Samples from 2950 teenagers aged 12–18 years are collected for the analysis of biomarkers for phthalates, Hexamoll® DINCH, and per- and polyfluoroalkyl substances (PFASs), and samples from 3522 adults aged 20–39 years are collected for the analysis of cadmium, bisphenols, and metabolites of polyaromatic hydrocarbons (PAHs). The children’s group consists of 50.4% boys and 49.5% girls, of which 44.1% live in cities, 29.0% live in towns/suburbs, and 26.8% live in rural areas. The teenagers’ group includes 50.6% girls and 49.4% boys, with 37.7% of residents in cities, 31.2% in towns/suburbs, and 30.2% in rural areas. The adult group consists of 52.6% women and 47.4% men, 71.9% live in cities, 14.2% in towns/suburbs, and only 13.4% live in rural areas. The study population approaches the characteristics of the general European population based on age-matched EUROSTAT EU-28, 2017 data; however, individuals who obtained no to lower educational level (ISCED 0–2) are underrepresented. The data on internal human exposure to priority chemicals from this unique cohort will provide a baseline for Europe’s strategy towards a non-toxic environment and challenges and recommendations to improve the sampling frame for future EU-wide HBM surveys are discussed.Human biomonitoring has become a pivotal tool for supporting chemicals’ policies. It provides information on real-life human exposures and is increasingly used to prioritize chemicals of health concern and to evaluate the success of chemical policies. Europe has launched the ambitious REACH program in 2007 to improve the protection of human health and the environment. In October 2020 the EU commission published its new chemicals strategy for sustainability towards a toxic-free environment. The European Parliament called upon the commission to collect human biomonitoring data to support chemical’s risk assessment and risk management. This manuscript describes the organization of the first HBM4EU-aligned studies that obtain comparable human biomonitoring (HBM) data of European citizens to monitor their internal exposure to environmental chemicals. The HBM4EU-aligned studies build on existing HBM capacity in Europe by aligning national or regional HBM studies. The HBM4EU-aligned studies focus on three age groups: children, teenagers, and adults. The participants are recruited between 2014 and 2021 in 11 to 12 primary sampling units that are geographically distributed across Europe. Urine samples are collected in all age groups, and blood samples are collected in children and teenagers. Auxiliary information on socio-demographics, lifestyle, health status, environment, and diet is collected using questionnaires. In total, biological samples from 3137 children aged 6–12 years are collected for the analysis of biomarkers for phthalates, HEXAMOLL The presence of chemical pollutants in our environment is ubiquitous and part of our modern way of life . Some ofIn 2017 the European Human Biomonitoring Initiative HBM4EU) was launched with the ambition to coordinate and advance human biomonitoring in Europe. The project is a joint effort of 30 European countries, and the European Environment Agency, co-funded by the European Commission under Horizon 2020 [EU was laSince some European countries already have a recurrent HBM program, i.e., Germany , Belgium® DINCH, flame retardants, per- and polyfluoroalkyl substances (PFASs), polycyclic aromatic hydrocarbons (PAHs), bisphenols and cadmium (from the first list of priority substances) and pesticides, arsenic species, UV filters (benzophenones), mycotoxins and acrylamide (from the second list of priority substances). The resulting HBM data indicate the present chemical exposure of European citizens . It can be used to identify (sub)populations at risk and highlight inequalities, to compare with exposure levels measured in internationally established HBM campaigns such as NHANES [In HBM4EU, a total of 18 chemical substance groups were prioritized over two rounds . In the s NHANES , CHMS [1s NHANES , KNHANESs NHANES , JECS [1s NHANES  or previs NHANES  and to is NHANES . All thiThe aim of the HBM4EU-aligned studies is to collect comparable internal exposure data for priority substances in a sample of the European population that is representative of sex  and includes individuals from cities, towns/suburbs, and rural areas, with different socio-economic status (SES), and recruited from the four geographical regions of Europe  as defined by the UN geoscheme. The population sample was selected by utilizing a sampling scheme designed to guide the inclusion of eligible studies. The scheme is based on the inclusion of 11 to 12 primary sampling units (PSUs) per age group , distributed proportionally to the number of inhabitants in the four geographical regions  of Europe, with a maximum contribution of 300 participants per PSU. The PSUs are HBM studies in European countries that fulfilled the preset inclusion criteria: (i) completed studies with available biobank samples, (ii) studies that were initiated before the start of the HBM4EU project but with sampling within the stipulated timeframe, (iii) new studies, adopting the HBM4EU protocols. Furthermore, samples had to be collected between 2014 and 2020, fall within the aforementioned age groups, analysis had to be performed in laboratories that successfully participated in the HBM4EU QA/QC program , and theResults will be stratified according to sex, residence’s degree of urbanization, and educational level of the household. Therefore, additional criteria were set for PSUs to contribute with a 50:50 ratio of male and female participants, with individuals living in rural areas, in towns/suburbs, and in cities, and with at least 10% of individuals from low, medium, and high educational level. The residential area of participants  was characterized by a high, medium, and low degree of urbanization according to the DEGURBA classification from EUROSTAT (2018) . EducatiThe following section includes an overview table of the studies that were selected as PSUs and participated in the HBM4EU-aligned studies. In total, 25 studies from 21 countries contributed to the HBM4EU-aligned studies. Some studies provided samples for more than one age group, e.g., ESTEBAN, GerES V, SLO CRP, CROME, and NEB II. Furthermore, some of the studies had a larger sample size than the maximal contribution of 300 samples; in those cases, a selection of 300 individuals was performed following a step-wise selection procedure. In short, the total study population was stratified into mutually exclusive subgroups followed by a random selection of the participants adhering to the subgroup proportions defined , degree of urbanization (at least 10% of each of the three levels should be represented), educational level (at least 10% of each of the three levels should be represented), sampling season (25% of each season), age .Contributing studies are listed alphabetically in The data from the PSUs are pooled into a European sample of children, teenagers, and adults. The baseline characteristics of the sampled population of each age group  are described per study (PSU) , per EurAn overview of the biological specimens collected and used within the scope of the HBM4EU-aligned studies is presented in ® DINCH is available for 2880 children and 2799 teenagers. Data on BFRs and OPFRs are available for 711 and 1770 children respectively. Data on PFASs exposure are available for 1957 teenagers and data on biomarkers for bisphenols, Cd and PAHs are available for 2756, 2510, and 2609 adults, respectively.A detailed overview of the individual studies and the number of participants with biomarker data available for a specific priority substance is presented in ® DINCH metabolites: OH-MINCH and cx-MINCH; 10 BFRs: TBBPA, DBDPE, 2,4,6-TBP, BDE-47, BDE-153, BDE-209, DP-syn, DP-anti, α-HBCD, γ-HBCD, and 4 OPFRs: DPHP, BDCIPP, BCEP, and BCIPP; 12 PFASs: PFPeA, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFBS, PFHxS, PFHpS and PFOS ; 3 bisphenol substances: BPA and substitutes BPS and BPF; 13 PAHs: 1-naphthol, 2-naphthol, 1,2 DHN, 2-FLUO, 3-FLUO, 9-FLUO, 1-PHEN, 2-PHEN, 3-PHEN, 4-PHEN, 9-PHEN, 1-PYR, 3-BaP, and cadmium. To safeguard the comparability of the data, analysis had to be performed in laboratories that successfully participated in the HBM4EU QA/QC program [In total exposure to the following 60 exposure biomarkers was assessed: 15 phthalate metabolites: MEP, MBzP, MiBP, MnBP, MCHP, MnPeP, MEHP, 5OH-MEHP, 5oxo-MEHP, 5cx-MEPP, MnOP, OH-MiNP, cx-MiNP, OH-MiDP, cx-MiDP; 2 HEXAMOLL program . The lab program ,43. As aThe HBM4EU-aligned studies build on existing capacity in Europe by aligning HBM studies in Europe. As a result of this approach, studies with different designs and degrees of representativeness were combined. In total 9609 European citizens  were sampled between 2014 and 2021. Twenty-five studies contributed to the HBM4EU-aligned studies. Sixty-eight percent of the studies were initiated or conducted before HBM4EU and biobanked samples were made available to the project, 32% of the studies were initiated specifically for HBM4EU such as in Greece, Czech Republic, Iceland, Croatia, Portugal, and Switzerland and implemented the guideline protocols developed under HBM4EU . The HBMThe participation rate strongly varied among the contributing studies ranging from 12.5% to 75.7%. Seventy percent of the studies offered a summary of the group results and a personal report with the participants’ individual results as an