Background: Diffuse lower-grade gliomas (LGGs) are infiltrative and heterogeneous neoplasms. Gene signature including multiple protein-coding genes (PCGs) is widely used as a tumor marker. This study aimed to construct a multi-PCG signature to predict survival for LGG patients.Methods: LGG data including PCG expression profiles and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). Survival analysis, receiver operating characteristic (ROC) analysis, and random survival forest algorithm (RSFVH) were used to identify the prognostic PCG signature.Results: From the training (n = 524) and test (n = 431) datasets, a five-PCG signature which can classify LGG patients into low- or high-risk group with a significantly different overall survival (log rank P < 0.001) was screened out and validated. In terms of prognosis predictive performance, the five-PCG signature is stronger than other clinical variables and IDH mutation status. Moreover, the five-PCG signature could further divide radiotherapy patients into two different risk groups. GO and KEGG analysis found that PCGs in the prognostic five-PCG signature were mainly enriched in cell cycle, apoptosis, DNA replication pathways.Conclusions: The new five-PCG signature is a reliable prognostic marker for LGG patients and has a good prospect in clinical application. Glioma is the most common primary CNS tumor and was classified into grades I–IV according to histopathological characteristics. Glioblastoma (WHO grade IV glioma) accounts for 70–75% of all diagnosed diffuse gliomas, with a median overall survival of 14–17 months . OverallGlioma is a fatal tumor that derives from glial cell and grows in the central nervous system, including diffuse gliomas and nondiffuse gliomas . DiffuseIn recent years, significant progress has been made in the study of molecular pathology of gliomas, and a series of molecular markers have been discovered that are helpful for clinical diagnosis, prognostic judgment, and treatment guidance, such as IDH1/2 gene mutation, chromosome 1p/19q co-deletion, and MGMT promoter methylation . EspeciaWith the development of next-generation sequencing technology, a large amount of high-throughput sequencing data and a variety of bioinformatics methods have prompted researchers to further understand tumorigenesis and find prognostic markers. Hu et al.  selectedIn the present study, the protein-coding gene (PCG) expression data from a total of 955 LGG patients were collected from the Cancer Genome Atlas (TCGA) database and the Chinese Glioma Genome Atlas (CGGA). We aimed to mine the large queue of gene expression data and clinical information to identify a prognostic PCG signature and explore its significance of treatment guidance.http://cancergenome.nih.gov/; https://xenabrowser.net/datapages/). Another independent dataset used as validation or test dataset was downloaded from the CGGA database (http://www.cgga.org.cn/). LGG cases with clinical survival information including survival status and survival time were selected for building the prognostic model. Clinical details of LGG patients in the training and test datasets are shown in The clinical information and mRNA expression data of LGG patients were obtained from the TCGA database (Using Kaplan–Meier (KM) and receiver operating characteristic (ROC) analysis, we identified the PCGs significantly associated with patients' OS with AUC > 0.6 from the TCGA group. Then we reduced the number of the PCGs by the random survival forest algorithm (RSFVH). Further, prognostic models were constructed as follows:N is the number of PCG, Expression is the PCG expression value, and coefficient is the PCG expression in Cox regression analysis. The final prognostic PCG signature was screened out with the largest AUC value in all the constructed models (where d models .www.r-project.org) with R packages including pROC, TimeROC, randomForestSRC, and survival was used to perform the above analyses.Kaplan–Meier analysis was used to assess the two survival risk groups separated by the median risk score. Cox regression analysis was performed to explore the independence of the signature. ROC and TimeROC were used to analyze survival prediction performance. Function prediction of prognostic PCGs was analyzed by clusterProfiler . R progrn = 524) and CGGA (n = 431) datasets, and a total of 16,246 expressed PCGs were identified. From All 955 patients diagnosed with LGG were collected from the TCGA  or low-risk group (n = 262). The Kaplan–Meier analysis results showed that patients in the low-risk group lived longer than patients in the high-risk group . After the median risk score in CGGA-separated patients into high- or low-risk group, Kaplan–Meier analysis found that the 5-year survival of patients with high risk scores was lower than that of patients with low risk scores , we found that the signature was related with clinical variables such as IDH mutation status and Grade by chi-square test  using the Pearson test in the TCGA and CGGA datasets, respectively, and then performed KEGG and GO analysis. The co-expressing genes of the five PCGs were significantly enriched in 425 Go terms and 21 KEGG pathways (P < 0.05), such as cell cycle, DNA replication, and p53 signaling pathway, indicating the specific pathway or mechanism in which the prognostic PCGs might play a key role , also named multidrug resistance-associated protein 3 (MRP3), is an organic anion transporter and contributes to drug resistance of cancer cells . ConsistOur study developed a prognostic five-PCG signature for LGG patients that can predict individual clinical outcome with high accuracy. Surprisingly, the five-gene signature can also predict radiotherapy response, which makes the biomarker have a broad clinical value.https://xenabrowser.net/datapages/; CGGA: http://www.cgga.org.cn/download.jsp.Publicly available datasets were analyzed in this study. This data can be found here: TCGA: QZ and WL: data collection, data analysis, interpretation, and drafting. X-JL, R-AX, LC, and ZS: study design, study supervision, and final approval of the manuscript. S-BL and F-CX: technical support and critical revision of the manuscript. All the authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Exosomes have emerged as a new drug delivery system. In particular, exosomes derived from mesenchymal stem cells (MSCs) have been extensively studied because of their tumor-homing ability and yield advantages. Considering that MSC-derived exosomes are a double-edged sword in the development, metastasis, and invasion of tumors, engineered exosomes have broad potential use. In this review, we focused on the latest development in the treatment of tumors using engineered and nonengineered MSC-derived exosomes (MSC-EXs). Nonengineered MSC-EXs exert an antitumor effect on several well-studied tumors by affecting tumor growth, angiogenesis, metastasis, and invasion. Furthermore, engineered exosomes have promising research prospects as drug-carrying tools for the transport of miRNAs, small-molecule drugs, and proteins. Although exosomes lack uniform standards in terms of definition, separation, and purification, they still have great research value because of their unique advantages, such as high biocompatibility and low toxicity. Future studies on MSC-EXs should elucidate the mechanisms underlying their anticancer effect and the safety of their application. The diagnosis and treatment of tumors, which are a key global health concern, have long been a focus of research. Although surgery is still an effective strategy for early cancer treatment, owing to the hidden onset of cancer and the limitations of diagnostic techniques, most patients with cancer have already reached intermediate and advanced tumor stages by the time their cancers are detected, minimizing the therapeutic effect of surgery . AlthougMSC-EXs, which are natural nanovesicles with low immunogenicity, good biocompatibility, and low cytotoxicity, have a unique antitumor effect. As MSC-EXs are high-quality drug delivery carriers, constructing engineered MSC-EXs for drug loading has long been a key research topic in the field of exosome-based therapy for cancer. Moreover, natural exosomes that function through their own inclusions or surface markers also exert antitumor effects; some of them may be used as biomarkers for cancer diagnosis or prognosis –7. Givenμm), microvesicles , and exosomes (30 to 150 nm) mainly based on their diameter and origin [Extracellular vesicles (EVs) are classified as apoptotic bodies . Among the various sources of exosomes, human umbilical cord MSCs (hUC-MSCs) and human umbilical cord Wharton's jelly MSCs (hWJ-MSCs) are the most commonly used. Whether natural MSC-EXs exert positive or negative effects on tumors is still controversial. A previous study reported that the dual effect seems to be related to the source of MSC-EXs, dose, and time of MSC injection, cancer type, and other factors .A group of studies has reported that natural MSC-EXs promote tumor progression . Howeverin vitro.Abnormal and excessive angiogenesis during cancer development could exacerbate the disease . In the in vitro from bone marrow MSCs (BM-MSCs) could enhance tumorigenesis by promoting oncogenic autophagy in osteosarcoma.MSC-EXs are a double-edged sword in tumor growth. Kalimuthu et al.  used floTumor metastasis and invasion are regulated not only by the cancer cells themselves but also by the entire tumor microenvironment. As a