The third most cited article  exploredBy elucidating these interactions, the research contributes to a deeper understanding of the complex relationship between oral bacteria and cancer, offering potential implications for therapeutic interventions and preventive measures. The findings of this highly cited study emphasize the importance of considering bacterial infections as possible contributing factors to the development and progression of oral cancer. As such, it highlights the importance of exploring novel strategies to target these interactions for better cancer management.Streptococcus anginosus were present in this cluster. The blue cluster comprised studies that focused on inflammation and the role of specific bacteria, particularly Fusobacterium and Porphyromonas, in oral cancer. The yellow cluster included studies that examined various risk factors associated with oral cancer. A We performed a keyword analysis using VOSviewer  to identify the prominent research themes in the literature related to the role of bacteria in the process of oral cancer development . Four clThis study provides a comprehensive evaluation of academic publications that focus on the association between oral cancer and bacteria from 2013 to 2022. The analysis reveals a consistent increase in the number of publications over time, indicating the growing interest in this research area. Moreover, the citations of these articles also demonstrate a positive trend, underscoring their influence and significance within the scientific community. This reflects the growing global severity of oral cancer  and the Among the authors investigated, Al-Hebshi NN emerges as the most productive, having published six articles exploring the impact of oral bacteria on cancer development, progression, and associated inflammatory processes ,28,29,30Our analysis highlights the substantial contributions made by China and the United States in terms of publication output, citation impact, and overall influence in the field. Additionally, we observe emerging research activities in India, Finland, Japan, and Taiwan, indicating their increasing presence and impact in this domain. Collaborative efforts between these geographic regions have the potential for knowledge exchange and further advancement of research in the field. This academic cooperation is also evident among research institutions, as demonstrated by the co-author network of affiliations analyzed using VOSviewer see .Regarding the journals that have published the most studies in the field, many of them focus on oncology, microbiology, and dentistry. This indicates the multidisciplinary nature of the research conducted in this area, where various fields intersect to contribute to the understanding of the topic.Fusobacterium, Prevotella, Porphyromonas, and Lactobacillus could potentially serve as biomarkers for assessing cancer risk [The most cited articles identified in our study have made significant contributions, addressing various aspects of the topic, including changes in the oral microbiota, the role of specific pathogens, and associations with tumor progression. In particular, the dynamics of the oral microbiota community ,48 have cer risk ,51.F. nucleatum and P. gingivalis, have been associated with periodontitis that can contribute to the pathogenesis of oral cancer [The influence of bacteria on oral cancer extends beyond its composition to encompass the concept of an inflammatory bacteriome ,28. The l cancer ,53.Through the application of keyword analysis using VOSviewer, our study identified four distinct research themes in the field of oral cancer and bacteria. The green cluster focused on cancer mechanisms, delving into the underlying cellular and molecular processes involved in oral cancer development. This theme sheds light on key factors and pathways that contribute to tumorigenesis. The red cluster explored the intricate relationship between periodontitis, the oral microbiome, and oral cancer. This theme highlighted the impact of microbial communities on disease progression, emphasizing the role of the oral microbiota in the development of oral cancer. The blue cluster investigated inflammation and the specific bacteria involved in oral carcinogenesis. The yellow cluster focused on identifying and understanding various risk factors associated with oral cancer. This theme aimed to aid in the development of preventive strategies by identifying factors that can increase susceptibility to oral cancer.F. nucleatum emerged in our keyword analysis as a prominent focus in the field of oral cancer. F. nucleatum, a Gram-negative anaerobic bacterium initially identified as a periodontal pathogen, has recently been implicated in colorectal cancer development. Studies have demonstrated that F. nucleatum can contribute to cancer progression through multiple mechanisms. It can activate cell proliferation, promote cell invasion, induce inflammation, and evade immune surveillance, all of which play crucial roles in carcinogenesis [The bacterium ogenesis ,55.P. gingivalis. This bacterium promotes cancer cell proliferation by reducing apoptosis through PI3K/Akt signaling. P. gingivalis can stimulate tumor growth and metastasis by inhibiting p53 expression [P. gingivalis has been shown to improve the aggressiveness of oral cancer cells through epithelial–mesenchymal transition-like changes and the acquisition of stemness. Prolonged exposure to P. gingivalis also promotes the migration and invasiveness of cancer cells while providing resistance against chemotherapeutic agents [Another bacterial strain that stood out in our keyword analysis was pression . When grc agents .F. nucleatum and P. gingivalis have also been found to activate cell transformation. All