The results showed that relative abundances of carbohydrate-active enzyme (CAZy), nitrogen, and sulfur cycling genes were 92.7–116.5, 15.1–18.7, 50.8–63.9 per 1,000 amino acid coding reads, respectively. The Shannon diversity indices of CAZy and sulfur cycling genes decreased with increasing salinity, whereas nitrogen cycling gene diversity showed an opposite trend. Relative abundances of many CAZy , nitrogen  and sulfur  cycling gene categories decreased with increasing salinity, whereas some CAZy , nitrogen  and sulfur  gene categories showed an increasing trend. The compositions of CAZy, nitrogen, and sulfur cycling genes in the studied lake sediments were significantly (p < 0.05) affected by environmental factors such as salinity, total organic carbon, total nitrogen, and total phosphorus, with salinity having the greatest influence. Together, our results suggest that salinity may regulate the biogeochemical functions of carbohydrate metabolisms, nitrogen, and sulfur cycles in lakes through changing the diversity and composition of microbial functional genes. This finding has great implications for understanding the impact of environmental change on microbial functions in lacustrine ecosystems.Exploring functional gene composition is essential for understanding the biogeochemical functions of lakes. However, little is known about the diversity and composition of biogeochemical cycling genes and their influencing factors in saline lakes. In this study, metagenomic analysis was employed to characterize the diversity and composition of microbial functions predicted from genes involved in carbohydrate metabolisms, nitrogen, and sulfur cycles in 17 surface sediments of Qinghai-Tibetan lakes with salinity ranging from 0.7 to 31.5 g L Lake sediments are inhabited by a variety of microbial communities, which are widely involved in the biogeochemical cycles of carbon, nitrogen, and sulfur . It has The diversity and composition of microbial functions can usually be revealed by cloning library , GeoChip−1) that are an important part  of the inland aquatic ecosystem  characterize the diversity and compositions of microbial functions predicted from genes related to carbohydrate metabolisms, nitrogen, and sulfur cycles in the studied lake sediments, and (2) quantify the relative importance of environmental factors influencing the composition of microbial functions predicted from genes.To fill the abovementioned knowledge gaps, metagenomics was applied to analyze the diversity and composition of microbial functions predicted from genes that are involved in carbohydrate metabolism, nitrogen, and sulfur cycling processes in the surface sediments of seventeen lakes with salinity ranging from 0.7 to 31.5 g LA sampling cruise was carried out in the summer of 2018. In the present study, seventeen sampling sites were chosen from 10 lakes . The sam−1) and the resulting extracts were analyzed for the content of total phosphorus (TP) using colorimetric methods . The contents of total organic carbon (TOC) and total nitrogen (TN) of the sediments were determined using a multi N/C 2100S analyzer . Freeze-dried sediments were digested with concentrated perchloric acid  with 350 bp library inserts. Each sample obtained ~30 Gbp of raw paired-end reads. The pair-end raw reads were de-replicated and trimmed using “fastp” with parameters of −D, −q 20 and −l 50 . The res v2.0.11  with par v2.0.11 , NCycDB  v2.0.11 . In thisferences . The fre “vegan” . For eac “vegan” .envfit in the “vegan” package was used to identify significant (p < 0.05) environmental factors that influence functional gene composition  correlated with TOC and TN; TOC was positively correlated with TN and the ratio of carbon to nitrogen  and saline  lakes, and they, respectively, accounted for 93.6, 90.3, and 95.7% of total numbers of the CAZy, nitrogen, and sulfur cycling gene families detected in this study  and 4  were present in the sediment samples from freshwater and saline lakes, respectively  were present in the saline lake samples  correlated with salinity, pH, the contents of TOC, and TN, C/N or TP (nasA) of assimilatory nitrate reduction, 2 genes  of dissimilatory nitrate reduction, 3 genes  of denitrification, 4 genes  of organic degradation and synthesis; the sulfur cycling genes contained 4 genes  of assimilatory sulfate reduction, 13 genes  of dissimilatory sulfur reduction and oxidation, 11 genes  of link between inorganic and organic sulfur transformation, 8 genes  of organic sulfur transformation, one gene  of SOX systems, one gene  of sulfur disproportionation, 3 genes  of sulfur oxidation, 3 genes  of sulfur reduction, and 8 unclassified sulfur cycling genes  affected by salinity, TOC, and TN (p < 0.001) predictions of the CAZy, nitrogen, and sulfur cycling gene compositions with R2 values of 0.526, 0.295, and 0.398, respectively  that participate in the synthesis of amino acid derivatives are classified as nitrogen cycling genes  significantly affect the compositions of the CAZy, nitrogen, and sulfur cycling genes in this study. These factors have long been recognized as significant influencing factors in the taxonomic composition of microbial communities in lakes. For instance, salinity can cause microbial physiological constraints on osmoregulation and energy , so it wBetaproteobacteria) are limited to grow under high salinity due to energy constraints  decreased with increasing salinity in this study. In addition, it was notable that the relative abundances of some functional gene categories  increased with increasing salinity. This finding may be explained by the fact microbial groups involved in AA, assimilatory sulfate reduction, denitrification, and sulfur oxidation were very active in high salinity environments  in influencing the compositions of the CAZy, nitrogen, and sulfur cycling genes. This finding may be explained by the fact that salinity usually has a stronger influence on the microbial community composition in lake sediments than other environmental factors . There istraints . So it wronments , 2021.Interestingly, the relative abundance of many CAZy genes involved in the decomposition  of refractory organic matters  increased with increasing salinity in the studied lake sediments, suggesting that microorganisms under high salinity may exploit refractory organic matter as energy sources for their growth. Indeed, it has been reported that at high salinity, many halotolerant/halophilic microbes possess multiple enzymes capable of degrading refractory organic matter derived from plant and microbial cell walls . One of gdh_K15371), betaine synthesis , and sulfur oxidation  increased with increasing salinity in this study. Betaine and β-glutamate are typical organic osmotic solutes that aids microbial resistance to salinity, so microorganisms with synthesis function of such organic osmotic solutes may be highly active at high salinity  can be found in the article/HJ conceived this study. HJ, JY, WL, and BW collected the samples. BW performed the geochemical analysis. QL, ZH, and JY conducted the metagenomic analysis. QL, JY, and HJ drafted the manuscript. All authors reviewed the results and wrote, revised the manuscript.This research was supported by grants from the National Natural Science Foundation of China (Grant Nos. 92251304 and 41972317), the 111 Program , Introduction Project of High-Level Talents in Xinjiang Uygur Autonomous Region, the Second Tibetan Plateau Scientific Expedition and Research Program (STEP) (2019QZKK0805), the Science and Technology Plan Project of Qinghai Province (Grant No. 2022-ZJ-Y08), and State Key Laboratory of Biogeology and Environmental Geology, CUG (No. GBL11805).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.


