The main objective of this study is to explore the effects of hepatitis C (HCV) on the prevalence rate of kidney stones in US women.Dates for HCV infection and kidney stones were collected from National Health and Nutrition Examination Survey (NHANES) database, a cross-sectional study. The analysis samples included adults aged ≥20 years and women from six consecutive cycles of the NHANES 2007–2018. The association between HCV infection and kidney stones was performed by using logistic regression models. Subgroup analyses were conducted to find sensitive crowds.A total of 13,262 participants were enrolled, including 201 infected with HCV. After adjustment for potential confounders, we revealed a positive relationship between HCV and kidney stones . The crowds' statistically significant difference was characterized by other races  and BMI within 25–29.9 kg/m2 .HCV infection may affect the prevalence of urolithiasis in US women, even the causal relationship remains unclear, the relation deserves special attention. We considered such a study an ideal way to begin exploring the effects of HCV on kidney stones. When it comes to the urinary system, nephrolithiasis (NL), also known as kidney stones, is a prevalent problem in the study field, with high rates of occurrence and recurrence –3. The mHepatitis C virus (HCV) is a single-stranded RNA virus with an envelope that belongs to the Flaviviridae viral family . It is rAs a consequence, we undertook a large population-based cross-sectional investigation using the National Health and Nutrition Examination Survey database to determine if there is a link between HCV and the occurrence of kidney stones in the general population. Subgroup studies were conducted at the same time to identify the most vulnerable population. All of the studies aimed to provide some kind of proof for the prevention of renal illness on some level.www.cdc.gov/nchs/nhanes/) has further information on the data.Data for this study were obtained from the NHANES database based on big data mining methods and were conducted by the Centers for Disease Control and Prevention (CDC) , 22. NHAn = 25,163); (2) undetermined HCV infection status ; and (3) men   unknown kidney stone  . A totalTo identify kidney stones, the results from the KIQ026 (Do you have kidney stones?) questionnaire were used. To confirm the diagnosis of HCV infection, laboratory tests were completed. The methodologies for detecting HCV-Ab and HCV-RNA were developed from the laboratory data column's “Description of Laboratory Methodology.” HCV-Ab(+)or HCV-RNA(+) were used to define positive HCV infection. Age, race, education level, marital status, PIR (Ratio of Family Income to Poverty), physical activity, total water consumption, high blood pressure, diabetes, and alcohol users were all included in the questionnaires. The laboratory test yielded the BMI.Regarding the selection of weights, the principle of the official guidelines provided by NHANES is to first specify the variable that examines the smallest population and then proceed with selecting the weights corresponding to that variable. In this study, our data included MEC examination data, and according to the recommendations of the weight selection guidelines, we selected the sub-weights corresponding to MEC. According to the NHANES analysis guidelines, the new sampling weights for the combined survey cycles were constructed by dividing the 2-year weights for each cycle by six .Categorical, dichotomous, and continuous variables were used to record the data. Continuous variables were expressed as mean standard deviation (SD), and dichotomous and categorical variables were expressed as counts proportions. Weighted Chi-square tests  and weighted one-way analysis of variance (ANOVA)  or weighted Kruskal-H Wallis's test (skewed distribution continuous variables) were used to evaluate differences in clinical characteristics between groups. When <10% of the data were missing, the missing item value was replaced by means. For variables with an additional category, missing indications were produced. Because HCV-Ab data was unavailable from 2015–2016, the infection status gap was filled by the total HCV infection prevalence from 2007 to 2018.Figure 3). To investigate the independent connection, three logical regression models were created in our study: (1) unadjusted; (2) adjusted for age and race; and (3) adjusted for all factors. In addition, we used stratified multivariate logistic regression to conduct subgroup analyses to find acceptable groups. Statistical analyses were carried out using R 3.5.3 (http://www.r-project.org/) and Empower Stats software (http://www.empowerstats.com), with a P-value of 0.05 being considered statistically significant.We employed machine learning to predict the effect of each research variable on kidney stone prevalence to assess the risk of the factors linked to kidney stone prevalence (P for trend<0.001). However, this tendency did not hold for HCV infection prevalence (P for trend >0.05). In comparison to the nonstone former group, the stone former group had a greater prevalence of HCV infection (p < 0.0001). The results are depicted in A total of 13,262 people were included in our study, and the necessary variables are listed in 2   statement . In an u24–4.83) .Nephrolithiasis is characterized by a high prevalence, a high recurrence rate, and a varied prognosis , 26. ProOur investigation indicated that the prevalence of kidney stones was increasing every 2 years, and the findings in the literature corroborated our findings , 5. Howe2 and other races. Overweight (BMI 25–29.9 kg/m2) and obesity (BMI ≥ 30 kg/m2) are risk factors for the development of kidney stones, and Parvin  and nephrolithiasis, the most significant crowds were those with BMI of 25–29.9 kg/md Parvin  found a d Parvin  in 2019 Simultaneously, machine learning was utilized to determine whether certain variables have an effect on the occurrence of kidney stones in this study. Data may be ranked using machine learning according to their influence. The most relevant factors in the model of kidney stone development were the albumin creatinine ratio, BMI, serum creatinine, age, non-Hispanic white, high blood pressure, HCV infection status, and so on. Some research have been carried out to compare the advantages and disadvantages of machine learning approaches to traditional regression techniques. As of yet, however, the findings have been considerably disparate. Studies have revealed that logistic regression may be as accurate as, or, perhaps, more accurate than other machine learning algorithms in certain situations . Other rOur research shows for the first time that HCV infection may have an effect on kidney stone development, utilizing a cross-sectional study. As a result, there has been no research on its putative mechanism. We hypothesize the following causes based on past research on its correlation: It is widely established that renal tubular epithelial cell injury is a critical stage in the processing of kidney stones prevalence. Although chronic kidney disease (CKD) is now recognized as an extrahepatic manifestation of hepatitis C virus, it is often advanced. Researchers are reporting that tubulointerstitial damage is the early stage of renal manifestation rather than glomerular damage , which iThe following are some of our study's limitations: (a) Because this was a cross-sectional research, it cannot prove a causal link between HCV infection and the likelihood of kidney stone development; (b) It should be noted that the NHANES only included “self-reported” data on kidney stone history, which excluded asymptomatic stones. Another drawback is that we were unable to determine the sort of renal calculi that were present; and (c) Eating habits may have an impact on kidney stone development. However, no dietary information or characteristics related with kidney stone production were collected.Participants with HCV infection had a higher chance of acquiring kidney stones. Infection with HCV may be a risk factor for the production of kidney stones in US women.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/The studies involving human participants were reviewed and approved by NCHS's Institutional Review Board reviewed and approved the study protocol. The patients/participants provided their written informed consent to participate in this study.YC: conceptualization, methodology, and software. XS: data curation and writing—original draft. HL and GL: visualization and investigation. KH: supervision and software. CL and ZH: writing—review and editing. All authors contributed to the article and approved the submitted version.This work was supported by the National Natural Science Foundation of China (82070724) and Natural Science Foundation of Anhui Province (1908085MH246).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.