part of the tumor microenvironment, the role of exosomes in information transmission cannot be ignored. Gu et al.  observedConsidering the heterogeneity of tumors, different tumor types may be among the reasons for the seemingly contradictory effects of MSC-EXs.in vitro [in vivo contain various miRNAs that regulate epithelial-mesenchymal transition (EMT), they can promote breast cancer cells to enter the dormant phase, which is related to higher chemoresistance [in vitro are rich in miR-100, which modulates the mTOR/HIF-1α/VEGF signaling axis and inhibits the angiogenesis of breast cancer  accounts for about 10% of all hematological malignancies, with an overall survival in affected patients of only 3 years . ExtensiGastric cancer (GC) is one of the most common malignancies worldwide . Chemothin vitro. Moreover, intratumor administration of BM-MSC-derived MVs in vivo remarkably inhibited tumor growth [Extensive research has shown that MSCs and MSC-EXs have considerable potential for the treatment of liver cancer. MVs derived from BM-MSCs inhibit cell cycle progression and induce apoptosis in HepG2 cells r growth . hUC-MSCr growth .In recent years, the morbidity and mortality of bladder cancer have had an evident upward trend, making bladder cancer among the most common urinary system malignancies. Exosomes and the engineered ones are of great importance to bladder cancer patients for their future research and treatment. The inhibitory effect of MSC-EXs on bladder cancer is greater than that on other major tumors. Cai et al.  investigIn cancer targeted therapy research, up- or downregulation of the expression of a certain molecule often arouses the interest of researchers, who then, through interference measures, attempt to reverse this phenomenon and observe whether it has clinical value. Che et al.  chose MSOvarian cancer has the highest mortality rate among gynecological malignancies; its detection in early stages is challenging . Even wiExosomes were originally considered cell cleaners for the disposal of unnecessary components –64. HoweCurrently, targeted drug delivery for tumors has been investigated to target specific subcellular compartments, and receptor-mediated endocytosis is the most promising approach . As promβ-catenin, a key molecule of the Wnt/β-catenin signaling pathway, plays an important role in tumor EMT. Wan et al. [β-catenin in nasopharyngeal carcinoma (NPC). They obtained exosomes overexpressing miR-34c by transfecting MSCs with lentivirus, and they found that exosomes overexpressing miR-34c considerably increased radiation-induced apoptosis in NPC cells. miR-34c reduced the expression of β-catenin by directly targeting the 3′-UTR region of β-catenin mRNA, which contributes to a reduction in EMT and radioresistance. In addition, Jeong et al. [Gene modification is the most commonly used strategy for miRNA transfection of MSC-EXs . For exan et al.  first cog et al.  used 2D g et al.  construcChemotherapeutic drugs can be loaded onto MSC-EXs for administration, which can help address concerns related to their low aqueous solubility and specificity; this loading can improve the effects of related cancer therapy .Taxol is a widely used chemotherapy drug. Melzer et al.  treated Some researchers have focused on doxorubicin (DOX), which is also a common chemotherapy drug. Wei et al.  mixed exHonokiol is a newly discovered chemotherapy drug for tumor treatment. Kanchanapally et al.  loaded hin vitro; it effectively reversed the multidrug resistance of tumors and improved the sensitivity of chemotherapy drugs. In another study, researchers obtained CXCR4/TRAIL-rich exosomes from MSCs overexpressing both CXCR4 and TRAIL, and these exosomes acted synergistically with carboplatin (a first-line drug for the treatment of metastatic breast cancer) to exert antibreast metastasis effects in vivo [In addition to the application of single drugs, the combined use of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and other drugs is also a popular research direction for tumor treatment. Qiu et al.  obtained in vivo .Drug resistance has reduced the efficacy of chemotherapy and radiotherapy, which are first-line cancer treatments . TherefoThe cargos carried by engineered exosomes are mainly short RNA sequences, small-molecule drugs, and proteins . Few stuMizrak et al.  first reCXCR4+TRAIL, and they observed that ExoCXCR4+TRAIL exerted a significant synergistic effect with carboplatin in the mouse model.As previously mentioned, Liu et al.  were theγ or PTGDR2 (prostaglandin D2 receptor 2) on the surface of tumor cells, thereby inhibiting the malignant progression of tumors. By combining the carrier advantages of MSC-EXs and the antitumor effect of L-PTGDS, we applied genetic engineering technology to construct MSC-EXs carrying L-PTGDS to inhibit the malignant progression of GC in order to provide new ideas and methods for the biological treatment of GC  in GC tissue was significantly reduced, and low expression of L-PTGDS was associated with shorter patient survival time . Overexpnt of GC .Since Rothman, Schekman, and Sudhof won the Nobel Prize in 2013 for revealing the transport regulation mechanism of intracellular vesicles such as exosomes, perspectives on exosomes have finally transformed; they were once considered to be “cell cleaners” but are now taken seriously in the field of scientific research.Although the role of natural MSC-EXs in cancer is still controversial and a group of studies has proved that MSC-EXs play a role in promoting cancer progression, their tumor suppressor effects have also been reported. However, some scholars attribute these antitumor effects to differences in the materials and methods used in these studies, indicating that their effects are not universal.In addition to the functions of surface markers and the content of MSC-EXs, MSC-EXs themselves are also high-quality drug delivery carriers. Further research is required to explore the role of MSC-EXs in cancer development and treatment and to identify solutions to the following challenges. First, the identification of exosomes lacks uniform international standards. Second, the low yield and high cost of this process limit its application. Third, traditional centrifugation methods require a long time to extract exosomes, and existing kits are expensive; moreover, the purity of the isolated exosomes is not ideal. Finally, because the quality of exosomes is greatly affected by temperature and time, the storage of exosomes is also challenging . In shor


Electronic visits (e-visits) involve asynchronous communication between clinicians and patients through a secure web-based platform, such as a patient portal, to elicit symptoms and determine a diagnosis and treatment plan. E-visits are now reimbursable through Medicare due to the COVID-19 pandemic. The state of evidence regarding e-visits, such as the impact on clinical outcomes and health care delivery, is unclear.To address this gap, we examine how e-visits have impacted clinical outcomes and health care quality, access, utilization, and costs.We conducted a systematic review; MEDLINE, Embase, and Web of Science were searched from January 2000 through October 2020 for peer-reviewed studies that assessed e-visits’ impacts on clinical and health care delivery outcomes.Out of 1859 papers, 19 met the inclusion criteria. E-visit usage was associated with improved or comparable clinical outcomes, especially for chronic disease management . The impact on quality of care varied across conditions. Quality of care was equivalent or better for chronic conditions, but variable quality was observed in infection management . Similarly, the impact on health care utilization varied across conditions . Health care costs were lower for e-visits than those for in-person visits for a wide range of conditions . No studies examined the impact of e-visits on health care access. It is difficult to draw firm conclusions about effectiveness or impact on care delivery from the studies that were included because many used observational designs.Overall, the evidence suggests e-visits may provide clinical outcomes that are comparable to those provided by in-person care and reduce health care costs for certain health care conditions. At the same time, there is mixed evidence on health care quality, especially regarding infection management . Further studies are needed to test implementation strategies that might improve delivery  and to assess which conditions can be managed via e-visits. Telemedicine—or the delivery of health care at a distance—can improve health care access and quality while reducing health care utilization and costs . For insE-visits involve asynchronous communication between clinicians and patients through a secure web-based platform, such as a patient portal. Generally, patients answer questions about their medical history and symptoms through a structured questionnaire and upload photos (if relevant). The data are then reviewed by a clinician, who develops a diagnosis and treatment plan. Although e-visits often involve clinicians who the patient is familiar with, they can also involve a third-party clinician through direct-to-consumer telemedicine. E-visits offer notable benefits, such as allowing patients and clinicians to communicate at a convenient time  and improving documentation of patient-clinician communication  ,16. HoweBecause of COVID-19, e-visits are being implemented more frequently and