Sepsis is diagnosed in millions of people every year, resulting in a high mortality rate. Although patients with sepsis present multimorbid conditions, including cancer, sepsis predictions have mainly focused on patients with severe injuries.In this paper, we present a machine learning–based approach to identify the risk of sepsis in patients with cancer using electronic health records (EHRs).We utilized deidentified anonymized EHRs of 8580 patients with cancer from the Samsung Medical Center in Korea in a longitudinal manner between 2014 and 2019. To build a prediction model based on physical status that would differ between sepsis and nonsepsis patients, we analyzed 2462 laboratory test results and 2266 medication prescriptions using graph network and statistical analyses. The medication relationships and lab test results from each analysis were used as additional learning features to train our predictive model.P<(.001). Our model outperformed the model trained using only common EHRs, showing an improved accuracy, area under the receiver operating characteristic (AUROC), and F1 score by 11.9%, 11.3%, and 13.6%, respectively. For the random forest–based model, the accuracy, AUROC, and F1 score were 0.692, 0.753, and 0.602, respectively.Patients with sepsis showed differential medication trajectories and physical status. For example, in the network-based analysis, narcotic analgesics were prescribed more often in the sepsis group, along with other drugs. Likewise, 35 types of lab tests, including albumin, globulin, and prothrombin time, showed significantly different distributions between sepsis and nonsepsis patients We showed that lab tests and medication relationships can be used as efficient features for predicting sepsis in patients with cancer. Consequently, identifying the risk of sepsis in patients with cancer using EHRs and machine learning is feasible. Sepsis is a life-threatening organ dysfunction in which a pathogen infection leads to a dysregulated host response to the infection . Sepsis Sepsis has shown a substantial incidence in patients with low immunity, such as patients with cancer, patients who are elderly, and newborns . PatientVarious studies have been conducted to identify the risk of sepsis, including a statistical model–based approach for emergency room (ER) patients , a machiOur study aimed to predict the risk of sepsis in patients with cancer at an early stage using clinical information and a machine learning approach. We utilized the deidentified electronic health records (EHRs) from the Samsung Medical Center (SMC) in Korea of 8580 patients with cancer, including inpatients, outpatients, ICU patients, and ER patients. Drug prescriptions and laboratory test results are known to reflect the physical status of patients . In our Based on the results of the analyses, we propose a machine learning–based sepsis predictive model that can reflect the physical conditions of patients with cancer and is trained on the prescribed drug and lab test patterns as well as EHRs, which are widely used in the reported sepsis prediction approaches ,17.Data were prepared from the Clinical Data Warehouse (CDW) and the SMC cancer registry, Seoul, South Korea, and deidentification was performed on the collected data. The study population included adult patients diagnosed with lung, liver, and breast cancer who visited the ER within 5 years of being diagnosed with cancer. The inclusion criteria were patients with cancer registered at the study sites. Patients were excluded from the study cohort if they met the following exclusion criteria: those under 18 years of age, those with multiple cancers, those who had not visited the emergency room within 5 years after the first cancer diagnosis, and those with ICD-10 codes not matched with C22, C34, and C50. The data were constructed by reflecting various EHR information such as hospitalization data, diagnosis code of cancer or other underlying disease, vital signs, genomic information, medication prescription, surgical history, radiation treatment, and lab test information for 5 years (2014-2019) before and after the cancer diagnosis of 8580 patients with cancer, including inpatients, outpatients, ICU patients, and ER patients. Most of the currently published sepsis prediction models use information within 48 hours before the onset of sepsis. However, due to the high risk of sepsis, it was considered necessary to predict in advance, so information 2 days prior to the ER visit was used. Data earlier than 7 days were somewhat difficult to consider as having an effect on the onset of sepsis, so the filtration criteria was set to 2-7 days.The institutional ethics committee of SMC approved this study .We identified patients with sepsis using the Sequential Organ Failure Assessment (SOFA) scores of Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) guidelines  for a toNursing records, inspection records, clinical information, and medication prescription data were extracted from the CDW.The variables were preprocessed to obtain the SOFA scores.SOFA scores for each patient were calculated each time.The time window was set by checking whether antibiotics were administered intravenously within 24 hours before and after the bacterial culture test.Patients with sepsis were identified if their SOFA score changed by 2 points or more within the time window.In accordance with the Sepsis-3 guidelines, if the SOFA score could not be measured in advance, it was considered 0. Consequently, if the change in the SOFA score was 2 or higher in the first visit to the ER, the patient was considered to be experiencing sepsis.We aligned the collected EHRs of 8580 patients with cancer based on the date of the ER visit and filtered patients with information 2-7 days prior to the ER visit. Each patient's diagnostic code was recorded as an ICD-9 code and standardized to 3 digits for use as a categorical feature. Because there was a possibility of information leakage from giving hints to the machine learning–based predictive model, lab test results centered on specific disease groups were removed, and only the lab test information performed on over 60% of the patients was used. All categorical features were preprocessed using one-hot encoding, and all binary categorical features were encoded as 0 or 1. In addition, missing values were imputed with the mean value of patients with the same type of cancer, the same sex, and the same age, and extreme outlier values were removed.i → DjS(D)), defined as in Equation (1), implied how often the sets go together when items are being tied up simultaneously, where N(s) represents the total number of prescriptions, and i,Dj)N ) comprised the interaction (I), the harmonized average (H), and the arctangent (T), in which (I) determined the level of interaction, (H) determined the overall intensity in a sensitive manner, and (T) determined the geometric angle difference as a single scalar value for each pair, defined as in Equation (2), where Di and Dj indicate the i-th and j-th drug of the s-th prescriptions for the p-th patient, respectively. The D value represents the prescription frequency of each medication.We vectorized the relationships found through graph network–based association rule analysis to be used as an input for the machine learning–based sepsis prediction model. After multiplying each one-hot encoded drug selected through the aforementioned analysis by the number of prescription days, the relationship for each pair of values was vectorized using the 3 formulas proposed in our previous study . These 3We trained models on vectorized drug relationships and selected lab test types, along with the common EHRs that are widely used in the reported sepsis prediction models ,17. We cAll proposed approaches were implemented using the Python 3.7 library, such as PyTorch 1.5, Scikit-learn, and SHAP, on an NVIDIA TITAN RTX 24 GB × 2. The source code is available on GitHub .The overall process of our study is shown in In the control group , there were 490 (52.8%) males and 438 (47.2%) females. The mean age was 58.2 (SD 11.0) years, and the average weight was 63.7 (SD 10.7) kg. In terms of the initial cancer diagnosis of each patient, 180 (19.4%) had liver cancer, 533 (57.4%) had lung cancer, and 215 (23.2%) had breast cancer. Meanwhile, in the sepsis group, there were 324 (71.2%) males and 131 (28.8%) females, with a relatively higher proportion of males than the control group. The mean age of the sepsis group was 60.3 (SD 0.5) years, and the average weight was 64.3 (SD 11.3) kg. In the sepsis group, 140 (30.8%) patients had liver cancer, 274 (60.2%) had lung cancer, and 41 (9%) had breast cancer. With these prepared data sets from SMC, we analyzed the differences in medication patterns by group.Using the FP-growth algorithm, we analyzed patterns of the medications prescribed on the same day in 2666 prescriptions from the preprocessed and filtered EHR data. According to the analysis results, only group sets with a minimum support value of 0.05 or greater were selected. Of a total of 101 different drug types, 406 relationships among 29 drugs and 378 relationships among 28 drugs were selected for the sepsis group and nonsepsis group, respectively. To visualize the associations between the drug prescriptions, we constructed 2 graph networks with nodes representing the selected drugs and edges depicting the relationships among the nodes . The sizThe patterns of medications between the sepsis and control groups were different. Nodes for medications such as “saline solution,” which are commonly prescribed for most patients, showed similar patterns in both networks , whereast test, we analyzed the 2462 lab test results of the preprocessed and filtered EHR data to find lab test items with significantly different distributions between the sepsis and nonsepsis groups. P is symbolized .Using a P<.001. A decreased albumin/globulin ratio (A/G ratio) was recently reported as a novel independent predictor of the development of postflexible ureteroscopic sepsis [P<.001. Furthermore, several studies found that activated partial thromboplastin time (APTT) and prothrombin time (PT) [APTT value of 6.89 (SD 15.01) to 14.06 (SD 19.72), PT(%) value of 17.51 (SD 35.82) to 33.27 (SD 42.26), PT(INR) value of 0.23 (SD 0.46) to 0.49 (SD 0.63), and PT(sec) value of 2.9 (SD 5.84) to 6.14 (SD 7.69), with P<.001. With favorable consistency between the identified lab test differences of our candidates and known biomarker candidates of sepsis, we felt confident that the SMC EMRs successfully recapitulated the physical and biological signatures of the patients with sepsis. In other words, these results suggested that the 35 selected biomarkers could characteristically reflect the biological features of the patients with sepsis. Thus, we utilized these 35 lab test results as learning features to establish our prediction model for sepsis, as shown in c sepsis . In thisime (PT) ,31 are pUsing vectorized drug relationships and the values of the selected lab test types along with common EHRs, we trained 2 machine learning models (logistic regression and random forest) and 3 deep learning models  to build a sepsis prediction model based on the physical status of patients with cancer. A total of 465 relationships between 31 drugs selected through association rule analysis were vectorized using the 3 formulas described in the Methods section. A total of 1395 (465 × 3) drug relationship vectors, the values of the selected 35 lab test types, and common EHR information including anonymized personal information, hospitalization data, and cancer diagnosis code were used as inputs for model training. We used simple logistic regression (LR) and RNN-LSTM for the logistic regression–based and RNN-LSTM–based models, respectively. The random forest–based model comprised 20 trees, and the ANN-based model comprised input and output layers, as well as hidden layers. In addition, we used ResNet10 consisting of 10 convolution layers, fully connected layers, and residual connections for the CNN-based model. All hyperparameters, such as the number of trees in the random forest model, batch size, learning rate, and number of layers in the deep learning models, were selected as optimal values for each model through grid searches . The lisThe overall performance of the proposed models with EHRs, lab data, and drug relationships were superior to that of the other models. The proposed random forest–based model showed the highest value in all the evaluation metrics except for recall . In the case of recall, the proposed ANN-based model showed the highest value . In particular, the proposed random forest–based proposed model recorded the largest performance improvement in all the metrics compared to the model trained on drug relationships and common EHRs . In addition, the proposed RNN-LSTM–based model showed the greatest performance improvement in accuracy, the AUROC, the AUPRC, and precision , and the ResNet10-based model showed the highest improvement in recall and the F1 score  compared to the model trained on only common EHRs. These findings suggest that the drug relationships and the selected lab test types were the main contributors to the proposed sepsis predictive models for patients with cancer.To evaluate the contributions of the learning features, SHAP, an XAI technique, was utilized for the proposed random forest–based model, which showed the best performance when investigating important features that contributed to the prediction. t test and association rule analysis, respectively. The 15 drug relationships contained narcotic analgesic drugs such as “opioid alkaloids” and “synthetic narcotics,” which were prescribed more, along with other drugs, in the sepsis group. Among the characteristics of the patients with cancer, the number of cancer-infiltrating lymph nodes (Ca_LN_no), the degree of cancer extent (Extend_CD), and the size of the primary tumor (T_CD) were observed as decisive contributing factors.The top 50 important features include 26 lab test types and 15 drug relationships among the 31 drugs and the 35 lab test types selected by “band neutrophil,” “nucleated RBC,” and “carbon dioxide, total,” as well as 49 drug relationships comprising 22 selected drugs, were included. These results show that the selected drug relationships and lab tests were important features in the proposed sepsis predictive model, suggesting that these features contributed to the accurate prediction of the model.As expected, prognostic biomarkers of sepsis, such as the albumin level, PT, A/G ratio, total protein level, and cholesterol level, ranked high. The blood platelet count has also been identified as a major contributor, and platelets are involved in mechanisms that promote immune responses and coagulation activation. Thrombocytopenia is common in ICU patients with sepsis and is reportedly associated with fatal outcomes . The migThis study presents a machine learning–based approach to identify sepsis risk in patients with cancer at an early stage (2 days before onset). We elucidated that the relationships of prescribed medications and lab test patterns were distinct in the sepsis and control groups. Based on these analysis results, we built a machine learning–based sepsis prediction model trained on lab test items and vectorized drug relationships, along with EHRs. The proposed model outperformed the model trained on medication relationships or common EHRs. In particular, the proposed random forest–based model showed the best sepsis prediction performance  and showed the greatest performance improvement. Furthermore, we demonstrated that the selected lab test results and drug relationships were indeed important features and mainly contributed to the accurate prediction of our proposed model. Therefore, lab tests and medication relationships can be used as efficient features for predicting sepsis. Consequently, it will be possible to use EHR information and deep learning methods to identify the risk of sepsis in patients with cancer.Several limitations of the study should be noted. First, health records are not intended specifically for research; nonbilling-related data, including self-reported data such as smoking status, would be partially inaccurate. As depicted in As we hypothesized, our network-based analysis disclosed distinct patterns of medications used between sepsis and nonsepsis patients with cancer. For example, synthetic narcotics and opioid agents appeared to be more frequently prescribed with other agents. These features  mainly contributed to the high performance of our prediction model. Because the usage of opioids is a known risk factor for sepsis , the posTo our knowledge, previous prognostic evaluation tools and models primarily use patient information obtained after admission to the ICU, and there are many limitations for medical interventions. However, since most patients with cancer are hospitalized through the emergency room for the initial diagnosis of sepsis, an appropriate evaluation tool is needed to identify the risk in advance. This study can be referenced as a baseline for efficiently predicting the onset of sepsis in patients with cancer, and the model is expected to be able to identify sepsis risk more accurately and earlier than before in the medical field.


