Public health agencies widely adopt social media for health and risk communication. Moreover, different platforms have different affordances, which may impact the quality and nature of the messaging and how the public engages with the content. However, these platform effects are not often compared in studies of health and risk communication and not previously for the COVID-19 pandemic.This study measures the potential media effects of Twitter and Facebook on public health message design and engagement by comparing message elements and audience engagement in COVID-19–related posts by local, state, and federal public health agencies in the United States during the pandemic, to advance theories of public health messaging on social media and provide recommendations for tailored social media communication strategies.We retrieved all COVID-19–related posts from major US federal agencies related to health and infectious disease, all major state public health agencies, and selected local public health departments on Twitter and Facebook. A total of 100,785 posts related to COVID-19, from 179 different accounts of 96 agencies, were retrieved for the entire year of 2020. We adopted a framework of social media message elements to analyze the posts across Facebook and Twitter. For manual content analysis, we subsampled 1677 posts. We calculated the prevalence of various message elements across the platforms and assessed the statistical significance of differences. We also calculated and assessed the association between message elements with normalized measures of shares and likes for both Facebook and Twitter.P<.001), experts (P=.01), and nonpolitical personalities (P=.01) were significantly more present on Facebook posts compared to Twitter. Infographics (P<.001), surveillance information (P<.001), and certain multimedia elements  were more prevalent on Twitter. In general, Facebook posts received more  likes (0.19%) and  shares (0.22%) compared to Twitter likes (0.08%) and shares (0.05%). Elements with greater engagement on Facebook included expressives and collectives, whereas posts related to policy were more engaged with on Twitter. Science information  comprised 8.5% (73/851) of Facebook and 9.4% (78/826) of Twitter posts. Correctives of misinformation only appeared in 1.2% (11/851) of Facebook and 1.4% (12/826) of Twitter posts.Distributions of message elements were largely similar across both sites. However, political figures (In general, we find a data and policy orientation for Twitter messages and users and a local and personal orientation for Facebook, although also many similarities across platforms. Message elements that impact engagement are similar across platforms but with some notable distinctions. This study provides novel evidence for differences in COVID-19 public health messaging across social media sites, advancing knowledge of public health communication on social media and recommendations for health and risk communication strategies on these online platforms. Social media have become integral tools for public health messaging and online communication of health and risk information worldwide -3. As ofThere is ample research on social media use by public health agencies ,14,15,16content and purposes of messages and (2) audience (or user) engagement with the messages. Analyses of message content have focused on “themes,” such as “closures,” “risk factors,” “case updates,” “reassurance,” and others, in various pandemic and crisis contexts [textual and media message design elements that identify the various objective characteristics of the text—focusing on the content, not on the purpose—which may be useful for multiple health and risk communication scenarios and related research [Research on public health messaging on social media has focused on 2 broad areas: (1) the contexts ,27, inclcontexts . Analysecontexts , increascontexts , “fight contexts , and othresearch .Like button, a Share button, and a Comment function, the content or count of which is appended to the message. Facebook also offers other sentiments or reactions to be expressed that are formalized as buttons and counts . Although social media reactions to messages may not directly relate to behavioral intent or actual behavior change, analyses of this engagement provide some insight into public interest in and acceptance of the messaging [Audience or user engagement on social media is often formalized in the platform via a essaging  and may essaging . There iessaging ,32, 33. essaging .affordances—the functions or action possibility [newsfeed that presents users with posts of their friends, or those followed, the organization of which is determined by the platform algorithms [Although studies in the social media literature recognize the distinct sibility —of thesesibility ,25. Althsibility . On bothgorithms .In practice, Facebook is more widely adopted than Twitter across all demographic groups . TwitterFor this study, we aim to assess differences in public health message design elements and audience engagement with the various message elements across Twitter and Facebook regarding COVID-19 during 1 year of the pandemic. We therefore ask the following research questions (RQs):RQ1. How do public health message design elements differ across Twitter and Facebook?RQ2. How does audience engagement with public health message elements differ across Twitter and Facebook?In the following sections, we describe the methods of the study, the results, and the discussion in relation to the literature and provide evidence-based policy recommendations for better-targeted health communication strategies.ncov, covid, corona, pandemic, or sars-cov. To retrieve these posts, we used the standard Twitter application programming interface (API) and the Facebook API via Crowdtangle [original posts and not retweets (shared posts) or replies (comments on other posts).We identified 11 major federal health agencies in the United States associated with infection prevention and control , the majwdtangle . Note thpopulation data set.On Twitter, we identified 11 federal accounts , 48 state accounts , and 33 local accounts  that matched the criteria. On Facebook, we identified 10 federal accounts , 49 state accounts , and 38 local accounts  that matched the criteria. On Facebook, it is more difficult to differentiate original posts from shared posts; the figures just reported for Facebook include both. This data set of all COVID-19–related posts from all identified agencies in 2020 was called the sample data set. The rationale for the sampling was based on similar studies and generating a manageable number of posts to manually code. For example, Reuter et al [final sampledata set consisted of a total of 1677 (93.2%) posts  that were coded. For Twitter, this included 82 (9.9%) federal posts, 482 (58.4%) state posts, and 262 (31.7%) local posts. For Facebook, this included 60 (7.1%) federal posts, 560 (65.8%) state posts, and 231 (27.1%) local posts. For manual content analysis, we used a stratified random sampling technique where we sampled 900 posts from Twitter and 900 posts from Facebook proportional to the amount of posts made by agency level , the er et al  analyzeder et al  used 501textual and media elements. The framework integrates message elements into 8 major dimensions: speech function, topic, threat focus, type of resource, audience, speaker, rhetorical tactic, and media. Each of these dimensions includes more granular message features (or elements). We adapted an existing framework  for the representative and not an expressive. These coding rules are summarized in The content analysis consisted of manual binary coding for the presence or lack of each element in a post. As the definition of the categories became apparent, the nature of some definitions made some categories mutually exclusive, especially within each textual or media dimension. For example, a question is, by definition, not a sample data set, where at least 2 coders double-coded the same post to calculate the Cohen κ statistic of interrater reliability (IRR).A random training sample of 150 posts  was first retrieved for training and category development. Using these 150 posts, during training, 3 authors updated and defined the message categories. Once this training was accomplished, the 3 authors independently began coding a 20% subsample of the representative and request speech functions, the external speaker, and some of the rhetorical dimensions. For example, it was not clear whether a slogan on an image, such as “COVID-19 news update,” was to be considered a representative sentence. We ultimately agreed on the definitions as shown in After obtaining IRR measures, the coders discussed the results. At this point, the results were not perfect and discrepancies in coding existed and needed to be reconciled. In particular, there were issues with the To address our first RQ, we calculated the distribution of each message element on Twitter and Facebook and then compared this total across platforms via an independent 2-sample Z-test of proportions, where the null hypotheses assumed that the proportion of each message element is equal on both platforms. Although Z-tests expect normal distributions, and social media phenomena are notoriously not normally distributed, given the relatively large sample of most message elements, we found it reasonable to apply the Z-tests .To address our second RQ, we operationalized audience engagement as normalized frequencies of likes and shares. Other studies have used the CTR to measure audience engagement , seemingm) as the number of likes of each message “m,” divided by the follower count of the account that posted the message. NLm is the percentage of the agency’s follower count that liked the message. Although Facebook includes additional positive and negative measures of audience engagement—namely love, care, ha-ha, wow, sad, and angry—these were not included as part of the NLm measure to make it more comparable with the single like feature of Twitter. Although we considered and analyzed the more negative measures of Facebook sentiment, namely sad and angry, these overly complicated the research and ultimately seemed out of scope, since our aim was to compare Facebook and Twitter elements. This study thus focused on only likes and shares on Facebook and Twitter, both of which are types of positive engagement. Generally, in this study, engagement refers to “liking” or “sharing” a message.We calculated a measure of normalized likes (NLm) of each message “m.” The NSm measure, compared to likes, can be more directly considered a diffusion rate [retransmission rate [Similar to normalized likes, we created a measure of normalized shares  test, given the skewness of the data and as similar studies have approached it [P≤.05 as statistically significant.For every message element, we then computed the ached it . We consExternal, political, and expert actors, along with video, photograph, and other language, were the features more frequently used in Facebook posts compared to Twitter posts. Policy, directive, infographic, surveillance, hyperlink, and hashtag features were used more frequently on Twitter compared to Facebook. Personality and positive framing features were not included in policy was included in the graph, although at the significance boundary.love, care), as previously discussed under Methods.P values for the WMW test comparing these 2 sets. For example, in the Facebook sample, on average, 0.16% of the (count of the) account’s followers liked the message that contained a representative, whereas 0.26% liked the messages that did not contain a representative. Therefore, on Facebook, messages that did not contain a representative were liked more than messages that did. However, this was not a statistically significant difference (P=.22). On Twitter, however, on average, 0.08% of the account’s followers liked messages