incentive, one study presented the results to participants on the group level only. In some European countries, e.g., Finland, the provision of monetary incentives is not allowed. Furthermore, it can be noticed that those studies with a higher participation rate provided additional incentives in the form of a small present .The children of the HBM4EU-aligned studies were recruited in 12 different PSUs (European countries). Teenagers and adults were recruited in 11 different European countries. The baseline characteristics of each age group  are described for the total sampled population The HBM4EU sampled population of children has slightly more boys (50.4%) than girls (49.5%), which reflects the European population based on EUROSTAT 2017 data (boys: 51.3% vs. girls: 48.7%) . The HBMThe residence’s degree of urbanization, based on the DEGURBA classification by EUROSTAT , is simiThe educational level of the household of children and teenagers was compared to the educational level of the European population from 15–64 years as reported by EUROSTAT (EU-28 population in 2017). Moreover, 26.0% of Europeans of that age group attained no to lower secondary education, 46.1% upper secondary to post-secondary non-tertiary education, and 27.9% tertiary education or higher. Most of the sampled children and teenagers live in households with one of the parents attaining tertiary education or higher (ISCED level ≥5 for 58.4% of the children and 54.5% of the teenagers) . Only 4.It was preset that the children must be between 6 and 11 years of age. However, 3.9% of the children sampled are 12 years of age. PCB cohort, ESTEBAN, and GerES V-sub (unweighted) have 12 years old participants included . Some chThe teenagers’ age group was predefined from 12 to 19 years; however, no 19-year-old individuals are present in the sample. Similar to the children group, not all ages are equally represented in the teenagers’ group. Some studies cover the entire age range from 12–18, whereas other studies such as FLEHS IV and BEA include a narrower age range see . This leThe adults age group was predefined from 20 to 39 years of age because it provides a more homogeneous group with a more similar health status (reproductive age group) and it mirrors the age stratification used in NHANES and CHMS . The samples were collected between 2014 and 2021 with most samples collected in more recent years (2017–2021). Samples from 2014–2016 were only obtained in Western Europe while samples from Eastern Europe covered only 2017 and 2019 . Differehttps://doi.org/10.5281/zenodo.6414615. Questionnaires had different components and were differently administered . In some studies, different collection methods were applied for separate questionnaire modules. An overview per study is available in https://doi.org/10.5281/zenodo.6598404); HBM4EU Harmonized Codebook Children-Aligned studies|Zenodo (https://doi.org/10.5281/zenodo.6598519); HBM4EU Harmonized Codebook Teenagers-Aligned studies|Zenodo (https://doi.org/10.5281/zenodo.6598532).As part of the HBM4EU project, new harmonized questionnaires have been developed based on knowledge and experience in different EU countries . As the HBM4EU-aligned studies combine ongoing and newly planned studies, the questionnaires used by the studies differ. Four studies, that were still in the planning phase, adopted the HBM4EU questionnaires or developed their own questionnaire based on the HBM4EU questionnaire . The HBM4EU questionnaires are available online: https://www.hbm4eu.eu/eu-hbm-dashboard/) and IPCHEM (https://ipchem.jrc.ec.europa.eu/), where it can be accessed. Data sharing of individual-level data is possible upon request.For each of the studies included in the HBM4EU-aligned studies, metadata are available in IPCHEM, the European Commission’s Information Platform for Chemical Monitoring. The summary statistics  of the exposure biomarkers will be integrated into the openly accessible online European HBM dashboard , 2950 teenagers (12–18 years), and 3522 adults (20–39 years) which is comparable to the general European population . The HBM4EU-aligned studies provide a large coherent dataset that allows making robust conclusions regarding internal exposure to pollutants in European children, teenagers, and adults, as well as stratified by sex, educational level, degree of urbanization, and European region. Furthermore, the quality and comparability of analytical results are guaranteed through the extensive QA/QC scheme organized as part of HBM4EU . WorkingThe HBM4EU-aligned studies dataset combines information on socio-economic characteristics, health status, lifestyle, food habits, and residential environment, from the different studies into a large EU-wide and comprehensive dataset for the interpretation of internal exposure levels. The post-harmonization approach applied, is a time-consuming process and also presents some limitations. For example, information on the consumption of canned food items was available for only 4/11 studies in adults. Missing variables in some studies will reduce the sample size available for the analysis of exposure determinants. Upfront alignment of questionnaires in future surveys will increase the comparability and use of the European pooled dataset.Pooling data from different studies increases the sample size and statistical power to study exposure–effect associations. For a European study that is only partly financed with EU funds, and which requires financial commitments from the member states, it is not feasible to impose a fully harmonized questionnaire. It was emphasized by the participating countries that flexibility with regard to questionnaires is necessary, on the one hand, to guarantee continuity with previous campaigns, for those countries that already have a recurrent HBM program, but on the other hand, also to include culturally and nationally bound information. As a feasible solution, a basic list of variables must be defined that can be retrieved in a harmonized way in all studies.Another challenging obstacle is to enhance comparability of the exposure levels measured in different urine sample types . Exposure biomarkers in urine samples can be reported on a volume basis but can also be standardized for urinary dilution. Several methods are available; however, there is no consensus on the most appropriate method to account for the variations in dilution among spot urine samples . The useThe HBM4EU-aligned studies dataset provides a good picture of the internal exposure of European citizens. However, there are some points that can be improved. Individuals with lower secondary education attainment are underrepresented in our population sample. This has been observed previously in epidemiological studies . Future Comparison of results from the individual contributing studies (PSUs) should be performed with caution as not all studies are representative on the national level and therefore results may not in all cases be generalized to the particular country in which they were collected.Finally, combining HBM studies in Europe also allowed HBM experts from different European countries to exchange information on best practices. The resulting network is of great value to support capacity building and future harmonization of HBM studies in Europe such as under the new partnership on chemical risk assessment (PARC).With the completion of the HBM4EU-aligned studies, quality-assured human biomonitoring data will be available to support policies and the upcoming chemicals strategy for sustainability and for a non-toxic environment . The resIn a later phase, additional biomarkers will be measured in the samples of the HBM4EU-aligned studies, i.e., pesticides  and acrylamide  in children and adults, arsenic species (As(III), As(V), arsenobetaïne, DMA, MMA and total As) in teenagers, UV-filters  in teenagers and adults and mycotoxins  in adults. These additional biomarkers are included in the second list of HBM4EU priority substances.Two more studies joined the HBM4EU-aligned studies for these additional analyses: ORGANIKO  and RAV-MABAT  in children and adults. Overall, the adopted approach results in a European population sample of 3137 children (6–12 years), 2950 teenagers (12–18 years), and 3522 adults (20–39 years) that is representative of sex and has European wide coverage. In most sampling sites, it was difficult to recruit children and teenagers from lower-educated households and adults attaining lower secondary education resulting in underrepresentation in the HBM4EU sample. It is anticipated that the HBM4EU-aligned studies will facilitate qualified statements regarding the internal exposure of Europe’s children, teenagers, and adults to HBM4EU priority substances, stratified by sex and European region. However, when comparing exposure data from the individual contributing studies (PSUs), caution is needed for the interpretation at the country level as not all studies are nationally representative. In addition, heterogeneity among PSUs in sampling years, age, season of sampling, and number of subjects within an age group should be considered if exposure data between studies are compared. More upfront alignment will improve the potential of the European HBM dataset to extrapolate exposure results to the entire European population. To compare exposure levels between European countries, stricter criteria will need to be applied to achieve an equal age distribution per PSU, a shorter time frame, and representativeness on the national level for the collected subsample per PSU. In practice, these criteria are difficult to achieve within the context of alignment of HBM studies where the studies are only partially funded through European projects, and thus national or regional interests in terms of target population and time frame cannot simply be ignored. Gradually, these points can be improved by streamlining national/regional HBM programs.With the chemicals strategy for sustainability, the European Parliament called upon the commission to collect HBM data to support chemicals risk assessment and risk management. It underlines the need for a clear commitment to securing funds for HBM and environmental monitoring of impacts and exposure to chemicals in order to improve chemical risk assessment and management, as well as for improved sharing and use of local, regional, national, and EU-level monitoring data between countries, sectors, and institutions in relevant policy areas  . This wi