these changes contribute to the maintenance of the chronic inflammatory process and induce carcinogenesis. At the cellular level, these alterations can induce permanent genetic changes in epithelial cells due to continuous exposure to cell metabolites, leading to abnormal cell divisions and, ultimately, the development of carcinoma [Periodontitis, a persistent advanced inflammatory gingival disease caused by bacterial dysbiosis, is associated with an increased risk of cancer development ,59,60. Parcinoma . Therefoarcinoma ,63.F. nucleatum, P. gingivalis, and other bacteria involved, we can potentially uncover novel therapeutic targets and approaches to mitigate the impact of these bacterial strains on oral cancer.The identification of these specific bacterial strains and their roles in the development of oral cancer underscores the complex interaction between bacteria and the progression of the disease. Understanding the mechanisms through which these bacteria influence oral cancer is crucial for the development of targeted therapeutic strategies and preventive interventions. By elucidating the contributions of This study uses bibliometric methods to explore the development of research on the influence of bacteria on oral cancer. This approach has provided us with a deep understanding of the diverse aspects of the research. However, it is important to acknowledge and address several limitations in our approach. First, we utilized only one database (WoS), which may have resulted in the exclusion of relevant articles from other sources. To mitigate this limitation, future studies should consider incorporating multiple databases to ensure a more comprehensive coverage of the literature. Secondly, this study focused exclusively on original articles, which may have resulted in the exclusion of highly cited review articles. While our intention was to capture the real trends and research hotspots, it is important to recognize that review articles provide valuable summaries and interpretations of the existing literature. Future studies could consider incorporating review articles to provide a more comprehensive understanding of the field. Lastly, although citation analysis has been used in this study, it should be noted that a combination of quality assessments would be beneficial to identify truly high-quality articles. Unlike systematic reviews and meta-analyses that selectively include high-standard studies, bibliometric analysis aims to provide a broad and comprehensive overview of a research area. Incorporating additional quality assessments can further enhance the evaluation of the included articles. Despite these limitations, this study offers valuable information on the advancements and evolving trends in research on bacterial influence on oral cancer over the past decade. By acknowledging these limitations, future studies can build on our findings and employ more robust methodologies to further explore this important research area. The knowledge gained from our study contributes to the appreciation of the advancement of scientific understanding in the field of oral cancer and offers a deeper understanding of the disease at a fundamental level. In general, our study underscores the critical need for continued research and exploration in the field of oral cancer and bacteria.Fusobacterium, Prevotella, Porphyromonas, and Lactobacillus or dysbiosis within the oral microbiota can serve as potential biomarkers for assessing cancer risk. Targeting the inflammatory bacteriome and modulating the oral microbiota may hold promise for the prevention and treatment of oral cancer. More research is warranted on the role of periodontal pathogens, such as Fusobacterium and Porphyromonas, in persistent infection and inflammation during carcinogenesis. However, to develop effective preventive and therapeutic strategies, more research is required to elucidate the precise mechanisms underlying these interactions and explore potential therapeutic interventions in this field. In addition to studying pathogenic bacteria, exploring the role of relative benign bacteria that inhibit local inflammation or reduce the inflammatory potentiation of the entire bacteriome may also hold promise for preventing cancer development. Advancements in this area of research have the potential to revolutionize oral cancer management and improve overall health outcomes for affected individuals.In general, these findings highlight the significant impact of the oral microbiota on the development and progression of oral cancer. Understanding the dynamics and interactions between the microbial communities and the host’s immune response provides insight into the underlying mechanisms of carcinogenesis. Specific bacterial species such as


The global food-production crisis and lack of sustenance affordability can create further regional food-security and political disruptions and trigger further socioeconomical injustice among various nations. Innovations to reshape global food systems through improving local food-production capabilities, enabling infrastructure for agricultural innovation, and facilitating knowledge flow as well as technology dissemination are necessary to curb food shortages and security. Developing and applying new and emerging technologies, including synthetic biology and artificial intelligence, to modernize food production and processing would strengthen efforts to overcome supply challenges in the future.In the coming decades, feeding the growing world population is going to become a global food-supply challenge for our existing food systems. At present, the global food-supply chain has been severely affected due to disruptions caused by the COVID-19 pandemic, climate change, and political