that contained a representative and 0.05% liked messages that did not contain it, which was a significant difference (P<.001).P values from the WMW test comparing differences between them. Results here can be similarly interpreted as the results in Expressives and the use of a collective frame in messages were associated with more likes across both platforms. Surveillance information as well as infographics were also associated with more likes and shares across Facebook and Twitter. References to material resources, surprisingly, were generally associated with fewer likes and shares on both platforms. We speculate this may be due to the repeated posts about testing and vaccine sites coded under material. Although political figures were more present on Facebook compared to Twitter, they were associated with less engagement on both platforms, especially Facebook. Requests were particularly popular on Facebook but not significant on Twitter. Correctives and policy information were associated with higher engagement on Twitter but less so or not significantly on Facebook.This study analyzed 1677 COVID-19–related posts on Facebook and Twitter, by public health agencies across the United States in 2020, and found differences and similarities in the overall use and popularity of these sites in terms of message design elements and audience engagement. Our results show that Facebook posts received 2.25 times more likes and 4.4 times more shares, in general, than posts on Twitter. However, within each platform, messages received more shares than likes within Facebook—as a percentage of account followers that liked or shared the message—whereas on Twitter, measures were more liked than shared.surveillance information , policy information, infographics, and hyperlinks. Moreover, federal agencies are more active and more popular on Twitter compared to Facebook, whereas local and state agencies are more active or more popular on Facebook. We also observe that messages on Facebook, compared to Twitter, have significantly more references to political figures, public health experts, and  personalities  as speakers in the messages. From this, we may conclude a type of data and policy orientation for Twitter and a local and personal orientation for Facebook.Our results show that messages on Twitter, compared to Facebook, are significantly more focused on infographics, surveillance data) and policy information had significant positive associations with audience engagement on Twitter but not at all or not as much on Facebook, further suggesting this data and policy characterization for Twitter. Although Facebook was the platform where political figures and health experts were more highlighted as speakers in the messages, this personalization was generally not associated with higher engagement on both sites. However, we observe that photographs, which are often of people, and rhetorical elements, such as a collective framing , positive framing , and emphasis , which may trigger sentiment and personal connection, received more or significantly more audience engagement on Facebook but not as much or not at all on Twitter. This further suggests the local and personal orientation for Facebook.We observed that data , were significantly associated with greater engagement on Facebook but were present in few posts (2%) on Facebook. Ultimately, the use of expressives  and collective frames  were particularly well engaged with on Facebook.For public health agencies using Twitter, we recommend caution on the use of hyperlinks and hashtags on Twitter messages if the goal is to increase message likes and overall message diffusion, but continued use of surveillance information and infographics is recommended. Moreover, we recommend a greater focus on messages containing emergent issues , and the use of correctives to address misinformation, because these were both not prevalent but were associated with greater positive engagement.infodemic [Our results show that messages on Twitter, compared to Facebook, are significantly more focused on policy and surveillance information and include significantly more hyperlinks and hashtags compared to messages on Facebook. Since the hashtag is a textual construction first popularized on Twitter, this is not surprising. However, both hashtags and hyperlinks were generally associated with less engagement on Twitter. Surveillance information and infographics, however, were generally associated with greater engagement on Twitter. Emergent issues, and correctives, were particularly well engaged with on Twitter. However, correctives were included in a minority of tweets (1.4%). Given that social media is part of a misinformation crisis , or infonfodemic ,50, it iFor public health agencies using both platforms, we recommend careful use of images in their messages, including photographs, illustrations, and videos, as these were all media types associated with less engagement across both platforms. However, including text-in-image is a reasonable recommendation, since these were associated with greater engagement across platforms.In general, our results show that not all types of images are similarly engaged with. On both platforms, photographs were significantly associated with fewer shares, whereas infographics were generally associated with greater shares and likes. Although illustrations were associated with fewer likes and shares on both platforms, this negative impact was only significant for Facebook likes. Infographics about the pandemic were associated with higher engagement on both platforms, but they were also largely prevalent. Therefore, the amount of use of these features in this context is likely sufficient. Lastly, text-in-image was generally associated with greater likes and shares on Twitter and greater sharing on Facebook, highlighting the importance of textual and semantic content along with visual content.This study intended to show how public health agencies construct their messages across Facebook and Twitter and how users respond to these messages similarly or differently across platforms. To control for aspects of the message topic, we only focused on COVID-19–related messages. COVID-19 is also a major health and risk issue and one that we could expect public health agencies in the country to be communicating about in 2020. However, the focus on COVID-19 puts a limitation on the extent to which we can generalize the findings to health and risk communication more broadly. Moreover, the statistical tests used could be improved with a regression model that assesses and controls for other variables on audience engagement. Nevertheless, our random sampling technique, over multiple kinds of agencies and an entire year, helps us generalize and have confidence in the results.quality of engagement across platforms, political issues in public health communication, and examining the nature of the comments to public health messages.Health communicators should consider that social media algorithms themselves are problematic as they lead to echo chamber effects  and are There were few posts with personalities featured on Facebook  and Twitter  posts. We could thus not properly assess the impact of this message element on engagement. However, celebrities and personal stories can positively influence health behavior and may be further studied in this context ,57. In aIn general, we find a data and policy orientation for Twitter messages and users and a local and personal orientation for Facebook, although also many similarities across both platforms. Message elements that impact engagement are similar across both platforms but with some notable distinctions. This study provides novel evidence for differences in COVID-19 public health messaging on social media, advancing health communication research and recommendations for health and risk communication strategies.


Enho gene, plays a crucial role in energy homeostasis. The literature review indicates that adropin alleviates the degree of insulin resistance by reducing endogenous hepatic glucose production. Adropin improves glucose metabolism by enhancing glucose utilization in mice, including the sensitization of insulin signaling pathways such as Akt phosphorylation and the activation of the glucose transporter 4 receptor. Several studies have also demonstrated that adropin improves cardiac function, cardiac efficiency and coronary blood flow in mice. Adropin can also reduce the levels of serum triglycerides, total cholesterol and low-density lipoprotein cholesterol. In contrast, it increases the level of high-density lipoprotein cholesterol, often referred to as the beneficial cholesterol. Adropin inhibits inflammation by reducing the tissue level of pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin-6. The protective effect of adropin on the vascular endothelium is through an increase in the expression of endothelial nitric oxide synthase. This article provides an overview of the existing literature about the role of adropin in different pathological conditions.Adropin is a novel 76-amino acid-peptide that is expressed in different tissues and cells including the liver, pancreas, heart and vascular tissues, kidney, milk, serum, plasma and many parts of the brain. Adropin, encoded by the  Peptides are short linear chains of amino acids that are often stabilized by disulfide bonds. Peptides can be synthesized and used for different purposes and the sequence can also be modulated using various chemical and biological techniques ,5,6,7,8.Therapeutic peptides have several important advantages when compared to proteins and antibodies. They are smaller in size, easy to synthesize and have the ability to penetrate cell membranes. They also have high activity, specificity and affinity. An added benefit of using peptides as a therapeutic agent is that they do not accumulate in specific organs such as the kidney or liver, which can help to minimize their toxic side effects . Therape−/−Mc3r ). Kumar and his team distinguished a novel transcript in the liver. This transcript encoded a short and highly conserved amino acid sequence (76 aa), which was downregulated in the obese mice. Further investigation revealed that the coding gene was associated with energy homeostasis and lipid metabolism, so it was named the Energy Homeostasis Associated (Enho) gene. The name “adropin” was derived from the initials of Latin names “aduro”, which means “to set fire to”, and “pinquis”, which means “fats” [Adropin was discovered by Kumar et al. in 2008 , while ss “fats” . Enho gene expression was reduced, compared to that of lean mice, explaining that the long-term intake of a high-fat diet disrupts the normal activity of adropin. This finding linked the Enho gene to metabolic disorders, such as obesity [Adropin level has been shown to be related to nutrient intake. For example, the investigation of Kumar et al. showed that lean C57BL/6J mice that were fed a high-fat diet (HFD) expressed higher adropin in the liver, compared to the control group, while fasting lean C57BL/6J mice showed a diminished adropin level. Interestingly, another experiment in which diet-induced obesity (DIO) mice were used demonstrated that the level of liver  obesity . Further obesity ,16.It has been reported that adropin is a secreted, as well as membrane-bound peptide. Previous reports show that adropin is secreted by HEK293 cells and C57BL/6J mice . Other rIn contrast, a study that was conducted by Wong et al. showed that adropin was a membrane-bound peptide . InitialEnho gene is in chromosome number 9 (9p13.3), position 34,521,043–34,522,990 and it has a size of 1948 bp. It is composed of two exons and one intron  and has a molecular weight of 4.499 KDa (1−33 (amino acids 1–33) is a secretory signal peptide [34−76 (amino acids 34–76) is biologically active when it is administered to rats [In human, the e intron A. Adropi.499 KDa B. The am peptide , and