The rapid development of artificial intelligence (AI) has led to the emergence of many new technologies in the healthcare industry. In dentistry, the patient’s panoramic radiographic or cone beam computed tomography (CBCT) images are used for implant placement planning to find the correct implant position and eliminate surgical risks. This study aims to develop a deep learning-based model that detects missing teeth’s position on a dataset segmented from CBCT images. Five hundred CBCT images were included in this study. After preprocessing, the datasets were randomized and divided into 70% training, 20% validation, and 10% test data. A total of six pretrained convolutional neural network (CNN) models were used in this study, which includes AlexNet, VGG16, VGG19, ResNet50, DenseNet169, and MobileNetV3. In addition, the proposed models were tested with/without applying the segmentation technique. Regarding the normal teeth class, the performance of the proposed pretrained DL models in terms of precision was above 0.90. Moreover, the experimental results showed the superiority of DenseNet169 with a precision of 0.98. In addition, other models such as MobileNetV3, VGG19, ResNet50, VGG16, and AlexNet obtained a precision of 0.95, 0.94, 0.94, 0.93, and 0.92, respectively. The DenseNet169 model performed well at the different stages of CBCT-based detection and classification with a segmentation accuracy of 93.3% and classification of missing tooth regions with an accuracy of 89%. As a result, the use of this model may represent a promising time-saving tool serving dental implantologists with a significant step toward automated dental implant planning. The placement of dental implants to restore missing teeth is now recognized as a standard dental procedure . A priorWith the widespread use of dental implants nowadays, automatic detection of missing tooth areas is necessary to develop an automatic implant plan. Unfortunately, due to the lack of automated technologies, clinicians had to plan to place dental implants manually, which is not efficient as it requires more time and effort ,7. ThereOne of the main types of machine learning based on artificial neural networks is deep learning (DL), which uses multiple layers of processing to extract knowledge and insight from the data. DL has been applied for several medical applications, such as computer-aided diagnosis and surgical planning, disease classification, tumor detection, and anatomic modeling . In dentThis paper further extends the research of applying artificial intelligence and deep learning in dentistry. It aims to enhance the 3D missing tooth area planning using pretrained deep learning models by automatically detecting and classifying the CBCT images and passing only those which need further planning.Nowadays, healthcare is one of the basic needs of all people, and smart healthcare has become essential to provide efficient services for several healthcare sectors that improve the quality of people’s lives. Different advanced technologies have been recently used in smart healthcare, which includes artificial intelligence (A.I.), machine learning (ML), deep learning (DL), Internet of Things (IoT), big data analytics, medical sensors, and others . For insAnother important application of A.I. in dentistry is the automated detection of teeth and small edentulous regions. In these applications, cone beam computed tomography (CBCT) images of different patients  were used for this purpose. Gerhardt et al.  used theSimilarly, Zhang et al.  and ChenIn , Liu et Similarly, in , Kurt BaDeep learning methods have recently been used for dental implant planning to detect missing tooth regions. A dataset of 455 panoramic radiographic images was used in  to annotIn this paper, several pretrained deep learning models were applied for enhancing 3D missing tooth area planning, including the AlexNet, VGG16, VGG19, ResNet50, DenseNet169, and Mo-bileNetV3 models.In this study, deep learning models were trained to detect and classify the missing teeth region from a dataset segmented from CBCT images of confidential patients who regularly visited the Taibah University dental hospital. The experimental part of this study was implemented jointly at the Faculty of Dentistry and the College of Computer Science and Engineering at Taibah University, K.S.A. Generally, the proposed approach is divided into three main stages: the data acquisition stage, the data preprocessing and segmentation stage, and the feature extraction and classification stage. To ensure that the proposed model was able to classify the images correctly, the collected images were of different patients of different ages. As a result, 500 CBCTimages were collected. Since the images were in 3D dimension, an expert with more than 10 years of professional experience in dental implant planning was to be responsible for slicing and extracting 2D X-ray images from the original CBCT images. The professional dentist was also asked to manually annotate the sliced/extracted images as well as manually segment the missing tooth regions and positions. As a result, the obtained images were used as ground-truth masks for training the proposed deep learning models. In the second stage, the dataset along with the masks, were fed to the segmentation stage, in which augmentation was also performed. In this study, we designed two experiment types based on the presented segmentation techniques. For this purpose, the U-Net model was used in the segmentation stage. In terms of classification models, several deep learning architectures were implemented and tested, including the AlexNet, VGG16, VGG19, ResNet50, DenseNet169, and MobileNetV3 models. These models were used to classify the resulting binary masks from the segmentation stage well as to classify the original images without segmentation. As the pretrained DL models are originally capable of classifying up to 1000 different classes, the last fully connected layer of these models was replaced so that it can be capable of classifying the binary classes of the used dataset. We also compared the output of the proposed models to the ground-truth dataset that was annotated by the domain expert. Generating a real dataset of images, which are more than confidential patients’ CBCT images representing different missing tooth positions of patients with different age ranges, the CBCT images were officially obtained from patients between 16 and 72 years of age. The research ethics committee, College of Dentistry, Taibah University, Madinah, Saudi Arabia, approved this study protocol . Due to the non-interventional retrospective design and anonymous analyzed data, the institutional review committee waived the requirement for individual informed consent.This study screened scans from patients who had visited Taibah University Dental Hospital (TUDH) and had undergone CBCT imaging between 2018 and 2022. CBCT images of patients between 16 and 72 years of age were included. Because image quality is an important factor affecting the performance of deep neural networks in computer vision tasks, poor-quality images were excluded from the collected dataset to avoid impacting the effectiveness of the applied deep learning models and their results. Therefore, images belonging to patients with a history of trauma, pathology, surgical intervention congenital syndrome, fracture, or any other foreign body (which produced artifacts in the image) were excluded from the study. Moreover, blurred images, such as those containing an ill-defined and unclear definition of bony borders, were excluded from the study. Of 890 screened scans, 500 images fulfilled the eligibility criteria. Anonymous code was given to each subject, all the data was saved in an excel sheet with a security password, and the computer was secured with a password. Notably, visualizing anatomical structures depends on technological parameters such as image resolution and CBCT reconstruction time. In this study, all CBCT scans performed in the TUDH adhered to a standardized scanning protocol with the same machine  at the same specified device settings  as a change in any of these factors may affect the visualization of anatomical structures.Images were reconstructed in C.S. 3D Imaging Software . The head positions were standardized anteroposteriorly and sagittally according to a standard method. From CBCT volumes, the panoramic images were reconstructed by selecting a custom focal trough that passed through the lingual cusps of the maxillary teeth and extended posteriorly to the condyles. .Algorithm 1 Conversion of CBCTimages to X-ray Images1.  