conflicts. These disruptions have led to substantial increases in food prices  and the presence of antinutrients  require urgent evaluation. Novel food-production approaches are equally important for improving food-handling and transportation practices, developing processing technologies to enhance the utilization of foods, and providing maximum nutritional benefits to the consumer. Food safety and public health protection are also key elements of emerging global food systems.2 with a lower production input (90–95% less water use and less pesticides) and better opportunities to include smart technologies that reduce energy input [Food security requires a sustainable, adequate supply of food that is accessible to the population to ensure normal physical and biological activities; subsequently, social and economic activities are maintained. Many factors affect food security, including factors related to food production  and factors that affect overall economic growth , with the latter not directly controlled by food-production systems. Agro-systems, especially vertical indoor stations, underground horizontal farming, or hybrid horticulture plus fish-farming systems appear to be very promising; the underground system used by PlantLab (Netherland) was reported to produce three times the output of the best greenhouse system and 40 times that of open-field production . Hydropogy input . The sysFood innovations envisaged to ensure food security integrate novel  and re-emerging  sources that enable the production of new food ingredients and the biotransformation of foodstuffs to reduce or remove antinutrients and undesirable food components. The latter technologies appear to offer the advantages of producing large amounts of food at a low production cost, in addition to the high nutritional quality of the generated foods.One of the key United Nations Millennium Sustainable Development Goals (SDG) is the third SDG, which aims to promote the production of healthy food that delivers adequate nutrition and supports health and wellbeing. Current innovative food technologies place great emphasis on the sensory aspects of foods. For examples, most producers of alternative animal-based products focus on creating products that have similar sensory attributes to those of animal products. Additionally, the production of bioprinted products for senior citizens and special-needs consumers mostly focuses on acceptable sensory attributes and conferring health benefits. Recent innovations of in vitro, formulated, 3D-printed foods offer the opportunity to tailor the composition of foods through the supplementation of health-promoting nutrients or functional components that could improve certain targeted benefits . Nevertheless, the major change in food-production systems associated with future foods is yet to be fully appreciated and evaluated in terms of their safety and health impact. We do not have the same depth of understanding of novel foods that we do of conventional foods, and there are concerns over their safety due to the possible bioaccumulation of toxic contaminants, their microbiological safety, the deficiency of some essential amino acids, and protein digestibility , and witFood safety and public health is global issue that affects millions of people around the world each year. According to the World Health Organization’s estimate, 600 million people  suffer from food poisoning after eating contaminated food, and 420,000 die every year . There aThis Special Issue aims to published quality articles on novel foods on a wide range of aspects including their role in food security, nutrition and health, and public health.


Since February 2022, the nation of Ukraine has become entangled in an escalating conflict that erupted after coronavirus outbreak fostering a situation of indeterminacy and precariousness, which adversely affected several facets, especially psychological well-being. However, there is a lack of empirical evidence on the psychological well-being of Ukrainians during the Russo-Ukraine war, as well as their coping strategies in response to the war’s repercussions. Consequently, this investigation endeavors to explore the prevalence of symptoms associated with depression, anxiety, stress, and insomnia and to correlate these symptoms with Ukrainians’ effective coping mechanisms during the ongoing war.An online survey was administered in Ukraine from June to August 2022 due to the ongoing Russo-Ukraine conflict. The survey employed a quota sampling technique, targeting 2,664 individuals (≥18 years). Out of the total sample, 1,833 valid responses were obtained, yielding a response rate of 68. 81%. Depression, anxiety, and stress were measured using the depression, anxiety, and stress scale-21 (DASS-21), while the Pittsburgh sleep quality index (PSQI) was utilized to evaluate insomnia symptoms. In addition, Brief-COPE was adopted to evaluate the coping mechanisms of the selected study participants.Of 1,833 Ukrainian adults, 60.5% had symptoms of stress; 62.4% of them reported symptoms of anxiety; and 58.2% reported symptoms of depression. Symptom criteria for insomnia were found in about 21.8% of the study sample. The factors of sex, living area, area occupied by Russian forces, and having older adults and children in the house were statistically significant with symptoms of depression, anxiety, stress, and insomnia. The productive coping strategies of self-distraction, using instrumental support, planning, and behavioral disengagement, were observed as statistically significant with four psychological constructs.The study outcomes highlight a substantial prevalence of symptoms related to depression, anxiety, stress, and insomnia attributed to the accumulated consequences