Although the results showed that both groups’ anthropometric parameters improved, a more significant decrease was observed in the experimental group compared to the control.Prediabetes is a pathological condition in which the blood glucose concentration is higher than normal concentrations but lower than those considered necessary for a type 2 diabetes mellitus diagnosis. Various authors have indicated that the Mediterranean Diet is one of the dietary patterns with the most healthy outcomes, reducing high levels of HbA1c, triglycerides, BMI, and other anthropometric parameters. The main objective of this study was to determine the efficacy of the nutritional intervention for children with prediabetes, including the effectiveness of this nutritional education regarding anthropometric parameters. A randomized pilot trial with two groups, an experimental group (EG) and a control group (CG), using intervention in dietary habits with nutritional reinforcement was carried out on 29 children with prediabetes from a rural area. The nutritional intervention was analyzed through astrophotometric and glycemic measurements and validated surveys. Results: The results indicated improvement in eating habits, adherence to the Mediterranean diet, anthropometric measurements, mainly body mass index and perimeters, and analytical parameters, with a significant decrease in glycated hemoglobin in the EG compared to the CG ( Nutrition can be defined as incorporating nutrients for adequate development and growth, nourishment, and metabolic balance . During High body mass index (BMI), associated with overweight and metabolic disorders, is a risk factor for severe health problems during adulthood ,7, such Children with high BMI have a greater risk of suffering from metabolic syndrome, a clinical entity that can damage the vascular endothelium, favoring the appearance of atherosclerosis and the subsequent development of CVDs ,16,17,18Specifically, a concerning disorder increasing in adolescents and young adults is prediabetes . PrediabIn children, prediabetes has been linked to age, gender, high BMI, family history of diabetes, low physical activity, living in an urban area, dietary habits, lifestyle, and sociodemographic and economic factors ,27,28,29Various authors have indicated that the Mediterranean diet is one of the dietary patterns with the healthiest outcomes, reducing high levels of HbA1c, triglycerides, high BMI, and other anthropometric parameters ,32,33,34In Spain, a nutritional intervention based on the Mediterranean diet was shown to decrease BMI and reduce or maintain blood glucose control (reducing HbA1c 0.3–2.0% at three to six months in young adults) , therebyTherefore, the objectives of this study were as follows: to determine the efficacy of the nutritional intervention on children with prediabetes; to evaluate the improvement of an individualized and directed nutritional intervention compared to a standardized diet ; and to determine the effectiveness of nutritional education regarding anthropometric parameters and adherence to a Mediterranean diet in children with prediabetes.This research focused on a pre-and post-nutritional, randomized, single-blind intervention on parallel groups of schoolchildren, EG and CG, with prediabetes in a rural area, with an average income per household of around EUR 19 thousand. https://clinicaltrials.gov/ct2/show/NCT05424107?type=Intr&cond=PreDiabetes&cntry=ES&draw=2&rank=5, accessed on 21 June 2022).The study design was divided into two phases, pre-and post-intervention, comparing a nutritional intervention based on the adapted catalog with recommendations of healthcare professionals with an adapted Mediterranean diet (EG) and a standardized healthy diet based on the current nutritional advice from healthcare centers (CG). In each phase, a follow-up was carried out with five visits (32 days apart), from the initial visit (v0) in weeks one and two, in which the study variables were gathered , to a final visit (v4), when the study variables were collected after the nutritional intervention. The study was approved by the Regional Ethical Committee, registered on the regional database (ID:2353) and at Clinical Trials (NCT05424107) , a confidence interval of 95%, and a precision of 4.5. The minimum sample was set as 233 children based on BMI, estimating 2.47 with a 95% IC 0.93–4.02 of the sample with prediabetes in rural areas .The participants were recruited through non-probabilistic convenience sampling between March 2018 and February 2019. For the recruitment of the participants, informative sessions were held in the educational centers for legal guardians, parents, and participants. In these sessions, the study objective and planning were explained, along with the voluntary nature of their participation, and the questions or doubts raised by the tutors, parents, and pediatric patients were answered. After these information sessions, the last session was held before data collection. The interested parties signed the informed consent, which was ratified by the tutors, patients, and researchers who were present.https://www.random.org/lists/ accessed on 1 January 2019). Such program allowed to the randomly assigned each child to permuted group. One child was not included because the guardians’ decision followed the CONSORT flow diagram [Most of the participants (238 out of 254 (93.7%)) agreed to undergo blood tests measuring different analytical data, including HbA1c. Out of this sample, 30 students  met the inclusion criteria for this intervention, which matched the prevalence of children with prediabetes in European countries  [ diagram   are described according to four visits distributed over six weeks. The structure of the nutritional intervention and planification implemented was as follows .Visit 0 (weeks one and two): The initial one-hour visit was conducted individually on all study subjects (29 children). The anthropometric parameters were taken on these visits. The first assessment of the children’s eating habits and adherence to a Mediterranean diet was carried out. In addition, a socioeconomic evaluation was carried out on all the parents through an original and specific questionnaire consisting of nine questions. During the same visit, the EG received targeted nutritional education, with specific recommendations on the Mediterranean diet. On the other hand, the CG only received an information sheet with standardized recommendations for healthy eating, called the Decalogue of Healthy Eating.Visits 1 (week six), 2 (week eleven), and 3 (week fifteen): These three visits took 30 min to complete. They included an evaluation of dietary adherence, the resolution of doubts about diet and food, and nutritional reinforcement for the children and families in the EG. Visit 4 (week twenty): The final evaluation was conducted for both groups’ children. The Mediterranean diet adherence questionnaires were filled out, and the anthropometric variables and blood samples were retaken.2), weight (kg), waist circumference (cm), hip circumference (cm), arm circumference (cm), BMI (kg/m2), validated nutritional assessment questionnaire focused on adherence to the KIDMED, Food Frequency Questionnaire (FFQ), and the decalogue of healthy eating. All these measurements were taken up to six months from the V0. The parameters measured were HbA1c levels, height  includes 137 foods classified into 14 groups . Frequencies were recorded using a 9-category Likert-type scale (from “rarely” to “6 or more times per day”). In addition, the rate of consumption of common foods in this population group, such as juices , sweets or sugary breakfast cereals , was collected, along with the habitual culinary techniques used in the children’s houses. Energy and nutrient intakes were calculated using Spanish food composition tables.The quality index of the KIDMED aimed at children and adolescents comprises 16 questions related to adherence to the Mediterranean diet and seven items complementary to the test. All questions were answered positively or negatively. Of the 16 main questions, question numbers 6, 11, 14, and 16, in their affirmative answers, had a negative meaning; therefore, they were worth (−1). On the other hand, the remaining questions whose affirmative answers represented a positive value concerning the Mediterranean diet were scored with (+1). Negative responses received no score (0). According to the test, the results were grouped into different levels of adherence to the Mediterranean diet: low (score 0 to 3), medium (score 4–7), and high (8 to 12).Lastly, the decalogue of healthy eating, developed for the internal control of adherence to the prescribed dietary recommendations, allowed the dietitians and the children/parents to determine which nutritional aspects were quickest and simplest to improve. On the test, the results were grouped into different levels of adherence to the diet: low (score 0 to 3), medium (score 4–7) and high (8 to 10).Furthermore, the educational material designed and prepared specifically for the intervention group included printed documents and PowerPoint presentations for the group visits, focused on food cards and hidden nutrient techniques, healthy menus, diabetes, and the decalogue of the Mediterranean diet.p = 0.24), although there were differences for the total sample (p < 0.05). Differences in continuous variables between groups (EG and CG groups) were analyzed by Student’s test or Mann–Whitney Student when adequate. Paired measurements, and categorical variables were analyzed using the chi-squared test. All statistical analyses were performed using the statistical package SPSS (version 28.0) for Windows.The descriptive analysis of the categorical variables was expressed as a percentage, and the quantitative variables were expressed through measures of central tendency . The normalization test (Shapiro–Wilk) indicated normalization inside the sample .p < 0.01). Despite the initial differences regarding gender, there were no significant differences between girls and boys regarding the Hb1Ac (p = 0.085). Regarding the family characteristics, most of the guardians or parents were married (89.7%), with a primary education level (48.3%), a housewife (37.9%), with an 8-day shift (47.4%), with a period of unemployment between 6 months and one year (41.7%), with two dependents (62.1%) and received more than EUR 900 per month (62.1%).Twenty-nine children with prediabetes participated in the study, with a mean age of ten years, fifteen of whom were male (52% of the sample). The boys showed higher values than the girls in terms of weight , height , waist circumference (82.03 ± 8.67 vs. 60.82 ± 5.61), arm circumference (24.47 ± 3.06 vs. 18.57 ± 1.74), and BMI (23.6 ± 4.49 vs. 17.54 ± 2.09)  (Both groups (CG and EG) had no significant differences for the variables studied during the initial visit (V0) . In thisinsulin) .p < 0.05). The