adr to rats .Enho gene expression is regulated by Liver X receptor (LXR) [The literature has not stated a specific receptor upon which adropin exerts its biological activities. In the brain, Stein et al. showed that adropin acts on the orphan G protein-coupled receptor (GPR19) to inhibit water deprivation in rats , while ior (LXR) . LXR is or (LXR) .It was demonstrated that adropin stimulated angiogenesis, proliferation and migration of the human umbilical vein and coronary artery endothelial cells. It was also proposed that this novel peptide may exert its activities on vascular endothelial growth factor receptor-2 (VEGFR2) in endothelial cells . The early discovery of adropin demonstrated the expression of the peptide in the liver  and braiIn the pancreas, adropin was detected in acinar cells  and in tIn the circulatory system, Lovren et al. showed that adropin was expressed in endothelial cells—specifically, in cultured human umbilical vein and coronary artery endothelial cells (ECs) . MoreoveEnho gene has been detected in the lung tissue of C57BL/6J mice [Enho gene after analyzing myeloperoxidase (MPO) and anti-neutrophil cytoplasm autoantibody (ANCA) in patients with vasculitis and healthy individuals [Furthermore, mRNA expression of the /6J mice . Interesividuals .It was demonstrated that biological fluids such as milk, serum, plasma and cheese whey milk-derived fluid of cow diary contain numerous amino acids and proteins including adropin, nesfatin-1, apelin-12, ghrelin and salusin peptides . AdditioThe biological process of regulating energy inflow (food intake) and energy expenditure through biosynthetic reactions is identified as energy homeostasis. To maintain energy homeostasis, the amount of energy intake must be at equilibrium with the amount of energy that is expended. As the body intakes nutritional molecules such as carbohydrates, lipids and proteins, which are considered fuel, the required energy is utilized by the body and the excess is stored in a form of adipose tissue and held constant over a period of time .The gastrointestinal tract (GI tract), pancreas and liver are known to provide hormonal signals to specific nuclei of the central nervous system that regulate the energy that is consumed and the energy that is utilized. These hormones include ghrelin; gastric leptin; secretin; glucagon-like peptide 1, secreted by the stomach and intestines; and insulin and glucagon, released from the endocrine pancreas. Adipose tissue is also a major source of energy-related signals—specifically, signals that reflect lipogenesis, storage and lipolysis. These signals send feedback to the region of the central nervous system that controls energy balance .The brain, specifically the medial and lateral nuclei of the hypothalamus, plays a major role in energy homeostasis, with the help of hormonal, as well as nutritional signals. Food intake is controlled by hunger and regulated by the hypothalamus. There are several models related to food intake and energy homeostasis. The lipostatic model says that adipose tissue produces signals such as leptin, which is proportionate to the fat mass and acts on the hypothalamus to decrease food intake and increase energy output, while the GI tract-peptide model, hypothesizes that when the food enters the gastrointestinal tract, the release of cholecystokinin and glucagon hormone are induced. These hormones have receptors in the hypothalamus, which produce the feeling of fullness. Another model of energy balancing and food intake involves glucose utilization in brain neurons .Enho expression is regulated by the leptin and melanocortin receptor, as obese leptin knockout mice (Lepob/Lepob) and melanocortin 3 receptor knockout mice (Mc3r−/−) exhibited downregulation in Enho expression [Mc3r gene causes increased adiposity in tissues [ob gene and is secreted into the blood circulation by adipose cells. It also acts on hypothalamic receptors to inhibit feeding and initiates increased thermogenesis. It is an important regulator of energy homeostasis [Enho mRNA expression, was that a high-fat diet increased Enho mRNA expression in lean C57BL/6J mice. However, introducing a high-fat diet to diet-induced obesity (DIO) C57BL/6J mice in a period of 3 months was associated with reduced liver Enho mRNA expression, compared to lean controls. This suggests that a chronic obese state caused metabolic disorder, which consequently disturbed adropin expression.During feeding and fasting cycles, carbohydrates and fatty acids are the two primary substrates in oxidative metabolism to keep energy balanced. Several studies have reported the role of the hormonal peptide, adropin, in regulating substrate oxidation preferences. Initially, when adropin was discovered, its biological role was linked to glucose homeostasis and lipid metabolism . Kumar epression . Melanoc tissues . Leptin eostasis . AnotherAdditionally, adropin metabolism is not only associated with lipid, but also with carbohydrate metabolism and energy status. It is worth mentioning that adropin-overexpressing transgenic C57BL/6J mice that were fed a high-fat diet showed improvement in glucose homeostasis, as well as delayed development of obesity. Normally, a high-fat diet leads to obesity and disruption in glucose homeostasis ,44.In another study, elevated fasting glucose level in DIO mice was controlled and regulated by administrating an intraperitoneal injection of adropin. It was found that endogenous hepatic glucose production was reduced in adropin-treated obese mice ,46,47,48The levels of adropin in blood circulation have been proposed to direct the metabolic state in skeletal muscle by influencing fuel selection preference towards glucose oxidation in the fed state . StudiesWhen adropin was first discovered, most of the attention was given to its role in lipid and carbohydrate metabolism and insulin resistance. Interestingly, some studies show that adropin deficiency plays a role in the development and progression of chronic diseases, such as diabetes mellitus. Zang et al. reported that serum concentrations of adropin were significantly decreased in Chinese type 2 diabetic patients, compared to control subjects . Other sAdditionally, low adropin levels have been shown to correlate with a risk of developing diabetic complications such as diabetic retinopathy , diabetiEnho gene expression in the diabetic rats was suggested to be through STAT3 activation [As it was reported that serum adropin levels vary between diabetic and normal subjects, several investigations tried to understand the mechanisms underlying these variations. For instance, it was demonstrated that hyperglycemia was associated with increased adropin expression, as well as the signal transducer and activator of transcription 3 (STAT3) activation in the liver of streptozotocin-induced diabetic rats. The mechanism underlying the elevation of adropin levels and tivation . During the discovery of adropin, its physiological role was linked to glucose homeostasis. It is thus important to understand the potential role of adropin in controlling hyperglycemia and its effect on insulin-sensitive tissues. In skeletal muscle, a study that was performed by Gao et al. showed that adropin played a crucial role in modulating glucose utilization in DIO mice with insulin resistance . AdropinIn contrast, a study utilizing insulin-resistant hepatocytes showed that adropin could reduce glucose production in the liver. Adropin treatment downregulated the transcription of hepatic gluconeogenesis genes by inhibiting the binding site of transcription factors forkhead box protein O1(FoxO1) and cAMP-response element binding protein (CREB), along with their co-activators, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and CREB regulated transcription coactivator 2 (CRTC2), respectively, to the promoter of gluconeogenesis genes ,66. FoxOInterestingly, this effect of adropin was not observed in insulin-sensitive hepatocytes . This reFurthermore, it was reported that adropin was associated with incretins in obese males with type 2 diabetes receiving a 3-month treatment of liraglutide . There wIt is worth mentioning that irisin, which is a peptide hormone involved in glucose homeostasis ,74, has Obesity is a major health problem worldwide ,81. StudEnho gene expression, while fasting reduced the expression of this gene, when compared to the control mice. However, liver Enho gene expression declined when a high-fat diet was introduced to the mice for a longer period of time, suggesting a regulatory role of the Enho gene in nutrition, but the expression of adropin is diet-dependent [C57BL/6J mice that were fed a high-fat diet exhibited a rapid increase in ependent . Moreoveependent .In humans, adropin level was negatively correlated with body mass index (BMI)  in diabeThere is overwhelming evidence that cardiovascular diseases are common in patients suffering from diabetes mellitus ,90,91,92High cardiac fatty acid oxidation rates and impaired cardiac insulin signaling are associated with decreased cardiac efficiency and various cardiac diseases . AltamimHyperlipidemia is a risk factor that is associated with cardiovascular diseases . AkcilarInterestingly, a recent meta-analysis found an association between serum adropin and coronary artery disease (CAD) . The stuResearchers and scientists have also investigated the role of adropin in inflammation and related diseases such as atherosclerosis. Atherosclerosis is a chronic inflammatory disease in response to injury of the arterial wall and the formation of plaque . VasculaIn the case of obesity, the infiltration of macrophages into adipose tissues causes chronic inflammation. Adipocytes secrete cytokines such as TNFα and MCP-1 that attract macrophages and regulatory T cells, leading to fat inflammation. Adropin regulates the expression of PPAR-γ by activating the AKT pathway, thus inhibiting the differentiation of 3T3-L1 preadipocytes into mature adipocytes and consequently reducing fat accumulation and fat inflammation . In another study, lower adropin plasma levels and increased inflammation markers such as TNFα and interleukin-6 (IL-6) were reported in male patients with moderate and severe obstructive sleep apnea, compared to healthy individuals .Furthermore, in order to investigate how adropin could affect hepatocyte inflammation and injury in nonalcoholic steatohepatitis (NASH), immunohistochemistry using the inflammation markers F4/80, CD45 and MCP-1, and a gene expression analysis for TNFα and IL-6 genes, were performed using liver tissues from adropin knockout C57BL/6J mice and the control wild-type, which were fed a methionine-choline deficient diet . MethionFar beyond the classical action, adropin can stimulate cell proliferation and differentiation. Lovren et al. showed that adropin has the ability to induce the proliferation and capillary-like tube formation of endothelial cells that stimulate angiogenesis . AdropinFurthermore, in rat primary preadipocytes and 3T3-L1 cells, preadipocyte proliferation was increased by adropin treatment, while the differentiation of those preadipocytes into mature adipocytes was reduced . The supOn the other hand, it was reported that adropin downregulated the proliferation and migration of human aortic smooth muscle cells (HASMCs) in vitro, providing evidence that the peptide is also protective against atherosclerosis  Table 1Table 1. Knockout mice are usually used to study what happens in an organism when a particular gene is absent. Studying knockout mice can provide information about how the knocked-out gene normally functions, including the gene’s biochemical, developmental, physical and behavioral roles.Enho gene—specifically in exon 2—and carried out Cre-mediated deletion using Cre-LoxP recombination technology [It was shown that adropin knockout C57BL/6J mice exhibited remarkable insulin resistance, dyslipidemia, failure in the suppression of