of ongoing conflict and the COVID-19 outbreak. The aforementioned findings emphasize the imperative of providing healthcare services and facilitating effective coping strategies among Ukrainians amid the ongoing war. The impacts of warfare extend to both combatants and civilians, leading to detrimental physical and psychological manifestations for both groups. War can result in various deleterious physical consequences such as mortality, harm, sexual assault, starvation, diseases, and disabilities. Additionally, individuals exposed to war may experience post-traumatic stress disorder (PTSD), which further exacerbates the overall impact on their well-being. Depression and anxiety are among the emotional manifestations experienced by individuals , 2. The The historical trajectory showcases the severe ramifications on national welfare resulting from armed conflicts . One of The present confluence of the Russo-Ukraine conflict and the prevailing coronavirus outbreak has fostered an exacerbation of the obstacles confronting the younger segment of the Ukrainian population . The ongPrevious pieces of evidence have shown that exposure to terrorism and conflicts can have disastrous effects on the psychological well-being of individuals, leading to various mental health issues including depression, acute stress reactions, personality changes, cognitive impairments, anxiety disorders, and PTSD. This holds for those directly involved in the conflict such as combatants and veterans, as well as innocent civilians like refugees and the general population . The armAs individuals undergo traumatic events and endure the stress of a prolonged war, there is a heightened likelihood of mental health issues and a decline in psychosocial well-being . HoweverKhraban analyzed discourses extracted from posts and comments shared on social media platforms by individuals residing in northern Ukraine throughout the initial 15-day period of the conflict. The research revealed a fluctuating utilization of coping mechanisms, specifically emotion-focused and problem-focused strategies, employed by civilians. These coping mechanisms served the purpose of expressing and alleviating negative emotions while simultaneously striving to mitigate the impact of distressing situations. Furthermore, they aimed to foster positive emotions such as benevolence and solidarity among the affected individuals  was conducted utilizing the PSQI, which comprehensively assesses sleep quality through the examination of 19 indicators categorized into seven distinct dimensions . The evaAn adapted version of Brief-COPE was used to assess the coping mechanism of Ukrainian individuals . The queThe translation of all instruments was carried out in accordance with pertinent guidelines, in the Ukrainian language. Two autonomous translators were engaged in the process, wherein the adaptation encompassed a direct translation from English to Ukrainian language. This was followed by a reversed translation, and subsequently, psychological interviews were conducted with an initial set of participants. The reversed translated iteration was juxtaposed with the genuine rendition and any complications encountered throughout the process were deliberated upon and effectively tackled prior to the culmination of the conclusive rendition of the instruments.In order to gain insight into the respondents’ attributes and the prevalence ratio of symptoms related to mental well-being, an initial implementation of basic descriptive analyzes was conducted. Pearson’s correlation analysis was also performed to detect the multicollinearity among the study variables. Before we put the variables into the regression analysis, we checked for the assumptions. Shapiro–Wilk Test has been used to test the normality of the data. Subsequently, a series of multivariate analyzes were performed to evaluate the relationships between coping mechanisms and symptoms of mental well-being. The aforementioned cutoff rates were employed to categorize the four psychometric constructs as binary variables. In a parallel manner, logistic regression was executed to explore the association between coping strategies and mental health outcomes. We also tested the reliability of the constructs using Cronbach’s alpha in the present investigation. All the analyzes were performed using SPSS (v26) with a significant threshold of <0.05 and < 0.01.Furthermore, the outcomes indicate a negative correlation between the utilization of instrumental support and behavioral disengagement coping strategies and the presence of stress symptoms. The utilization of self-distraction as a coping mechanism exhibited a negative correlation with symptoms of anxiety, depression, and insomnia while demonstrating a positive connection with symptoms of stress. There was a substantial linkage between active coping and anxiety symptoms, while a positive relationship was noted between planning and symptoms of insomnia. The utilization of instrumental support exhibited a positive correlation with anxiety symptoms. The findings of this study also demonstrate a substantial correlation between behavioral disengagement and the manifestation of depressive symptoms and sleep disturbances.The present study represents the first comprehensive investigation of the associations between depression, anxiety, stress, insomnia, and coping strategies among Ukrainian citizens within a more diverse sample size. The advent of armed conflict generally poses a significant risk to the mental well-being of non-combatant individuals as a whole. In comparison with the incidence rates documented in 2016 regarding anxiety and depression , a compaIn response to the detrimental effects of the conflict, we further endeavored to explore the coping