An artificial intelligence-based system was implemented for preoperative safety management in cataract surgery, including facial recognition, laterality (right and left eye) confirmation, and intraocular lens (IOL) parameter verification. A deep-learning model was constructed with a face identification development kit for facial recognition, the You Only Look Once Version 3 (YOLOv3) algorithm for laterality confirmation, and the Visual Geometry Group-16 (VGG-16) for IOL parameter verification. In 171 patients who were undergoing phacoemulsification and IOL implantation, a mobile device  camera was used to capture patients’ faces, location of surgical drape aperture, and IOL parameter descriptions on the packages, which were then checked with the information stored in the referral database. The authentication rates on the first attempt and after repeated attempts were 92.0% and 96.3% for facial recognition, 82.5% and 98.2% for laterality confirmation, and 67.4% and 88.9% for IOL parameter verification, respectively. After authentication, both the false rejection rate and the false acceptance rate were 0% for all three parameters. An artificial intelligence-based system for preoperative safety management was implemented in real cataract surgery with a passable authentication rate and very high accuracy. The term wrong-site surgery usually encompasses operations on the wrong patients, performing the wrong surgery (other than the one indicated or intended), or performing surgery on the wrong body part or, for body parts that are symmetric, on the wrong side . Even wiIn ophthalmic procedures, common surgical confusions include incorrect intraocular lens (IOL) implantation, incorrect eye procedures , and incorrect patients or procedures ,8,9. WroAn iOS-based app was developed by the Tsukazaki Hospital AI team for facial recognition of patients, laterality confirmation (right or left eye), and IOL parameter verification.The facial recognition system involving two main tasks, face detection and recognition, was constructed based on the facial recognition development kit . Prior to the day of surgery, a face photo of the patient not wearing a mask was taken with a mobile device  camera and stored in the referral database. The mobile device was used just as a camera without using the facial recognition function of iOS. Approximately 100 facial key points were utilized for identification of individual faces. On the day of surgery, before entering the operating room, the patient’s face photo without a mask was captured with a mobile device camera, which was then checked with the reference photograph stored in the database.The laterality confirmation system was developed with a two-stage object detection model of the You Only Look Once Version 3 (YOLOv3) algorithm ,12. ThisThe IOL parameter verification system was constructed and trained in three stages: detection of the information area on IOL packages by YOLOv3, identification of the IOL model number by the Visual Geometry Group-16 (VGG-16) architecture ,14, and A total of 171 patients who were undergoing phacoemulsification and IOL implantation at the Tsukuba University Hospital between February and May 2022 were included. There were 67 males (91 eyes) and 55 females (80 eyes), and their age averaged 66.8 ± 16.0  years. Due to partial consent given by some patients and incomplete AI training for new IOLs, different numbers of patients participated in the three trials: 162 patients in the facial recognition test, 171 in the laterality check, and 135 in the IOL parameter verification.The authentication rate on the first attempt, the cumulative authentication rate after repeated attempts, false rejection rate, and false acceptance rate were evaluated. Eighteen clinicians took part in the photographing and authentication processes. One patient was verified by a single clinician.The Institutional Review Board of the Tsukuba University Hospital approved the study protocol (R02-252). This study was conducted in accordance with the Declaration of Helsinki. Informed consent for data acquisition was obtained from all subjects involved in the study.The cumulative authentication rate and number of attempts for facial recognition are shown in Laterality (right or left eye) confirmation was successful in 82.5% on the first attempt, which increased to 98.2% after the seventh trial . In threIOL parameter verification was more difficult with low authentication rates even after several attempts . The iniAfter authentication, both the false rejection rate and the false acceptance rate were 0% for all three parameters: facial recognition, laterality confirmation, and IOL parameter verification.In the current study, we evaluated the authentication rate and accuracy of the AI-based app for facial recognition, laterality confirmation, and IOL parameter verification in cataract surgery. Once the app recognized a patient’s face, eye, or IOL parameters, both the false rejection rate and the false acceptance rate were 0% for all three parameters, indicating the high accuracy of this identification system. On the other hand, the authentication rate was not satisfactory, especially for IOL parameter verification.Facial recognition technology has been increasingly applied in the healthcare industry for its perceived accuracy in identifying individuals and has been proposed as one of the reliable ways to improve patient security. Especially with the COVID-19 pandemic in recent years, facial recognition technology has a significant advantage compared to other methods of identification; it doesn’t require any physical contact and can be used from a distance. Besides simplifying the check-in and check-out process and improving the overall patient experience, facial recognition helps prevent fraud and misidentification of patients. In the current study, facial recognition failed in six cases (3.7%). The reasons for failure include inadequate face photos registered in the referral database and poor photographing before surgery, both of which are human errors and can be avoided with due diligence.We employed the YOLOv3 algorithm for laterality confirmation. A similar deep learning method has been used to distinguish the right and left foot using plantar pressure images . Since tIncorrect IOL implantation is the leading cause of medical mishaps in cataract surgery ,8,9. ActIt is obvious that the AI-based system cannot completely replace the current human checklist system for surgical information confirmation. As shown in this study, the authentication rate of the app is not and will not be 100%, and the referral database cannot always be perfect. In particular, the IOL verification system needs to be trained and updated regularly when a new IOL is introduced or even when the package design is modified. In addition, the patient profile database including face photo and information, which is created and maintained by humans, may be defective. Nevertheless, the human checklist system is not flawless, either, and thus the AI-based app system is considered to be a powerful safety-net guarantee to help reduce thoughtless mistakes. The performance of an AI-based confirmation system, involving photo shooting with an iPad or iPad mini, adds a few seconds to the “time-out” duration in the operating room, and the implementation of a new system requires additional costs. Once implemented, however, the AI-system is tireless and consistent, and its running cost is far lower than the salary for a human medical staff. Once surgical confusion occurs, its consequences can be devastating. Introduction of a reliable AI-based system would be beneficial in terms of related time- and cost-effectiveness.There are several limitations to this study. First, the current study has no control group. It is ideal to compare the data before and after the implementation of our AI-based app system to prove its efficacy. With an extremely low incidence of surgical confusion in the real world, however, it is difficult to quantitatively demonstrate the differences before and after implementation. Second, the subjects of our study were not consecutive cases. Some patients refused to participate, and others consented to participate in a part of the study; specifically, several patients declined to have their faces photographed. Participants and non-participants were randomly mixed in our study population. This was one of the reasons why the study was confused especially for IOL parameter verification. Third, we only assessed the authentication rate and accuracy of three parameters, and other factors were not evaluated, such as time and effort required for the implementation of this system. We suppose that additional time and effort are needed in the early period of system introduction, but the workflow will eventually be improved when staff members become more familiar with the process, making the preoperative safety management more precise and smoother than the conventional analog approaches.We implemented a deep learning-based system for preoperative safety management in cataract surgery. The final authentication rate for facial recognition, laterality (right and left eye) confirmation, and IOL parameter verification was 96.3%, 98.2%, and 88.9%, respectively. After authentication, both the false rejection rate and the false acceptance rate were 0% for all three parameters.


Fecal microbiota transplantation (FMT) is an emerging therapy for diseases associated with intestinal flora imbalance that has attracted increasing attention in recent years. This study aims to provide an overview of research trends in the field, and act as a reference point for future scientific research by analyzing the state of current research, identifying hotspots, and potential frontiers of FMT.Articles relating to FMT that were published between the years 2012 and 2021 were retrieved from the Web of Science Core Collection. Bibliometric analysis was performed using Microsoft Excel and CiteSpace.PLoS One journal. Alexander Khoruts was identified as a prominent, productive researcher in the field. Keyword analysis revealed that research hot spots included gut microbiota, Clostridium difficile infection (CDI), and diseases. Burst detection indicated that future research frontiers include clinical practice guidelines and strategies.A total of 2,403 English language articles relating to FMT research were published over the last ten years. Most of this research was carried out in the United States of America, with Harvard Medical school being the most productive institution. Much of the research was published in the Our analysis explored hot spots and emerging trends in the FMT field. Indications for use of FMT extended from digestive system diseases to other systemic diseases. Additionally, areas such as risk assessment and control, along with application methods were also a focus of current research. Moreover, research relating to optimization of clinical practice has excellent prospects. Clostridium difficile (C. difficile) infection (CDI)  is a method for treating intestinal and extra-intestinal diseases. FMT can be used to reconstitute the intestinal microbial community in recipients by transplanting the functional flora in the feces of healthy donors into the gastrointestinal tract of patients . Historion (CDI) , ulceraton (CDI) . Moreoveon (CDI) , obesityon (CDI) , and hepon (CDI) . In receon (CDI) , the eston (CDI) , and theon (CDI) .Gut microbiota dysbiosis is involved in the pathology of many diseases . The intAs the field of FMT has developed rapidly and shows great potential in treating various diseases, we carried out a bibliometric analysis of relevant articles published between 2012 and 2021. The bibliometric method allows quantitative and qualitative analyses of specific topics and articles to evaluate academic productivity and trends. CiteSpace is a network analysis and visualization software developed by Chaomei Chen based on the JAVA platform . It can The literature retrieval was conducted on March 24th, 2022, using the Web of Science Core Collection. The search formula used was “) OR TS=) OR TS=) OR TS=) OR TS=) OR TS=) AND PY=(2012-2021)) AND DT=(Article)) AND LA=(English).” We placed restrictions on the publication date (2012-01-01 to 2021-12-31) and the language (English). Inclusion was limited to original research articles. Other literature types such as review articles, meeting summaries, and editorial materials were excluded. Ultimately, we identified 2,403 eligible records  