endogenous glucose production in a hyperinsulinemic condition and increased adiposity in liver . These kchnology .In another study, adropin knockout C57BL/6J mice were used to investigate the pathogenicity of fatty pancreas . InteresEnho single-guide RNA, the latest tool in genome editing, to generate adropin knockout C57BL/6J mice [Chen et al., as well as Gao et al., used clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) technology and /6J mice ,58. They/6J mice .In summary, adropin, a 76-amino acid peptide, is membrane-bound and secreted by cells. It is present in the endothelial cells of the capillaries of the brain, liver and kidney. Adropin is involved in several biological activities, and it is regulated by nutrients including lipids and carbohydrates. The administration of adropin can enhance the oxidation of glucose, with a concomitant reduction in fatty acid oxidation in skeletal muscle cells. Adropin has a protective effect in type 2 diabetes mellitus, as it can reduce insulin resistance and prevent the development of obesity by enhancing lipid catabolism. It promotes insulin signaling pathways through Akt phosphorylation and the cell surface expression of GLUT4. Additionally, adropin modulates lipid metabolism by regulating the expression of hepatic lipogenic genes and the PPARγ receptor, the major regulator of lipogenesis. Therefore, adropin-based treatments could emerge as a new line of therapy against glucose and lipid metabolism-related diseases.It has also been shown that adropin improves coronary blood flow and cardiac function. Adropin promotes cardiac glucose oxidation and the inhibition of cardiac fatty acid oxidation, enhancing cardiac energy metabolism and cardiac efficiency. Moreover, the anti-inflammatory effect of adropin can suppress TNFα expression in atherosclerosis.Enho gene expression, adropin serum/plasma levels and/or protein expression level in tissue can fluctuate, according to the type of illness. These conditions include but are not limited to diabetes mellitus, obesity, cardiovascular diseases and inflammation. Thus, adropin could also be used as a diagnostic biomarker to detect these clinical conditions, especially metabolic and cardiovascular diseases. However, more research needs to be carried out to understand its mechanism of action in specific tissues and to discover if it acts on a specific receptor, other than GPR19.Studies showed that


In this manuscript a POD-Galerkin based Reduced Order Model for unsteady Fluid-Structure Interaction problems is presented. The model is based on a partitioned algorithm, with semi-implicit treatment of the coupling conditions. A Chorin–Temam projection scheme is applied to the incompressible Navier–Stokes problem, and a Robin coupling condition is used for the coupling between the fluid and the solid. The coupled problem is based on an Arbitrary Lagrangian Eulerian formulation, and the Proper Orthogonal Decomposition procedure is used for the generation of the reduced basis. We extend existing works on a segregated Reduced Order Model for Fluid-Structure Interaction to unsteady problems that couple an incompressible, Newtonian fluid with a linear elastic solid, in two spatial dimensions. We consider three test cases to assess the overall capabilities of the method: an unsteady, non-parametrized problem, a problem that presents a geometrical parametrization of the solid domain, and finally, a problem where a parametrization of the solid’s shear modulus is taken into account. Fluid-Structure Interaction (FSI) problems are a wide spread topic in the applied mathematics community, and despite their instrinsic complicated nature , theThe complex nature of these problems is reflected not only by their theoretical treatment, but also by the way they are treated numerically. There are two approaches that can be adopted in order to address a FSI problem: the first approach consists of a monolithic procedure –19, whersimultaneously: this results in algorithms that show good stability properties, with respect to time, independently of the density of the fluid and the solid, and independently of the geometrical properties of the physical domain; indeed the monolithic algorithm does not suffer from the so called added mass effect  point of view: indeed, in the online phase of the Reduced Basis Method –39, we hIn this manuscript we design a segregated procedure, combined with a Reduced Order Model based on a Proper Orthogonal Decomposition. The goal is to extend the work done in , moving This manuscript is structured as follows: in Sect. In this section we are going to introduce briefly the Arbitrary Lagrangian Eulerian (ALE) formalism, in order to set the notation that will be used throughout the rest of this manuscript.Arbitray Lagrangian Eulerian formulation  be a time interval, and let reference configuration for the fluid.Let ; Fig. The goal is to simulate the behavior of an incompressible, Newtonian fluid interacting with a linear elastic solid, in the time interval  with an equispaced sampling f with a first backward difference: Hereafter we present the offline phase of the partitioned procedure in the presence of a parameter. We employ again a Chorin-Temam projection scheme for the Navier–Stokes equation; we define a time-stepping procedure by sampling the time interval [0, reference configurations (both parameter—and time—independent). Again we discretize in space the FSI problem, using second order Lagrange Finite Elements for fluid velocity resulting in the discrete space In the following, we use the same function spaces that we have introduced in Sect. once and for all for every timestep In this case the lifting function ented in  in the cdeed, in  the authThe space discretized version of the partitioned procedure now reads as follows: for find find Fluid projection substep (pressure Poisson formulation) find Structure projection substep find In the fluid projection step, in order to enhance the stability of the method we have employed again a Robin boundary condition, which in the case of shape parametrization reads as follows:for any i has to be considered as a single index, in the case of geometrical parametrization only  of the algorithm proposed, to this kind of situations: again, this represents another interesting future line of research. Another remark that we would like to make concerns the timestep used in our numerical simulations: in the results that we have showed, a timestep of ample in  for a mo


Optimal treatment of intracranial stenoses in varicella zoster virus (VZV)-associated vasculitis is unknown. This study aims to evaluate the merits and potential pitfalls of a specific therapeutic strategy, initially proposed by Don Gilden in 2015.We describe three patients with intracranial stenoses caused by VZV vasculitis successfully treated by a long-term combination of valacyclovir and prednisolone.All three patients were young men suffering from stroke. Only one reported a first contact to VZV in adulthood. All three presented stenoses in the intracranial part of the internal carotid artery or the proximal segments of the middle cerebral artery as well as an elevated cell count and positive VZV antibody index in cerebrospinal fluid. They received a combination therapy regimen with prednisone and valacyclovir about a minimum of one year. Intracranial stenoses improved markedly in one and almost resolved completely in the other two patients. Side effects of corticosteroid treatment occurred in two patients.Long-term combination treatment with prednisone and valacyclovir proved to be effective in three young men suffering from intracranial stenosis due to VZV vasculitis. Vasculitis associated with varicella zoster virus (VZV) is a rare cause of stroke. It can, however, be assumed that the condition is often not recognized and misdiagnosed . VZV vasIn VZV vasculopathies, it was shown that VZV infection results in significantly increased levels of interleukin 8 in human vascular adventitial fibroblasts, in human perineurial cells, in human cerebral vascular smooth muscle cell, and in human fetal lung fibroblasts . InterleProper treatment of VZV vasculitis remains unclear and has not yet been widely discussed . TypicalIn the following, three cases of VZV vasculitis are described which were treated with a long-term corticosteroid and valacyclovir therapy based on the recommendation of the late Don Gilden. An analysis of the demographic data, symptom presentation, CSF and serum parameters as well as response to treatment and side-effect profiles was performed for three consecutive patients with large-vessel vasculitis. This study aims to evaluate the merits and potential pitfalls of a specific therapeutic strategy, initially proposed by Don Gilden in 2015.Case 1: A 19-year-old male patient suffered from an episode with amnestic aphasia for 60 min combined with headaches for a few days. He was admitted to another neurological hospital. His neurological examination was normal. Concerning his medical history, he reported inpatient treatment five months before due to chickenpox and Epstein Barr virus infection with a, from the patient’s point of view, good consequent recovery. However, magnetic resonance imaging (MRI) revealed a left sided stroke. Magnetic resonance angiography (MRA) and transcranial ultrasound studies demonstrated left-sided high-grade stenoses of the proximal parts of middle and anterior cerebral arteries, which was revealed in conventional cerebral angiography without any other hints for vasculitis. At that time, his cerebrospinal fluid (CSF) studies showed inflammation with 100 cells per µl and positive VZV antibody index and a positive VZV PCR. There was no oligoclonal banding. Other serum studies including HIV testing and vasculitis screening were negative. He was treated with acyclovir 800 mg five times per day for 14 days and got antiplatelet therapy with aspirin 100 mg per day.Two months later, he suffered from right-sided prickling of the arm and heavy headaches. There was a new left-sided stroke in the basal ganglia with 8 cells per µl and a positive VZV IgG antibody index in the CSF. A combination therapy with high dose corticosteroid pulses of 1000 mg methylprednisolone for five days and antiviral therapy with valacyclovir 3 times daily for one week was started  in MRA, ultrasound and angiogram studies  corticosteroid side effects under long-term therapy. Based on the case series, it cannot be excluded that a shorter corticosteroid treatment or faster tapering would have shown a similar response and improvement of the stenoses. The main limitation of this regimen consists in the commonly known side effects of glucocorticoids, such as weight gain, increased blood glucose, iatrogenic diabetes mellitus, striae rubrae, or other signs of Cushing’s syndrome. Consequently, the intake of oral glucocorticoids, exceeding the threshold of 7.5 mg/d might cause serious health issues for the respective patients. This regimen showed in Table On the other hand, the excellent improvement of the intracranial stenoses and, as a result, the decrease in the associated risk of stroke as a result of the administered therapy in our case series are a strong argument speaking in favor of this treatment regimen. Almost all side effects related to corticosteroid medication (despite striae) were reversible, the prolonged valacyclovir therapy appears to be generally well tolerated, and just renal dysfunction should be considered.In conclusion and in the absence of a more specific and better compatible treatment, combined long-term corticosteroid and valacyclovir therapy of intracranial stenoses associated with VZV vasculitis/vasculopathy is effective and remarkably safe in a younger population. Appropriate dosage and duration of treatment needs to be determined as well as whether oral treatment is as effective as intravenous application of corticosteroids and antiviral therapy.