Input: 3D cone beam CBCTdataset2.  Output: X-ray images3.  Begin4.5.  for all do:6.    if image_quality is poor Then:7.8.    else:9.10.11.12.13. end forReturn X-ray imagesThis conversion process is summarized in Algorithm 1.The X-ray images dataset obtained by applying algorithm 1 was passed to the next stage. In the data preprocessing phase, the images were standardized, and all panoramic dental X-ray images were resized to 512 × 512 pixels and normalized in the range of 0 to 1.After preprocessing, the datasets were randomized and divided into 70% training, 20% validation, and 10% test data, as shown in A total of six pretrained CNN models were used in this study, which include AlexNet, VGG16, VGG19, ResNet50, DenseNet169, and MobileNetV3. Each of these models is described in detail in the following subsections.AlexNet is a CNN model proposed by Krizhevsky et al. . It has VGG16 is also a type of CNN model that consists of 21 layers. Out of these, there are only 16 weight layers with learnable parameters. Precisely, the model consists of 13 convolutional layers, 3 fully connected layers, and 5 max pooling layers . The VGGThis network has about 138 million parameters, which is quite large. The original VGG16 architecture and its configuration settings are depicted in VGG19 is a variant of the VGG16 model in which three new convolutional layers were added up to the previous VGG16 model. There are 19 layers (16 convolution layers and 3 fully connected), 5 max-pooling layers, and 1 SoftMax layer. 9 floating point operations. Since the vanishing gradient problem is common in CNN-based models during backpropagation, the ResNet-based model uses a “skip connection” to overcome such a problem, as shown in ResNet50 is a variant of the ResNet model, which has 48 convolution layers along with 1 MaxPool and 1 average pool layer. It has 3.8 × 10A dense convolutional network (DenseNet) is an expansion of the Residual CNN (ResNet) architecture. Indeed, there are several DenseNets such as, DenseNet121, DenseNet169, and DenseNet201. In this paper, the DenseNet169 was used. As indicated in its name, the architecture of this model contains 169 layers. The reason for this choice is due to the ability of DenseNet169 to handle the vanishing gradient problem compared to the other versions . In addiThe MobileNetV3 proposed by Howard et al.  is an enThe proposed approach is implemented on a machine that meets the following specifications: Intel(R) Core (T.M.) i9-10980HK CPU @ 2.40 GHz 3.10 GHz processor and a 32 GB RAM running Windows 11 with an NVIDIA GeForce MX graphics card. The Jupyter Notebook provided with Anaconda distribution  and KeraSeveral metrics were used to evaluate the proposed models’ performance depending on the model type . Among aIn addition, we use the Matthews correlation coefficient (MCC) to measure how predictions match labels. The MCC is defined as follows:This section summarizes the findings of the experiments performed on the dataset by applying the U-Net segmentation model and without segmentation.The U-net model was trained and validated on a dataset of 120 images, and then the test set was used to evaluate the overall performance. The confusion matrix presented in This section presents the performance of the pretrained DL models  using various performance metrics. It is important to mention that the obtained images from the segmentation stage were fed to the DL classifiers. Since the main goal of this paper is to help dentists in future planning for placing dental implants, we need models that can predict the missing position of teeth more accurately. Thus, the highest F1-score of class 1 (the missing teeth class) indicates that the model detects the position of missing teeth more accurately. Regarding the normal teeth class, the performance of the proposed DL models in terms of precision was above 0.90. The obtained results of these deep learning models (such as DenseNet169) show that they overcome the performance of the models proposed in the previous studies. For instance, the precision values of the detected missing tooth regions were 95%, 90%, and 59.09% in ,22, respThis subsection summarizes the findings of the experiments performed on the dataset without applying any segmentation model. The results in The Matthews correlation coefficient (MCC) shows that AlexNet, ResNet50, and MobilenetV3 failed to predict the class label, whereas DenseNet169, VGG19, and VGG19 were, to some extent, capable of predicting the class label as shown in The previous sections showed that DenseNetV3 could predict the teeth’s class label more accurately than the other models. As a result, we chose it as the recommended approach for predicting missing teeth. However, to show that the choice is statistically significant, the statistical significance of the results was measured using the Mann–Whitney–Wilcoxon test and the Wilcoxon signed-rank test. For this purpose, we formulated the null hypothesis, cant See .Several pretrained deep learning models were implemented in this study, including AlexNet, VGG16, VGG19, ResNet50, DenseNet169, and MobileNetV3, and their performance in detecting and classifying the missing tooth regions was also investigated in terms of different performance evaluation metrics. In addition, two types of feature extraction were investigated. The feature extraction was based on the U-Net model, and the other type used the bare image without segmentation. A binary classification-based dataset was obtained to facilitate the process of identification of the missing teeth bone area. For future planning and implanting of the predicted missing tooth areas, a domain expert verified the resulting dataset manually.https://labelstud.io/, accessed on 3 October 2022). An improved algorithm and more data will make implant placement more automated in the future.The experimental results showed that the segmentation process played an essential role in enhancing the performance of the pretrained DL models. Among the proposed DL models, the finding showed the superiority of DenseNet169, with an F1-score of 0.94 for the missing teeth class and 0.93 for the class of normal teeth class. The use of this model may represent a promising time-saving tool serving dental implantologists with a first step toward automated dental implant planning. In addition, this study also constructed a ground-truth dataset for tooth instance segmentation and missing tooth region detection in panoramic radiographic images which were officially obtained, sliced, and extracted and reviewed by an expert with more than 10 years of professional experience in dental implant planning. The domain expert manually annotated the X-ray images to obtain ground-truth masks using the well-known annotation tool called Label Studio (


Longevity, as a complex life-history trait, shares an ontogenetic relationship with other quantitative traits, such as epigenetic and environmental factors. Therefore, it is important to identify environmental factors that may modify the epigenome to establish healthy aging. This study explored the association between tap drinking water and longevity in Cilento, Italy, to understand whether trace elements in local drinking water may have an influence on old, nonagenarian, and centenarian people and promote their health and longevity. Data on population and water sources were collected through the National Demographic Statistics, the Cilento Municipal Archives, and the Cilento Integrated Water Service. Ordinary least squares (OLS) regression and a geographically weight regression (GWR) model were used to study the spatial relationship between the explanatory and outcome variables of longevity. The results of the study showed that the prevalence of longevity is concentrated in the central, northern and southeastern areas of the territory and that some trace elements present in tap water may contribute to local longevity in Cilento. Specifically, all Cilento municipalities had alkaline tap water, and the municipalities with the highest longevity concentrations had higher alkalinity levels than the other municipalities, soft to medium-hard water hardness, an amount of total dissolved solids equivalent to the level of excellent water, lower amounts of sodium, adequate iron concentration, and adequate dietary intake of manganese per day.  