and quartile were obtained from Journal Citation Reports 2021. The IF is determined by the number of citations and total articles in the last two years  and reflMicrosoft Excel 2016 was used for basic calculations and plotting of annual trends of publications and citations. Publications and citations were represented by bar and line charts. The trend test was performed using polynomial curve fitting.CiteSpace (5.8. R 3 64-bit) was used for bibliometric and visual analysis. The visual map consists of nodes and links. In the network, the nodes were used to represent the countries, institutions, authors, references, etc. Meanwhile, the size and frequency of the node were in direct proportion. The different colors of nodes correspond to different periods. The connection link between nodes indicates the relationship between them, and the thickness of the connection line indicates the strength of the association. The number of nodes and connections from the network are represented by N and E, respectively. Betweenness centrality was used to measure the centrality of the vertices of the shortest path in a network. It indicated the importance of a node and the relationship between neighboring nodes. Nodes with a betweenness centrality greater than 0.1 were usually marked with purple circles and were considered turning points or key points in the field.This study included 2,403 English articles related to FMT. A total of 42,796 articles were cited, with a total citation number of 92,290, and an average citation number of 38.41 times. The H-index was 134.2 = 0.9943, R2 = 0.9948). The above results demonstrate that FMT research has received increasing attention in recent years. It is expected that the number of related articles and citations will enter a sustained growth stage in the future.The number of FMT publications trended upwards over the period from 2012 to 2021, especially after 2018 Figure 1Scholars in 81 countries published research articles . Among these top 10 journals, the fields of gastroenterology & hepatology, and microbiology were represented by five and two journals, respectively, further illustrating that the digestive system is an important area of focus for FMT research. In addition, all the listed journals were distributed in Q1 or Q2, indicating that the above journals had strong academic influences on FMT research.In total, 728 journals were identified as publishing FMT-related articles, and There were 465 authors who published articles related to FMT Figure 3According to the category analysis of Web of Science, FMT research mainly focuses on microbiology, gastroenterology, hepatology, and immunology Figure 4“clostridium difficile infection,” “disease” and “infectious bowel disease”, indicating that the damage to the gastrointestinal tract caused by CDI and other inflammatory diseases were hot topics in FMT research. According to the centrality, the top five keywords are “antimicrobial resistance” (0.19), “mouse model” (0.18), “gut” (0.15), “immune response” (0.15), and “diet” (0.14). This indicates that FMT has a potential role in counteracting the side effects of certain drugs and lifestyles, and relevant animal experiments have been widely conducted  was reported by Vrieze and colleagues in 2012. It demonstrated that the transplantation of intestinal microflora from lean human donors could improve insulin sensitivity in recipients  Poterganisms , and therganisms .Emerging trends can be identified through the analysis of burst keywords . Burst kIn this study, we used CiteSpace to reveal the cutting-edge hot spots and dynamic changes in the FMT research field over the past decade. Our study found that FMT can improve the intestinal microenvironment and has prominent advantages in the treatment of many diseases. However, the large-scale application of FMT also faces safety, legal, and regulatory challenges. Furthermore, there are some limitations to this study. Firstly, all articles were retrieved from the Web of Science Core Collection only. Secondly, search strategies are not guaranteed to cover all FMT-related articles. Thirdly, due to the dynamic database updates and the rapid development of FMT research, our study cannot include all of the latest findings.Clostridium difficile”. In recent years, the research of Chinese scholars has advanced at a rapid pace. Research hotspots and trends mainly involve the treatment of digestive system and other system diseases, with a particular focus on CDI and ulcerative colitis. In addition, new indications, new technologies, and new norms of FMT are also focuses of research. Overall, this study reports the advances in the field over the past 10 years from multiple dimensions through visual analysis of FMT research, paving the way for the follow-up research.From 2012 to 2021, publications and citations relating to FMT research increased year by year. The USA has played a leading role in the field, with Harvard Medical School and Alexander Khoruts being the most prolific institutions and authors, respectively. A few key studies have pushed FMT into the spotlight, including the widely cited and influential study from Noude and colleagues titled “Duodenal infusion of donor feces for recurrent The original contributions presented in the study are included in the article/Conceptualization: LZ and MY; methodology: FZ and PY; software: YC; formal analysis: JW; data curation: LZ; writing—original draft preparation: FZ and PY; writing—review and editing: RW and BL; visualization: FZ, PY and YC; supervision: MY; project administration: LZ; funding acquisition: LZ. All authors have read and agreed to the published version of the manuscript.This work is supported by the National Natural Science Foundation of China (grant number: 81973730).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.


Waste management workers experience high stress and physical strain in their work environment, but very little empirical evidence supports effective health management practices for waste management workers. Hence, this study investigated the effects of worker characteristics and biometric indices on workers’ physical and psychological loads during waste-handling operations. A biometric measurement system was installed in an industrial waste management facility in Japan to understand the actual working conditions of 29 workers in the facility. It comprised sensing wear for data collection and biometric sensors to measure heart rate (HR) and physical activity (PA) based on electrocardiogram signals. Multiple regression analysis was performed to evaluate significant relationships between the parameters. Although stress level is indicated by the ratio of low frequency (LF) to high frequency (HF) or high LF power in HR, the results showed that compared with workers who did not handle waste, those who did had lower PA and body surface temperature, higher stress, and lower HR variability parameters associated with higher psychological load. There were no significant differences in HR, heart rate interval (RRI), and workload. The psychological load of workers dealing directly with waste was high, regardless of their PA, whereas others had a low psychological load even with high PA. These findings suggest the need to promote sustainable work relationships and a quantitative understanding of harsh working conditions to improve work quality and reduce health hazards. Waste management workers responsible for collecting, transporting, and sorting waste face various challenges ,2. They Waste management facilities are mainly involved in processes such as crushing, sorting, compacting, and incineration. In areas where automated operations are difficult, waste work can be labour-intensive and dangerous. The Japan Construction Occupational Safety and Health Association (JCOSHA) regulates safety management efforts in the manufacturing and construction industries . In laboSignificant advancements in wearable technology in recent years have enhanced opportunities to monitor the biometric data and physical condition of workers in the workplace. The use of wearable devices to observe working conditions through the measurement of heart rate (HR), body temperature, and physical activity (PA) is rapidly gaining popularity ,9. AssesThis cross-sectional study of workers in the waste treatment industry compared biometric information and workload index of workers completing two different types of tasks—industrial waste handling vs. non-industrial waste handling—at the same waste treatment facility. In this study, two groups were set up: “waste handling workers” and a “control group” who were not involved in waste handling tasks.Based on the research objectives and literature review, the following hypotheses were proposed:Hypothesis 1 (H1):Differences in the biological parameters of the workers are apparent in the comparison between waste treatment and non-waste treatment workers.Hypothesis 2 (H2):Worker workload in a waste management facility is positively correlated with PA and body surface temperature.Hypothesis 3 (H3):Using the measured parameters of waste workers, their workload and psychological load can be estimated.This study was approved by the Research Ethics Review Committee of Ritsumeikan University (BKC-2019-009) in accordance with the Declaration of Helsinki, United Nations Educational, Scientific and Cultural Organization’s Universal Declaration on the Human Genome and Human Rights.The specifications of the measurement devices and equipment used in this study are listed in A flowchart of the background, objectives, and analysis in this study is presented in The data were collected from 3 to 4 September 2019, and 24 to 26 August 2020, at the Kyoto Environmental Conservation Corporation, a waste management facility in Fushimi-Ku, Kyoto, Japan. The participants were recruited from among the facility’s employees; workers who responded to the call from the facility took part in this experiment. The participants were defined as healthy adults aged 20–63; those with neurological or cardiovascular diseases were excluded. All the participants were men. A total of 29 workers : 15.7 years; average body mass index (BMI): 21.5, SD 3.2; average work experience (EXP): 7.7, SD: 4.2 years) were included in the final sample.n = 22) was responsible for the transport, dismantling, and sorting of industrial waste, and Group B (n = 7), for the maintenance and repair of the facility. The list of participants in each group is presented in Based on their job profile or responsibilities, the participants were allocated to two groups. Group A  were assigned to each participant during the experiment and data analysis.Statistical analysis was conducted using SPSS Version 26 for Windows  and Excel add-in software Bell Curve  for Excel version 3.21 . In addition, the following statistical tests were performed on the three hypotheticals:Hypothesis 4 (H4):When comparing waste treatment workers to non-treatment workers, we tested whether there were significant differences in the biological parameters of the two populations of workers. The normality of data was tested using the Shapiro–Wilk and Kolmogorov–Smirnov tests . First, Hypothesis 5 (H5):To analyse the relationship between changes in biological parameters and temperature fluctuations that cause heat stroke and other physical ailments experienced by waste treatment workers, the effect of workers’ biological parameters on body surface temperature was analysed. Multiple regression analysis was performed, with the independent variable being the biological parameters of the workers and the dependent variable being body surface (BS) TEMP.Hypothesis 6 (H6):To investigate whether the measured biological parameters of waste treatment workers could be used to estimate workload and psychological load, a multiple regression analysis was conducted with the workers’ biological parameters as independent variables and physical and psychological load as dependent variables. The multiple regression analysis conducted in this study investigated the presence or absence of multicollinearity among candidate variables and proceeded by combining dependent and independent variables with no multicollinearity.Human performance is affected by various environmental factors in a working system, including heat stress ,19. The Studies using non-invasive wearable devices have found a significant correlation between human HR and body surface temperature measurements and the thermal environment ,27,28,29Heart rate variability (HRV) is not only related to its effect on physical load, but also to autonomic control, such as self-regulation and psychological and physiological stress, making it useful for psychological load analysis ,34. A loIn a previous study, RMSSD was related to workers’ perception of mental stress , with loHRV metrics have shown promise in multiple applications for healthcare professionals, and several researchers have focused on this field ,42,43,44HRV measurements are derived from RR data and are influenced by the length of the time series (number of data points), body posture, and activity type. In the present study, these factors were derived using the five-minute RRI, which provides values for each activity. Fuentes-García et al.  reportedOutliers or error beats due to artefacts are typically found in the time series of heartbeat intervals and have no physiological significance. Artefacts can significantly distort measurements in the time and frequency domains and increase the power over a wide band of frequencies . In HRV l, data points outside the interval were excluded, and the mean of the data points within the moving window was calculated, excluding the centre point; a is a positive number equal to or less than one. In this study, l = 41 and a = 0.2 were used.The data set collected in this study consisted of evaluation data collected at five-minute intervals and was filtered based on previous studies to exclude the effect of artefacts on HR ,57. Brieworking is the average working heart rate, HRresting is the resting heart rate, and HRmaximum is the maximum heart rate based on age [resting was defined as the lowest stable five-minute heart rate in the work break.To determine the physical load during waste management work, the HR and PA of workers were used as indicators. The basic relationship equations are presented in d on age . In thisX, horizontal axis: Y, and vertical axis: Z) [A small accelerometer (WHS-2) attached to the sensing wear placed on the chest was used to obtain the composite acceleration along three axes  . Five-miaxis: Z) . Detaileaxis: Z) .We collected data on the participants’ HR, physical acceleration, and body surface temperature at various times during the working day. The WBGT of each group was measured in their respective work areas. A total of 1945 data points, measured approximately every five minutes, were collected from the 29 participants. The monitoring of workers was conducted throughout the working day, which included a one-hour break, and observations were made from 9:00 a.m. to 4:30 p.m. The data are presented in The research team did not monitor participants’ behaviour but recorded their work activities using two cameras installed near each work area. Prior to the experiment, we told the participants that we would not measure their operating skills and instructed them not to deviate from their daily working routines, thereby avoiding the Hawthorne effect .p = 0.05 [The normality of data was tested using the Shapiro–Wilk and Kolmogorov–Smirnov tests . In bothp = 0.05 . Howeverp < 0.05, the null hypothesis is rejected, indicating a statistically significant difference in the distribution of data for each group [The Mann–Whitney U test does not require a normally distributed data set , and itsch group . StatistIn addition, the time-domain parameters related to the autonomic nervous system, NN50, pNN50, and RMSSD, were low in waste management workers, thus indicating a decrease in parasympathetic activity or a state of relaxation. In the frequency-domain parameters, they may also have lower LF power associated with the parasympathetic nervous system and higher LF/HF, indicating stress. The ratio of LF power to HF power (LF/HF) is a classic indicator of sympathetic balance . This vaThe data collected in each work environment were merged and analysed for their effects on the body surface temperature of the workers. Multiple regression analysis was performed to evaluate significant relationships between each parameter. The results are presented in As shown in The data collected from each work environment were merged to evaluate the relationship among worker characteristics, PA, BS TEMP, HRV index, and physical and psychological loads as dependent variables. 2 of 0.449. The results of the analysis are shown in First, we obtained a multiple regression equation that demonstrated the effects of the independent variables PA, BS TEMP, and age on the workload. The regression equation, as shown in Equation (2), has an adjusted R2 of 0.356. The results of the analysis are given in Subsequently, we obtained a multiple regression equation showing the effects of the independent variables RRI, BS TEMP, LF power, and EXP on psychological load. The multiple regression equation, as shown in Equation (3), has an adjusted RThe biometric data of waste treatment workers were analysed to obtain a multiple regression equation for estimating their load at work, and the results established that BS TEMP was significantly affected by both workload (%HRR) and psychological load (LH/HF).This study investigated the effects of workers’ individual characteristics and biometric indices on their physical and psychological loads during waste-handling operations. The results indicated significant differences in the workers’ HRV time-domain parameters , and HRV frequency parameters  when comparing waste handling and non-waste handling operations. Compared with workers who did not handle waste, those who did had a lower PA and BS TEMP; lower HRV parameters  associated with higher psychological load, and higher LF/HF and LF power were associated with stress. There were no significant differences in HR, RRI, and %HRR. These results suggest that waste disposal workers work under a high psychological load, regardless of their HR and workload %HRR due to their work.2 = 0.449), and psychological load LF/HF was estimated from the autonomy-influenced RRI, LF power, BS TEMP, and years of experience (adjusted R2 = 0.356). PA and BS TEMP had a positive effect on workload %HRR [Workers’ workloads and psychological loads were estimated using measurement parameters. Although studies have analysed the relationship between body temperature, WBGT, and HR ,68, thisoad %HRR , and theoad %HRR ,70. Theroad %HRR  confirmeUEMAE et al.  observedIn the estimation of %HRR, body surface temperature was affected as an explanatory variable, but there was no effect of environmental temperature on WBGT. This relationship indicates a low correlation between body surface temperature and WBGT, as evident from The participants of this study were exposed to low physical load and high mental stress. This indicates that waste workers may experience higher psychological stress due to the characteristics of their jobs, such as taking extra care in regards to the safety of their environment and working with hazardous waste, than those engaged in hard physical labour. Eggenberger et al.  demonstrIn the estimation of workers’ psychological load, experience was inversely correlated with LF/HF (standard β of EXP = −0.018). Experience is negatively correlated with LF/HF because, as workers gain more experience, they have more knowledge about dealing with the waste. Thus, the psychological load may be reduced by improving inexperienced workers’ knowledge of health literacy, waste to be handled, protective gear, and tools and education and training. Studies using questionnaire surveys of waste workers have established that worker demographics  and working conditions  are significantly related to psychological load levels ,77,78. WThis study makes the following theoretical contributions. The psychological load LH/HF by HRV and %HRR as workload were used to quantify the workload of waste management workers. In addition, equations for estimating these loads using physical and psychological loads from HR and biometric data, including PA and body surface temperature, were developed.Regarding practical contributions, the study found that the physical and psychological loads of waste workers, which have not been clarified previously, differ depending on the type of work. This evidence and monitoring of workers will assist the waste management industry to reduce health risks and enhance the working conditions of workers, and it can suggest new management concepts to companies by considering these factors from the perspective of health psychology.This study has several limitations. First, physical characteristics and age were not equally balanced in the sample. Although physical characteristics affecting workload and stress vary with age and gender ,80, the In this study, physical and psychological loads in the workplace were investigated among workers at a waste management facility in Japan. The workers performed their daily tasks in an environment exposing them to high stress depending on environmental temperature and task. Those who directly handled waste had lower PA, lower body surface temperature, and lower HRV parameter values associated with the autonomic nervous system than maintenance workers at the facility. Workload and stress among waste management workers, which has not been investigated in previous studies, suggested a significant relationship between HR variability, body surface temperature, PA, age, and years of experience. The workers’ body surface temperature was significantly related to HR, PA, environmental temperature, and age. The psychological load LF/HF was affected by the HRV parameters, RRI and LF power, body surface temperature, and years of experience.Regular monitoring of biometric and physical information such as HR, body surface temperature, and activity can help understand the working environment of workers with high physical and psychological loads and promote the maintenance of sustainable relationships among them in harsh manufacturing and construction environments . A quant


Plecoglossus altivelis altivelis, is commercially important to inland fisheries in Japan and popular as a summer delicacy owing to its unusually sweet flavor. Ayu is also a popular recreational fishing species, especially for anglers using the Japanese fishing method “tomozuri.”Ayu or sweetfish, https://www.e-stat.go.jp/en), the commercial catch of ayu in 2020 has decreased by 88.3% compared with the maximum catch of 16,414 tons in 1991. In the manuscript, the current knowledge of BCWD in ayu, which inhabits Japanese rivers, was compiled.Bacterial cold-water disease (BCWD) was first recorded in an ayu farm in the Tokushima Prefecture in 1987 . The cauTwo forms of native ayu exist, amphidromous and landlocked ayu, with an assumed genetic distance and divergence time of approximately 100,000 years . AmphidrFlavobacterium psychrophilum. Amphidromous stock is genetically more resistant to BCWD than landlocked and domestic stocks  and divides the isolates into two genotypes: A and B types , and topoisomerase IV (parE) genes to improve genotyping performance and potentially allow the classification of 16 genotypes.The single PCR–RFLP assay targets peptidyl-prolyl cis-trans isomerase C  were present in the lower basin for spawning.The on/off switch assay identifies two single nucleotide polymorphisms of ding ayu . This asF. psychrophilum in ayu populations in Japanese rivers and Lake Biwa . In late June 2014, there was a mass die-off of ayu in the upper reaches. F. psychrophilum from all the collected dead individuals, and almost all isolates were identified as A/G-C types. The Kagami River, located in central Kochi Prefecture, is 31 km long with a drainage basin area of 170 km2. The Monobe River, located in central Kochi Prefecture, is 71 km long with a drainage basin area of 508 km2. The two rivers are considered Class A rivers, which are assigned by the government of Japan as important for the conservation of national land or for the national economy, and are famous for ayu, especially the Shimanto River, which possesses an abundance of native amphidromous ayu resources  ayu stocks were not released and (2) no anglers fished on the river because of a fishing ban. F. psychrophilum isolates from the dead individuals, determined their draft genome sequences, and examined their genotypes, which were in agreement with the genotypic results of F. psychrophilum over winter in the Nahari River and possible reinfection of the ayu population in the next spring.The findings presented in this manuscript indicate that ri River , which iAll authors contributed to the article and approved the submitted version.