are now reimbursable by Medicare and other payers in the United States ,33. As tWe conducted a systematic review based on PRISMA  guidelines .MEDLINE, Embase, and Web of Science were searched to locate peer-reviewed studies published from January 2000 through October 2020. The start date for the search was chosen because electronic visits were developed recently, and the authors did not anticipate any studies published prior to 2000 . A preliminary search was done to confirm this. Studies were limited to those in the United States as systemic factors, such as reimbursement, may influence the results. All reference lists for included studies were cross-searched. Duplicate studies were removed. Two reviewers  independently screened papers identified from the search strategy, and assessed each for inclusion eligibility using a spreadsheet . Any discrepancy encountered was discussed until a consensus was reached.E-visits were defined as any asynchronous electronic visit where a clinician assesses a patient’s health status, makes a diagnosis, and develops a treatment plan via a secure messaging system  ,35. ThisP-value <.05 was considered significant.For each included study, 2 investigators  noted study design, outcome measurements, care setting, medical conditions studied, sample size, and major findings. Since most of the studies included were observational, the authors used the Risk of Bias Assessment Tool for Nonrandomized Studies to assess criteria specific to observational studies . A P-valDue to the heterogeneity of outcome measures used in our included studies, it was infeasible to conduct a meta-analysis. Consequently, findings were qualitatively grouped by outcome type .After reviewing 1859 studies, a total of 19 studies met our inclusion criteria. Most studies assessed clinical outcomes, quality of care, health care utilization, and costs. None reported access outcomes. Most studies were observational in design, with one study using a randomized experimental design, another study using a case study design, and another 2 studies employing quasi-experimental designs. Sixteen studies used cross-sectional or pooled cross-sectional data. Three studies used a panel design. Detailed results of the quality assessment are summarized in Associations between e-visit usage and clinical outcomes were reported by 7 studies. A total of 13 different measures were used among the studies. Overall, the studies reported an association with improved outcomes or null findings across the medical conditions examined.1c, P<.001)  repNo studies investigated the association between e-visits and access to care.Fourteen studies assessed health care utilization associated with e-visits. An overall mixed impact was observed across these studies.P=.005) and 90-day follow-up  compared to those associated with in-person visits. Another study [Some studies evaluated the impact of e-visits on subsequent health care utilization, such as primary care, specialty care, and emergency care ,49-51. Fer study  examininP=.04).Some studies ,40,41 reP<.001), at 30-day follow-up , and at 60-day follow-up  than those of in-person visits; however, at the 90-day follow-up, costs were comparable to those of an in-person visit  [P<.001) compared to in-person care [Three studies ,40,49 foson care  calculatThis was a systematic review that assessed the impact of e-visits on clinical outcomes and health care delivery. To our knowledge, this is the first systematic review to assess the state of evidence for asynchronous e-visits. Most studies found that e-visits were associated with lower treatment costs and comparable clinical outcomes to in-person visits. Studies reported mixed effects on health care utilization, and no studies evaluated the impact of e-visits on health care access, suggesting future research is needed in this area. We provide implications for research and practice below.Our review found that e-visits may be an adequate substitute for in-person care for chronic disease management. Studies showed that e-visits were effective for the treatment of diabetes, hypertension, and gout. Our findings are consistent with those of previous studies  that sugOur review found mixed evidence for the effect of e-visits on quality of care. For example, prior studies ,24-29 haOur review found that e-visits had mixed effects on health care utilization compared to in-person visits. These findings are consistent with those of reviews on other forms of telemedicine ,58-62. SThe findings on favorable cost implications align with those of other works that evaluated the effects that synchronous alternatives for care  had on cost outcomes for patients -70. NotaAdditional research is also needed on how e-visits impact health care access and the digital divide. There is growing evidence that patient-level disparities exist across adoption and usage patterns of patient portals -76. SimiSome of the included literature cited implementation barriers in their discussion that should be further explored in future studies . Clinicians may need assistance with adjusting their workflows when being trained on e-visits . Best prThis systematic review has several limitations. First, a majority of the studies used an observational design, limiting our ability to draw causal conclusions on the effect of using e-visits on quality of care, access to care, costs or clinical outcomes. Second, we found heterogeneity in how studies measured the impact of e-visits, making it impossible to quantitatively pool study estimates. Third, we excluded non-English studies, which may limit our ability to determine the effect of e-visits outside of English-speaking regions. Fourth, the follow-up periods among the studies varied , limiting our comparisons of findings between studies. Fifth, a majority of the studies examined e-visits that are hosted by the health care delivery organization rather than by a direct-to-consumer vendor or insurer, limiting the generalizability of our results to e-visit programs sponsored by entities external to the health care delivery organization. Lastly, most e-visits occurred in outpatient ambulatory and academic medical center contexts, limiting our ability to comment on inpatient settings.Overall, the evidence suggests that e-visits can provide equivalent outcomes to in-person care and reduce health care costs for certain health care conditions. There are still notable quality concerns  that warrant further study. It is also unknown how e-visits have affected access to care. Furthermore, many studies in the review lacked a rigorous design, making it difficult to draw firm conclusions about the state of evidence regarding e-visits. Future trials should be conducted to test the effectiveness of e-visits and determine what factors drive effective implementation.


Regulatory B cells perform pivotal anti-inflammatory functions in non-infectious uveitis. Rituximab may work by depleting pro-inflammatory B cells and restoring the quantity and function of regulatory B cells in this disease. Identifying the levels of B-cell participation and the associated roles is beneficial for optimizing therapy. Diversified experimental model choices and emerging tools and/or methods are conducive for future studies on this topic.Non-infectious uveitis is an inflammatory disorder of the eye that accounts for severe visual loss without evident infectious agents. While T cells are supposed to dominate the induction of inflammation in non-infectious uveitis, the role of B cells in the pathogenesis of this disease is obscure. Therefore, this review aimed to discuss diverse B-cell participation in different non-infectious uveitides and their roles in the pathogenesis of this disease as well as the mechanism of action of rituximab. Increasing evidence from experimental models and human non-infectious uveitis has suggested the participation of B cells in non-infectious uveitis. The participation levels vary in different uveitides. Furthermore, B cells play multiple roles in the pathogenic mechanisms. B cells produce autoantibodies, regulate T cell responses  Uveitis is an inflammatory disorder of the eye . AlthougNon-infectious uveitis is mainly regarded as a T cell-induced disease, and the role of B cells in the pathogenesis of this disease is not yet fully understood . RituximUveitis is an inflammatory disorder of the eye and involves the vascular uveal tract, retina, optic nerve, and vitreous , 13. EtiCorticosteroids are the mainstay of therapy for non-infectious uveitis. In patients with acute and anterior uveitis, topical corticosteroids and cycloplegic and/or mydriatic agents may help to achieve good results. Unfortunately, patients with chronic, intermediate, posterior uveitis, or panuveitis require more aggressive therapy. Systemic steroids are initially administered, followed by immunosuppressants such as methotrexate and mycophenolate if further anti-inflammatory intervention is required , 19. CorExperimental autoimmune uveitis (EAU) is the most widely studied disease model for human non-infectious uveitis . In EAU,Studies on EAU demonstrated that non-infectious uveitis is a T helper (Th)1/Th17 cell-driven disease . ActivatHowever, some studies show results contradicting the pathogenic mechanisms derived from EAU. For example, IFN-γ knockout mice developed even more severe uveitis than did wild-type mice . Phase IIn humans, B cells develop from hematopoietic stem cells in the bone marrow. After an