mechanisms embraced by Ukrainians and their correlation with the manifestation of psychological disorders. The results of our investigation indicate that the act of pursuing instrumental support exhibits a negative correlation with stress and a positive relationship with anxiety. This phenomenon may be attributed to the heightened propensity of individuals experiencing anxiety to actively solicit instrumental support. Based on empirical findings, it is apparent that instrumental social support coping emerged as a prominent coping mechanism employed by individuals residing in Israel in response to traumatic stress and the symptoms of PTSD after acts of terrorism. According to empirical research on the coping mechanisms used by Ukrainian military troops in counterterrorism missions, post-traumatic symptoms and the coping technique of soliciting social support have shown a negative correlation , 39.Furthermore, our investigation revealed a positive correlation between active coping strategies and symptoms of anxiety. Similarly, we observed a positive association between planning strategies and symptoms of insomnia. Previous studies have reported that individuals tend to employ active coping and strategic planning mechanisms as a means of managing stressful situations. In another investigation it was discovered that Ukrainian students employ proactive coping mechanisms, specifically through the utilization of problem-solving planning, to navigate stressful situations successfully . PositivBehavioral disengagement coping, characterized by the act of relinquishing efforts to cope with stressful situations, exhibited an unfavorable correlation with stress symptoms. However, its association with depression and insomnia was observed to be positive. The utilization of self-distraction coping strategies was found to have a positive correlation with indications of stress, yet a negative correlation with anxiety, depression, and insomnia symptoms. These outcomes are aligned with the results reported in previous investigations. In an investigation, it was observed that following the implementation of a threshold level of interventions, the adoption of avoidance and distraction methods was significantly associated with reduced post-Persian Gulf War stress responses . AccordiThe findings of our study indicate that there exists a positive association between the implementation of problem-focused coping mechanisms by Ukrainians and their mental health symptoms. Conversely, the effects of emotion-focused coping strategies displayed a varied pattern, displaying positive correlations with certain symptoms while demonstrating negative relationships with others. According to Hobfoll et al.  the implRegrettably, the current repertoire of interventions provided by mental healthcare practitioners and centers in Ukraine frequently lacks a foundation in empirical evidence introducing a critical concern. According to a survey carried out in Ukraine in 2017, data suggests that mental illness has a prevalence rate of 33% within the population. However, a mere 4.9% of individuals grappling with such conditions are reportedly undergoing treatment . There iSeveral limitations need to be recognized when it comes to the interpretation of the findings of the current study. The current study is grounded in a cross-sectional design conducted amidst the ongoing Russo-Ukraine conflict. Consequently, it is imperative to acknowledge that we are limited in our ability to establish a causal connection between psychological manifestations and coping mechanisms. It is conceivable that a circular association would exist between coping strategies and symptoms, wherein coping strategies exert an influence on symptoms, which subsequently instigate alterations in coping. There is a need for further investigation to elucidate the specifics of this association and establish the probable course of causation in prospective longitudinal investigations focusing on examining the links between symptoms of psychological manifestations and adopted coping mechanisms over an extended period. The present study directed its attention toward examining efficacious coping strategies. Strategies such as substance abuse, namely through drugs and alcohol, possess the potential to be counterproductive measures when attempting to handle the threat imposed by warfare. Subsequent inquiry may explore maladaptive coping mechanisms, such as substance and alcohol misuse, to ascertain their effects and potential interventions.An upsurge in psychological manifestations has been attributed to the simultaneous effects of the coronavirus outbreak and the Russo-Ukraine conflict. Given the prevalence of societal prejudices and restrictions, psychological wellness is frequently neglected in Ukraine; this propensity is exacerbated in times of conflict and epidemics, emphasizing the necessity for boosting essential backing for preventative services for emerging psychological demands and actions aimed at enhancing accessibility to care for ongoing and developing psychological disorders.Our research offers preliminary insights regarding psychological health indicators such as depression, anxiety, stress, and insomnia amidst the upheaval as a consequence of the Russo-Ukraine invasion. Ukrainian individuals subjected to the Russian invasion have displayed a range of effective problem-solving coping mechanisms, including active coping and planning, in addition to adopting emotion-focused approaches such as seeking instrumental support, practicing behavioral disengagement, and resorting to self-distraction as means to mitigate these challenges related to psychological wellbeing. The aforementioned statistics highlight the imperative nature of providing expert medical care and psychotherapist services to individuals amidst times of invasion.