Bioimpedance devices estimate body water and fat by measuring opposition to an electrical current applied via the skin. The most commonly reported device from existing dialysis literature is the Fresenius Body Composition Monitor (BCM), which uses bioimpedance spectroscopy (BIS). Although sometimes used interchangeably, BIS is not synonymous with bioimpedance analysis (BIA). BIA traditionally used only a single frequency before multifrequency BIA devices were developed, which measure impedance at 50–200 discrete frequencies from 3 to 1000 kHz. BIS extends this range by extrapolation to zero and infinity kHz. Greater frequency range improves discrimination of extracellular (ECW) from intracellular water. All BIS/BIA devices also estimate lean and fat tissue, but the BCM uniquely specifically quantifies fluid overload independent of body composition using the three-compartment model [The BCM reports two key parameters: absolute fluid overload in litres and percentage relative fluid overload . These parameters are the most widely studied bioimpedance indices in kidney disease cohorts but are unique to the BCM device. Measurement in litres is arguably more meaningful to dialysis clinicians, while relative fluid overload may be favoured in research to simplify between-individual comparisons. Based on a healthy population, the normal limits of BCM-measured fluid status (i.e. euvolemia) are ±1.1 L . In dialClinically, accurate volume assessment is an essential component of dialysis prescription. Although routine clinical assessments may often be sufficient to avoid extremes of hydration status, adjunctive BCM assessments have theoretical advantages in KFRT. Tracking fluid status using a BCM can be achieved with minimal training and should provide objective measures with less potential for between-observer differences than clinical assessments. When used in peritoneal dialysis, the presence or absence of indwelling dialysate is not clinically important if serial measurements follow a consistent approach.Small randomised controlled trials have shown that using bioimpedance (both BIS and BIA) improves volume status and systolic blood pressure relative to usual care , 7. HoweIn research, the BCM has been used to assess eligibility and outcomes. In the BVM-Reg trial of different techniques to monitor ultrafiltration (NCT01416753), BCM-assessed severe fluid overload ≥15% was an inclusion criterion. The SOLiD trial (ACTRN12611000975998) found that although allocation to a lower dialysate sodium of 135 mmol/L versus 140 mmol/L did not lead to any significant effect on the primary outcome of left ventricular mass index, the intervention did reduce BCM-measured ECW by ∼0.6 L over the 12-month trial.The use of bioimpedance is relatively unexplored in CKD without KRT, but observational studies are emerging. These have focused on moderate fluid overload (>1.1 L or >7%) as an exposure since severe fluid overload is relatively uncommon before kidney failure develops. In a recent systematic review we identified 11 CKD without KRT cohorts reporting associations between bioimpedance indices of fluid overload and mortality, cardiovascular outcomes and/or CKD progression . There iwww.empakidney.org) is assessing whether empagliflozin reduces the risk of a composite of kidney disease progression or cardiovascular death in 6609 participants with CKD. In a substudy of ∼10% of participants, BCM has been used to assess the effects of empagliflozin on fluid overload and adiposity. The substudy includes a secondary outcome combining clinical outcomes with bioimpedance data. The outcome is defined as a composite of death due to heart failure, hospitalisation for heart failure or the development of new moderate (>7%) or severe (>15%) fluid overload.Bioimpedance is also being explored in CKD research: the placebo-controlled EMPA-KIDNEY trial , which may provide justification for the use of bioimpedance as a component of telemedicine consultations. Unique to the heart failure setting, intra- and transthoracic impedance are also available via some devices used for rhythm monitoring.Bioimpedance devices—and particularly the BCM—have a range of potential clinical and research applications in a range of patient groups, not just kidney failure with replacement therapy Fig. . We enviData sharing is not applicable to this article as no datasets were generated or analysed during the current study.Core funding is provided to Clinical Trial Service Unit by the UK Medical Research Council (MRC) (MC_UU_00017/3) and the British Heart Foundation. Outside the submitted work, K.J.M. and W.G.H. report funds from Boehringer Ingelheim and Eli Lilly paid to their institution, the University of Oxford. W.G.H. was funded by an MRC–Kidney Research UK Professor David Kerr Clinician Scientist Award (MR/R007764/1). J.S.L. was funded by a Chief Scientist Office Postdoctoral Lectureships Award (PCL/20/10). Outside the submitted work, J.S.L. has received lectureship honoraria from Pfizer, AstraZeneca and Bristol Myers Squibb.


MYB‐NFIB fusion gene or show overexpression of MYB by immunohistochemistry. Diagnosis of PCACC is primarily based on the characteristic histological appearance, as there are no distinguishing clinical features. The diagnosis of PCACC requires careful exclusion of infiltration or metastasis from other primary lesions. Treatment of this rare tumour is wide surgical excision with at least 2 cm of tumour‐free margins to reduce the risk of local recurrence, and long‐term follow‐up for possible recurrence of PCACC is recommended. This case emphasizes the importance of careful inspection for the diagnosis of PCACC after initial surgery and pathological evaluation of the mass lesion for appropriate diagnosis and therapy.Primary cutaneous adenoid cystic carcinoma (PCACC) is an uncommon adnexal skin tumour with fewer than 200 cases studied in detail in the English literature. We describe the diagnosis and treatment of a few Southeast Asian cases of PCACC on the scalp of a 70‐year‐old Thai female. She presented with a slow‐growing, painless, solid to cystic, skin‐coloured tumour on her scalp. When excisional biopsy was done, histopathological findings showed dermal tumour that had a classic histologic appearance composed of basaloid cells arranged in a cribriform pattern with ‘punched‐out’ pseudocysts filled with mucin (swiss cheese pattern) and had perineural invasion. The clinical and histopathological findings, and complete investigations confirmed the diagnosis of PCACC. Our case illustrates that PCACC, is an important histopathological differential diagnosis to bear in mind due to its locally aggressive nature and tendency to recur due to perineural invasion. A wide local excision with at least 2 cm of tumour‐free margins was performed, which revealed no residual carcinoma. The patient remained disease‐free for 16 months after diagnosis. PCACC is usually located on the head or neck of people in their sixth decade of life, with a female predominance. The aetiology of PCACC is unclear. The majority of PCACCs have the   She denied any history of trauma, pruritus or bleeding in the area and had no history of weight loss, fever or fatigue. She had no known underlying disease and no history of skin tumours in her family. The size of the papule gradually increased in size and became more painful over the next month.Physical examination revealed a solitary, firm, tender, 5‐mm, flesh‐coloured papule on left lateral posterior of her scalp Figure . The resThe lesion was surgically excised and histopathology revealed an adenoid cystic carcinoma (ACC) and perineural invasion. The immunohistochemical stains proved positive for carcinoembryonic antigen (CEA) Figures , 3, 4. TA thorough examination of the ears, nose and throat was performed, which was unremarkable. Computed tomography scan and magnetic resonance imaging were done of the paranasal sinus regions, maxillomandibular region, neck and thorax. Both investigations were unremarkable, supporting a cutaneous origin for this tumour. The diagnosis is compatible with primary cutaneous adenoid cystic carcinoma (PCACC).The wide excision specimen showed no residual tumour. The patient remains on six‐monthly follow‐up and, to date, shows no signs of recurrence.3ACC is a very rare, homogeneous subtype of the well‐defined group of malignant sweat gland tumours.PCACC, a rare tumour first described by BoggioPCACC is a low‐grade inactive malignancy with a favourable prognosis compared with salivary ACC, which shows more aggressive behaviour. PCACC has a high degree of local invasiveness, with the majority of cases remaining confined to the skin, but only a few cases of distant metastases  have been reported.There are approximately 200 reported cases in the current literature.MYB‐NFIB or showed high levels of MYB by immunohistochemistry, which suggests that salivary and PCACC share a common development process.The aetiology of PCACC is unclear. They are probably driven by somatic mutations. However, somatic mutation patterns are unexplored.Diagnosis of PCACC is primarily based on characteristics of histological features because there are no distinguishing clinical features of the tumour. PCACC has been misinterpreted as having metastatic lesions. As a result, a full clinical and radiological examination needs to be done to look for signs of primary disease elsewhere, especially in the salivary glands.PCACC is a dermal tumour that is not connected to the epidermis. It has a classic histologic appearance and is composed of dermal islands of basaloid cells arranged in a cribriform pattern with ‘punched‐out’ pseudocysts filled with mucin (swiss cheese pattern). Tumour cells are basaloid with a number of mitotic figures, no true palisading and a tendency to show perineural infiltrates, particularly at the periphery, which is characteristic for this tumour. From viewpoint of histopathology, microscopic differential diagnoses include basal cell carcinoma with adenoid cystic differentiation, cylindroma, mucinous apocrine carcinoma and apocrine mixed tumour of skin and metastasis arising from other malignancies with histological features of ACCs.True luminal spaces are surrounded by modified myoepithelial cells that are periodic acid‐Schiff‐positive and diastase‐resistant. The mucin is sialomucin, detected by an Alcian blue stain (pH 2.5).Immunohistochemistry is characteristic but not diagnostic. Immunohistochemical study of the tumour shows two differentiated patterns, epithelial/ductal lines and myoepithelial line.PCACC is a locally invasive cancer; 70% of 130 PCACC cases had a localized stage, 25% had regional metastasis and 5% had distant metastasis.Wide surgical excision with at least 2 cm tumour‐free margins is advised to reduce the risk of local recurrence, and long‐term follow‐up for recurrence is recommended.In conclusion, we described a few cases of scalp PCACC in Southeast Asia. PCACC is a rare malignancy that should be considered in the differential diagnosis of adnexal neoplasms and, when occurring on the head and neck, must be distinguished from cutaneous involvement by salivary ACC and requires careful exclusion of infiltration or metastasis from other primary lesions. PCACC is divided into two sections histologically: ductal and myoepithelial (like ‘punched‐out’ pseudocysts filled with mucin in a ‘swiss cheese’ pattern). Treatment of this rare tumour is wide surgical excision with at least 2 cm of tumour‐free margins to reduce the risk of local recurrence in which perineural invasion plays a role after resection, and long‐term follow‐up for possible recurrence of PCACC is recommended.The authors declare no conflict of interest.Bhakinai Temnithikul: Conceptualization (lead); Data curation (lead); Formal analysis (lead); Project administration (lead); Resources (lead); Writing – original draft (lead); writing – review & editing (lead). Suthat Rungrunanghiranya: Conceptualization (support); Formal analysis (support); Project administration (support). Piyakan Limtanyakul: Conceptualization ; Data curation ; Formal analysis (support); Supervision ; Project administration ; Resources ; Writing – original draft (support); writing – review & editing (support). Suthep Jerasuthat: Conceptualization (support); Data curation (support); Project administration (support); Resources (support). David G. Paige: Conceptualization (support); Data curation (support); Writing – original draft (support); writing – review & editing (support).