Blocking the activity of neurons in a region of the brain involved in memory leads to cell death, which could help explain the spatiotemporal disorientation observed in Alzheimer’s disease. Related research article Zhao R, Grunke SD, Wood CA, Perez GA, Comstock M, Li MH, Singh AK, Park KW, Jankowsky JL. 2022. Activity disruption causes degeneration of entorhinal neurons in a mouse model of Alzheimer’s circuit dysfunction. eLife11:e83813. doi: 10.7554/eLife.83813.Alzheimer’s disease is a neurodegenerative disorder that affects approximately 55 million people globally . One ser– throughout life. In mouse models of Alzheimer’s disease, however, the role of hippocampal and entorhinal cells in learning and memory is impaired  converges into layers II and III of the entorhinal cortex, which form the major input sources for two regions in the hippocampus, called the dentate gyrus and CA3. These areas of the brain are part of a pathway that ultimately terminates in another hippocampal region known as CA1 . It is tThe findings of Zhao et al. hold promise for potential new treatment strategies targeting the cell population in layer II of the entorhinal cortex early on in the Alzheimer's disease. These interventions have the potential to slow down the cascade of events leading to the onset of the condition.


P < 0.05) for female and 0.1% (P > 0.05) for male individuals, compared with a decrease of 4.9% for female and 3.7% for male individuals in South Korea (both P < 0.05). Age–period–cohort analysis revealed that the attributable stroke mortality decreased along with the time period, and increased along with age. Significant gender differences were observed, male individuals in both countries were at higher risk than their female counterparts, especially in China. Joinpoint analysis suggested that the attributable stroke mortality for both genders in South Korea and female individuals in China showed a decreasing trend, while it is stable for male individuals in China. Although prominent reductions were observed during the past decades, the attributable stroke mortality risk in China and South Korea is still high. Our findings indicate that controlling the intake of red meat may be a cost-effective strategy to reduce stroke mortality risk and the corresponding disease burden, especially for Chinese male individuals.The high intake of red meat is well recognized as a major health concern worldwide. It has been recognized as a risk factor for several non-communicable chronic diseases, including stroke. However, previously published studies have not performed a comprehensive analysis of the long-time trend of stroke mortality attributable to high red meat intake in China and South Korea, two countries with similar dietary patterns and changing trends. Therefore, this study aimed to reveal the influence of age, time period, and birth cohort on long-term trends of stroke mortality attributable to high red meat intake and relative gender differences in China and South Korea. Data were obtained from the Global Burden of Disease 2019 database. The age–period–cohort model was used to estimate the effect of age, time period, and birth cohort. The average and annual percent changes were estimated using the joinpoint regression analysis. Results indicated that the overall attributable age-standardized mortality rates of stroke in China decreased by 1.0% ( Stroke is the second leading cause of death and the third leading cause of disability worldwide . CompareThe incidence of cardiovascular and cerebrovascular diseases is usually closely related to an unhealthy diet structure, unreasonable living habits, and other diseases . Among tBoth China and South Korea are countries with high standardized stroke and DALYs in the East Asia region . Stroke The same tradition in dietary patterns and similar changing trends make China and South Korea have good comparability in analyzing stroke mortality attributable to dietary factors. Through literature review, we found that studies on the long-time trend of dietary factors attributable to stroke mortality have mostly focused on the intake of salt, vegetable, fruit, and alcohol ; therefoTherefore, in this study, we aim to analyze the long trend of high red meat intake attributable to stroke mortality in China and South Korea—two Asian countries with similar eating habits, traditions, and changing trends—and the corresponding gender difference during the period from 1990 to 2019. Research data were obtained from the Global Burden of Disease (GBD) 2019 study, and we used the age–period–cohort (APC) frame to explore the effects of age, year period, and birth cohort, as well as the long time trends.1 In the GBD study, all data were expressed as numerical values and their 95% confidence intervals. The GBD 2019 study is a comprehensive health loss study using a harmonized and comparable approach to the burden of disease by gender and age-group in 195 countries and territories based on reliable and representative data from multiple global sources from 1990 to 2019  of red meat  higher than 23 (18–27) grams .Stroke mortality was defined according to the WHO International Statistical Classification of Diseases and Related Health Problems, Ninth (ICD-9)  or TenthThe attributable mortality was estimated using the population-attributable fraction (PAF) considering genders, each year, and age-groups in GBD 2019 study. The PAF was the proportion of stroke mortality reduced if HRMI was reduced to the level of theoretical minimum risk exposure level (TMREL). For stroke mortality attributable to HRMI, the TMREL refers to the average daily consumption of red meat of no more than 23 grams . In the joasgt is the PAF for cause (of death) c, for age-group a, sex s, location p, and time period  t; RRjcasl(x) is the relative risk of exposure level x for risk factor j, for cause c, controlling age a, sex s, and location p; l and u were the lowest and highest observed exposure levels (the lower and the upper boundary) of x; and TMRELjas is the TMREL for risk factor j, age-group a, and sex s. For the HRMI attributable stroke mortality, the risk factor is HRMI, the cause is stroke, and the location is China and South Korea, respectively. In the GBD 2019 study, stroke mortality attributable to HRMI was defined as the (basic) stroke mortality multiplied by the PAF  were also analyzed in this study. In the GBD 2019 study, it was defined as follows:ai was the specific age ratio. The weights wi were derived from the GBD 2019 global standard population  and RStudio  software. All statistical tests were two-tailed, and the level of significance was set at 0.05.2  model using the APC Web Tool2 . To convWe estimated coefficients for age, period, and cohort effects for attributable stroke mortality using the APC model. The APC model can be expressed as follows , 36:R represents the mortality rate, ε is the residual, and c is the constant; Age, Period, and Cohort represent the three factors including age-group, year period, and birth cohort, which may affect the mortality; and α, β, and γ are the coefficients of the three factors, representing the effect of age-group, year group, and birth cohort. In the APC analysis, the exponential values of the coefficients denote the relative risk (RR) of attributable stroke morbidity of a given age, period, and birth cohort, relative to the reference groups  across time periods, in this study, we performed the joinpoint regression analysis to estimate the long-time trends of stroke mortality attributable to HRMI. The joinpoint regression was also called change-point regression, which was first introduced by Kim et al. . It can y represents the mortality rate, Year is the observation year, β represents the coefficient of Year, τk is the unknown turning time point (joint point) that needs to be identified, and c is the constant.Here, To determine the magnitude of trends in attributable stroke mortality, the annual percent change (ANPC), average annual percent change (AAPC), and its corresponding 95% confidence interval (CI) were estimated by joinpoint regression analysis. The ANPC and AAPC were defined as follows:ib is the estimation of β on the ith identified trend and iw is the length of the ith identified trend.Here, The joinpoint model analysis was conducted by the Joinpoint Regression Program .The long-term trend of stroke ASMRs attributable to HRMI by gender in China and South Korea is presented in P-values > 0.05 after the year 2008), and the attributable ASMRs in China for male individuals showed an overall relatively stable trend (P > 0.05) from 13.383 (95% CI: 6.166∼20.008) to 13.587 (95% CI: 8.278∼19.130), while for female individuals, ASMRs slightly decreased (thought P > 0.05) from 10.179 (95% CI:4.328∼15.416) to 7.513 (95% CI: 4.603∼10.498) per 100,000, as shown in The stroke ASMR attributable to HRMI in China is higher than that in South Korea for both genders  per year, as shown in The CMRs of male individuals in South Korea show an inconsistent trend from 1990 to 2019. The overall AAPC is −0.2% (95% CI: −0.4%∼0.0%) per year, as shown in Overall, for both CMRs and ASMRs, there are downward trends for both genders in