results indicated no significant differences between the GE and GC regarding the decrease in the perimeters. Nonetheless, the children from the EG showed a more statistically significant decrease in waist circumference  and hip circumference . Furthermore, the fat-free mass percentage increased after the intervention, and this increase was greater in the CG compared to the EG . The results also showed that there was no significant difference after the nutritional intervention regarding BMI and body fat percentage (p > 0.05) (The results of the intervention  showed t > 0.05) .p = 0.001 in CE and p < 0.001 in CG), but insulin had a significant change only in the intervention group , indicating significant differences between EG and CG for insulin level (p = 0.046) (Another parameter that showed improvement after the intervention was HbA1c and insulin levels . In both= 0.046) . In addi= 0.046) .n = 29) had low adherence to the Mediterranean Diet, 48.3% showed medium adherence, and only 6.9% showed good compliance with the healthy dietary model. The results of the KIDMED were 3.2 ± 2.1 (95% CI 2.01–4.39) for the CG and 4.57 ± 2.47 (CI 95% 3.14–5.99) for the EG, with no significant differences between groups at the beginning (p = 0.69). After the intervention, the results of the KIDMED test improved in both groups, significantly improving the EG and compared to CG   . In thisp < 0.01). The FFQ indicated a significant decrease in food intake, mainly in terms of carbohydrates and fat, in both the EG and the CG (p < 0.01). Furthermore, the results after the intervention regarding the FFQ score showed that the children from the EG experienced a higher reduction in food intake . Before the intervention, the mean energy intake of the 29 children with prediabetes was 2883 ± 430 kcal/day. The primary energy contribution in the diet was made by carbohydrates , followed by fats , and proteins (15%); the intake of carbohydrates and fats in the EG decreased after the intervention (p < 0.001) (p = 0.021) compared to the GC . The EG children decreased their weekly consumption of red and processed meats by 70%; half of them did not consume carbonated and sugary drinks, industrial pastries, snacks, or sweets (p < 0.05), indicating no significant differences between groups (p = 0.89)  . Althoug< 0.001) , the resr sweets . Finally = 0.89) .This pilot study analyzed the efficacy of a nutritional intervention based on the Mediterranean diet in comparison with a healthy standardized diet to reduce HbA1c and insulin levels and, therefore, reduce the prevalence of prediabetes in a rural pediatric population. Furthermore, this study analyzed the impact of nutritional interventions guided by health care providers to promote healthy habits and control risk factors, such as high BMI.The initial results of the data indicated that the frequency of prediabetes in a rural town seemed to be in line with the data from European countries and lower-income areas . These iThe results for both groups indicated that the BMI did not significantly decrease in the Mediterranean or healthy diet, which matched the results of several studies regarding the possibility of no significant decrease in weight or BMI ,32,33,34Moreover, the changes in the HbA1c in both groups highlighted how the Mediterranean diet and healthy diet, monitored by health care professionals, are effective interventions to control and reduce the risk of MD2. These results also matched the findings of the last executive summary of the Spanish Atherosclerosis Society , which hAnother exciting result was the improvement in adherence to the Mediterranean diet and the modifications in food consumption. Both groups experienced a reduction in food intake, with a corresponding reduction in energy, possibly associated with the lessening of the anthropometric parameters and improvements in Hb1Ac. However, the children from the EG experienced a significantly decreased frequency of low adherence to the diet and increased consumption of healthy foods, with a simultaneous increase in Mediterranean diet adherence. Moreover, after the intervention, the five most frequently consumed foods among our study population were carbonated and sugary drinks, skim milk products, whole-milk products, vegetables, and fruits. The pre-intervention data coincided with a previous analysis in Croatia, which reflected how children (8 and 9 years old) have low adherence to the Mediterranean diet, with their consumption of processed and sugary foods at levels higher than those recommended, which can lead to insulin resistance and other health issues ,36,45. HDespite the differences regarding the children’s preferences, these previous findings ,36,45,48As with any research, this study has limitations. The major limitation was the sample size of 29 individuals, 15 in the CG and 14 in the EG, resulting from the study’s voluntariness and the established inclusion criteria. This limitation implies that the findings may be exaggerated. It is, therefore, relevant to conduct this type of analysis with a larger sample. Another limitation was related to the coexistence of other health programs carried out in schools; furthermore, sociodemographic and individual conditions need to be considered since income or parental status may have modified the food preferences and the effectiveness of the results. In this sense, since the groups were located in a rural area of Southern Spain, the results could be limited in their generalizability to other children with prediabetes, even with similar-sized samples. Despite these limitations, the presented results showed how the eating habits of children with prediabetes improve with a dietary intervention based on nutritional education that allows them to discern unhealthy consumption. The eating habits improved exponentially in both groups, particularly through the adaptation to and inclusion of the Mediterranean diet, indicating that the role of healthcare specialists in any nutritional intervention results in improved healthy eating . Given tAdditionally, since there is currently a lack of studies aimed at the pediatric population , this stFor this reason, future research will be focused on a nutritional intervention carried out by health care professionals (such as nurses) with school-based follow-ups, monitored by a nutritionist with a larger sample of children and during a minimum period of 36 months.This pre-and post-intervention research aimed at a rural pediatric population with levels close to diabetes showed how the Mediterranean diet effectively reduces biochemical and anthropometric parameters. This efficacy was measured through a nutritional evaluation using validated questionnaires, visits to the children to improve their eating habits, and their adherence to the Mediterranean diet.


Introduction: Type 2 diabetes mellitus (T2DM) has been associated with higher rates and poorer prognosis of infections, mainly due to poor glycemic control, reduced response of T-cells and neutrophils, and impaired migration, phagocytosis, and chemotaxis of leukocytes. However, the impact of T2DM on acute cholangitis (AC) has not been assessed so far. Thus, we aimed to explore this association by means of a systematic review of the literature. Methods: This systematic review was carried out based on the recommendations stated in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the PubMed/MEDLINE, Web of Science and SCOPUS databases to identify relevant publications depicting an association between T2DM and AC from the inception of these search services up to present. Results: We detected a total of 435 eligible records. After we applied the inclusion and exclusion criteria, a total of 14 articles were included in the present systematic review. Included manuscripts focused on the potential role of T2DM as a risk factor for the development of AC and on its contribution to a worse prognosis in AC, e.g., development of sepsis or other complications, the risk of AC recurrence and the impact on mortality. Conclusions: As compared to non-diabetic individuals, patients with T2DM have a higher risk of AC as a complication of choledocholithiasis or gallstone pancreatitis. Several oral hypoglycemic drugs used in the management of T2DM may also be involved in the onset of AC. Diabetic patients who suffer from AC have a higher likelihood of longer hospital stays and sepsis, as well as a higher risk of mortality and more severe forms of AC as compared to non-diabetic individuals. Biliary tract infections (BTI), which include acute cholecystitis and cholangitis (or angiocholitis), are relatively frequent and, in most cases, potentially life-threatening bacterial infections of the intra- and/or extrahepatic bile ducts ,2,3,4. TEarly biliary decompression and rapid initiation of empiric broad-spectrum antibiotics represent the mainstays of treatment for AC. The restoration of the bile flow can be achieved surgically, percutaneously, or by endoscopy, but the 2018 TG for the management of AC recommend early endoscopic retrograde cholangiopancreatography (ERCP)  to be performed within 48 or 72 h ,6,17. BeAlthough diabetic patients can also develop AC, the impact of T2DM on AC development and outcome has not been assessed so far. Thus, the aim of this systematic review was to provide an overview of the implications of T2DM in patients with AC, namely the risk of readmission, the severity of AC, or the risk of AC complications. Although it is well known that patients with T2DM are prone to acquire infections of any kind, which complicates the management of this cardiometabolic disorder, no systematic review or meta-analysis have been conducted so far to identify and analyze the impact of T2DM on AC. This manuscript was prepared following the recommendations mentioned in the PRISMA guidelines . Three iThe following inclusion criteria were taken into consideration for the final selection of the articles: 1. Original studies which evaluated the prognosis, risk factors, outcomes, or management strategies of cholangitis and its complications OR original studies which evaluated the relationship between cholangitis and diabetes. 2. Studies conducted on the adult population . 3. The included articles were written in English, French, Italian, or Romanian (the languages spoken by the main investigators of the review). 4. The publication year of the included articles was after 1 January 2000. Exclusion criteria were as follows: 1. Studies performed on a population with subjects aged less than 18 years old, on cell cultures, or on animals. 2. Manuscripts written in a language that was not spoken by the authors. 3. Reviews, letters to editor, case reports, or abstracts presented at scientific events. 4. Studies published before 1 January 2000. 