In addition, recipients with ESKAPE pathogens or Candida species had a notably higher rate of bloodstream infections  and graft-site infections  than those with other positive pathogens. Preemptive antibiotic therapy decreased the bloodstream infection rate  when preservation fluid was positive for ESKAPE pathogens. (4) Conclusions: Culture-positive preservation fluid has potential implications for kidney transplant recipients. ESKAPE pathogens or Candida species in preservation fluid as well as their antimicrobial resistance properties and non-preemptive antibiotic therapy could pose a risk of early infection-related events.(1) Background: The need to elucidate the microbial patterns in preservation fluid and explore their relationship with early infection-related events post kidney transplant and investigate antimicrobial resistance and the effects of preemptive antibiotic therapy. (2) Methods: This retrospective study analyzed the clinical data of 514 kidney transplant donors and 808 recipients from April 2015 to October 2020. Clinical data of donor and recipient characteristics, preservation fluid microbes, early infections (≤30 days), probable donor-derived infections (P-DDIs), antimicrobial resistance and preemptive antibiotic therapy was collected. (3) Results: The incidence of bloodstream (10.3% versus 5.2%,  Kidney transplant recipients are particularly prone to infections due to prolonged immunosuppression. Preservation fluid, which is critical to maintain kidney graft viability during transportation, could pose serious infection risks. Donor-derived pathogens may be present in the preservation fluid. A nationwide survey in France showed that approximately one in five kidney transplant preservation fluid samples yielded positive cultures , with a Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), could lead to an increased risk of early post-transplant infections [Donor-derived pathogens are associated with early infection-related events after kidney transplantation. Some virulent pathogens in the preservation fluid may derived from the donor, associating with early infection-related events after kidney transplantation. High-risk pathogens, including ESKAPE pathogens  was used for graft perfusion during organ procurement and storage during graft transportation. Preservation fluid samples (10 mL each) were collected from the kidney storage bag before the back-table kidneys preparation. Each sample was inoculated into a blood culture bottle under aseptic conditions. Identification and antimicrobial susceptibility test were performed if there was microbial growth during incubation. A final report of sterile growth was recorded if there was no microbial growth after 7 days of incubation. Any microbial growth was recorded. Samples of preservation fluid for microbial assessment were processed using the Bact/Alert 3D system . We performed Antimicrobial Susceptibility Testing (AST) with the VITEKEarly infection-related events included early infection events and P-DDIs. Early infection events , pathogeCulture-positive preservation fluid was defined as growth of any pathogen in the preservation fluid. Coagulase-negative staphylococci was categorized according to the Institute of Medical Microbiology guidelines . MultidrAll recipients received empirical perioperative antibacterial treatment, with cephalosporins prior to 31 December 2018, and carbapenems afterwards. Echinocandins (Caspofungin or Micafungin) was given to recipients at high risk for fungal infection. Linezolid was given to recipients at high risk of Gram-positive coccus infection. Specific antibiotics or antifungal coverage were based on the discretion of transplant surgeons. The immunosuppressive protocol included induction with basiliximab or anti-thymocyte globin and a tapered dose of steroid, plus tacrolimus or cyclosporin A plus mycophenolic acid.p < 0.05 was considered statistically significant. All data analyses were performed using SPSS version 26.0  and GraphPad Prism 9.3.1. Categorical variables were characterized by percentages and compared with chi-square tests or Fisher exact tests. According to their distribution, continuous variables were expressed as means and standard deviations (SD) or as medians and interquartile ranges (IQR); comparisons were made using the Student’s t-test or Mann–Whitney U test. Comparison among multiple groups were corrected by Bonferroni test. A 2-tailed p < 0.01) and warm ischemia time  in those having a positive preservation fluid culture.The study flowchart was shown in A total of 490 isolates were obtained from 329 recipients with culture-positive preservation fluid. Coagulase-negative Staphylococcus accounted for 34.5% (169/490) of the isolates. ESKAPE pathogens accounted for 30.4% (149/490) of the isolates. Of these, Enterococcus faecium accounted for 28.2% (42/149). Candida species accounted for 10.6% (52/490), of which Candida albicans accounted for 32.7% (17/52) .p = 0.271). Twelve recipients (1.5%) were diagnosed as P-DDIs, which accounted for 3.7% of recipients with culture-positive preservation fluid. The incidence of bloodstream infections was significantly higher in recipients with culture-positive preservation fluid than those with negative result . Recipients with culture-positive preservation fluid also had a notably higher rate of graft-site infections . A higher incidence of wound infections was observed in recipients with culture-positive preservation fluid, though there was no statistical difference between the two groups . No significant difference was observed in the incidence of pneumonia, urinary tract infections or infectious diarrhea between recipients with culture-positive preservation fluid and recipients with culture-negative preservation fluid  had at least one episode of early infections while the percent of those with negative result is 24.2% (on fluid .p = 0.033). They also had a remarkably higher rate of graft-site infections than those who were positive for other pathogens . Though recipients who were positive for ESKAPE pathogens or Candida species had a higher rate of urinary tract infections and wound infections, no statistically significant difference was observed (p = 0.011). Most P-DDIs in the kidney transplant recipients were associated with ESKAPE pathogens or Candida species. Only two cases were caused by other pathogens   . In addiophilia) .One hundred seventy-nine (54.4%) recipients had had MDR microbes in the preservation fluid used for their respective kidney transplant. Recipients with MDR microbes in preservation fluid accounted for 73.5% (25/34), 66.7% (6/9) and 71.9% (23/32) of those who developed bloodstream infections, wound infections and graft-site infections, respectably. In addition, among the recipients who developed P-DDIs, 83.3%(10/12) had received transplants when there were MDR microbes in the preservation fluid . Sixty-oSimilarly, we further analyzed the antimicrobial resistance of ESKAPE pathogens. MDR microbes were present in 65.3% (81/124) of recipients who had ESKAPE-contaminated preservation fluid. In addition, MDR microbes accounted for 77.8% (14/18) of bloodstream infections, all (6/6) wound infections and 75.0% (15/20) of graft-site infections in recipients who had ESKAPE-contaminated preservation fluid. Moreover, MDR microbes accounted for 88.9% (8/9) of P-DDIs in recipients who had ESKAPE-contaminated preservation fluid. In addition, 30.7% (38/124) of recipients who had ESKAPE-contaminated preservation fluid had XDR microbes in preservation fluid. Recipients who had ESKAPE-contaminated preservation fluid had XDR microbes for 6 out of 9 P-DDIs .p = 0.065) (p = 0.164) and P-DDIs  were observed in recipients who received preemptive antibiotic therapy than recipients who did not. However, there was also no statistical difference between the two groups. Furthermore, among recipients wtih ESKAPE-contaminated preservation fluid, those who received preemptive antibiotic therapy had a lower rate of bloodstream infections .In our study, 11.3% (14/124) and 9.6% (5/52) of recipients did not receive targeted antimicrobial treatment against ESKAPE pathogens or Candida species in preservation fluid, respectively, on a pre-emptive basis. Among recipients with ESKAPE pathogens or Candida species in preservation fluid, those who received preemptive antibiotic therapy had a lower rate of bloodstream infections, but there was no statistical difference between the two groups  . A lowerCandida species in the preservation fluid were significantly more likely to develop bloodstream infections, graft site infections and P-DDIs than those with other pathogens. Furthermore, preemptive antibiotic therapy with targeted antimicrobial treatment against ESKAPE pathogens or Candida species was beneficial to lower the incidence of early infection-related events. Notably, MDR was associated with a higher incidence of bloodstream infections and graft-site infections as well as P-DDIs. Our study demonstrated the possible impact of culture-positive preservation fluid on kidney transplant recipients and added evidence to suggest preemptive antibiotic therapy targeted antimicrobial treatment against ESKAPE pathogens or Candida species detected in preservation fluid.Infections are a significant cause of morbidity and mortality after kidney transplantation . DDI, alThe incidence of culture-positive preservation fluid at our center was 40.7%. Different studies report different levels of culture-positive preservation fluid incidence in solid-organ transplantation, which range from 10% up to >90% . MultiplMany studies have shown that culture-positive preservation fluid is associated with the incidence of early infection-related events in kidney transplantation ,13. In oCandida species were associated with a higher incidence of early infection events compared to other pathogens, notably bloodstream infections, graft-site infections and P-DDIs. Yu et al. also showed a high rate of preservation fluid-related infections following contamination by ESKAPE pathogens and Candida species [Candida infections can cause considerable morbidity and mortality in solid organ transplant [Candida species. Candida species can be transmitted to the recipient via the donor kidney, and it is prone to cause Candida arteritis, which is a possible and common manifestation of graft-site candidiasis and can pose a life-threatening situation by causing anastomotic leakage or rupture and subsequent hemorrhagic shock [Candida species in preservation fluid also demand attention [Recipients with highly virulent pathogens isolated from the preservation fluid are more susceptible to early infection-related events after kidney transplantation ,16. In o species . ESKAPE  species . Up to 2 species . Candidaansplant . We founic shock . Consistttention .Candida species supports a prediction of early infection-related events