intricate developmental process, B cells ultimately develop into plasma cells that secrete antibodies or memory B cells . B cellsNon-infectious uveitis is a group of heterogeneous diseases with diverse etiologies. Differences exist between EAU and humans non-infectious uveitis, and the pathogenic mechanisms may also be different, as discussed above. Seemingly, differences also exist in multiple clinical subtypes of human non-infectious uveitis. Cytokine and chemokine profiles were found to be different between human non-infectious uveitis subtypes , 42. LymThe number of B cells infiltrating the ocular tissue during uveitis is different depending on the experimental model used. The cell population in the eye also changes over time: while neutrophils dominate the acute stage of retinal inflammation, lymphocytes dominate the chronic stage . In mostIn juvenile idiopathic arthritis (JIA), uveitis is the most common extra-articular manifestation. The morbidity of uveitis in children with JIA is approximately 10%, among which non-granulomatous anterior uveitis is the most common form , 75. UnlSympathetic ophthalmia (SO) is defined as bilateral granulomatous panuveitis following penetrating ocular injury to one eye . The resBehçet disease (BD) is characterized by occlusive vasculitis and can affect many different systems. Ocular manifestations are usually bilateral non-granulomatous panuveitis and occlusive retinal vasculitis . SeveralIn other clinical entities of uveitis, evidence of B-cell participation is rare and derived from earlier research. As observed in eyes with BD, immunohistochemical studies showed the predominance of T cells and the presence of a relatively fewer number of B cells and plasma cells in ocular infiltrates of patients with VKH , 63, sarWe have provided evidence of B-cell participation in EAU and several common human non-infectious uveitides in terms of the number of B cells and plasma cells infiltrating the ocular tissue; antibodies found in eyes; gene and protein expression profiles of B cells; and serum components including changes in the numbers of peripheral B cells and antibodies. From these data, diverse B-cell participation in different cases of non-infectious uveitis can be concluded. In most cases, B cells play a minor role in EAU, but exceptions still exist. In human non-infectious uveitis, B cells seem to highly contribute to the pathogenic mechanisms of JIAU, SO, and multifocal choroiditis. Particularly in JIAU, strong evidence confirmed the pro-inflammatory functions of B cells in uveitis by producing antibodies. In other human non-infectious uveitides, B cells appear to play a minor role in the pathogenesis. However, as the number of cases in each experiment is relatively small and the accessible ocular tissue is usually derived from advanced diseases, it is difficult to draw a precise conclusion, especially regarding the onset of the disease.Several comparative tests have also explored this subject. A report revealed that the number of CD19+ B cells in the aqueous humor derived from patients with idiopathic uveitis (including anterior uveitis and panuveitis) is lower than that in patients with systemic disease-associated uveitis  . Two expOverall, B-cell participation in non-infectious uveitis differs on a case-to-case basis. Identifying the types of uveitides that show high B cell participation may be beneficial for selecting patients suffering from refractory non-infectious uveitis for B-cell depletion therapy or other biologics targeting B-cell-related molecules. According to the concrete mechanisms of B-cell participation, the elevated antibodies found in the ocular tissues or sera of patients with non-infectious uveitis demonstrate that B cells promote inflammation in patients by producing antibodies. However, other mechanisms of B cell-participation in non-infectious uveitis are not shown by the above evidence. This will be discussed in detail in the subsequent section.B cells have been viewed as central contributors to autoimmunity because of their ability to produce antibodies . The antAutoantibodies produced by plasma cells promote inflammation in multiple ways, as reviewed in other studies , 90: autIn non-infectious uveitis, the existence of autoantibodies against ocular tissues has been confirmed in several different uveitides. Especially in JIAU, autoantibodies were found both in the eye and in the bloodstream. Antibodies cannot pass through the complete blood-eye barrier . Thus, avia antigen presentation, co-stimulation, and cytokine secretion. B cells present antigens to T cells via major histocompatibility complex (MHC)-I or II   have been identified as suppressive components of autoimmunity . Bregs aof Bregs . In addiof Bregs . IL-10 aof Bregs , 126. In (PD-L1)  or killi (PD-L1) .In non-infectious uveitis, using flow cytometry analysis, Bregs were found in the retina during EAU and surprisingly accounted for >40% of all B cells detected . This prvia antigen presentation, co-stimulation, and cytokine secretion. Rituximab can also abrogate the establishment of ELSs. However, at the same time, Bregs, the pivotal regulatory components in uveitis, are also eliminated. There is a possibility interpretation for this. The quantity and function of Bregs are adversely affected during non-infectious uveitis. The number of Bregs decreased in the peripheral blood of patients with SLE .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In this era of Big Data, the volume of biological data is growing exponentially. Systematic profiling and analysis of these data will provide a new insight into biology and human health. Among diverse types of biological data, gene expression data closely mirror both the static phenotypes and the dynamic changes in biological systems. Drug-to-drug or drug-to-disease comparison of gene expression signature allows repurposing/repositioning of existing pharmaceutics to treat additional diseases that, in turn, provides a rapid and cost-effective approach for drug discovery. Thanks to technological advances, gene expression profiling by mRNA-seq became a routine tool to address all aspects of the problem in modern biological research. Here, we present how drug repositioning using published mRNA-seq data can provide unbiased and applicable pharmaco-chemical intervention strategies to human diseases and aging. In specifics, we profiled over a half-million gene expression profiling data generated from various contexts, and using this, we screened conditions that can suppress age-associated gene expression changes. As a result, our analysis identified various previously validated aging intervention strategies as positive hits. Furthermore, our analysis also predicted a novel group of chemicals that has not been studied from an aging context, and this indeed significantly extended the life span in model animals. Taken together, our data demonstrate that our community knowledge-guided in silico drug-discovery pipeline provides a useful and effective tool to identify the novel aging intervention strategy.


Protein glycosylation is one of the most common post-translational modifications that are essential for cell function across all domains of life. Changes in glycosylation are considered a hallmark of many diseases, thus making glycoproteins important diagnostic and prognostic biomarker candidates and therapeutic targets. Glycoproteomics, the study of glycans and their carrier proteins in a system-wide context, is becoming a powerful tool in glycobiology that enables the functional analysis of protein glycosylation. This ‘Hitchhiker's guide to glycoproteomics’ is intended as a starting point for anyone who wants to explore the emerging world of glycoproteomics. The review moves from the techniques that have been developed for the characterisation of single glycoproteins to technologies that may be used for a successful complex glycoproteome characterisation. Examples of the variety of approaches, methodologies, and technologies currently used in the field are given. This review introduces the common strategies to capture glycoprotein-specific and system-wide glycoproteome data from tissues, body fluids, or cells, and a perspective on how integration into a multi-omics workflow enables a deep identification and characterisation of glycoproteins — a class of biomolecules essential in regulating cell function. O-GlcNAc glycosylation acts within the cytosol in a dynamic interplay with phosphorylation and is biosynthetically independent from the membrane and soluble glycoproteins trafficked to the extracellular environment after their formation [Protein post-translational modifications (PTMs) enable the cell to produce profound structural and functional diversity from a limited number of protein-encoding genes . Glycosyormation ,6.In Eukaryotes, glycosylation is crucial for cell functions such as protein folding, regulating signalling or protein activity ,7,8. ConEssentials of Glycobiology textbook [This review aims to provide an ‘easy-to-digest’ introduction to the analytical approaches relevant for studying protein glycosylation. For a comprehensive introduction to the diverse biological functions of protein glycosylation, readers are referred to the freely available textbook . Understtextbook ) and glytextbook ) technolThere are five common stages in glycoproteomics analyses . Within The first step of any glycoproteomics experiment is to access the glycoproteins of