South Korea and an upward trend for male individuals in China. Detailed results are presented in Stroke has long been identified as one of the leading cause of death worldwide . It was via gut flora and then further oxidized to trimethylamine N-oxide (TMAO) by flavin monooxygenase (FMOS)  . Severale (FMOS) , 44. Pree (FMOS) , 42.via the oxidative injury mechanism (Second, iron is also abundant in red meat . Most ofechanism , which mechanism . Moreoveechanism . Thus, cIn the APC analysis, we found that the local drift of both genders in South Korea was below 0 in all age-groups, indicating a stable decreasing trend for the stroke mortality rate attributable to HRMI. While for male individuals in China, the local drift is higher than 0 before the age-group of 45–49 years and after the age-group of 65–69 years. The local drifts for female individuals in China was also below 0 for all age-groups. The overall net drifts for both genders in South Korea and female individuals in China suggested a downward trend, while that for male individuals in China is above 0. The local and net drifts indicated that for male individuals in China, especially the middle-aged Chinese male individuals, the stroke risk is upraising.This study also observed that the longitudinal age curves of stroke mortality attributable to HRMI were growing faster for Chinese people than for Korean people with age, especially for Chinese male individuals. The longitudinal cohort curve also suggested that the attributable stroke mortality for both genders in both countries was higher in earlier birth cohorts. Those findings all suggested that the attributable stroke mortality was associated with age. Previous studies have proved that age is one major non-modifiable risk of stroke . StudiesHowever, for both genders in South Korea, we also found a mild decline in attributable stroke mortality for age-groups after 85–89 years. A previous study showed that the senior population in South Korea had significant physical changes such as deterioration of oral conditions, decreased chewing function, weakened digestive function, and loss of taste or appetite due to psychological factors . All theIn both countries, we found that stroke mortality risk for male individuals is higher than that of their female counterparts, and a significant gender difference was observed. Gender differences in stroke mortality have long been observed, while the related mechanism still remained unclear in the current literature . HoweverDuring 1990–2019, ASMRs showed an overall mild fluctuated rising trend for male individuals, while a decreasing trend for female individuals in China. A previous study in China also showed that the stroke mortality trend is volatile, and two peaks in the past three decades appeared in 2005 and 2010 , which iThe period RR for stroke mortality in China for male individuals decreased from 2004 to 2019, and increased from 1994 to 2004, while for female individuals, the period RR showed deceasing trend from 1994 to 2019. According to the China Statistical Yearbook , the chaThe period RR for both genders in South Korea has been declining in the past three decades and fell below 1 in 2004. With the development of the socioeconomic status, the consumption of red meat increased over time. However, in 2002, a diet guideline  has beenNowadays, red meat is leaner and lower in fat content than that 10 years ago . This isThe cohort effect showed consistent downward trends in both genders in both countries. The cohort effect is dependent on age and period effects; indeed, it is hard to explain them separately in the real world. Recently published APC analyses of stroke mortality attributable to diet  or hyperThrough literature review, we found this study is the first research focusing on the temporal trends of stroke mortality attributable to HRMI and providing a comprehensive quantified comparison between China and South Korea. However, there are also some limitations to this work. Because the GBD data were summarized statistics, substantial bias may not be totally avoided. Future cohort-based studies may be of great value to verify our findings. Then, due to the complexity of the diet in China and South Korea, the estimation of the red meat intake amount may also be influenced by potential bias. In addition, the results obtained using the data from China and South Korea may not be able to extend to other countries in the same region.In summary, the mortality of stroke due to high consumption of red meat is more serious in China than in Korea. In both the countries, male individuals had a higher risk of stroke than their female counterparts. Male individuals, especially middle-aged to old male individuals in China, are at higher risk of HRMI attributable stroke risk. Our findings suggested that controlling the intake of red meat could be a cost-effective strategy to reduce stroke risk and the corresponding disease burden.http://ghdx.healthdata.org/.Publicly available datasets were analyzed in this study. This data can be found here: JM and FC: conception and writing – critical revision. FC and WH: data acquisition. WH and SC: software. FC, JM, and WH: formal analysis and writing – original manuscript. WH, SC, AS, and YZ: investigation. All authors contributed to the article and approved the submitted version.


Multimorbidity is common, but the prevalence and burden of the specific combinations of coexisting disease has not been systematically examined in the general U.S. adult population.To identify and estimate the burden of highly prevalent combinations of chronic conditions that are treated among one million or more adults in the United States.Cross-sectional analysis of U.S. households in the Medical Expenditure Panel Survey (MEPS), 2016–2019, a large nationally-representative sample of the community-dwelling population. Association rule mining was used to identify the most common combinations of 20 chronic conditions that have high relevance, impact, and prevalence in primary care. The main measures and outcomes were annual treated prevalence, total medical expenditures, and perceived poor health. Logistic regression models with poor health as the outcome and each multimorbidity combination as the exposure were used to calculate adjusted odds ratios and 95% confidence intervals.Frequent pattern mining yielded 223 unique combinations of chronic disease, including 74 two-way (dyad), 115 three-way (triad), and 34 four-way combinations that are treated in one million or more U.S. adults. Hypertension-hyperlipidemia was the most common two-way combination occurring in 30.8 million adults. The combination of diabetes-arthritis-cardiovascular disease was associated with the highest median annual medical expenditures , and the combination of diabetes-arthritis-asthma/COPD had the highest age-race-sex adjusted odds ratio of poor self-rated health .This study demonstrates that many multimorbidity combinations are highly prevalent among U.S. adults, yet most research and practice-guidelines remain single disease focused. Highly prevalent and burdensome multimorbidity combinations could be prioritized for evidence-based research on optimal prevention and treatment strategies. An estimated 42% percent of American adults 18 and older suffer from multiple chronic conditions  .Despite the high frequency of multimorbidity in the population, most clinical practice guidelines, and the evidence they are based upon are single disease focused. Adhering to multiple, sometimes conflicting, guidelines for multiple individual diseases is burdensome  and convUnderstanding the rate that disease coexist or cluster together at higher-than-expected rates, may also provide clues about the etiology between two or more conditions. For example, inflammation has been shown to be a mechanism for numerous conditions including cancer, cardiovascular disease, chronic kidney disease, and diabetes . Damage specific combinations of multimorbidity. Most prevalence studies of multimorbidity are based on counts of conditions  combinations of multimorbidity treated among adults in the United States. An innovative machine learning algorithm –association rule mining – was used to identify all combinations of multimorbidity occurring in one million or more U.S. adults. The association with average and median per capita direct medical expenditures and perceived fair or poor health status was also examined, to identify combinations associated with the most burden.n ≤ 10). The final unweighted sample was 89,947 adults . The MEPS is a large-scale panel survey of a nationally representative sample of households in the United States and is administered by the Agency for Healthcare Research and Quality (AHRQ) . The MEP7 adults .The MEPS data used in this study is publicly available and de-identified. The Case Western Reserve University Institutional Review Board reviewed the protocol for this study and deemed it to be exempt under U.S. federal law.Health conditions were self-reported through open-ended questions about conditions reported to be treated with prescription medications or associated with health care utilization . The resPerceived health was