after kidney transplantation. Lacking an adequate surveillance system during donor management as well as monitoring of preservation fluid and delayed treatment are the causes of serious infections. If donor cultures are positive for the above pathogens, antimicrobial drugs should be administered prior to the donation procedure and organs procured with repeated negative cultures. In addition, routinely monitoring the culture of pathogens in preservation fluid is necessary. Timely administration of the antimicrobial drugs according to drug sensitivity results should be undertaken if these pathogens are found in the preservation fluid or recipient. Therefore, strategies for ESKAPE pathogens or Candida species in kidney transplant should include donor management, monitoring of preservation fluid and timely therapy of antimicrobial resistance.Preservation fluid containing ESKAPE pathogens or Candida species in preservation fluid, preemptive antibiotic therapy had the effect of lower rates of bloodstream infections, graft-site infections and P-DDIs, suggesting that such pathogens in the preservation fluid should be targeted with antimicrobial treatment by prophylactic empirical antibiotic or antifungal drugs. However, Ranghino et al. found that preemptive antibiotic therapy made no difference to the rate of infections from preservation fluid related pathogens [Preemptive antibiotic therapy based on preservation fluid is still controversial. A recent national questionnaire survey in France found that antibiotic prophylaxis in the perioperative period of kidney transplantation is very heterogeneous in the absence of well-established guidelines . A prospathogens . This isAntimicrobial resistance could increase the risk of early infection-related events after kidney transplantation. DDIs caused by MDR pathogens can have devastating consequences for organ transplant recipients . We founThere are several limitations in this study. Firstly, it was a retrospective study with a single-center design. In addition, DDIs events were not eligible for detection, so we used the concept of P-DDIs instead. Lastly, the sample size of wound infection recipients was relatively small, which may lead to unreliability of the results presented for preemptive antibiotic therapy analysis about wound infections.Candida species in preservation fluid as well as their antimicrobial resistance properties and non-preemptive antibiotic therapy could pose a risk of early infection-related events. Therefore, we suggest that preemptive antibiotic therapy should always be used when ESKAPE or Candida pathogens are detected in preservation fluid, especially if they are determined as having resistance to antimicrobial treatments.There is a potential impact of culture-positive preservation fluid on kidney transplant recipients. ESKAPE pathogens or


Intraoperative ABR results should account for sex differences and be interpreted with caution and be verified. Ultimately, parents should be engaged in a preoperative discussion to decide if an ioABR should be postponed if mucoid fluid was found.Intraoperative auditory brainstem response (ioABR) testing following tympanostomy tube (TT) placement may be biased due to temporary threshold shifts (TTS). The purpose of the study was to assess the evidence for TTS in children who have undergone ioABR using prolonged latencies of wave I  as a marker of a persisting air–bone gap. Eighty-three children underwent ioABR following surgical procedures at University Hospital Bonn, Germany. The primary outcome measure was the latency of wave I at 80-dB SPL. The total sample consisted of 66 males (79.5%) and 17 females (20.5%) with a mean (SD) age of 46.4 (26.6) months. Of 163 operated ears (83 children), 72 (44.2%) had no middle ear fluid, 19 (11.6%) serous fluid, and 72 (44.2%) mucoid fluid. The risk of having a prolonged latency of wave I at 80-dB SPL was OR 4.61 (95% CI 2.01–10.59;  Auditory brainstem response (ABR) testing is an objective diagnostic tool ,2,3 and However, several authors ,9,10,11 Griffiths et al.  could deDornan et al.  reportedRegarding time-to-normalization, a study by Boudewyns et al.  investigFinally, a recent pilot study by Martinovic et al.  investigThere is still a paucity of data to guide clinical practice with regard to ioABR measurements post-TT insertion. Therefore, the purpose of the study was to determine evidence for TTS based on the prolonged latencies of wave I (Jewett I = J I) in a large retrospective sample of children including those who have undergone ioABR following surgical procedures such as myringotomy and TT insertion. The ABR latency delay of wave I (J I) indexes with high accuracy the presence or absence of an otitis media with effusion  and can The retrospective study included pediatric patients who between February 2008 and December 2013 underwent click ioABR at University Hospital Bonn in part with prior adenoidectomy, myringotomy, and if needed TT insertion. The Ethics Committee of the University of Bonn determined the study to be exempt from review. Age, height, and weight were recorded as well as the presence of adenoids , middle ear fluid , and surgical procedures such as adenoidectomies, myringotomies, and TT insertions. Intraoperative ABR latency times of wave I at 80-dB, or 90-dB and 100-dB SPL if needed, were collected as well as the latencies of waves III, V, and the interpeak latency I-V. Wave V (Jewett V = J V) correlates well with the actual hearing threshold and can be found approximately 0–10 dB below the threshold of detection . Wave IIIn addition, pre- or post-operative notes about binocular-microscopic results and available audiometric data were collected . Lastly, comorbidities and noteworthy family history, duration of surgery, anesthesia, and ABR examinations were documented. Total time of anesthesia refers to the sum of surgical procedures, which may include adenoidectomy, unilateral or bilateral myringotomy, unilateral or bilateral TT placement or change , as well as the additional ioABR. Follow-up audiometric tests typically took place at the referring otolaryngologist’s office.p < 0.0091). We reviewed ABR data from 98 ears with normal tympanograms collected between January 2021 and September 2022 . The age ranged from 2 months to 89 months with a mean of 29.5 months (SD = 23.0). Wave I values for both ears combined had a mean of 1.67 (SD = 0.14) with a range from 1.21 to 1.90 ms. For male ears the values were a mean of 1.72 (SD = 0.12) with a range from 1.44 to 1.90; mean of 1.62 (SD = 0.14) with a range of 1.21 to 1.89 for female ears. Using the formula M + (1.95 × SD), the threshold for boys remains at 1.96 (>1.95) but is lower for girls at 1.89 (>1.88). If wave I could not be elicited at 80-dB SPL, then measurements were taken at 90-, 100-dB SPL. For testing with elevated sound pressure levels, a generally accepted norm value is missing. For this study, a threshold of 1.90 ms for the measurement of latency of wave I at 90-db SPL was chosen. Greater SPLs lead to faster conduction velocity and thus to a shorter latency.The primary outcome measure was the latency of wave I. A latency of >1.95 ms was historically considered abnormal at 80-dB SPL at the study site, but significant sex differences in the control data set required a different cut-off for females . We describe the overall presence of mucoid fluid groups in the study population using mean values and standard deviations for normally distributed variables, and median values and interquartile ranges for non-normally distributed variables. The values of categorical variables are presented as frequency distributions with percentages. For the outcome presence of prolonged latencies, a mixed-effects model was used to account for the hierarchical nature of the data (ears nested in patient), including mucoid fluid or fluid in the ear as covariables. The resulting odds ratios (ORs) are presented with 95% confidence intervals. A two-sided The initial study sample included 95 consecutively enrolled children between 4 and 202 months (median 42) who between February 2008 and December 2013 underwent click ioABR at University Hospital Bonn in part with prior adenoidectomy, myringotomy, and, if needed, TT insertion. Of those, 83 children between 4 and 134 months have undergone an ioABR post-unilateral or bilateral myringotomy with subsequent TT insertion as needed and are the focus of the study. There were 66 males with a mean age of 47.6 months  and 17 females with a mean age of 42.1 months  had no fluid, 19 (11.6%) serous fluid, and 72 (44.2%) mucoid fluid. Slightly over half of the patients  had mucoid fluid compared to no mucoid fluid, i.e., no fluid or serous fluid. Of those, twenty-nine had bilateral, seven left, and seven right mucoid fluid. Descriptive data of operative procedures by effusion type are shown in Latencies of wave I were measured in 83 children and can be found in In both groups, with and without mucoid fluid, there were children with prolonged latency of wave I at 80-dB SPL. In children without mucoid fluid, the prolonged latency of wave I could only be determined in 21 of 72 ears (29.2%), whereas in the group of children with mucoid fluid it could be determined in 38 of 52 ears (73.1%). As a function of sex, the percentage of male ears (n = 101) with mucoid fluid and prolonged latency of wave I at 80-dB SPL was 28.7 % . Respective data for female ears (n = 23) were 39.1 % and 26.1 %.For children tested at 90-dB SPL (n = 8), the corresponding results to testing at 80-dB SPL were as follows. Patients with mucoid fluid had a mean (SD) latency of 2.05 (0.34) ms on the left side and 2.19 (0.44) ms on the right side, while patients without mucoid fluid had latencies of 1.69 (0.06) ms on the left side and 1.87 (0.67) ms on the right side. However, this effect did not persist at the 100-dB SPL testing level. Seven children at this SPL had mucoid fluid with a mean (SD) latency of 1.61 (0.96) ms on the left side and 2.12 (0.32) ms on the right side. Without the presence of mucoid fluid, the value was 2.13 (0.45) ms on the left and 2.24 (0.53) ms on the right side.p < 0.001). The risk increased to OR 6.92 [95% CI 3.02–15.86] in those with fluid in the ear (serous or mucoid) as compared to those without fluid (p < 0.001).When the statistical model was tested for wave I values at 80 dB only, the results were as follows. The risk of having a prolonged latency of wave I was OR 4.61 [95% CI 2.01–10.59] in those with mucoid fluid as compared to those without mucoid fluid (p < 0.001). The risk was OR 7.61 [95% CI 3.67–15.79] in those with fluid in the ear as compared to those without fluid (p < 0.001). Across all testing levels for wave I , the risk of having a prolonged latency of wave I was OR 8.24 [95% CI 4.01–16.92] in those with mucoid fluid as compared to those without mucoid fluid , which was on average greater in