interest from the complex biological matrix. Methods for tissue or cell lysis and protein extraction are diverse, and often depend on the type and available amount of the biological sample. Following tissue homogenisation or sonication and cell-disruption, the extraction step facilitates access to the (glyco)proteins of interest, in particular as many membrane glycoproteins require the presence of detergents to ensure sufficient solubility . EstabliIf other biomolecules such as DNA, RNA, metabolites, proteoglycans, glycosaminoglycans, lipids, glycolipids or glycans released from proteins are also to be analysed as part of a multi-omics study, the extraction conditions need to be adapted accordingly. In the case of glycolipids, for example, the frequently used chloroform–methanol precipitation method can be used to separate glycolipids from glycoproteins and other lipids ,50 Figu. ImportaIn Stage 2, the extracted glycoproteins need to be prepared for downstream MS or LC–MS-based characterisation (see Stage 3). While there are some examples where top-down glycoproteomics of semi-purified, intact proteins is successfully applied to diagnose CDGs (reviewed in ) and natIntact glycoproteins or glycoprotein complexes can be fractionated by targeted affinity strategies such as immunoprecipitation, 2D gel electrophoresis, SDS–PAGE or lectin chromatography before proteolysis. Alternatively, glycopeptide enrichment is performed after the proteolytic digestion, or the glycopeptides may be pre-fractionated using conventional separation techniques to increase the analytical coverage of the sample of interest ,55.In system-wide glycoproteomics, glycopeptide enrichment remains an essential step since glycopeptides exhibit reduced ionisation efficiency in mass spectrometry compared with unglycosylated peptides, which is further aggravated by the intrinsic macro- and micro-heterogeneity of their glycan moieties ,56. TogeProteases are the ‘scissors’ used in bottom-up glycoproteomics experiments, producing a mixture of glycopeptides and peptides ,58. TrypO-protease requires the presence of an O-glycan on a serine/threonine residue to cleave N-terminally before this site of glycosylation. Thus, this cleavage preference generates peptides that feature N-terminal O-glycosylation, and its application has resulted in the successful mapping of approximately 3000 O-glycosites [O-glycopeptides from mucins, which significantly improved O-glycosite mapping [However, these proteases often inefficiently digest mucin or mucin-like glycoproteins ,66,67. Tycosites ,70. Neveycosites , has als mapping .Generally, glycoproteomics workflows rely on proteases with defined specificity such as the ones mentioned above. However, multiprotease mixtures such as Pronase, or proteases with very broad substrate specificity such as Proteinase K, can be of value when characterising single glycoproteins or simple mixtures ,73. ThesEnrichment strategies that take advantage of the presence of the glycan moiety are fundamental to improve glycoproteome coverage ,74. AntiO-GalNAc structures such the ones derived from glycoengineered SimpleCell lines [O-GlcNAc glycoproteins [O-GlcNAc glycosylation sites, followed by thiol-Sepharose affinity-enrichment of these modified peptides have also been successfully employed for O-GlcNAc glycoproteomics [Lectin affinity chromatography (LAC) has been used to successfully enrich protease-produced glycopeptides with short ll lines ,81 or onproteins ,82. Chemoteomics . Multi-Loteomics .Probes based on bacterial and human lectins or specific anti-glycan antibodies generally appear to exhibit affinity to more specific glyco-epitopes than plant-derived lectins, but their commercial availability can be limited . Unfortu2) for the enrichment of sialylated glycopeptides [N-glycopeptide enrichment [N-glycosidase F (PNGase F), inevitably leading to a loss of structural information of the formerly attached glycan moiety. For more details on the many methods available for glycopeptide enrichment, the readers are referred to several excellent reviews on this topic [A variety of enrichment strategies are based on non-biological reagents that target the physicochemical properties of the glyco-moieties of glycopeptides such as hydrophilicity, size, negative charge or the chemical properties of specific monosaccharides. These include approaches such as acetone precipitation ,86, titapeptides , boronicpeptides ,91, elecpeptides ,93 or thpeptides ,94–96. Trichment  is not sis topic ,100–104.No enrichment strategy (or combinations thereof) can quantitatively capture all glycopeptides in complex mixtures, and enrichment also results in the loss of quantitative information on site occupancy levels. Thus, compromises between selectivity and enrichment efficiency will have to be made based on the specific experimental aims of a project.N-glycans can be enzymatically removed using the hydrolytic enzyme PNGase F that efficiently cleaves between the innermost GlcNAc residue of all types of N-glycans [N-glycans by PNGase F converts asparagine to aspartate, and care should be taken to avoid misinterpretation of this conversion with the same mass increment (+0.98402 Da) induced by spontaneous deamidation that frequently occurs on asparagine residues in an asparagine–glycine (…NG…) sequon [18O into the newly generated aspartate residue, and be used to discriminate spontaneous deamidation from de-glycosylation of asparagine residues [-glycans , unless -glycans , or are -glycans ,108. PNG-glycans . The enz) sequon ,110,111.residues ,113.N-acetylglucosaminidase (Endo) H  and PNGase F, using 18O-labeling, Cao and co-workers screened and successfully quantified site occupancy levels on HIV gp120 [Applying de-glycosylation enzymes with different specificities can avoid such false positive identifications of glycosylation sites while indirectly providing some limited, but still useful structural information. Combining endo-β-IV gp120 . This apIV gp120 .In contrast with these endoglycosidases, exoglycosidases digest specific terminal monosaccharide residues from glycans, providing an opportunity to gain insights into key structural features including biologically relevant glyco-epitopes. Exoglycosidase-assisted glycopeptide analysis can be used to determine the level of e.g. α2–3 linked NeuAc residues in a protein- and site-specific manner , or unamPeptide labelling approaches such as tandem mass tags (TMT)  or isobain situ visualisation. If used for enrichment, the glyco-moiety is frequently removed from the peptide for subsequent de-glycosylated peptide analysis [in vivo by significantly reducing their cellular toxicity [in vitro and animal model focussed glycoproteomic studies [Metabolic derivatization methods are available based on the incorporation of isotopically labelled amino acids (e.g. SILAC)   or electrokinetic separation  coupled with ESI–MS to detect and characterise intact glycopeptides. The past decade has seen tremendous advancements in both off- and online separation and detection technologies that have increased the sensitivity, accuracy and throughput of glycoproteomics workflows ,141. It In principle, any ultra- or high-performance liquid chromatography (UPLC/HPLC) based separation method that can be performed using MS-compatible solvents can be used to separate complex glycopeptide mixtures prior to MS analysis. RP-LC is without doubt the most widely used separation technique for this purpose due to its unmatched peak capacity, versatility, simplicity and robustness ,128,143.Glycopeptides are usually less hydrophobic than their non-glycosylated counterparts, and very hydrophilic glycopeptides might not exhibit sufficient interaction with the RP-matrix when loading the sample in low concentrations of organic solvent as it is commonly done in standard peptide RP-LC. Using pre- and analytical columns optimised to work under completely aqueous conditions can help to capture such very hydrophilic glycopeptides , particuAnother attractive separation technique, though less widely used, is based on CE separation that can provide excellent separation and sharp peaks with high signal-to-noise ratios ,146. CE 197) [Nano-LC can alternatively be coupled with MALDI-TOF-MS detection, which has the advantage of having the MS analyses decoupled from the LC step, facilitating the re-analyses of each spot at a later time if necessary. This has found some applications for glycoprotein-centric analyses such as IgM , or chem197) . While s197) ), we areIon-mobility MS (IM-MS) is a recent technology that shows promise for improved analysis of glycopeptides ,155. IM-m/z range, the fragmentation of glycopeptides may in favourable cases generate sufficient product ion information to facilitate software-assisted identification [Identification of glycopeptides from complex samples would be impossible without fragmentation techniques optimised to deliver information on both the peptide and glycan moieties . In combfication ,167. Glyfication ,168,169 fication  and excefication ,163,165.Collision-induced dissociation (CID) techniques are often used in glycoproteomics but fundamentally differ if performed on ion trap (resonance-type activation) or Q-ToF (beam-type activation) instruments. In principle, both CID-types result largely in fragmentation of the glycan backbone but leave the peptide backbone relatively intact when performed at lower excitation levels sufficient to fragment non-modified