assessed by asking respondents to rate their health as excellent (1), very good (2), good (3), fair (4), or poor (5). The variable was dichotomized into two values: a response of excellent, very good, or good was categorized as good perceived health, while a response of fair or poor was categorized as poor perceived health.Medical expenditures were defined as the sum of direct payments for care provided during the year, including out-of-pocket payments and payments by private insurance, Medicaid, Medicare, and other sources. Expenditure data were collected in the MEPS through both self-report and through data collected from the respondents' physicians, hospitals, and pharmacies, when available. The MEPS provides imputed values when data are missing or payments are made under capitated plans . Total eThe main analytic techniques in this study were association rule mining and frequent pattern mining . In brie20) possible combinations of 20 conditions. The minimum support  threshold was set at 0.20% for the initial pass, and then after applying survey weights, any combinations with a point estimate of < 1 million adults (~0.40% of the U.S. adult population) was dropped.The method was applied here by treating each subject in the study data as the “transaction,” and each chronic condition as the “items” to find the most frequently coexisting combinations out of the 1,048,576  were used to account for stratification and clustering effects when estimating variances . Person-Combinations of conditions and corresponding prevalence estimates represent “at least,” rather than “exactly.” For example, people with hypertension-hyperlipidemia-diabetes would be a subset of the people with hypertension-diabetes.For each combination, we calculated the observed-to-expected prevalence ratio , which is the observed prevalence of the combination divided by the expected prevalence given all single diseases in the combination are independent of each other. Lift significantly greater (or lower) than 1 indicates the coexistence of diseases is unlikely due to chance alone.To identify specific combinations associated with the highest average cost and perceived poor health burden, we filtered out combinations that were redundant in that they offered little new information on the outcome measure over a more parsimonious  combination, using a minimum improvement criteria of 10% , 39.Survey-weighted logistic regression was used to estimate the age-race-sex adjusted odds ratios, with poor health status as the outcome, and each disease combination as the exposure, accounting for clustering and stratification. Adjustment variables were age as a continuous variable with splines, race , and sex. Subgroup analysis was performed by sex as a secondary analysis.Data pre-processing was performed using SAS version 9.4 for Windows. The analysis was conducted using R version 4.1.0, RStudio (v. 1.4.1717), and R packages: arules (v. 1.6-8) and survey (v. 4.1-1) , 41.The total weighted study population was 249.2 million adults age 18 and older, with 82.0 million (32.9%) reporting receiving treatment for two or more conditions  in a sinFrequent pattern mining yielded 223 unique combinations of chronic disease, including 74 two-way, 115 three-way, and 34 four-way combinations that affect one million or more of the weighted study population. There are eight combinations that affect 10 million or more adults, 32 combinations that affect 5 million or more adults, and 129 that affect 2 million or more adults per year. There were not any five-way or higher combinations that met the minimum prevalence threshold. The full table is included in the All 223 combinations identified as highly prevalent had lift  >1, indicating the coexistence of these two conditions is unlikely due to chance alone. The combination of hypertension, hyperlipidemia, diabetes, and cardiovascular disease had the highest lift of 38.6 (36.4–40.9). Cardiovascular disease and heart failure had the highest lift of 7.4 (95% CI: 6.8–8.2%) for dyad combinations and hypertension, cardiovascular disease, and diabetes had the highest liftof 11.4 (10.8–12.0) for triad conditions.The top ten combinations among male and female adults in the study population is shown in This study combined data mining with survey epidemiology to comprehensively identify and estimate the treatment prevalence of the most frequent combinations of multimorbidity in the United States. This analysis showed that certain multimorbidity combinations of disease are not idiosyncratic, but actually quite common in the US, occurring in one million or more adults.This paper adds several new contributions to the literature. First, we provide important public health data on the prevalence and associated outcomes of specific multimorbidity combinations. While it was not surprising to find hypertension and hyperlipidemia as the top combination, a fact that is well-established , the appDespite the high prevalence of these disease combinations, most evidence-based practice guidelines are single-disease focused . This reThe highly prevalent combinations identified in this study could be prioritized for future evidence-based research. Some combinations show the possibility that a single medication could target multiple diseases thus reducing the polypharmacy. For example, a low-dose antidepressant for anxiety, can also treat pain from arthritis or diabetic neuropathy. Other common combinations show the potential of physical activity, diet, and tobacco cessation interventions to positively affect multiple conditions and reduce medication burden.This was, to the author's knowledge, the most comprehensive, population-based study in the U.S. on the prevalence and associated impact of multimorbidity combinations in terms of the number of conditions, the examination of higher-order combinations , and the broadness of the study population. Ward and Schiller examined common dyad and triad combinations of ten conditions using the National Health Interview Survey . The mosSeveral studies have been conducted in specific subpopulations of the U.S. using ARM or similar methods to examine combinations of multimorbidity. Koroukian et al. used ARM to identify combinations of multimorbidity associated with high expenditures among Medicare enrollees . Ho et aComparable studies have been conducted internationally outside the U.S., including a study using the Korea Health Panel which found an overall multimorbidity rate of 34.8% in South Korea , and a sThe data mining allowed a more comprehensive identification of high frequency multimorbidity combinations than previous efforts , 24. ThiAssociation rule mining allows for the identification of highly prevalent combinations in a quick and computationally efficient manner, while filtering out combinations that have no observations or are sparse. While our study only focused on combinations occurring in over 1 million adults, the method could also be used to identify higher order combinations by setting a lower prevalence thresholds. Association rule mining is still relatively uncommon in clinical and epidemiological studies. The method could be applied to other areas of research, for example identifying high-risk combinations of risk factors associated with mortality , social MEPS provides accurate estimates of treated prevalence for chronic disease, but this is likely lower than the underlying population prevalence for some conditions, especially those that are less salient . On the This study used the most recent data (2016–2019) available at the time; therefore, the impact of the COVID-19 pandemic was not captured in these results. As comorbidities were among the greatest risk factors of COVID-related death, excess mortality in people with multimorbidity could have lowered population prevalence rates –68. HoweThis cross-sectional analysis of a nationally-representative survey showed that certain multimorbidity combinations of disease are quite common in the US, occurring in one million or more adults. The combinations reported here could be prioritized for evidence-based research and integration into practice guidelines, especially those most associated with poor health and high medical costs.https://www.meps.ahrq.gov/mepsweb/data_stats/download_data_files.jsp.Publicly available datasets were analyzed in this study. This data can be found here: Medical Expenditure Panel Survey. Available at: The studies involving human participants were reviewed and approved by Case Western Reserve University Institutional Review Board. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.NS is the sole author, had full access to the data, and takes responsibility for the integrity of the data and the accuracy of the data analysis, and the entirety of the manuscript, his contributions include conceptualization, design of the study, statistical analysis, interpreting the data, and writing and revising the manuscript.This project was supported in part by NIH/NCATS CTSA KL2TR002547. Its contents are solely the responsibility of the author and do not necessarily represent the official views of the NIH.The author declares 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.