There has long been a global desire to be able to achieve greater longevity, not only in terms of overall lifespan, but especially regarding the possibility of increasing the healthy part of the life. To activate the strategies necessary to achieve this goal, a whole range of factors and the complex interactions among them must be considered. Many studies have shown that longevity is closely linked to genetic factors ,2,3,4 anEpigenetics (a term coined in 1942 by Waddington) stufies the interconnected concatenations of factors that take place in the space between the genotype and phenotype. Environmental factors can trigger a series of changes in physiological developmental patterns through a process termed developmental plasticity, causing an individual to produce alternative phenotypes throughout life, and these changes can have beneficial effects on health . In recent years, among the macro-environmental factors, special attention has been paid to the relationship between drinking water and physical health . Water iSeveral studies have examined potential human health risks from As, F and heavy metals in low-quality groundwater ,18,19. SThe relationship between the characteristics of major drinking water elements in some typical longevity areas has been demonstrated by a number of studies ,30,31.In agreement with Hao et al. , a positTherefore, the quality of drinking water from different natural environments could have a direct impact on local human health and longevity ,31,32.Despite numerous studies on the topic of longevity and correlations with various environmental factors, to the best of our knowledge, no research conducted in Cilento or other Italian regions has investigated the possible relationship between longevity and trace elements in drinking water at the municipal level. Therefore, we hypothesized that some physicochemical properties of drinking water may be protective factors for longevity.The purpose of this study was to explore the association between tap drinking water and longevity in Cilento and to understand whether trace elements in drinking water can have a direct influence on local health and longevity and improve the living standards of the old, nonagenarians and centenarians.Geographically, Cilento is a subregion of the Campania region of southern Italy, in the territory of the province of Salerno, and has been declared a UNESCO World Heritage Site. The territory of Cilento covers an area of about 490,000 hectares and includes 102 municipalities. From the environmental point of view, it is a heterogeneous territory, characterized by the integration of different landscape types, including coastal, hilly and mountainous areas  and moutCilento has a population of about 278,093 and maintains relatively high proportions of long-lived people , with a ratio of 40.31/1000 inhabitants . The preDemographic data were collected through the Cilento Municipal Archives in the years 2021–2022 and compared with ISTAT demographic statistics . Longevi2+) and magnesium ions (Mg2+) [+), nitrate (No3−), sulfate (SO4), chloride (Cl), iron (Fe2+), manganese (Mn2+), and nickel (Ni)  , whose ls (Mg2+) ,45,46,47s (Mg2+) ; and catkel (Ni)  [15,45,4In this study, first, the municipalities in Cilento with the highest concentrations of long-lived people, including old, nonagenarians, and centenarians, were identified through geomaps; second, the annual means of the most significant physicochemical, mineral and metal parameters of tap drinking water served this region were examined, evaluating data from municipalities fed by the same catchment sources. Elements with zero values were not evaluated; the parameters were then geomapped and clustered to assess their significance at the spatial level; finally, the influence that the different properties of tap drinking water had on longevity was highlighted through ordinary least squares (OLS) and geographically weight regression (GWR) models. This study used STATA software  for descBased on the new longevity population data a–d, we cThe highest 85+ ratio was recorded in Sacco (13.1), Orria (10.9), Piaggine (10.9), Campora (10.6), and Magliano Vetere (10.3), while the lowest was recorded in Capaccio (1.0), Casal Velino (1.0), Novi Velia (2.5), and Agropoli (3.2) a. The highest 90+ ratio was recorded in Sant’Angelo a Fasanella (5.8), Sacco (5.7), Valle dell’Angelo (5.3), Piaggine (4.9), while the lowest was recorded in Capaccio (0.2), Casal Velino (0.2), Novi Velia (0.9), Castelnuovo Cilento (1) b. The highest centenarian ratio was recorded in Sacco (12.6), Perito Cilento (7.7), Pertosa (7.4), Campora (7.1), Sant’Angelo a Fasanella (7), Bellosguardo (6.7), while the lowest indices were recorded in Alfano (0), Romagnano al Monte (0), Rutino (0), Roscigno (0.1), Novi Velia (0.3), and Giungano (0.6) c. The highest CI% was recorded in Caselle in Pittari (9.3), Campora (8.3), Sacco (7.7), Moio della Civitella (7.1), while the lowest was reported for Albanella (0), Alfano (0), Casalbuono (0), Casaletto Spartano (0) d.Thus, we were able to state that the longevity indicators, according to the global autocorrelation values, were spatially clustered more than would be expected if the underlying spatial processes were random, so we rejected the null hypothesis. In fact, Moran’s Z-score I values indicated spatial autocorrelation at the 0.01 significance level for the 85+ ratio and for the 90+ ratio. No significance level was found for the centenarian ratio and centenarity index values .The descriptive statistics and spatial distribution of the tap water elements of the Cilento municipalities are shown in The tap drinking water in the 102 municipalities of Cilento falls within the WHO definition of fresh water .First of all, the water pH values in the various Cilento municipalities ranged from 7.4 to 8.3, which meant that the drinking water of this Southern region of Italy was all alkaline, and differentiated by the weakly to strongly alkaline level a. The mu2+ and Mg2+) [The TH (given by the concentration of Cand Mg2+)  of tap dThe TDS showed differences in levels among the 102 Cilento municipalities, with drinking water values ranging from excellent to poor c. +, No3−, So4 and Cl_ showed minimal spatial differences among the 102 Cilento municipalities , TDS (p = 0.003), iron (p = 0.02), nitrate (p < 0.001), chloride (p = 0.001).In addition, Moran’s I index was used to test for the presence of spatial autocorrelation and to identify whether case densities were randomly distributed in the study area. We found that longevity densities were clustered according to certain elements of tap drinking water, such as water pH , which causes many diseases such as cardiovascular problems, diabetes, kidney dysfunction, and neural diseases. According to our results, water varied between soft and medium-hard in the Cilento municipalities that hosted the long-lived groups; the regression outcome showed a significant inverse relationship between the long-lived  and hard water. In agreement with our results, many studies have reported an inverse relationship between drinking water hardness and cardiovascular disease [An important etiological factor worldwide is hard water . These results indicate that iron is an essential trace element for life, but can generate toxicity under overloaded conditions. According to Baschant et al. , the acc/L, respectively [In Cilento, with regard to heavy metals in the water, no traces of arsenic, lead, mercury, cadmium, and copper were detected, but only nickel was evident, with a minimum concentration of 1.7 μg/L, a parameter well below the values recommended not only by NS and WHOGV but also by the European Food Safety Authority, which established a tolerable daily intake (TDI) of 13 μg/L body weight. According to data reported in the United States on tap drinking water, nickel concentrations ranged from 0.55 to 25 μg/L; in Australia, nickel concentrations in drinking water were generally <10 μg/L , and, acectively . These dOf note, a trend of positive association was observed between manganese in Cilento tap drinking water and the centenarity index. This result is in agreement with the US National Research Council (NRC), which has established a safe and adequate dietary intake (ESADDI) of 2–5 mg/day of Mn for adults . Further2+ and Mg2+).On the basis of the data, this study has some limitations. First, longevity is the result of a combination of genes, the natural environment and socioeconomic status. Therefore, other factors could interfere with the relationship between the water environment and longevity. Second, it is not known whether the conclusions obtained in the Cilento region can be applied to other longevity areas, due to their different geological conditions, climate, etc. Therefore, it is of great importance to study the effects of tap drinking water on longevity based on the common characteristics of drinking water quality in multiple longevity areas. Furthermore, we did not evaluate the influence of Cilento tap water on common diseases in the region. In addition, the water monitoring data provided by the Cilento Water Service Company lacked some trace elements, such as potassium, zinc, and individual calcium and magnesium data, as we only had data on overall water hardness (sum of CaFurther research will be needed in the future to establish a holistic assessment between different areas of longevity in Cilento, tap water quality and common diseases in the region, including thorough in vivo research in mice.In conclusion, we can say, to the best of our knowledge, that this is the first study to investigate the possible relationship between longevity in Cilento and the elements present in tap water at the municipal level. The results of the study confirmed that there is a high prevalence of old, nonagenarians and centenarians in Cilento, concentrated in the north-central and southeastern areas of the territory, and that some elements in tap drinking water may contribute to local longevity. In particular, drinking water in the 102 Cilento municipalities was found to be alkaline and falls within the WHO definition of fresh water. Regarding heavy metals, no traces of arsenic, lead, mercury, cadmium and copper were detected, but only minimal concentrations of nickel, iron and manganese, well below the NS and WHOGV recommended values. The municipalities with higher longevity concentrations had higher alkalinity levels than the other municipalities, soft to medium-hard water hardness, total dissolved solids equivalent to excellent water levels, lower sodium concentrations, advantageous iron concentration, and an adequate dietary intake of manganese per day.