peptides .Increasing the energy to achieve higher-energy collisional dissociation (HCD) may result in the generation of sufficient peptide produced ions that facilitate peptide sequence assignment, next to glycan oxonium product ions. Stepped-HCD (sHCD), where the fragmentation energies are being modulated from low to high, delivers more balanced product ion spectra that usually contain more information on both the glycan and peptide moiety of glycopeptides .N-glycopeptides due to the well-known N-glycosylation sequon  [O-glycosylation or chemical glycosylation reactions [These fragmentation techniques rarely deliver reliable information on the site of glycan attachment, as achieved by ion-induced dissociation techniques (e.g. electron-transfer dissociation (ETD), electron-capture dissociation (ECD)) . While i/C; X≠P) , these feactions . Hybrid-eactions . HoweverAdequate software tools are the final key to successful glycoproteomics experiments. Different from many other types of PTMs, which can be considered as a single mass value that is either present or absent on the polypeptide chain, glycan modifications can range from a single monosaccharide residue to complex oligo- and polysaccharides, posing unique bioinformatics challenges. Like proteomics, the glycoproteome search space needs to be firstly appropriately defined. The current software for glycoproteomics differs in how the glycan search space is defined and incorporated into the process of glycopeptide identification . Some toA suite of computational tools has been developed over the past decade, which have strongly contributed to the maturation and application of glycoproteomics . While tData sharing and detailed reporting of MS-based glycoproteomics have become common practice ,182, prohttps://www.beilstein-institut.de/en/projects/mirage/) focussed on requirements for glycomics experiments that also contain aspects relevant to MS-based glycoproteomics experiments [This was recognised several years ago for proteomics and led to the development of essential reporting guidelines (MIAPE) . These geriments . These ghttps://glycopost.glycosmos.org/) platform has been established as a data repository that supports the storage of MS, LC and LC–MS glycomics raw and analysed data, in addition to glycoproteomics data [To facilitate sharing of glycomics and glycoproteomics data, the GlycoPOST (ics data .https://glyconnect.expasy.org/) [www.expasy.org), GlyCosmos (https://glycosmos.org/) [https://www.glygen.org/) [http://www.glyspace.org/ [Several international efforts have been actively connecting glycomics and glycoproteomics data with other relevant glycobiological information to make current glycoproteomics knowledge more accessible. Initiatives such as Glyconnect (sy.org/) , Glycomios.org/)  and GlyGen.org/)   have st-omics techniques, deliver previously overlooked functional insights into the ubiquitous modification of proteins by glycans. Glycoproteomics analysis is and will increasingly become an indispensable part of understanding the molecular basis of life.This review provides a concise overview of the methods now available for glycoproteomics analyses, with the intention to inform researchers that are new to the field, as well as experienced proteomics scientists that are considering jumping into the exciting wild waters of glycoproteomics. Glycoproteomics technologies have experienced a tremendous evolution over the past two decades, starting from the profiling of single glycoproteins, to now allowing large-scale system-wide analyses of complex samples as an integral part of multi-omics studies. Transcriptomics of glycosylation pathway relevant enzymes informs on how these pathways could be affected under studied conditions, metabolomics delivers important information on glycosylation precursors such as nucleotide sugar substrates that, in concert with (glyco)lipidomics and proteoglycomics, proteomics, glycoproteomics and genomics, can deliver a detailed picture of the highly interconnected cellular glycosylation pathways and how these are affected in diseases . These eGlycoproteomics is becoming a powerful tool in glycobiology that enables the system-wide mapping of protein-specific glycosylation features.Understanding of protein-specific glycosylation and how it is impacted in diseases provides novel opportunities for precision diagnostics and therapies.Integration of glycoproteomics (and glycomics) into multi-omics studies is important to capture the glyco-language of cells and organisms.


Finally, we proposed a GAN Mask R-CNN algorithm which achieved superior performance in comparison with the conventional Mask R-CNN, Mask-CNN, and k-means algorithms in terms of the Dice similarity coefficient (DSC) and the MICCAI metrics. The proposed algorithm also achieved superior performance in comparison with ten state-of-the-art algorithms in terms of six Boolean indicators. We hope that our work can be effectively used to optimize the segmentation and classification of liver anomalies.Liver image segmentation has been increasingly employed for key medical purposes, including liver functional assessment, disease diagnosis, and treatment. In this work, we introduce a liver image segmentation method based on generative adversarial networks (GANs) and mask region-based convolutional neural networks (Mask R-CNN). Firstly, since most resulting images have noisy features, we further explored the combination of Mask R-CNN and GANs in order to enhance the pixel-wise classification. Secondly,  Segmentation of computed-tomography (CT) liver images is currently a standard technique for computer-assisted diagnosis and therapy, which enjoys the advantages of high accessibility, acceptable acquisition time, and good spatial resolution , 2. The Although automated segmentation methods have been frequently proposed, those methods have not necessarily been implemented in routine clinical use . The cauk-means clustering was used to lock the image aspect ratio in order to get more essential anchors which can help boost the liver segmentation performance in computed tomography (CT) images. Indeed, the segmentation process is quite challenging and crucial due to the fuzziness of the liver pixel boundaries, the highly similar intensity patterns of the liver and its neighbouring organs, the high noise levels, and the large variations in tumor shape and appearance. Therefore, liver segmentation in CT images should be effectively performed before other tasks of target measurement, detection, and recognition. A GAN [We explored pixel-wise classification enhancements through the combination of Mask R-CNN and GANs, augmentation of the Mask R-CNN training data, and exploitation of the generated synthetic datak-means clustering to lock the image aspect ratio in order to get more key anchors which can help get better segmentation resultsWe used The performance of the proposed framework was compared against that of the conventional Mask R-CNN algorithm, in terms of the Dice similarity coefficient (DSC), volume overlap error (VOE), relative volume difference (RVD), the average symmetric surface distance (ASSD), root-mean-square symmetric surface distance (RMSD), and maximum symmetric surface distance (MSSD)Additionally, our proposed GAN Mask R-CNN achieved superior performance in comparison with ten state-of-the-art algorithms. The comparison is based on the other six indicators including the overall accuracy, sensitivity, specificity, precision, false discovery rate (FDR), and false omission rate (FOR)We further explored the combination of Mask R-CNN and GANs to enhance the pixel-wise classification performance. Also, n. A GAN , 20 is an. A GAN . In our Accurate diagnosis is highly required for liver therapy planning, liver size evaluation, and optimal clinical decision-making. Medical CT imaging provides accurate anatomical information for the human abdominal organs, especially liver segmentation and disease diagnosis . Also, lMoreover, the use of automatic segmentation in clinical applications requires evaluating and comparing the accuracies of different segmentation models. Recently, deep learning approaches have been employed to automatically obtain the most suitable segmentation model from given training data. Also, remarkable performance outcomes were achieved by these approaches through creating multiple levels of abstraction and descriptive embedding in a hierarchy of increasingly complex features . For exaIn our work, we further explore the combination of Mask R-CNN and GANs to enhance the pixel-wise classification performance. Similar approaches have been proposed in earlier studies. For example, Frid-Adar et al.  generatec-means clustering algorithm (FFCM), neutrosophic sets (NS), and a watershed algorithm. In order to increase the CT image contrast and remove high frequencies, histogram equalization and median filtering were used. An unsupervised medical anomaly detection GAN (MAD-GAN) method was proposed by Han et al. [Furthermore, unsupervised learning is also widely used in image segmentation. For example, an intelligent framework was proposed by Rundo et al. , where rn et al. . In thisn et al.  proposedThe Mask R-CNN architecture is an enhanced variant of the R-CNN, Fast R-CNN , and FasLcls is the target classification loss, Lbbox is the regression loss for the target bounding box, and Lmask is the target segmentation loss, which is defined based on the target segmentation requirements