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The study was conducted according to the guidelines of the Declaration and approved by the Ethics Review Committee of Prince Sattam Bin Abdulaziz, institutional review board, Deanship of scientific research (Ref: PS-04/25/2022). The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation in this study was provided by the participants’ legal guardians/next of kin.AK: Conceptualization, Formal analysis, Investigation, Methodology, Writing – review & editing. AA: Funding acquisition, Investigation, Methodology, Resources, Writing – original draft, Writing – review & editing.The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The authors extend their appreciation to Prince Sattam bin Abdulaziz University for funding this research work through the project number (PSAU/2023/01/224253).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Infective endocarditis (IE) is still a life-threatening disease with frequent lethal outcomes despite the profound changes in its clinical, microbiological, imaging, and therapeutic profiles. Nowadays, the scenario for IE has changed since rheumatic fever has declined, but on the other hand, multiple aspects, such as elderly populations, cardiovascular device implantation procedures, and better use of multiple imaging modalities and multidisciplinary care, have increased, leading to escalations in diagnosis. Since the ESC and AHA Guidelines have been released, specific aspects of diagnostic and therapeutic management have been clarified to provide better and faster diagnosis and prognosis. Surgical treatment is required in approximately half of patients with IE in order to avoid progressive heart failure, irreversible structural damage in the case of uncontrolled infection, and the prevention of embolism. The timing of surgery has been one of the main aspects discussed, identifying cases in which surgery needs to be performed on an emergency (within 24 h) or urgent (within 7 days) basis, irrespective of the duration of antibiotic treatment, or cases where surgery can be postponed to allow a brief period of antibiotic treatment under careful clinical and echocardiographic observation. Mainly, guidelines put emphasis on the importance of an endocarditis team in the handling of systemic complications and how they affect the timing of surgery and perioperative management. Neurological complications, acute renal failure, splenic or musculoskeletal manifestations, or infections determined by multiresistant microorganisms or fungi can affect long-term prognosis and survival. Not to be outdone, anatomical and surgical factors, such as the presence of native or prosthetic valve endocarditis, a repair strategy when feasible, anatomical extension and disruption in the case of an annular abscess , and the choice of prosthesis and conduits, can be equally crucial. It can be hard for surgeons to maneuver between correct pre-operative planning and facing unexpected obstacles during intraoperative management. The aim of this review is to provide an overview and analysis of a broad spectrum of specific surgical scenarios and how their challenging management can be essential to ensure better outcomes and prognoses. Infective endocarditis represents an infection involving specific cardiac tissues: the endocardium, native heart valves at any position, prosthetic heart valves, or any implanted cardiac devices. IE can be clinically insidious since epidemiology and natural history are in constant evolution, reflecting the complex interaction between an aging population, multiresistant microorganisms, evolving patterns of healthcare, available therapies, and the application of aggressive surgery. IE remains a relatively uncommon condition, with an annual occurrence of approximately 3–10 cases per 100,000 individuals . This chS. aureus and fungi), female sex, age, prosthetic valve IE, and multivalvular involvement [American College of Cardiology/American Heart Association (ACC/AHA) and the European Society of Cardiology (ESC) guidelines widely focus on diagnostic and therapeutic management, surgical indications and patient selection, operative risk assessment, and timing of surgery in relation to specific systemic circumstances. Given the paucity of randomized or large-scale observational data in IE, we base our knowledge on a few large registries reporting, among other information, operative risk assessment in order to predict and improve the clinical outcomes of patients. Cohorts and registries, such as the International Collaboration on Endocarditis (ICE), Society of Thoracic Surgeons-Infective Endocarditis Cohort (STS-IE), and The European Society of Cardiology (ESC) EURObservational Research Programme (EORP) European Endocarditis (EURO-ENDO) registry, mainly relate operative risk and short-term outcomes to a higher and heterogeneous number of variables, including comorbid medical conditions, acute status, and systemic or embolic complications. The first systematic review and meta-analysis, derived from 11 studies, with a specific focus on prediction models of postoperative mortality in patients with IE, underlined 11 preoperative factors that are related to increased postoperative mortality: the presence of cardiogenic shock, NHYA class ≥ III, a need for urgent surgery, the presence of paravalvular abscess, preoperative renal failure, previous cardiac surgery, etiology , a higher rate of long-term survival , and a decreased likelihood of recurrence. Additionally, the decisions made prior to surgery, including the timing of the procedure and the rationale for surgical intervention, exhibited a correlation with the