Surgery is an effective way for treating SFT, but it is often difficult to resect completely due to a large size, with a high recurrence rate and mortality rate after operation. Additionally, SFT is relatively resistant to chemotherapy, and there is a lack of effective systemic drug treatment. These lead to certain difficulties in the treatment of SFT. We report a case of a rare MSFT in the pelvic cavity. With a history of recurrence after two surgeries, this patient underwent surgical removal combined with  This approach can increase the radiation dose to the tumor target, and dramatically decrease the dose to surrounding normal tissues, showing great advantages of safety, minimal invasion, definite benefit, few complications, low level of radioactive contamination, and convenience for protection. In recent years, it has been used for treating solid tumors at various sites and has achieved good performance  is a rare spindle cell tumor originating from CD34-positive dendritic mesenchymal cells . It has formance –13. We r125I seed implantation was performed, in which 30 seeds (0.3 mCi) were implanted into the tumor bed near the right iliac vessels, with D90 of 62.0 Gy, and 32 seeds (0.5 mCi) into the tumor bed of the left pelvic cavity, with D90 of 58.0 Gy; the operation was smooth, and postoperative pathology came back as a recurrent low-grade MSFT. In August 2015, a residual tumor was observed on CT in the posterior wall of the bladder. On August 27, 2015, under the guidance of CT, 50 125I seeds (0.3 mCi) were placed percutaneously into the tumor in the left posterior wall of the bladder, with D90 of 64.8 Gy measured post implant. On September 21, 2015, under CT guidance, 28 125I seeds (0.3 mCi) were implanted into the tumor in the right posterior wall of the bladder, with D90 of 49.7 Gy measured post implant. Dose-volume histogram parameters were applied for the evaluation of target volume and organs at risk (OARs).The patient’s regular examinations after implants revealed a complete remission . On April 8, 2014, she underwent pelvic mass resection; postoperative pathology showed a borderline or low-grade malignant spindle cell tumor, consistent with SFT, and the immunohistochemistry results were as follows: Ki-67 (5% positive), Bcl-2 (-), Desmin (-), SMA (-), DOG-1 (-), CD68 (-), CD117 (-), S-100 (-), CD34 (blood vessels +), CD99 (+), and Calretinin (-). Two months later, her CT displayed a walnut-size mass each under the abdominal wall and in the vaginal stump, with no specific treatment. On June 29, 2015, the patient visited our hospital and had abdominal and pelvic CT examination, which indicated multiple space-occupying lesions in the abdominal wall and pelvic cavity (125I seeds (0.4 mCi) into the wall tumor, with D90 of 77.8 Gy. Her regular examinations thereafter demonstrated a complete remission all the way until October 2018, when CT displayed recurrent tumors in the abdominal wall and pelvic cavity. On October 16, 2018, with the help of CT guidance, 54 125I seeds (0.5 mCi) were embedded into the SFT (5.0×3.0×5.0 cm) under the right side of the bladder, with D90 of 97.6 Gy; on October 23, 2018, 30 125I seeds (0.5 mCi) were embedded into the SFT (3.6×1.5×3.0 cm) in the abdominal wall, with D90 of 101.3 Gy. The patient achieved a complete remission, no complications were found, and the brachytherapy was well tolerated by the patient, The patient had no recurrence of abdominal and pelvic tumors during the 4-month follow-up (In January 2016, CT showed that a tumor recurred in the abdominal wall, with a size of about 4.0×2.5×4.5 cm. On January 6, 2016, she underwent implantation of 29 The diagnosis of SFT mainly depends on the pathologic features and immunophenotypes. Histologically the tumor was composed of abundant and dense cells, which were separated by rope like collagenous fibrous stroma. The tumor cells were spindle to short-spindle shaped with marked nuclear atypia and increased mitotic activity. The tumor cells arranged in fascicular or swirl pattern. In focal areas, hemangiopericytoma-like structure, coagulative necrosis, focal hemorrhage and invasive margin were presented. MSFT is usually grossly indistinguishable from conventional forms, but it may also show a more irregular cut surface, with evidences of necrotic areas or infiltration of the nearest tissues . Immunoh125I seed implantation in MSFT, providing a novel solution to the treatment of the disease.Generally, the most effective treatment for SFT is surgical resection. However, in most cases, when patients feel discomfort and visit doctors, tumors have grown to large masses — beginning to press on adjacent organs to produce the warning symptoms — and there are usually abundant blood vessels and collateral circulation around the tumors, often making surgery difficult. Relevant literature has shown that patients with benign SFT undergoing surgical removal have a median 10-year overall survival rate of 54%-89% –23, and 125I seed implantation for the tumors in the left pelvic cavity and near the right iliac vessels showed a surprising benefit: the patient attained a complete remission, and no relapse was observed as of the end of follow-up, with a PFS of 43 months (125I seed implantation alone for the tumor behind the bladder continued to work: a complete remission was achieved, with a PFS of 35 months (et al. described that the median PFS with doxorubicin alone and combined with ifosfamide was 4.0 months and 6.7 months, respectively (et al. evaluated the efficacy of temozolomide combined with bevacizumab in 14 patients with advanced SFT, and the median PFS was 10.8 months (125I seeds than to chemotherapy, which often causes severe side effects. Moreover, seed implantation costs less than chemotherapy and targeted drug therapy. However, seed implantation is a local therapy. If there is widespread metastasis, a combination of seed implantation and chemotherapy or targeted drug therapy may be a possible solution.This patient was initially diagnosed with SFT in 2014 and then underwent tumor removal, but relapsed just two months later. In July 2015, surgical resection alone was performed on the tumor in the abdominal wall, and the tumor recurred in the abdominal wall six months later. While surgery alone failed to improve the outcome, surgical removal combined with ectively . Park et8 months . Compare125I seed implantation, which supports seed implantation as a potential solution to repeated local recurrence. As MSFT is very rare, there has been no more research than case reports, not to mention clinical randomized controlled trials. Our report could provide a reference for the treatment of MSFT.In this report, the patient experienced repeated recurrence after surgery, but benefited from The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.ZG performed the bibliographic search and wrote the manuscript; ZG, HY, XD and JW revised the manuscript; YL, JZ and ZL took part to the equipment preparation and follow-up; HZ made the decision to submit the article for publication. All authors read and approved the final manuscript.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.


The total fats of the three samples were between 12.5 and 15.5 g/100 g dry basis. In addition, Corixidae eggs are excellent protein sources. Thus, water boatmen’s eggs can be considered to be a food rich in bioactive compounds.The group of aquatic insects collectively called “water boatmen” or “Axayacatl” (Hemiptera: Corixidae) and their eggs, called “Ahuahutle”, have been consumed and cultivated since the pre-Hispanic era in Mexico. Nevertheless, food composition databases contain limited information on the nutritional composition of these eggs. This work evaluates the macronutrients and bioactive compounds of water boatmen eggs obtained from three different locations in Mexico. The primary analyses to be determined for the first time were some bioactive compounds in the eggs, such as phenolic compounds, total flavonoids, condensed tannins content, antioxidant activity (DPPH and ABTS), and, additionally, fatty acids and proximal composition. The results showed that the sample from Hidalgo (AMC) presented the highest number of phenolic compounds (855.12 ± 0.52), followed by ALT (125.52 ± 0.05) and, with the lowest amount, AMT (99.92 ± 0.13), all expressed in an mg GAE/g sample. ALT indicated the highest mol TE/g sample concentration for ABTS (25.34 ± 0.472) and DPPH (39.76 ± 0.054), showing a significant difference in the DPPH method with the AMT samples. The three Corixidae egg samples had between 15 to 18 different fatty acid profiles, and there were statistically significant differences (Student’s  The projected population increase by 2050 of approximately two billion people compared to the current 7.7 billion ,2 exposeAcceptance of edible insects has focused on studies targeting adults, while acceptance studies targeting the next consumers, such as children, are scarce . The accKrizousacorixa spp, Corisella spp., Corixa spp. (Hemiptera: Corixidae), and Notonecta spp. (Hemiptera: Notonectidae). The eggs are 0.5 to 1.00 mm long [Mexico has vast biodiversity of insects, with almost 48,000 registered species , includi mm long ,22. It i mm long . AdditioPolyphenols have in their chemical structure two phenyl rings and one or more hydroxyl substituents; the structural diversity of flavonoid molecules arises from variations in the hydroxylation pattern and oxidation state of the central pyran ring, resulting in a wide range of bioactive compounds . In receAccording to Singla et al., polyphenols are natural compounds synthesized exclusively by plants  with cheH. parallela evaluated with the DPPH method [Rondotia menciana can produce flavonoids that are not present either in the bud or in its food [Pieris brassicae were fed [A. pernyi that come from eight subclasses, namely, flavones (103), flavonols (34), flavonoids (28), flavanones (20), polyphenols (19), isoflavones (9), anthocyanins (9), and proanthocyanidins (4) [Tenebrio molitor  larvae represent one of the most interesting edible insects and could be reared on alternative feeds, such as former foodstuff products. ABTS, DPPH, and FRAP varied significantly as their diet changed. In addition, antioxidant compounds such as δ-tocopherol, γ-tocopherol, and α-tocopherol were identified with significant differences in the different diets [Studies such as Yu’s have explored the antioxidant activity in two extracts, ethanolic and