5. Studies that did not show any relationship between diabetes and cholangitis or any impact of this comorbidity on the prognosis, management, or treatment.All the articles included in the study met the inclusion and exclusion criteria as agreed unanimously by all the investigators. Any disagreement between the investigators was resolved by consultation with the senior author (C.C.D.) to allow for the final selection of the papers to be included in this systematic review. We evaluated the methodological quality and the risk of bias of the analyzed studies using the Methodological Index for Non-Randomized Observational Studies (MINORS) and the Mixed Methods Appraisal Tool (MMAT), respectively ,26. Thisn = 231), 204 original articles were selected for full-text review. After we applied the inclusion and exclusion criteria, a total of 14 articles were included in the present systematic review. The flow-chart diagram of the literature search process is reported in The 14 selected manuscripts were published between 2011 and 2022 ,38,39,40Overall, T2DM increased the risk of AC onset in patients with choledocholithiasis, gallstone pancreatitis, patients who underwent ERCP, and subjects with T2DM who were treated with oral hypoglycemic agents. T2DM was associated with longer hospital stay, sepsis, higher risk of mortality, and more severe forms of AC as compared to non-diabetic individuals ,38,39,40This systematic review focused on the impact of T2DM in patients with AC and discovered that T2DM is associated with worse outcomes in AC patients. T2DM also increased the risk of AC onset in patients with choledocholithiasis, gallstone pancreatitis, patients who underwent ERCP, and patients on oral hypoglycemic treatment for T2DM. T2DM was associated with a longer hospital stay, sepsis, higher risk of mortality, and more severe AC as compared to non-diabetic patients. As per our search in the explored databases, we were not able to identify any systematic reviews or meta-analyses on the association of T2DM and the outcome of AC. We believe this systematic review provides valuable information about how the changes in severity, mortality risk, length of hospital stay, and risk of bacteremia in AC are associated with T2DM. In our systematic review, 14 studies were included. Eight studies were focused on predicting bile duct complications in individuals with AC ,35,39,40Common bile duct (CBD) blockage due to choledocholithiasis, sclerosing cholangitis, malignancy, and bile duct instrumentation superimposed by intraductal bacterial overgrowth causes AC. Increased intraductal pressure secondary to CBD blockage is transmitted to biliary ductules, which increases their permeability to bacteria and bacterial toxins. Entry of pathogens and their products into the blood stream or surrounding tissues leads to complications, e.g., sepsis and hepatic abscess ,42,43,44Based on the analyzed data, we identified the following risk factors for suppurative AC: age above 70 years old, being a smoker, impacted duct stones, and the presence of gallstones . Renal dT2DM is known to cause dyslipidemia, as evident by the higher levels of triglycerides (TG), intermediate-density lipoproteins (IDL), very low-density lipoproteins (VLDL), and the lower concentrations of high-density lipoproteins (HDL) in individuals with T2DM as compared to subjects without this cardiometabolic disorder. While low-density lipoprotein (LDL) levels remain the same in T2DM, the levels of small dense LDL particles increase . This leSeveral investigations have highlighted that T2DM promotes bacterial proliferation in the bile ducts and also increases the risk of infected gallstones. As a result of diabetic neuropathy and angiopathy, blood flow to the bile ducts and gallbladder reduces, along with lower gallbladder contractility. This leads to bile stasis and increases the risk of biliary infections . GallstoAutonomic neuropathy in T2DM also causes the sphincter of Oddi dysfunction resulting in a high resting tone in fasting states, promoting cholestasis. Gastrointestinal dyskinesia in T2DM elevates gut anaerobic bacteria and gut pH, which hastens the production of deoxycholic acid. Higher levels of hydrophobic bile acids through the enterohepatic circulation lead to crystallization of cholesterol, hence leading to gallstones .Choledocholithiasis complicated by AC was highlighted in two studies ,33. A rep = 0.002) [One of the first studies which demonstrated the relationship between diabetes and AC in patients with common bile duct stones (CBDS) was the one developed by Khoury and Sbeit, which compared 101 patients with AC and CBDS  and 586 patients without AC and CBDS . They found that the presence of T2DM was more frequently associated with AC development, the association being statistically significant  .p = 0.33) [Listeria monocytogenes infection of the biliary tract, which is an infection that develops mostly in patients with an immunocompromised status. The study evaluated 20 patients  of whom only 4 associated diabetes as a comorbidity [In a study conducted by Kim et al. on 290 patients with acute biliary pancreatitis , a higher number of bile duct-related complications  occurred in patients with diabetes compared to those without this comorbidity, but the difference was not statistically significant ( = 0.33) . Anotherorbidity .p < 0.05). Other risk factors for complications mentioned in the study which were statistically significant were age, hypertension, previous ERCP, pancreatography, interventional placed biliary stent, balloon dilatation techniques, obstruction on different sites of ducts, and calculus extraction by endoscopic techniques [The risk of cholangitis after ERCP is well-known, and multiple studies have delineated different risk factors for post-ERCP complications. In a retrospective study that included 110 patients  who were treated by ERCP and developed cholangitis and 2174 patients who were subjected to ERCP but did not experience any complication, T2DM emerged as a risk factor for post-ERCP complications  [n  =  326) were of malignant etiology, with an increasing incidence over time . The average value of the Charlson Comorbidity Index was 1.4, with an increase over time . Malignant obstruction etiology was associated with 30-day mortality . Overall, 30-day mortality was 12% (n  =  91). After adjustment for confounding factors, no significant changes in 30-day mortality were observed over time  [Mohan et al., in a retrospective study of 388 patients diagnosed with AC between January 2009 and December 2016, looked at establishing predictive factors for in-hospital mortality. Thus, T2DM was diagnosed in 46.8% of those with a definite diagnosis, compared to 39.6% of those with an uncertain diagnosis and 38% of those with an excluded diagnosis, without having a statistically significant value. In addition, diabetes was present in a higher proportion in severe forms (48%), compared to moderate (37.8%) and mild 40.3%) ones ( = 0.19) . In Tan .3% ones p = 0.09) [Another retrospective study by Garcia-Alonso et al. , 51.7% women, 117 patients with diabetes), which evaluated the risk factors for cholecystectomy after an acute event , underlined that diabetes was associated more frequently with a non-surgical approach ( = 0.09) .p < 0.01) was an important variable together with age, ventilator-support time, systolic blood pressure, and coagulopathy [Diabetes seems to also be an important predictive factor for sepsis development after AC. Liu et al. created a predictive model for the risk of sepsis in which diabetes  for severe cases with admission in HDU. In addition, diabetes was the second most encountered comorbidity in those patients (34.7%) after hypertension (55.6%) [A prospective study conducted by Mak et al. in Singapore on 124 patients  with hepatobiliary infections evaluated the presence of factors associated with admission in high-dependency units (HDU) or prolonged hospital stay. They underlined that diabetes was an independent predictive factor on multivariable analysis ( (55.6%) .T2DM patients have a higher risk of contracting resistant infections because of an impaired immune system and frequent hospital visits. Obesity, which is closely associated to T2DM, leads to high proinflammatory cytokines  and adipokines which further hinder the subjects’ immunity. Due to a high BMI and fat distribution in obese patients with T2DM, blood concentrations of antibiotics remain suboptimal, elevating the risk of antibiotic resistance in this patient population . Addressp = 0.003) than in the patients without this comorbidity. Thus, T2DM is a risk factor for readmission of patients with AC, together with age, morbid obesity, and other choledocian complications/interventions [A retrospective cohort study conducted on 182 patients  by Jirapinyo et al. found that stent exchange at the time of AC was more effective in preventing recurrence than stent sweeping or the stent-in-stent approach. Thirty percent of the study participants had a history of T2DM, and absence of T2DM did not decrease the risk of disease recurrence. T2DM is a risk factor for recurrent bouts of AC; hence, caution must be practiced while using stents that are not designed for removal—for example, uncovered metal stents . Regardiventions .The authors of this review recommend that future clinical trials on this topic be conducted with larger sample sizes and comparison or control arms. We would also recommend the use of TG for risk and severity stratification criteria for AC . QuantitAs compared to non-diabetic individuals, patients with T2DM have a higher risk of AC as a complication of choledocholithiasis, gallstone pancreatitis, or ERCP. Some oral hypoglycemic drugs used in the management of T2DM may also cause AC. Diabetic patients suffering from AC have a higher likelihood of a longer hospital stay, sepsis, elevated risk of mortality, and more severe forms of AC as compared to non-diabetic individuals. Hence, this systematic review found an association between T2DM and worse outcomes in patients suffering from AC. The statistical significance of these findings may be found by performing quantitative analysis in future studies. Given the small number and the limitations of the studies included in this systematic review, the authors recommend that further large prospective studies are needed to investigate how not only T2DM as a whole, but, more importantly, its duration, glycemic control, and other components of the metabolic syndrome, influence the prognosis of patients with AC. A comparison or control arm and the use of the 2018 TG for risk and severity stratification criteria for AC should also be used to further increase the quality of the results. Last but not least, it is equally important to identify which are the best management options for these particular patients in order to achieve lower mortality and incidence of complications. Quantitative analysis may provide a stronger scientific value to papers as compared to qualitative analysis conducted in systematic reviews.