in comparison with the traditional detection network.The Mask R-CNN can be employed for multitask learning, with the following loss function formulation:k-means clustering. In the network training stage, as more training iterations are performed, the network learns the global liver characteristics in the CT images; the prediction box parameters are progressively adjusted; and finally, the ground-truth boxes are approached. In order to accelerate the convergence speed and improve the liver localization accuracy, the liver height and width characteristics are analyzed in the CT images, and hence, k-means clustering is applied to the height and width data using the Euclidean distance. This clustering algorithm measures the distance between patterns using the Euclidean distance and identifies the cluster centers through a given bounding box of anchors, where the output box is chosen as the closest one to an anchor. This process is repeated until the anchors reach a prespecified number. k-means clustering.With additional training iterations, the Mask R-CNN learns the global features of liver images, while the prediction box parameters are iteratively adjusted until they are really close to the true box parameters. In this paper, we strive to accelerate the convergence and improve the localization precision for liver detection and segmentation. We achieve these goals by analyzing the distribution of the aspect ratios of the liver images via G captures the distribution of data, while a discriminative model D estimates the probability that a data sample came from the training samples rather than from G. The discriminative model D is trained to maximize the probability that both the training samples and the samples obtained from G are correctly labelled. The generative adversarial networks (GANs) were initially proposed by Goodfellow et al. in 2014. A generative model z is sampled from the latent space and fed into the generative model G, a sample x = G (z) is generated. For neural networks, the probability distribution PG (x) of the generated samples might be significantly more complicated. The generative model G is trained to make the probability distributions PG (x) and Pdata (x) as close to each other as possible. The generative model G seeks to generate fake data to confuse the discriminative model (D), while the discriminator D seeks to differentiate between the real and fake data samples. This adversarial learning enforces the distribution generated by G to gradually approach the real data distribution.When the noise PData(x) and PG(x). The function of the discriminator D can be mathematically defined asD and G interact through a two-player minimax competitive game with the objective function V :The adversarial learning scheme can be formulated as the following optimization problem:Thus, the GAN parameter optimization problem can be formulated asG and D are updated through alternating optimization. As the adversarial learning process evolves, the model G will generate data that gradually resembles the real data.The two models The training algorithm workflow is shown in Use the momentum learning rule (or any other standard rule) for the gradient-based updates.We describe here the experiments we performed for evaluating the performance of our proposed GAN Mask R-CNN method. Also, we report and analyse the results of comparing our method against several state-of-the-art methods: FCN-8s , U-Net , 2D-FCN2https://competitions.codalab.org/) [In our experiments, we used a CentOS7 system with an Intel Core i7 CPU with 128 GB memory and an NVIDIA RTX8000 48 GB GPU. We used Python 3.6 to implement the corresponding algorithms. Experiments were performed on the Codalab dataset (ab.org/) . We emplWe use the DSC to assess the performance of the compared methods of liver image segmentation . The DSCU1 and U2 denote corresponding output and ground-truth segmentation results, respectively. A higher DSC value indicates better segmentation performance. The DSC value ranges between zero  and one .First of all, the DSC metric can be defined asU1 and U2 denote corresponding output and ground-truth segmentation results, respectively. Also, S(U1) and S(U2) denote the outlines of the segmented liver region and the associated ground-truth region, respectively. In addition, d ) denotes the shortest distance between any image pixel v and S(U1). That is, d) = minSU1∈S(U1) ‖v − SU1‖, where ‖•‖ is the Euclidean distance operator. Apart from the DSC, lower values of four MICCAI metrics  indicate better matching between the output and ground-truth segmentation results. The RVD absolute value should be used in segmentation performance evaluation, since this metric might take negative values in the case of undersegmentation. The smaller the RVD absolute value is, the better the segmentation performance is. In general, the five MICCAI metrics are 0 when the segmentation is perfect. The other five MICCAI metrics are defined as follows. Once more, the symbols Overall accuracy: the ratio of the correctly labelled pixels to the total pixel count(2) Sensitivity: the ratio of the correctly detected liver pixels to all true liver pixels is called the sensitivity or the recall(3) Specificity: the ratio of the correctly detected background pixels to all true nonliver background pixels is called the specificity(4) Precision: the ratio of the correctly detected liver pixels relative to the total number of pixels labelled as liver pixels(5) The false omission rate (FOR) of the liver pixels is defined asP, the false detection rate (FDR) can be defined as(6) Based on the precision Several other metrics were exploited as well for evaluating the performance of liver segmentation algorithms, where image segmentation was cast as a binary classification problem with positive and negative classes corresponding to the liver and nonliver image pixels, respectively . The terk-means clustering (for optimization of the fully connected layer parameters) [k-means clustering and GAN modules on the Mask R-CNN segmentation outputs. Experiments were conducted to compare the performance of three schemes: the conventional Mask R-CNN, the Mask R-CNN with ameters) , and thek-means clustering managed to correct these segmentation errors by incorporating the aspect ratio information of the liver image sequence. However, there are still visible segmentation errors in marginal liver regions. Our proposed GAN Mask R-CNN improved, to a certain extent, the segmentation accuracy and robustness for each slice in the sequence. This is an obvious advantage of our proposed scheme over the two other Mask R-CNN variants.As shown in As shown in k-means clustering (21.32%). In addition, it is clear that the GAN module significantly enhances the segmentation performance according to the other indicators.k-means clustering modules on improving the segmentation outcomes in comparison to the FCN-8s, U-Net, 2D-FCN2, 2D-FCN1, 2D-dense-FCN, 3D-FCN, H-DenseUNet, 3D U-Net, IU-Net, and GIU-Net algorithms. The performance was evaluated using the metrics of accuracy, recall, specificity, precision, FOR, and FDR. A comparison of the segmentation results of the ten algorithms is shown in Further experiments were made to assess the impact of the GANs and The results in This paper introduces a new method for liver image segmentation in CT sequences where the GANs and the Mask R-CNN methods are combined. However, we found that most images exhibited noisy features in one way or another in the liver segmentation process , 53. Undk-means clustering algorithm which was used to lock the image aspect ratio and reduce redundant and useless anchors. Secondly, we addressed the problem of the presence of noisy features in liver images, with no image enhancement typically applied, rendering a large number of images unusable and reducing the segmentation accuracy. Specifically, we employed a GAN architecture into our segmentation framework and demonstrated good performance in terms of six indicators: DSC, VOE, RVD, ASSD, RMSD, and MSSD. Thirdly, we compared our framework with that of FCN-8s, U-Net, 2D-FCN2, 2D-FCN1, 2D-dense-FCN, 3D-FCN, H-DenseUNet, 3D U-Net, IU-Net, and GIU-Net. This comparison was based on six indicators: overall accuracy, sensitivity, specificity, precision, FOR, and FDR. Our improved GAN Mask R-CNN architecture demonstrated the best overall performance. We hope that our work can help radiology practitioners to further improve the diagnosis, timely detection, and treatment of liver diseases and also reduce the risk of death due to liver cancer.In this work, we proposed a new CT-based liver image segmentation framework. Firstly, we sought to get more important anchors (and hence improve the segmentation results) through a In many studies, open-source deep learning tools may be applied for automatic liver segmentation. The performance outcomes of such tools could be compared with the outcomes of conventional knowledge-based planning tools, which typically yield acceptable accuracy levels as well as good reproducibility for clinical use. Additionally, patient-specific dose prediction improves the efficiency and quality of radiation treatment planning. In particular, this prediction can significantly reduce the treatment planning time. In the future, we envisage that deep-learning-based automatic segmentation will become clinically useful, especially for dynamic daily treatment plans based on multimodality imaging.