percentage of repair procedures performed and their favorable long-term effects. Essentially, the opportunity to undertake a repair technique for native valve endocarditis seems to be linked to the timing of the surgical intervention. Notably, data from North America indicated that the rate of repair was approximately 40–50% for resolved cases of IE but notably lower at 10–20% for acute cases [Independently of specific techniques, multiple retrospective trials have proven the effectiveness of MVr in favoring short- and long-term outcomes. Nana Toyoda et al.  retrospete cases . In a pate cases  conducteThe aortic valve is affected in 35–39% of cases , surgicap = 0.002) among younger patients. This result implies that younger patients experience a greater advantage in terms of freedom from reoperation when opting for mechanical prostheses.Klieverik et al.  found noCompared to left-sided infective endocarditis (IE), the incidence of right-sided IE tends to be lower, possibly due to the relatively infrequent prevalence of typical pathological conditions affecting the right-sided valves. This variation may stem from differences in the properties of the right-sided endothelium and disparities in right-side hemodynamic patterns, characterized by lower pressure gradients and jet velocities across the right-sided valves, as well as reduced right-sided wall stress and lower oxygen content in venous blood . Over thThe outcomes of tricuspid valve repair (TVr) and tricuspid valve replacement (TVR) are indeed comparable in terms of long-term survival. Yanagawa B. et al.  conducteIn cases of right-sided IE, an alternative to surgery involves the utilization of percutaneous, vacuum-assisted devices designed for removing intracardiac masses. Such devices serve as a means to remove large tricuspid valve vegetations when the risks associated with surgery are prohibitive. In 2014, the US Food and Drug Administration approved the AngioVac system , a device designed for removing undesired intravascular materials, such as thrombi and emboli . George The epidemiology of infective endocarditis is changing and the incidence of prosthetic valve (PV) IE is increasing, as proven by the comparison of the different registries provided through the years. According to the latest, PV IE accounts for 30% of cases in the EURO-ENDO Registry, 25% in the 2008 French registry, and 21% in the International Collaboration on Endocarditis Prospective Cohort Study reported in 2009 ,39,40. PBoth mechanical and bioprosthetic valves are susceptible to infection, exhibiting no significant difference in prevalence within the first 5 years (5.7%). Interestingly, mechanical valves present a heightened risk of infection during the initial 3 months following operation , whereasAdditionally, a noteworthy and emergent concern in the context of prosthetic valve IE involves infections associated with transcatheter-implanted valves and percutaneous edge-to-edge mitral valve repair. Incidences of IE following transcatheter aortic valve implantation (TAVI) appear to be relatively low, with certain studies reporting around 1% incidence , albeit Endocarditis is a potentially destructive disease and the treatment can widely range in complexity from medical antimicrobial treatment to complex cardiac reconstruction. Endocarditic lesions may manifest as small vegetations originating from the cusps or leaflets, or fenestrations, which can often be easily treated with excision and valve replacement or valve repair, as already mentioned. If the disease progresses locally, it may lead to valvular annulus involvement and the development of an annular abscess. In turn, a deeper myocardial involvement may lead to damage to the fibrous skeleton of the heart and to the conduction system, as well as perforation into other cardiac chambers. The scope and nature of surgical intervention are directly contingent upon the extent of tissue damage, consistently adhering to the principle of thorough debridement, and may necessitate annular reconstruction. The choice of material for the new annulus is generally a matter of surgeon preference, with options including bovine pericardium, both fixed and fresh autologous pericardium, as well as Dacron, all being documented choices. Pericardial tissue holds the advantage of increased pliability and the capacity to conform to the underlying myocardium, thereby reducing the likelihood of flow beneath the patch that could potentially lead to the development of a pseudoaneurysm or shunt. Additionally, the utilization of autologous or heterologous pericardium has not demonstrated an elevated risk of reinfection. Following the placement of the patch, the decision between valve repair and replacement is determined by the extent of valve leaflet or cusp destruction. Approximately 15% of cases of mitral valve infective endocarditis (MVE) may involve a mitral annular abscess . These aManaging such lesions can be intricate due to extensive tissue damage, limited available area for prosthesis implantation, and, in more severe cases, potential left ventricular aortic discontinuity. Surgical intervention involves the thorough removal of the infected region and rectification of the annular defect. Multiple techniques have been outlined to address this condition. Typically, closure of the abscess cavity involves the implementation of a patch to rebuild the left ventricle outflow tract, followed by valve or root replacement. In instances where profound circumferential destruction of the aortic annulus is observed, some experts propose an alternative approach involving the reconstruction of the left ventricle outflow tract and the translocation of the aortic valve into the ascending aorta. This technique aims to position the new