Diversified strategies to incorporate healthier lipids in processed meat products are being developed. Alternative fat sources to replace animal fat associated with the reduction of fat content are some of the methods used to obtain healthier meat products well recognized by consumers. In order to create a healthier product that can also be consumed in the Halal and Kosher consumer markets, an experimental study was developed to assess the effects of replacing the pork fat (4%) with the same amount of hydrogel emulsion incorporating olive oil or sunflower oil. Three burgers were randomly selected from each lot manufactured and analyzed in triplicate. Burgers were physicochemical analyzed for pH, water activity, composition, fatty acid profile, color, yield, texture, oxidative stability, and volatile compounds and compared according to the fat source. Burgers with hydrogel emulsions can be considered reduced-fat meat products with a healthier fatty acid profile than pork fat burgers. The use of hydrogel emulsions did not negatively affect the quality characteristics assessed in the product and improved the oxidative stability during the storage of cooked burgers. By the characteristics and formulations evaluated, the replacement of pork fat with olive oil hydrogel emulsion proved to be the most effective strategy for obtaining a healthier goat meat product. Recent social changes have led consumers to a greater awareness of healthy eating  and the Goat meat is less popular by far than pork, beef, or chicken in the occidental countries’ daily diet. However, goat meat is part of local food traditions, goat meat eaters represent a niche market, and goat meat consumption appeared to show a trend to increase in the last decade ,14. The Previous studies have shown that several reformulation approaches, i.e., reducing fat content, using different fat sources, and adding cereal flours, in different goat meat products i.e., sausages, nuggets, or pâté, can result in better sensory and nutritional characteristics ,24,25,26® , a mixture composed of calcium sulfate, sodium alginate, wheat glucose, disodium diphosphate, and sodium ascorbate. The fatty acid profile of the pork fat used, coming from Bísaro pork belly, was C14:0, 1.3%; C16:0, 22.3%; C16:1, 2.1%; C18:0, 11.9%; C18:1n-9, 41.9%; C18:2n-6, 15.7%; C18:3n-3, 1.2%; and C20:1n-9, 0.78% [Three types of goat meat burgers were prepared, one using pork fat (GPF) and the other two using olive oil (GO) or sunflower oil (GSF) hydrogel emulsions as lipid sources . The mea9, 0.78% . The oli9, 0.78% . The sunBurgers were made at the Carcass and Meat Quality Laboratory at Agriculture School of Polytechnic Institute of Bragança , according to the Portuguese Standard NP 588/2008  and follw) was determined according to AOAC [Burger pH was measured according to the Portuguese Standard NP-ISO 3441/2008 , with a  to AOAC  using a  to AOAC  , was determined by extraction of malondialdehyde (MDA) as stated in NP-ISO-3356/2009 with modifications. In the extraction procedure, approximately 2 g of sample were used and after homogenization with 20 mL of distilled water, TCA 25% was added and centrifuged at 12,000 rpm for 15 min. The results were expressed as mg of MDA/kg of the sample .Moisture content was analyzed according to NP 1614/2002 ; brieflySets of three burgers per treatment and batch, were weighed, measured, and then cooked in a convection oven in the fan-forced and upper and lower heating mode at 200 °C for 20 min until the inside temperature reached 80 °C. Burgers were turned upside down once during cooking. After being temperate for 1 h at room temperature (15 °C), weight loss (WL) was evaluated by the weight difference between fresh and cooked burgers and expressed as a percentage (Equation (6)). Moreover, the dimensional changes due to cooking were determined by measuring the thickness increase (TI) and shrinkage, both expressed as a percentage and determined by Equations (7) and (8) .(6)%WeiBurgers were then cut into two halves. One-half was used for texture profile analysis (TPA). This half was refrigerated for 24 h at 4 °C and then three 1-cm-sided cubes were obtained from the central zone. TPA was analyzed with a texture analyzer TA.XT2i  is equipped with a 5-cm diameter cylindrical probe set to run at 1 mm/s and a compression depth of 80% of the thickness of the sample. Mean values for hardness, elasticity, and cohesiveness were obtained from the force–time curves, and chewiness was calculated as the product of hardness, cohesiveness, and springiness. The other half was used to analyze TBARS and headspace volatile contents. Previously, this half-burger was divided into two quarters. One quarter was homogenized with a food processor and analyzed (recently cooked burgers). The other quarter was wrapped with (high oxygen permeability) polyvinyl chloride cling film and analyzed after three days of aerobic refrigerated storage .6.TBARS contents were determined following de above-mentioned procedure. Volatile compounds were analyzed by gas chromatography-mass spectrometry using the solid-phase micro-extraction (SPME) technique following the procedure described by Carballo et al.  with the® Pro 16.0.0, 2021, SAS Institute Inc. ©  . When the ANOVA was significant, the predicted means were ranked based on pair-wised least significant differences and compared using Tukey’s HSD test for p < 0.05, p < 0.01, or p < 0.001 significance levels. A discriminant analysis was performed using the linear, common covariance, and stepwise variable selection methods . The efficiency of the discriminant model was assessed by the test of Wilks’ lambda value. Results were analyzed in terms of absolute assigned individuals to a pre-assigned group and the variance explained by each canonical resemblance as well as by the analysis of the scoring coefficients.To analyze the differences between burger formulations, a standard least square model was fitted using the statistical package JMPw of fat replaced burgers were higher than that of GPF ones. However, the aw of GPF burgers was the highest among the formulations tested. The aw-reducing effect of hydrogel could be attributed to its components, namely mineral salts , glucose, and Na+ from the alginate and ascorbate salts incorporated into the HE burgers. The OH-groups of glucose might have played a significant role in that effect [+ originated from the hydrogels were not high enough to cause a significant increase in ash and NaCl contents of GO and GSF burgers as regards to GPF burgers , finding GO to have the highest value. This difference can be caused by the presence of the olive oil HE as reported in other studies, implying that the color of the olive oil used had an impact on the product ,50. LipiConcerning the proximate composition, in agreement with burger formulations  and the The lipid sources caused major changes in the FA profile . As expeThe weight losses and shape changes of burgers during cooking and the TPA results in the cooked burgers are shown in The results of TPA analysis showed minor effects since only cohesiveness was significant, although slightly, influenced by the use of HE in goat burgers. The higher cohesiveness in the HE burgers suggests that the structuring agents, alginate, in this case, would have contributed to increasing the intermolecular links between meat particles without a significant effect on the other TPA characteristics. Different and variable results have been reported in other studies on the effect of hydrogels on reduced-fat burger TPA, i.e., increasing or decreasing the hardness and chewiness, affecting or not cohesiveness or elasticity ,63,64,65It was observed that the treatment did not show any statistically significant differences in TBARS immediately after cooking. In other words, the addition of HE did not affect the MDA values in recently cooked burgers despite having a higher amount of polyunsaturated fatty acids and, therefore, more susceptibility of lipid to oxidation in the substituted samples might have been expected, similar results were found by Barros et al. . On the Among the aldehydes detected, as expected for cooked meat in general, hexanal dominated. This study shows that the formulation (lipid source) of burgers had a significant effect on the levels of hexanal, and also in those of nonanal and the sum of aldehydes. Moreover, storage time resulted in a significant increase in the amounts of all aldehydes. Actually, the effect of treatment on the volatile aldehyde contents was only evidenced in burgers after 72 h of refrigerated storage, i.e., the effect was not observed in the recently cooked burgers. The increase in aldehydes observed in burgers during storage indicates that the process of lipid oxidation progresses in all three types of burgers during this step. It is well known that lipid oxidation in cooked meat during storage and eventually reheating elicits the formation of carbonyl compounds and the subsequent development of the characteristic off-flavor named warmed-over-flavor (WOF) .In our study, the significant interaction effect observed between burger type and storage time shows that the rate of lipid oxidation during cooked burger storage varied among burger types. This variation in the lipid oxidation rate was also observed in the TBARS results . In agreDifferences due to different FA profiles in hexanal and nonanal, and eventually in other FA-derived odor-active volatile compounds presumably generated in the burgers during storage, although not detected with the method used due to an insufficient concentration in the headspace, such as hept-(E)-2-enal, oct-1-en-3-ol, octane-2,3-dione, and alka-2,4-dienals, would have affected the stored burger flavors. Specifically, these differences would have affected the intensity and unpleasantness of the WOF developed . This isRegarding the straight-chain hydrocarbons, the lipid source showed a significant effect on octane concentration which was present at the highest amount in recently cooked GO burgers. In agreement, octane has been found to be a major degradation compound formed from oleate during heating . Most ofp < 0.0001 *; Wilks Lambda value: 0.00475) which is possible to see in By performing a stepwise discriminant analysis, it is possible to identify and correctly classify 100% of the burgers using only two variables corresponding to the FA, C20:2n-6 and C18:1n-9, and the model is highly significant , lipidic healthiness was improved. HE affected the TBARS and volatile compounds of the burgers’ headspace after 72 h post cooking, suggesting higher oxidative stability during cooked burger storage. The discriminant analysis performed, identified correctly all formulations using only two FA (C18:1n-9 and C20:2n-6), indicating that besides their similar behavior through other analyses, they have a differentiating trait. In addition to that and considering the results obtained, it is possible to affirm that among the vegetable oils used, olive oil presented better characteristics when it comes to lipidic healthiness. Moreover, GO burger flavor, due to the release of higher levels of specific volatile compounds from oleic acid, might be more positively perceived by consumers, although it can only be presumed as a sensory analysis is needed to confirm such affirmation.