children with mucoid fluid compared with children with serous and mucoid fluid combined  and more pronounced in contrast to measurements at 80, 90, and 100 dB combined. In direct comparison of 29 left and 23 right ears with mucoid fluid to 27 left and 27 right ears without effusion, there was still a difference by way of latency differences of wave I at 80 dB on the left with 2.18 ms vs. 1.86 ms, and on the right with 2.22 ms vs. 1.89 ms.Age and sex differences in latencies of waves I, III, and V in ABR responses in normal hearing participants have been reported with latencies of waves I and V linearly increasing with age in men . Data foAs in other studies, not all patients with surgically treated mucoid fluid showed post-operatively prolonged latency. Five patients with bilateral mucoid fluid  and without abnormal latencies in ioABR did have a normal hearing threshold of 10–20 dB based on the analysis of wave V potentials. Two patients with bilateral mucoid fluid and unilateral latency increases had interaural latency differences of 0.51 up to 1.47 ms, indicating that only one side had abnormal conduction. In three patients who showed a unilateral latency increase, the contralateral side could not be tested, because one child had a unilateral auricular deformation and auditory canal malformation and in two patients the hearing threshold up to 100-dB SPL could not be determined and thus, the potential of wave I up to 100 dB.An additional child with only a unilaterally abnormal latency post-TT insertion due to bilateral mucoid fluid also only had, unilaterally, a pathologic hearing threshold of 40–50 dB on the side with the increased latency, while the contralateral side was already at physiological 20–30 dB. In two patients with normal latencies, thresholds were 50–60 dB and 30–40 dB, respectively. A postoperative follow-up hearing test was unfortunately not available due to follow-up care in private practice. However, in one additional child with bilateral mucoid fluid, a unilateral latency delay, and a threshold of 30–40 dB, there was a bilateral normal result in follow-up OAE testing . In 18 of our patients with a TT insertion for bilateral mucoid fluid, there were still bilateral prolonged latencies of wave I during ioABR.The data on surgical and total anesthesia time show that the average duration of surgery was 10 min., while the total duration of anesthesia (surgery plus ioABR) was close to two hours. Thus, children were exposed to an average of a more-than-10-fold duration of anesthesia because of subsequent ioABR. Yet, the ioABR measurement may be biased due to persisting prolonged latency, and thus may indicate a TTS with poorer hearing acuity than the actual expected inner ear performance of these children. In fact, the updated clinical practice guideline for TTs briefly acknowledges the problem and recommends the shared decision making of stakeholders , which aThe study is limited by its retrospective nature. Unfortunately, most follow-up audiometric testing occurred off-site, so that it could not be determined with certainty in what time frame the thresholds returned to normal values. Bone-conduction testing was not included to help with the interpretation of the data. Other literature also recommended reporting anesthetic agents and other electronic equipment in the operating room .Intraoperative ABR results can be biased when obtained immediately post-TT insertion. Most patients who underwent TT insertion showed postoperatively prolonged latencies of wave I (at 80-dB SPL), which was on average greater in children with mucoid fluid compared with children with serous and mucoid fluid combined. The surgeon should inform parents accordingly and devise an individual plan.


TP53 mutations concordant with those in the tissue, and the ctDNA of a patient with positive cytology harbored both TP53 and POLE mutations, although none were detected in the tissue. This study is the first to demonstrate comprehensive genomic concordance between ctDNA from the peritoneal fluid and tumor gDNA in endometrial cancer at the whole-exome level.Studies on biomarkers for endometrial cancer using circulating tumor DNA (ctDNA) from liquid biopsy samples are lacking. The aim of this study was to analyze gDNA from tumor tissues and ctDNA derived from peritoneal fluid and plasma samples and determine their mutational concordance via microsatellite instability, copy number alteration, and mutational signature analyses using whole-exome sequencing and P53 immunohistochemistry. ctDNA of two patients with negative cytology presented KMT2C, NOTCH2, PRKAR1A, SDHA, and USP6) and genes related to EC  were identified with high frequencies among the three samples. TP53 and POLE mutations, which are highly related to the molecular classification of EC, were identified based on several key observations. The ctDNA of two patients with negative peritoneal fluid presented TP53 mutations concordant with those in tissues. ctDNA from the plasma and peritoneal fluid of a patient with positive cytology harbored both TP53 and POLE mutations, although none were detected in tissues. Additionally, the patient presented with wild type P53 immunohistochemistry, with a focal “high” expression in a “low” wild type background. The tissues and peritoneal fluid of 75% EC patients showed concordant microsatellite instability. Furthermore, we observed strong mutational concordance between the peritoneal fluid and tumors. Our data suggest that the ctDNA from peritoneal fluid might be a suitable biomarker for identifying the mutational landscape of EC and could complement tumor heterogeneity.Endometrial cancer (EC) is the most common type of gynecological cancer. Studies comparing tumor gDNA and ctDNA isolated from the plasma and peritoneal fluid of EC patients are limited. Whole-exome sequencing and P53 immunohistochemistry of 24 paired tissue, plasma, and peritoneal fluid samples from 10 EC patients were performed to analyze somatic mutations, copy number alterations, microsatellite instability, and mutational signatures. Mutations in cancer-related genes ( TP53 mutational testing/p53 immunohistochemistry (IHC) to determine p53 status as a surrogate for classification of the CN-high TCGA group . Th. ThPOLE,l burden . The presubtypes . ctDNA fmegabase .ARID1A harbored four nonsense and two missense mutations in seven patients with EC. One nonsense mutation (p.Q537X) in ARID1A was identified in both the peritoneal fluid ctDNA and tumor gDNA of EC2  in PIK3CA was identified in both the peritoneal fluid and plasma ctDNA of EC4  in 401 cancer-related genes were analyzed in peritoneal fluid ctDNA, plasma ctDNA, and tumor gDNA samples a,b. We fIn addition, PolyPhen-2, PROVEAN, and SIFT analyses revealed that most putative driver mutations  had damaging effects on protein function, as detected with at least two of the three methods employed . SixteenTP53 mutations in the peritoneal fluid and plasma ctDNA, but not in the tissue  . EC1 shoe tissue , indicatPOLQ and PREX2 in the regions of gains and CASP8 and SF3B1 in the regions of loss were found in all samples, including the tissue, plasma, and peritoneal fluid  were identified in tissue, plasma, and peritoneal fluid samples from 10 patients with EC . We founal fluid a–f.PREX2 and SOX17 were found among the three DNA sources in the EC4 patient, who showed a recurrence of the disease after 15 months   . Common  patient . In addid PIK3CA  [1,32,33d PIK3CA . Most end PIK3CA .We identified the MSI status in all EC genomes, as it makes a crucial contribution to diagnosis and therapeutic decisions in EC . MSI staTP53 and human tumors with oxidative DNA-damaging effects, were abundant in all three DNA sources [Mutational signatures of somatic mutations were analyzed in peritoneal fluid ctDNA, plasma ctDNA, and tumor gDNA samples using the NMF algorithm. We found that C > T transitions, which are frequently found in  sources ,45. Muta sources . SBS15 i sources . SBS1 is sources . Ageing- sources . Notably sources .https://www.nccn.org; accessed on 20 September 2021). Peritoneal fluid was obtained from 10 patients with EC, and WES was performed on four samples . Of these, EC1 and EC3 samples showed negative cytology results, while EC2 and EC4 displayed positive cytology  presented with important genetic features such as TP53 mutation and MSI-H status.According to the NCCN guidelines, peritoneal/ascitic fluid cytology is included in the principle of surgery, although cytology alone does not affect the FIGO staging , TP53mut , and MMRd   . These tTP53 mutations were found . Interestingly, KMT2C was the most frequently mutated gene among the three DNA sources in our study; this gene has been previously reported in EC as a chromatin remodeling-related gene [KMT2C, at least one of the same recurrent missense mutations was found in all samples  harbors important genetic biomarkers, and substantial correlations exist among them. We found that ECs harbored not only known mutations in driver genes, such as ted gene . In KMT2 samples a. AdditiPREX2 (8q gain) and POLQ (3q gain) in the peritoneal fluid, plasma, and tissue. Frequent losses on 2q33.1 in CASP8 from the peritoneal fluid, plasma, and tissue have not been reported in EC; however, they have been reported to be highly related to cell death and drug resistance [These findings suggest that chromosomal alteration information obtained using ctDNA from the peritoneal fluid and plasma could provide a valuable tool for identifying EC. Most recurrent CNAs of ECs in the current study were largely in agreement with those described in earlier EC genomic studies, gains on 8q24.21, 8q11.2, 12p12.1, and 3q26–27 and losses on 4p16.3 and 3p14.2 from tissue samples . To datesistance .MSI or MMR status was detected using mutational signature analysis and MSI analysis of tissues, the peritoneal fluid, and the plasma. Data showed that the majority of EC patients had the same MSI status in both tumor gDNA and ctDNA from liquid biopsy samples ; tumor gDNA and plasma ctDNA (50% concordance)). The mutational signatures SBS1, SBS5, and SBS15 have been found in uterine and cervical cancers, of which SBS15 is initiated by defective DNA mismatch repair . In addiPOLE mutations exhibited a high mutational burden in tumor gDNA, and a consensus in ctDNA was further identified by investigating all samples with POLE mutations [Among the four classified molecular subtypes of EC genomes, several interesting observations were made . TCGA shutations . In addiutations . All EC To the best of our knowledge, this is the first study to compare comprehensive genomic profiles of ctDNA from the peritoneal fluid, plasma ctDNA, and tumor gDNA samples in EC genomes at the whole-exome level. The data provide clues that ctDNA can be used clinically to identify the mutational landscape of endometrial cancer and complement tissue heterogeneity.