water extract, of adult H method . Anotherits food . Other wwere fed . Fu et adins (4) . Additiont diets . Accordint diets ,31.Few nutritional studies have been explored in aquatic insects, as in the Corixidae family, whose knowledge is limited to studies of the proximal composition and fatty acids of both adults and eggs ,33. HoweThe central states in Mexico where Ahuautle consumption has been identified are Michoacan, Hidalgo, and Estado de México ,33,36,37Chemical analyses of three water boatman eggs samples were performed. All values are expressed as the mean of a triplicate determination. The proximate composition was estimated by AOAC (2000) methods: ashes (method no 923.03), proteins , and fats (method no 920.39).w/v) anthrone in concentrated sulphuric acid. The absorbance of the reaction mixture was measured at 630 nm against a blank. Dextrose was used to construct a standard curve for quantification, and the results are expressed as mean g/100 g dry basis of sample. All samples were analyzed in triplicate. The caloric value was based on the theoretical energy value of 9 kcal per gram of lipids and 4 kcal per gram of proteins and carbohydrates.Determination of soluble carbohydrates. Total available carbohydrate content of the sample was measured according to the method described by Melo-Ruiz , with soThe extraction was carried out according to the methodology described by Cardador ; 200 mg The DPPH  method was accomplished by Zenil . The ana−1, then raised to 240 °C at 1 °C min−1 and held for 5 min. EI energy was set at 70 eV, and the mass range was set at m/z 50–1100. FAMEs were identified and quantified by comparison with a standard Supelco 37 Component FAME Mix, and data processing was performed using Chem-Station (Agilent Technologies) software version C.01.10.GC-MS analysis was carried out as accomplished by Lim . The supn = 3. The results content of total fats and fatty acids were analyzed with the minimum significant difference (MSD) using n = 2, and results were reported with mean with their standard deviation (SD). All of them were analyzed with a Student’s t-test α ≤ 0.05. Statistical calculation was performed using IBM SPSS Statistics 25.0 . The data obtained from proximate composition, antioxidant activity, and phenolic compounds content were statistically analyzed. The results of the analyses are reported as the mean with their standard error (SE) using Latebraria amphipyrioides) and the grasshopper , which provide 349 and 336 kcal per 100 g dry matter, respectively. However, there are also species with higher energy contribution, such as the Mexican moth (Phassus triangularis) with 761 kcal per 100 g dry matter. It is essential to highlight that the stage of development influences energy contribution, although most insects are not consumed in their adult stage [Insects are one of the most diverse groups of animals from terrestrial and aquatic ecosystems on the planet. Many insect species are considered edible in their various stages of development  ,48. In aThe total carbohydrates in the Ahuautle samples evaluated in this work is lower (7 to 7.5 g/100 g dry matter) than the range of 18 to 21 g/100 g dry matter previously reported ,52. HoweMoreover, chitosan, a component of active films and packaging with potential applications in food packaging, can be obtained from chitin due to its antimicrobial, antioxidant, and anti-inflammatory properties . The useThe amount of protein contained in insects makes them suitable candidates for the development of foods, additives, supplements, and alternative substitutes for protein sources for human and animal consumption, as suggested by the European Commission (EC) and Food and Agriculture Organization (FAO) . The autLipids are the second principal component in insects; additionally, in the larval and egg stage, the concentration of lipids is higher. The concentration of lipids in the samples of Ahuautle analyzed in this work is shown in a range of 9 to 14 g/100 g dry matter. Melo  report aThe composition of insects does not only comprise lipids, proteins, carbohydrates, and minerals. Insects provide other organic compounds such as vitamins, nucleic acids, and phenols . PhenoliChantawannakul  reportedAscra cordifera, Brachygastra mellifica, and Hermetia illucens. They were identified by liquid chromatography–electrospray ionization–tandem mass spectrometry (LC-ESI-MS/MS). In our study, we indicated the presence of total phenols in a range of 100 to 850 mg GAE/g of samples. Therefore, this is the first report on the presence of phenolic compounds in Ahuautle samples. As Baigts and collaborators [Baigts and collaborators  reportedborators  reportedborators . Insectsborators . Flavonoborators , chemicaborators , and visborators , and plaborators . On the Tenebrio molitor, Acheta domesticus, Gryllodes sigillatus, Bombyx mori, Hermitia illucens, and Lethocerus indicus as the most studied edible insects in relation to their antioxidant capacity. It should be noted that the present work reports the first known record of antioxidant activity in Ahuautle through the antiradical mechanism by the DPPH and ABTS+ methods. The analyzed Ahuautle samples from three different points of origin indicate a superior DPPH radical scavenging power (27.44 to 39.76 mol TE/g sample) compared to the ABTS+ radical scavenging capacity (6.34 to 25.34 mol TE/g sample), showing statistical differences between the samples evaluated in both methods.Edible insects have been consumed not only for culinary and cultural reasons; many edible insects are consumed for their biological properties, including antioxidant activity. Antioxidant activity is the ability of compounds in food to neutralize and/or eliminate reactive oxygen species (ROS) through various reaction mechanisms . A reseaSpodoptera littoralis) present high ferric ion-reducing antioxidant power (FRAP) in addition to presenting DPPH radical scavenging capacity. Di Mattia et al. [Gryllodes sigillatus) contain peptides with antioxidant properties and can be used as a functional food to combat stress.Antioxidant activity is generally related to the presence of polyphenolic compounds, which are also significantly present in the Ahuautle samples analyzed. Zhang and collaborators  indicatea et al.  reporteda et al.  indicateCorixidae and Notonectidae spp.) evaluated in this work are mostly the same as the terrestrial edible insects previously reported [Fatty acid composition in three Ahuautle samples was analyzed in this work to evaluate the potential of these eggs as a source of bioactive lipids. A high content of saturated and monounsaturated fatty acids is present in the samples; however, among the polyunsaturated fatty acids, the levels of C20:4, C20:5, and C22:6 (DHA) acids stand out, all of which have been proven to have a positive effect on human health. The monounsaturated fatty acids of the aquatic insect eggs .According to Twining , aquaticThe results obtained in this work support the statement of Hilaire , which sOleic acid is dominant in terrestrial insects. However, the same is not valid for aquatic insects. In our study, the AMC sample was the only one that presented 0.10 ± 0.01 of cis-oleic acid, while the AMT and ALT samples were not detected. Therefore, we can affirm that the diet of aquatic Hemiptera (Corixids) directly affects the fatty acid composition of their eggs (Ahuautle). However, we still know little about the absorption of lipids by insect oocytes , and stuThere are two primary sources of trans fats: natural and industrial. For the first, animals and their products, such as cows, sheep, goats, milk, and butter, have natural trans fats; the second source of trans fatty acids is the industrial process of hydrogenation of vegetable oils . This laAquatic insects have an average protein content of 59.55%, which is higher than that of conventional animal meats ,92. GeneGiven that over 2000 insect species are eaten around the world, edible aquatic insects account for about 15% of the total number. The species belong to eight orders. Among them, Coleoptera, Odonata, and Hemiptera contribute over 3/4 of the number of species, and they are all predatory. Since the quality of the water in which insects develop affects their composition, it is not recommended to consume large quantities of wild insects, as they are usually found in places with heavy metals, pesticide residues, and uric acid, which does not ensure their safety. For the large consumption of aquatic insects, it is better to standardize their rearing before they can be safely eaten ,98.To our knowledge, this is the first study demonstrating how the wild diet of aquatic insects may modify the nutritional composition of their eggs; in addition, it provides essential information, for the first time, about their nutritional composition, phenolic compounds, and antioxidant activity. This study aims to promote the consumption of aquatic insects. Accepting the water boatmen’s eggs in international gastronomy is good, mainly because of their flavor, which is related to dried shrimp or caviar used in international gourmet dishes . BesidesAquatic insects are an important source of protein that can be a sustainable alternative to combat world hunger. The feed, origin, and stage of development influence the composition and nutraceutical contribution of aquatic insects. Ahuautle is a food that provides macrocompounds that contribute to nutrition but also contains bioactive compounds such as phenolic compounds that provide antioxidant activity and, thus, health benefits. The compounds in Corixidae eggs can be an ecological alternative to modulate oxidative stress and a source of molecules with other biological activities that contribute to the prevention of chronic diseases. However, more studies are still needed to confirm the efficacy of these edible insects in this area. The fatty acid composition of insects can vary greatly, even in their eggs, depending on their feeding substrates. These substrates in aquatic life could contain feeding with polyunsaturated fatty acids. The amount of protein in Corixidae eggs in this work (72 to 74 g/100 g dry matter) is a possible solution to nutritional deficiencies. About 90% of the fatty acids contained in Ahuautle are beneficial to health. On the other hand, phenolic compounds stand out in this study, followed by antioxidant activity (ABTS and DPPH). Thus, Corixidae eggs can be considered to be a food rich in bioactive compounds.