Introduction: The perinatal period is an at-risk period for the emergence or decompensation of psychiatric disorders. Transcranial electrical stimulation (tES) is an effective and safe treatment for many psychiatric disorders. Given the reluctance to use pharmacological treatments during pregnancy or breastfeeding, tES may be an interesting treatment to consider. Our study aims to evaluate the efficacy and safety of tES in the perinatal period through a systematic literature review followed by three original case reports. Method: Following PRISMA guidelines, a systematic review of MEDLINE and ScienceDirect was undertaken to identify studies on tES on women during the perinatal period. The initial research was conducted until 31 December 2021 and search terms included: tDCS, transcranial direct current stimulation, tACS, transcranial alternating current stimulation, tRNS, transcranial random noise stimulation, pregnancy, perinatal, postnatal, and postpartum. Results: Seven studies reporting on 33 women during the perinatal period met the eligibility criteria. No serious adverse effects for the mother or child were reported. Data were limited to the use of tES during pregnancy in patients with schizophrenia or unipolar depression. In addition, we reported three original case reports illustrating the efficacy and safety of tDCS: in a pregnant woman with bipolar depression, in a pregnant woman with post-traumatic stress disorder (sham tDCS), and in a breastfeeding woman with postpartum depression. Conclusions: The results are encouraging, making tES a potentially safe and effective treatment in the perinatal period. Larger studies are needed to confirm these initial results, and any adverse effects on the mother or child should be reported. In addition, research perspectives on the medico-economic benefits of tES, and its realization at home, are to be investigated in the future. The perinatal period, from pregnancy to one year after delivery, is a period of physical, biological, emotional, and psycho-social transformation in a woman’s life, imposing a significant adaptation that exposes her to a higher risk of acute psychiatric disorders . Mood diManagement of psychiatric disorders during the perinatal period remains a challenge. Indeed, psychotherapies can be hardly accessible , and the2 sponges, 20 to 30 min of stimulation over 5 to 20 sessions) had superior efficacy to placebo stimulation with a respective response rate of 33.3% versus 16.56% , and a remission rate of 19.12% versus 9.78%  [2; 20 min of stimulation over 5 to 40 sessions) was more effective than placebo stimulation on positive symptoms (standard mean difference (SMD): 0.17, 95% CI: 0.001 to 0.33), negative symptoms , and auditory hallucinations  [tDCS  is a NIBS technique that modulates brain activity using a weak intensity direct electric current delivered over short periods of time through two electrodes placed on the scalp: the anode, which facilitates spontaneous neuronal activity, and the cathode, which reduces spontaneous neuronal activity . To dateto 3.16) . Concernto 0.70) . For PTSto 0.70) —to enhanto 0.70) ,36. The to 0.70) .It must be noted that among all tES techniques, tDCS is the most widely used and has the advantage of being easy to use (without anesthesia), safe (no serious side effects), and associated with a low dropout rate ,38,39 inThis systematic review of the literature was performed according to PRISMA systematic review guidelines . DatabasStudies were eligible if they strictly included humans. We selected studies that assessed tES–tDCS/tACS/tRNS—for a psychiatric disorder in women during the perinatal period. The studies also had to be written in English until 31 December 2021. In addition, we restricted our selection to peer-reviewed articles . Search terms were selected to target our population  and our subject of interest (treatment by tES) by using several keywords:  AND ). The systematic review was not registered on PROSPERO.One reviewer (AL) searched using the terms cited above (in the eligibility criteria) to identify relevant studies that involved tES in women during peripartum. Titles and abstracts were screened by AL in order to remove duplicates. They were then assessed independently by two reviewers (AL and NN). Articles were excluded if both reviewers decided that an article clearly did not meet the criteria or if articles involved the use of tES for any reason other than a psychiatric disorder. In case of disagreement, the two reviewers had to reach a consensus. The same process was applied to the full-text versions of the remaining articles. For each case, we collected sociodemographic data, the psychiatric diagnosis motivating tES treatment, the stage of pregnancy at which tES was performed, the type of stimulation used, the stimulation procedure, as well as efficacy, safety, and tolerance data concerning the mother and child, including gynecological and obstetrical data. The risk of bias was not assessed, given the small number of articles involved.After the systematic literature review, we described three clinical cases, including data on tDCS efficacy . As a result of the selection criteria, seven papers were selected see . In addiThe results of our review are summarized in Regarding depression, we found two cases reporting stimulation of the dorsolateral prefrontal cortex in women during the first trimester of pregnancy. In monotherapy, tDCS  and gammRegarding schizophrenia, there were two cases reporting the use of tDCS to reduce auditory verbal hallucinations (AVH). Both studies were inspired by the original study of Brunelin et al. , seekingtDCS in a pregnant woman with type 2 bipolar depression: Here, we present a 28-year-old female monitored for type 2 bipolar disorder. She had presented a first depressive episode at the age of 18 and had been hospitalized after a suicide attempt. She then suffered several depressive relapses. Several antidepressants were administered with no notable efficacy. A type 2 bipolar disorder diagnosis was finally made, as there were hypomanic periods between recurrent depressive episodes. Lithium treatment did not show any efficacy and was discontinued after a few months. The actual episode consisted of a moderate depressive relapse. Initially, treatment with lamotrigine 100 mg per day was prescribed, which was partially effective considering that the patient refused to increase the dosage. In view of the worsening depressive symptoms after a few months, the patient was offered adjunctive treatment by tDCS (see the following research protocol [® device) performed included 15 sessions of 30 min over three weeks, that is one session per day with a current intensity of 2 mA (15 s fade-in and fade-out) delivered on 25 cm2 sponges, with anode placement on F3 and cathode on F4 . The patient reported some minor general side effects, such as fatigue and paresthesia. No mood swings were noted. Four days after the end of the tDCS treatment, i.e., one month after its beginning, the MADRS score was 15/60, BDI-13 score was 12/39, EQ-5D score was 50/100, and MoCA score was 26/30. The patient reported being pregnant a few days after the 1-month assessment. The tDCS treatment, therefore, took place between the first and third week of pregnancy. At two months and six months follow-up, MADRS and BDI-13 scores were, respectively, 18/60 and 12/39, and 13/60 and 11/39. The pregnancy went well with no complication reported. Labor was induced at 40 weeks and 5 days, a healthy baby was born . One month later, the patient reported a stable mood, and there were no health issues regarding her child.Case report #1—protocol ). Beforeprotocol , the Becprotocol , the Eroprotocol , and theprotocol . The tDCSham tDCS in a pregnant woman with PTSD: We present a 34-year-old female referred by the victimology service for PTSD treatment by neuromodulation. The patient’s other notable medical history included severe fibromyalgia—treated with long-term analgesics—and hospitalizations in psychiatry wards for major depressive episodes with suicide attempts. At the time of her evaluation, the patient was receiving a treatment consisting of venlafaxine 75 mg per day, described as effective on her last depressive episode. The patient reported experiencing a traumatic event in 2019 when her nephew allegedly died suddenly at home of cardiac disease during a family event. Being a former caregiver, she allegedly performed cardiopulmonary resuscitation until the arrival of the fire department. A few days after this traumatic event, the first post-traumatic symptoms emerged before the full PTSD appeared two months later. We diagnosed chronic and non-dissociative PTSD. The Clinical Administered PTSD Score (CAPS-5) was 23/80 [® device, NeuroElectrics, NIC software version 1.4) —while reading a traumatic script—according to the following parameters: a bi-encephalic set-up with the cathode placed on Fp2 and the anode placed on F3, the current intensity at 2 mA  or sham stimulation (only 30 s fade-in and fade-out) delivered on 20 cm2 sponges, 20 min of stimulation, two sessions per day (30 min between two sessions) over 5 consecutive days with an interval of 20 min between two stimulations, i.e., a total of 10 tDCS sessions. Before the first tDCS session, a negative pregnancy test had been performed. Sessions were well tolerated, with no serious adverse events. The patient reported some minor and transient adverse effects during sessions, such as tingling, difficulty concentrating, fatigue, scalp pain, itching, burning, and redness. One month after tDCS treatment, the patient reported a slight clinical improvement confirmed by psychometric scales with the following scores: CAPS-5 = 17/80, PCL-5 = 35/80 and BDI-13 = 8/39. At this one-month visit, the patient informed us that she was pregnant and that the first ultrasound dated the pregnancy to the weekend before the first tDCS session. Therefore, tDCS took place during the first week of pregnancy. As soon as the patient learned she was pregnant, she stopped all medication on her own so as not to take any risks regarding her pregnancy. The patient’s pregnancy progressed seamlessly with a standard gynecological and obstetrical follow-up. At the end of the pregnancy, and in the absence of analgesic treatment, the increasing and disabling pain of fibromyalgia motivated a delivery by cesarean scheduled at 39 weeks and 2 days of amenorrhea. The cesarean section went very well, without any complications, and the patient delivered a healthy baby boy with a birth weight of 3.120 kg for a height of 52 cm. Apgar scores were 10/10 at one and five minutes, and arterial cord pH was 7.31. One week after delivery, the child was healthy, and the mother was in remission. Indeed, post-traumatic symptoms gradually improved throughout the pregnancy. The patient was very satisfied with tDCS. At the end of the study, the unblinding revealed that the patient had received a sham (or placebo) stimulation.Case report #2—as 23/80 , the PTSas 23/80 , and thetDCS in a postpartum nursing woman: Finally, we present a 28-year-old woman living with her husband and two children aged 19 months and 3 months. She had received brief psychological treatment in early childhood following her parents’ separation and had presented a first depressive episode at the age of 15 after a relationship break-up. Since then, the patient has described chronic depressive symptoms of variable intensity. She had sought medical attention before the birth of her second child, at four months of pregnancy, because of an intensification of depressive symptoms associated with suicidal thoughts. Treatment with sertraline 200 mg per day had then allowed a partial improvement in her condition. Given the persistence of depressive symptoms that had slightly worsened during the postpartum period, and given that breastfeeding prevented the multiplication of drug treatments, tDCS was finally offered at three months postpartum. tDCS protocol  included 15 sessions of 30 min over three weeks, i.e., one session per day with a current intensity of 2 mA (15 s fade-in and fade-out) delivered on sponges of 25 cm2 with the placement of the anode on F3 and the cathode on F4, followed by four maintenance tDCS sessions once a week. We observed a partial response to treatment after the tDCS course (MADRS scores range from 36/60 before tDCS treatment to 25/60 after tDCS treatment). The patient reported an improvement in mood and a decrease in attentional problems. The side effects reported were minor and transient and included mild fatigue, paresthesia of the scalp, and a transient low-intensity headache. She continued to breastfeed during treatment. One month later, when she was able to return to work, the patient reported a depressive relapse.Case report #3—The aims of our review were to identify available studies about tES during pregnancy and the postpartum period in order to investigate its efficacy and safety during the perinatal period. To our knowledge, several reviews have addressed this topic ,57,58, bCurrently, the available data are sparse and limited to the use of tDCS or tACS in schizophrenia and unipolar depression during pregnancy. Our paper describes three different original case reports, including one case of tDCS treatment of bipolar depression, one of PTSD with sham (or placebo) tDCS, both during pregnancy, but also one case of tDCS usage in postpartum depression in a nursing woman. Presenting a sham (or placebo) tDCS case report may raise questions. In most studies, as in our case report, sham tDCS consists in emitting an electric field for a few seconds in order to imitate the physical sensations of active tDCS. There is now more and more evidence that repeated tES of a few seconds duration does have biological effects . It seeRegarding safety, not all authors proposed the same monitoring of obstetrical and fetal parameters, but the available data report no consequences on pregnancy and birth, and all studies report good tolerance of tES, with minor and transient adverse effects well known for tDCS ,39. ThisRegarding perspectives, studies about the experience of these women treated by tES are needed to evaluate the feasibility, acceptance, and perceptions of tES more precisely. Vigod et al.  reportedAlthough our review strived to be systematic, it obviously has some limits. First, the number of included studies is low. Second, these studies’ designs were heterogeneous and mainly consisted of case reports. We included one RCT, but the sample size was small and most likely involved in the lack of significant results. Third, we included studies that had very disparate pregnancy terms. Finally, we must consider the publication bias where the failures of tES, or the case of an adverse effect on the mother or child, would not have been published.tES appears to be a safe and effective treatment for a number of psychiatric disorders during the perinatal period. Larger studies are needed to confirm these initial results, including during the postnatal period and using tACS or tRNS. All cases involving tES during the perinatal period—successful or unsuccessful, and with or without adverse effects on mother or child—should be reported to tES manufacturers: such feedback from the field can inform updated recommendations. Practitioners should also contribute to medical device safety surveillance efforts. In addition, research perspectives on the medico-economic benefits of tES, and its realization in patients’ homes, are to be investigated in the future.