valve prosthesis away from the infected area . AccordiThe aortic mitral curtain (AMC) is a complex component of the heart’s fibrous skeleton, situated between the lateral and medial trigones of the mitral valve. It forms connections between the left and non-coronary cusps of the aortic valve and links the anterior leaflet of the mitral valve to the aortic valve cusps and the roof of the left atrium, effectively separating the mitral valve from the aortic root. Given its invasive nature, managing this structure typically necessitates a complex surgical procedure. Initially proposed by Tirone David, the surgical approach involves double valve replacement using pericardial or Dacron patches to reestablish “neoaortomitral continuity” . This prThe literature and guidelines on the surgical management of infective endocarditis are based mainly on observational studies, given the difficulty in designing randomized trials in such a complex setting often present in urgent contexts. Due to the varying anatomical and clinical scenarios, heart teams are often brought to difficult decisions on the most appropriate strategy to adopt; moreover, the best choices are made through a shared decision-making process that should include the patient too. Decision making should take into account the localization and extent of the infection, patient preoperative status and comorbidities, and the choice of the best timing for surgery. Special relevance should be given to timing, which influences the risk of neurological complications and the extent of the infection, which, in turn, have a strong impact on post-operative outcomes and mortality rates. Whenever possible, surgeons should prefer a repair strategy over replacement in order to avoid the insertion of prosthetic material into infected tissue, limit the extent of the infection process, and better preserve ventricular function. Another important key step is the choice of the prosthesis or conduit. To date, guidelines do not support the selection of one substitute over another, and the selection of the most appropriate valve replacement strategy or conduit should consider the longevity of the substitutes, especially when biological, the potential recurrence of infection, and the risk of redo surgery. Surgeons should be able to maneuver and master all the reconstructive techniques described in the literature in order to manage all possible anatomical and pathological settings, particularly in consideration of the recent and future rise in cardiovascular device implantation and the consequent need for removal in case of endocarditis.


One of the most important complications of endometrial tumors, especially in UCS, is venous thromboembolism (VTE), with an incidence of 8.1%.6 Magnetic resonance imaging (MRI) is the best imaging modality for staging. Furthermore, it shows a typical high enhancement with a “spotty” distribution, which may suggest bleeding and is a distinct hallmark of carcinosarcoma.7While Trans-Vaginal Sonography (TVS) is the first-line method for the assessment of UCS, as it can detect neoformations of the myometrium, diagnosis can usually be made by the histopathological examination of targeted endometrial biopsies, possibly associated with hysteroscopy.8 the management of UCS requires a multimodality treatment comprised of surgery, systemic therapy, and radiotherapy. The estimated 5-year survival rate ranges from 33 to 39%, but the recurrence rate remains high.8Depending on the histopathologic assessment of the tumor (depth of invasion and presence or absence of metastases) and clinical presentation,Histopathologic examination of the mass revealed features of carcinosarcoma consisting almost entirely of a sarcomatous component and small foci of endometrioid- type adenocarcinoma, with neoplastic embolization of the intraparietal venous vessels. An inflammatory infiltrate associated with marked tumor necrosis was also noted  and 1D. At the end of all investigations, the cause of death was identified as massive pulmonary arterial thrombosis in a subject with uterine carcinosarcoma.For completeness, we also considered peritonitis and sepsis as possible co-participation in the cause of death. However, we considered this hypothesis unlikely based on the macroscopic and microscopic findings. Specifically, the peritoneum, abdominal viscera, and serosa were shiny, without fibrinous deposits, and of normal consistency. The purulent-looking material appeared free and not adherent to the abdominal wall and intestinal loops, as would be the case with recent extravasation, and was not organized. The histologic findings confirmed these considerations, which revealed no evidence of septic embolism. Overall, there were no postmortem findings suggestive of peritonitis and sepsis. Had the massive and acutely fatal pulmonary arterial thrombosis not occurred, local or systemic septic complications most likely could have developed.The case was considered of interest because of the rare neoplasm, its size, and the very advanced stage of the disease. Another peculiarity was that one of the most lethal direct complications of this neoplasm, pulmonary arterial thrombosis, was observed. Unfortunately, the absence of family members and health information does not allow further clinical considerations, but the severity of the disease found is glaringly the result of neglected and untreated disease. This case demonstrates that such scenarios are still possible today, despite the increased importance of prevention campaigns. In this context, the observed anatomopathological findings are crucial as they enrich the knowledge of uterine carcinosarcoma, and their images may help forensic pathologists who have not previously encountered this rare disease.