There was a substantial amelioration of rhinitis severity, with a significant reduction (p < 0.01) in drug use. A significant reduction was observed in the asthma symptom VAS score and asthma-worsening episodes requiring systemic steroids. None of the patients reported any severe adverse reactions. Finally, 90% of the patients reported full satisfaction with the treatment. Conclusions: the study showed that AIT with carbamylated monomeric allergoids of grass, pellitory, and mites was effective and well tolerated by patients.Background: real-life studies are encouraged to evaluate the effectiveness and safety of allergen immunotherapy (AIT). In this context, a retrospective cohort study was conducted to assess the effectiveness and safety of carbamylated monomeric allergoid subcutaneous immunotherapy (MA-SCIT), along with patient satisfaction. Methods: a total of 291 patients with rhinoconjunctivitis with or without asthma with inhalant  allergies were enrolled in this study. Perceived efficacy and perceived satisfaction with MA-SCIT, symptom score by VAS, ARIA classification of rhinitis, drug consumption, number of asthma worsening episodes, and asthma symptom control were evaluated by questionnaires before, after one year, at the end of treatment, and after one or two years of MA-SCIT. Results: the overall symptom score significantly decreased over the years of MA-SCIT, irrespective of specific sensitization ( Subcutaneous immunotherapy (SCIT) was introduced in 1911 ,3. The eIn recent years, real-life studies have been performed for AIT, demonstrating its effectiveness and safety and ensuring a better understanding of the best candidates for this therapy , thus leOver the past 5 years, real-life studies have been published on injection therapy ,22,23,24Safety is a further aspect that limits the use of both SCIT and SLIT as in some cases, severe adverse reactions have been reported for both SCIT  and SLITConsidering these premises, this real-life retrospective cohort study was conducted to assess the effectiveness, safety, patient satisfaction, and perceived effectiveness of three consecutive years of monomeric SCIT with carbamylated monomeric allergoids (MC-SCIT) for the most important allergens  in subjects with rhinoconjunctivitis with or without asthma.The study was conducted at the Universities of Chieti  and Tirana (Albania) and was approved by the respective ethics committees.All patients with rhinoconjunctivitis with or without asthma mono-sensitized to house dust mites, grass, or pellitory who had received MC-SCIT  for three consecutive years and had withdrawn from the treatment for 1–2 years were eligible for the study. The exclusion criteria were polysensitization to other allergens and previous AIT.Allergy was diagnosed in all patients using the skin prick test  and specific IgE. All patients with asthma underwent pulmonary function tests before treatment and almost every 12 months during the AIT and follow-up period.SCIT had been prescribed according to international guidelines ,31. The Treatments were performed at the allergy clinics in 48% of the patients, at the family doctors in the remaining cases. In either case, a control visit at the allergy unit was performed every year or as needed on request.All anti-allergic treatments, such as inhaled and oral steroids, antihistamines, and beta2 agonists, were prescribed by the allergy specialist at various control visits. All patients were given written instructions to treat their exacerbations and to record the drugs used and their dosage.Specific digital questionnaires for asthma and rhinoconjunctivitis were prepared  and admiIn particular, patients were asked questions about (a) perceived efficacy of the treatment measured through a digital VAS for symptoms with a score from 0 to 10, where 0 represents “no symptoms” and 10 represents “severe and extremely annoying symptoms”; (b) local and systemic antihistamine and steroid treatment (oculorhinitis patients) evaluated by a digital VAS where 0 represents “never used” and 10 represents “frequently used;”; (c) ARIA classification of rhinitis based on the criteria of duration and severity/impact of symptoms on the quality of life ,33  in view of the concurrent COVID-19 pandemic using software that guaranteed the anonymity and integrity of the data acquired and compliance with privacy legislation. All patients signed an informed consent form to participate in the study and were informed of the anonymity of the data acquired.U test for paired data was applied to evaluate the differences in various parameters between the same groups. The Wilcoxon test was applied for comparison before and after treatment. The Friedman test was used to evaluate differences in VAS scores within the same group. McNemar’s test was applied to the paired nominal data. Cochran’s Q test was applied where the response variable only had two possible outcomes. The statistical significance of the differences was evaluated at an alpha level of 0.05. Statistical analysis was performed using the SPSS software .All quantitative variables are summarized as mean and standard deviation, and the qualitative variables are summarized as frequency and percentage. Statistical analyses were performed using non-parametric tests. The chi-square test for unpaired data was used to compare the qualitative variables between the Albanian and Italian patients, while the Mann–Whitney A total of 291 patients  were enrolled in this study.p = 0.215; Mann–Whitney U-Test: p = 0.811). Rhinoconjunctivitis and sensitization to dust mites were the most frequent in both groups but were more prevalent in the Albanian group , 128 had severe/intermittent rhinitis , 13 had mild/persistent rhinitis , and 12 had mild/intermittent rhinitis .Furthermore, 60 of 67 asthmatic patients had uncontrolled asthma before treatment, since they reported frequent symptoms, activity limitation, sleep disorders, and need for asthma relievers, with an average of 3.5 exacerbations per year.p < 0.001), with a reduction in symptom score evident and significant already after the first year of MC-SCIT (Wilcoxon test: p < 0.01). Similar results were obtained by dividing the patients according to clinical manifestation  and throughout the treatment period (Friedman test: p < 0.001) . Significantly lower drug use was observed even after the first year of MC-SCIT in all three groups of patients (Wilcoxon test: p < 0.05)  A. A sign < 0.05) B.p < 0.001) (p < 0.01 (Friedman test) in patients allergic to mites and pellitory and p = 0.05 in patients allergic to grass (p < 0.05), whereas the change in VAS did not reach statistical significance in patients with grass allergies.The improvement of symptoms was also evident in patients with asthma, whether associated or not with oculorhinitis, with a significant improvement in VAS over the year of MC-SCIT (Friedman test: < 0.001) B. VAS reto grass . PatientAsthma improvement was confirmed by the significant reduction in asthma exacerbations per year requiring treatment with systemic corticosteroids, considering all patients together or by dividing them by allergic sensitization .p < 0.001)  .Patients, considered together or divided by disease or allergic sensitization, maintained the improvements found at the end of therapy 1–2 years after the end of MC-SLIT . Moreover, patients with asthma and oculorhinitis were asked to answer the RAPP questionnaire, all but two showed values lower than 15, demonstrating good disease control .The vast majority (90%) of the patients, regardless of the disease or specific sensitization, declared their satisfaction with the treatment received; five patients were unhappy, one was dissatisfied, and four were disappointed .Sixty percent of the patients completed the course of MA-SCIT with a maximum delay of five days in carrying out various maintenance doses. Twenty missed up to three injections during the course of therapy, eleven missed up to five injections, and nine missed up to seven injectionsDuring the 3 years of treatment, the maximal dose received by patients with mite allergies was 74.4 μg of major allergens (Der p 1 and Der f 1), patients with grass allergies received 93 μg , and patients with pellitory allergies received 27.9 μg (Par j 1 and Par o 1).No patient reported severe local and systemic adverse reactions, and only 12 patients reported a local reaction at the site of injection, not requiring treatment.This study showed that carbamylated monomeric allergoid-based SCIT is a safe and effective treatment for grass, pellitory, and mite respiratory allergies.The retrospective assessments in this study were performed using VAS for various items. The VAS is well-validated for the measurement of rhinitis and asthma symptoms and correlates well with the severity assessed by various questionnaires . It has been used in several treatment studies, demonstrating that VAS is highly effective in assessing disease control ,36,37.The concordance of the various results obtained in the present study confirms the accuracy of the results. The significant improvement in VAS for oculorhinitis symptoms correlates with the decrease in the severity of rhinitis over the year of MC-SCIT, evaluated by the ARIA questionnaire, and results corroborated by the significant reduction in the use of local and systemic antihistamines and steroids. The improvement in these parameters was progressive during the treatment, with early amelioration after the first year of MC-SCIT. These results were consistent when considering all recruited patients as well as selecting them according to the presence or absence of asthma or allergic sensitization, namely grass, pellitory, and mites.Similar results were obtained in asthmatic patients , where the improvement of VAS for symptoms correlated with reduction of sleep disorders, activity limitation, frequency of symptoms, need for a reliever, and severe exacerbations over the year of MC-SCIT, in all cases with a high statistical significance.The good clinical condition reached at the end of MC-SCIT was maintained 1–2 years after the end of treatment, as demonstrated by the almost perfect equivalence between values found at T2 and those found at T3 , confirming that the effect of MC-SLIT persisted after the end of treatment . Health Considering both the perceived health status of the patients  and the final questionnaire on their level of satisfaction with the treatment received, it may be concluded that the expectations of the patients are adequately fulfilled for all three sensitizing allergens. Patient satisfaction is a useful measure of the effectiveness of medical treatment. It affects health-related decisions and treatment-related behaviors of the patients, which in turn have a substantial effect on the success of treatment outcomes in many fields of medicine ,40. PatiData from large-scale real-life trials on subcutaneous AIT ,47,48,49Limitations of the study: although the number of enrolled patients was largely sufficient to evaluate the global effectiveness of MA-SCIT, selecting patients by specific sensitization, the number of pellitory allergic subjects should be increased to confirm the results obtained, even if they are already statistically significant. Equally, the number of asthmatic pollen-sensitized patients evaluated was small, in any case the evaluation of the entire group of asthmatics supports the conclusion reached.Moreover, it was impossible to examine drug consumption by checking drug prescription records, which would render the data more objective. However, the accordance of all the results obtained in this study minimizes this shortcoming.Conclusion and key messages:This study shows that carbamylated monomeric allergoid-based SCIT is effective in treating respiratory allergies to mites, grass, and pellitory. Moreover, this therapy does not cause severe local or systemic adverse reactions.