Therefore, Ti powder can effectively remove oxygen-containing impurities from commercial hexane and facilitate its use as an effective carburizing medium for the synthesis of high-purity tantalum carbide.Hexane is a safe, efficient, and cost-effective alternative to other commercial hydrocarbons for gaseous carburization; however, commercial hexane is not sufficiently pure. Titanium powder can remove oxygen-containing impurities from commercial hexane; however, research on the use of titanium powder remains limited. We investigated the purification of hexane using titanium, copper, and aluminum powders and used the purified hexane for the gaseous carburization of tantalum. Ti exhibited lower activation energy for oxidation (1.55 kJ/mol) than Cu (91.09 kJ/mol) and Al (150.25 kJ/mol) and a significantly higher oxidation rate (0.0269 g/h) in hexane at room temperature than Cu (0.0018 g/h) and Al (0.0001 g/h). The carbon content in tantalum carburized using the purified hexane was comparable to that carburized using unpurified hexane (approximately 6.22%); however, its oxygen content was significantly lower (1.39%), which indicates that the produced tantalum carbide has a higher purity. X-ray diffraction results revealed that the oxidation products of tantalum, such as Ta Owing to their unique properties, such as high corrosion resistance, excellent high-temperature mechanical properties, thermal and chemical resistance, low thermal expansion, wear resistance, and high hardness, carbide-based materials are receiving considerable attention . These m2O5) and graphite powders to simultaneously induce reduction and carburization reactions, are being studied for commercialization [Tantalum carbide powders are mainly manufactured via three methods: (1) heat treatment in a non-oxidizing atmosphere using a mixture of tantalum metal and graphite powders, (2) solid carburization, such as self-propagating high-temperature synthesis (SHS) using the reaction heat between reactants by mixing tantalum and graphite powders ,12,13, alization .Among these methods, solid carburization is limited by requirements of high reaction temperatures of 2000 K or higher, difficulties in controlling product uniformity, and residual-free carbons . FurtherThe purity of hexane commonly used in the industry is 95%, necessitating a process for the removal of impurities. However, there have been no reports on the removal of impurities from commercial hexane. For the first time, we have suggested the economically feasible method for producing of TaC ceramic compound material. We purified the commercially available hexane using irregularly shaped titanium powder, which is further used to produce the high purity TaC by means of gas carburization , as it cAfter all, in this study, in order to manufacture high-purity tantalum carbide more easily and efficiently compared to the conventional carburizing process, we intended to produce high-purity tantalum carbide more safely and with less energy and cost.2O5) as the raw material with reducing magnesium gas. Therefore, the tantalum powder for the carburizing reaction was prepared as per the method reported in our previous study [Hexane with 95% purity was used . The metal powders to be used for hexane purification—Ti, Cu, and Al powders—were obtained , with purities of 99.99% and average particle sizes of 30–40 μm. Furthermore, in a recent study, we manufactured tantalum metal powder using tantalum oxide . The tantalum metal powder was heated to 1273 K using the tube furnace at a heating rate of 10 K/min. The flask was connected to the tube furnace using a stainless-steel tube. Argon gas (99.999% pure) was selected as the carrier gas, which flowed through the branch of the flask at a flow rate of 200 cc/min, such that the hydrocarbon gas could reach the tube well. The hydrocarbon gas supplied to the tube through the argon gas reacted with the tantalum metal powder for 2 h at 1273 K. The temperature was raised at 10 K per minute up to the reaction temperature. The tantalum carbide powder was obtained by cooling the carburization reaction mass. The metal powders used for the purification of hexane were subjected to specific surface area and morphological analyzes, such as the Brunauer–Emmett–Teller (BET) analysis  and scanning electron microscopy . The tantalum carbide powder obtained via carburization was subjected to characteristic evaluation of phases and components using an X-ray diffractometer , an oxygen/nitrogen/hydrogen determinator , and a carbon/sulfur determinator .2O5) via heat treatment at 1573 K for 2 h, magnesium reduction was performed at 1173 K in an argon atmosphere for 20 h to prepare a Ta + MgO mixture. SEM and XRD analyzes were then performed on the pure tantalum powder, which was obtained by removing magnesium oxide, a byproduct of the reduction, by stirring and washing the reaction mass with an aqueous hydrochloric acid solution. SEM shows that the particles of the reduced tantalum metal powder are spherical, with an average size of 200–250 nm. The reduction was considered successful, based on the absence of magnesium oxide from the tantalum phase, as indicated by the XRD results of the reduced tantalum powder (see wder see . The oxy2), moisture (H2O), sulfuric acid (H2SO4), and carbon dioxide (CO2) [The oxygen-containing compounds present as impurities in hexane may include dissolved oxygen (Ode (CO2) . G. Grazde (CO2)  reportedde (CO2) . HoweverMoreover, as shown in Moreover, the oxidation rates of all metals increased with the temperature of hexane solution, depending on their activation energies. The activation energy for the oxidation reaction of each metal was determined from the slope of the line obtained from the relationship between ln k and the reciprocal of the hexane solution temperature (1/K) .The oxidation of metals generally occurs at temperatures more than half of their melting point, and not at temperatures as low as room temperature. However, oxidation was observed even at room temperature in this study and was attributed to a behavior different from the general oxidation behavior.The oxidation of the metals in hexane at room temperature was attributed to the corrosion of the metals in the fluid . The basAlthough the fluid used in this study was hexane and not water, some of the corrosion reactions that occur in water may have occurred owing to the presence of dissolved oxygen and moisture in hexane.2/g, respectively [2 [Another possible reason for the low-temperature oxidation, though insignificant, may have been the acceleration of corrosion because of the buoyant pressure experienced by the metal powder in the fluid . Next, wectively . Thus, tively [2 , respectively [2 ,32. Moreively [2 . Hence, ively [2 ,35. By c2O, TaO2, Ta0.8O2, and Ta2O5 were present, indicating that oxidation occurred during carburization. This is qualitatively consistent with the high-oxygen-content results of the carburization experiment using unpurified hexane , the lower activation energy of Ti results in a higher oxidation rate in hexane at room temperature. This indicates that Ti is more effective at removing oxygen-containing impurities from hexane at room temperature than copper and aluminum. In the carburizing reaction, the carbon content of the tantalum product was almost identical to the theoretical value, regardless of whether hexane had been purified, indicating successful carburization. Moreover, the oxygen content in the tantalum carburized using purified hexane was approximately six times lower than that of tantalum carburized using unpurified hexane, indicating that hexane purified using Ti powder yielded high-purity tantalum carbide, without producing undesirable oxidation products. Through this, we produced high-purity tantalum carbide faster and more efficiently than the traditional carburizing approach using a technology that used less energy and more safety. Thereafter, research on manufacturing tantalum carbide of higher purity is planned by further performing a process of removing impurities of hydrocarbon used before the carbonization process.