Chronic malnutrition and cachexia are common in chronic kidney disease (CKD), and importance should be given to these complications because they affect the patient's quality of life and prognosis. This study analyzed the correlation between the serum PTH level, nutritional status, and body composition of patients with CKD.  CKD patients were enrolled in Center for Kidney Disease, Second Affiliated Hospital of Nanjing Medical University, from December 1, 2016, to November 30, 2020. Bioelectrical impedance technology was applied to estimate the body composition. The characteristics of the body composition were compared among different stages of CKD patients, and then the correlation between PTH and body composition was analyzed. 2. PBF peaked in the CKD stage 3/4 group and gradually decreased with the progression of CKD. The PA and SMI differed significantly between the CKD stage 1/2 and stage 5B groups. The proportion of low SMI did not differ significantly between the CKD stage 1/2 and stage 3/4 groups, but it was obviously higher in the CKD stage 5A and 5B groups. PTH was significantly correlated with BMI, hemoglobin, albumin, total cholesterol, triglycerides, and SMI. Binary logistic regression of low SMI showed that the odds ratio for PTH levels was greater than the upper limit of the normal range, which was 11.769 , and the model predictive power was 0.986 after correction for age, sex, height, weight, hemoglobin, serum calcium, serum phosphorus, serum total cholesterol, serum triglyceride, and basal metabolic rate.  205 CKD patients were enrolled. Twenty-five patients were in stage 1 or 2 of CKD, 78 patients were in stage 3 or 4, 31 patients were in stage 5 without dialysis (referred to as CKD stage 5A), and 71 patients were in stage 5 with dialysis (referred to as CKD stage 5B). Body composition analysis showed that the patients had a phase angle (PA) of 5.02 ± 1.07°, a percentage of body fat (PBF) of 27.74 ± 8.8%, and a skeletal muscle mass index (SMI) of 7.4 ± 1.34 kg/m Bioelectrical impedance analysis might be useful in estimating the nutritional status of CKD patients in terms of fat and muscle parameters. High levels of PTH are an independent risk factor for developing low SMI in CKD patients. Chronic kidney disease (CKD) is a global health problem, and its prevalence is increasing every year due to the change in the disease spectrum. Chronic malnutrition and cachexia are common in CKD patients, and importance should be given to these complications because they affect the patient's quality of life and may even be associated with depression . Severe Previous physiological studies , 5 have Therefore, the purpose of this study was to analyze the nutritional status and body composition of CKD patients using bioelectrical impedance technology, investigate the differences in the nutritional status among patients at different stages of CKD, and analyze the correlation between PTH levels and body composition of CKD patients.The participants were enrolled from hospitalized patients in Center for Kidney Disease, Second Affiliated Hospital of Nanjing Medical University, from December 1, 2016, to November 30, 2020. The inclusion criteria included participants aged above 18 years old and diagnosed with CKD according to KDIGO guidelines . The exc2 in men and less than 5.7 kg/m2 in women [After seated for at least 20 minutes, the participants were examined for human body composition using the biological resistance technology InBody S10, Korea). Water drinking was forbidden for 2 hours before the examination. Hemodialysis patients were examined half an hour after hemodialysis. Based on the nutritional content estimated by InBody, the bioelectrical impedance results were categorized into three types of nutritional indicators. Total nutritional indicators included the following: phase angle (PA), body cell mass (BCM), protein, and basal metabolic rate (BMR); fat indicators included percent body fat (PBF), visceral fat area (VFA), and body fat mass (BFM); and muscle indicators included fat free mass (FFM), soft lean mass (SLM), skeletal muscle mass (SMM), and skeletal muscle index (SMI) , 9. Here, Korea. in women .The demographic and medical information of all subjects was collected. Fasting blood was sampled on the morning of the same day for routine laboratory examination, including hemoglobin, serum albumin, serum total cholesterol, serum triglyceride, serum urea nitrogen, serum creatinine, serum phosphorus, serum calcium, and plasma PTH. PTH was detected by chemiluminescence immunoassay , and the upper limit of the normal detection range, 88 mmol/L, was used as the cut-off value.T-test was used to compare the continuous variables of normal distribution between two groups, one-way ANOVA and LSD post hoc tests were used to compare among three or more groups, and nonparametric and Bonferroni's post hoc tests were used to compare the continuous variables of non-normal distribution. The chi-square test was used to compare the rates. The correlation between variables was analyzed by Pearson correlation analysis, in which the non-normal distribution data were transformed into normal distribution data by natural logarithm. Binary logistic regression was used to explore the risk factors of low SMI. All analyses were performed with SPSS 26.0. It is statistically significant when the p value is <0.05.The data of normal distribution were described in the form of mean ± standard deviation, the data of non-normal distribution were described in the form of median (interquartile range), and the classified variables were described in the form of frequency (percentage). This study enrolled 205 CKD patients, who were divided into groups based on their CKD stage. Twenty-five patients were in stage 1 or 2 CKD, 78 were in stage 3 or 4, 31 were in stage 5 without dialysis (referred to as CKD stage 5A), and 71 were in stage 5 with dialysis (referred to as CKD stage 5B). Sixty-two percent of the patients were males with a median age of 56 years old. Diabetic nephropathy was the most common etiology of CKD (30.7%) among the patients, followed by glomerulonephropathy (24.9%). As shown in 2, a median serum albumin level of 39.7 g/L, a median serum total cholesterol level of 4.14 mmol/L, and a median serum triglyceride level of 1.69 mmol/L. As summarized in 2. There were significant differences in the levels of overall nutritional and muscle indicators among the four groups, except for serum albumin level and proportion of patients with low PA. Apart from BFM, there were no significant differences in body fat indicators among the groups.As summarized in With the progression of CKD, BMI, total cholesterol, and triglycerides decreased gradually. The albumin level varied greatly among the patients in the CKD stage 1/2 group, but the level increased in the other three groups with the progression of CKD. A significant difference was present only between the groups of CKD stage 3/4 and stage 5B. PBF peaked in the patients of CKD stage 3/4 and gradually decreased with the progression of CKD. PA and SMI differed significantly between the groups of CKD stages 1/2 and 5B, but not between the groups of CKD stages 3/4 and 5A. Further analysis  revealedThe mean PTH level of the patients was 103.5 pg/ml at the time of enrollment, and it showed a marked increase with the progression of CKD. PTH was significantly correlated with BMI, hemoglobin, albumin, total cholesterol, triglycerides, and SMI but not with PA, PBF, and BMR .p = 0.043, 95% confidence interval: 1.078–128.536), and the model predictive power was 0.986  with paradoxical reduction in appetite, for which the International Society of Renal Nutrition and Metabolism proposed the concept of protein-energy wasting (PEW) in 2008 . PEW is D deficiency [A high PTH level is an important risk factor for poor prognosis in CKD patients. During the development and progression of CKD, PTH not only causes bone demineralization but also affects the proper functioning of the brain, heart, and immune system . This clficiency , and in ficiency , while tficiency . From a ficiency , 21. At ficiency . The preIn the present study, albumin levels first increased and then decreased with the progression of CKD, which was different from the trend for most nutritional indicators. The discrepancy may be attributed to the fact that the underlying conditions leading to CKD mainly include diabetic nephropathy and primary glomerulonephritis, which frequently cause proteinuria. The degree of proteinuria correlates with the patient's renal function outcomes , which eD in order to reduce the risk of developing low SMI is not known. These issues need to be resolved through long-term follow-up. Secondly, BIA is an indirect assessment method, and it can estimate but not measure body composition. In previous research, BIA was proven to apply well in normal hydration CKD patients, which was as reliable as DXA [There are some limitations in this study. First of all, this was a cross-sectional study and, thus, unable to reveal causality. Further research is needed to confirm whether intervention to reduce PTH levels can serve as an effective treatment for malnutrition and PEW in CKD patients. In view of the U-shaped relationship curve between the PTH level and the mortality risk of CKD patients , it is ne as DXA . Meanwhie as DXA . In a sie as DXA . We thinA preprint of this article has been published previously In summary, bioelectrical impedance might usefully estimate the nutritional status of CKD patients in terms of fat and muscle parameters. High levels of PTH are an independent risk factor for developing low SMI in CKD patients. It is necessary to pay more attention to the nutritional management of CKD patients and the remodeling of fat and muscle distribution. Moreover, PTH may be a potential therapeutic target for treating sarcopenia in CKD patients.