Proteus mirabilis among broilers in China. From January to April 2019, 40  blaNDM-1-carrying P. mirabilis strains were recovered from commercial broilers in slaughterhouse B in China. All the isolates were resistant to imipenem, meropenem and other β-lactams. These isolates belong to five clusters identified via pulsed field gel electrophoresis (PFGE). Further studies on twenty representative strains revealed that seven blaNDM-1 genes were located on plasmids with sizes of 104.5–138.9 kb. Notably, only three strains  were successfully transferred to Escherichia coli J53, while the other four isolates were located in nontransferable plasmids. The rest were harbored in chromosomes. Ulteriorly, based on whole genome sequencing (WGS), these twenty isolates showed four typical phylogenetic clades according to single nucleotide polymorphisms (SNPs) of a core genome and presented four main genomic backbone profiles, in which type II/III strains shared a similar genetic context. All of the above is evidence of blaNDM-1 transmission and evolution in P. mirabilis, suggesting that the prevalence may be more diverse in broiler farms. Accordingly, as intestinal and environmental symbiotic pathogens, blaNDM-1-positive P. mirabilis will pose greater threats to the environment and public health.Carbapenem-resistant pathogens mediated by metallo-beta-lactamases (MBLs) have spread worldwide, where NDM-1 is a typical and key MBL. Here, we firstly discussed the distribution characterization of NDM-1, which produces multidrug-resistant  Proteus mirabilis is an opportunistic pathogen belonging to the Enterobacteriaceae family, widely distributed in the natural environment and the intestines of humans and animals. Clinically, it can cause diarrhea, sepsis, respiratory issues and urinary tract infections, with a potential risk of zoonosis . ,18. blaNP. mirabilis infection in poultry and showed that the animal intestine is an ideal hotbed for Enterobacteriaceae bacteria and resistant genes, suggesting that animal-derived resistant bacteria and genes may be spread to communities through direct contact, food chains or the environment, posing a potential threat to human health [P. mirabilis in animal breeding, meat product processing, clinical patients and the environment can help to control the generation of resistance from the source and curb the spread of resistance in the food chain, which would have a far-reaching impact on the public.The results emphasized the severity of NDM-1-producing n health . In addin health . TherefoP. mirabilis. The diversity in the mediation of blaNDM via chromosomes with transfer elements, untransferable plasmid and mobile plasmid not only revealed the complexity of the spread of blaNDM but also suggested blaNDM increases the risk of widespread P. mirabilis infection among animals used as food sources. The reinforcement of the surveillance of resistance in the animal origin system is extremely urgent for curbing the transmission and persistence of NDM-producing P. mirabilis.In conclusion, this study reported an outbreak of infection in a chicken slaughterhouse caused by NDM-producing


Moreover, the CSM intervention was found to be particularly beneficial for IBS patients with greater baseline work and activity impairments . The CSM intervention may bring benefits to individuals and society through improving symptoms and reducing presenteeism associated with IBS.Individuals with irritable bowel syndrome (IBS) are more likely to miss work (absenteeism), have reduced work effectiveness (presenteeism) and experience activity impairment. This study compared the effect of a comprehensive self-management (CSM) intervention program  versus usual care on work- and activity-impairments in adults with IBS. This secondary data analysis used daily diaries and Work Productivity and Activity Impairment in Irritable Bowel Syndrome (WPAI-IBS) questionnaire data collected at baseline, 3, 6 and 12 months post-randomization from 160 adults with IBS. Mixed-effects modeling was used to compare the effect of CSM versus usual care on work- and activity-related outcomes. The effect of CSM was shown to be superior to usual care in improving WPAI-IBS and diary-measured presenteeism, overall work productivity loss and activity impairment with sustained effects up to 12 months post-randomization (all  Irritable bowel syndrome (IBS) is a disorder of Gut–Brain Interaction which highlights the link between emotional and cognitive brain systems with peripheral intestinal function . It is eMeta-analysis reviews support the use of cognitive behavioral therapy (CBT) and associated modalities as the best psychological strategy to treat IBS symptoms ,10. In CAlthough work and activity impairment are well-documented in IBS, few IBS interventions have addressed the impact on absenteeism, presenteeism, overall work productivity and daily activity. The few IBS interventions which address work and activity impairment are focused on pharmacological therapies; no studies have examined CBT-based therapies. For example, among IBS patients with constipation (IBS-C), treatment with linaclotide for treating constipation results in significant reductions in scores of presenteeism, overall work productivity loss and activity impairment, as well as improvement in overall work productivity through 26 weeks of treatment . In the This secondary data analysis used data from a three-arm randomized controlled trial (RCT) among adults with IBS. The three arms included the Comprehensive Self-Management (CSM) Intervention delivered in-person, CSM intervention delivered over the phone and usual care (UC). Since our previous study showed no significant difference between two CSM delivery modes , we collAll eligible participants gave informed consent prior to data collection. Next, they completed baseline questionnaires, including the Work Productivity and Activity Impairment in Irritable Bowel Syndrome questionnaire. In addition, the 28-day daily diary was completed each evening during baseline data collection. Participants were randomized to CSM intervention delivered in person, CSM intervention over the telephone and usual care. Randomization was based on a computer program that used adaptive randomization  to ensurParticipants randomized to the CSM group were scheduled for nine 60-min one-on-one sections over 10 to 13 weeks . The CSMWPAI-IBS is a self-reported questionnaire with good psychometric properties to retrospectively assess work productivity loss and impairment in daily activities other than work over the past 7 days among individuals with IBS . The WPADaily diary measures of work productivity and activity impairment were quantified with daily diary questions over 28 consecutive days at baseline, 3, 6 and 12 months. Every evening, participants rated 4 diary items: whether went to work/school today (yes/no). If no, the reason for missing work/school, i.e., not a work/school day, cold or flu, IBS symptoms, or other. If yes, “how much did your IBS symptoms affect your productivity while you were working?” and “how much did your IBS symptoms affect your ability to carry out normal activities other than work?” Participants responded on a 4-point Likert scale from “not at all” to “very much”. Four variables derived from the daily diary were (1) absenteeism, the percentage of missed work/school days due to IBS; (2) presenteeism, the average degree IBS affected productivity on work/school days; (3) overall productivity loss, incorporating both missed workdays and impaired productivity due to IBS; and (4) IBS interference, the average degree IBS affected ability to perform regular activities. Daily diary measures of absenteeism and presenteeism are only available for participants currently employed or are students.Demographic variables included self-reported age, gender, job, race and education.t-test or Fisher’s Exact tests were used to examine if baseline demographics, absenteeism, presenteeism, overall work productivity and activity impairment differed between CSM and UC groups.Data analyses were performed by using R version 3.6.1. To deal with missing data, linear mixed-effect modeling, using maximum likelihood estimation, was used , and parTo address our study purpose, changes in absenteeism, presenteeism, overall work productivity and activity impairment outcomes from baseline to each follow-up time were assessed separately, using linear mixed-effects modeling for numerical outcomes, with subject as a random effect, and with treatment group, measurement time, age, gender and baseline status-related to work and activity impairment as fixed effects. The main effect of treatment group was used to examine mean changes from baseline for each outcome measure in CSM versus UC. Since treatment effectiveness might vary depending on baseline work and activity status, the baseline-by-treatment interactions were also included in our mixed-effects models . Before We used an intent-to-treat approach in this secondary data analysis; that is, we made every effort to collect follow-up data on every randomized participant and analyzed their data based on assigned group, regardless of how many CSM sessions they received. Thus, all participants with both baseline and any follow-up data on work-related outcomes were included in the analysis .ps > 0.05).ps < 0.05), except for diary-measured absenteeism, which failed to converge due few participants reporting absenteeism. Significant small baseline-by-treatment interaction effects were also found in all outcome measures , except diary-measured absenteeism. A time-by-treatment interaction was examined for all models but was not significant (data were shown). As shown in r = 0.44~0.51, all p < 0.05), but not for absenteeism (p = 0.75).To our knowledge, this is the first study to examine how a CBT-based comprehensive self-management program affects absenteeism, presenteeism, overall work productivity loss and activity impairment in the USA. Our findings show that, compared to usual care, our CBT-based CSM intervention led to greater improvements in presenteeism, work productivity loss and activity impairment measured by WPAI-IBS and daily diaries. These effects are sustained up to 12 months post-randomization . Short-term improvement in presenteeism, overall work productivity and activity impairments following CSM is similar to that observed with pharmacological ,28,29 anThe mechanism of the CSM intervention leading to improvements in presenteeism, overall work and activity impairments remains to be elucidated. The positive impact of a CBT-based CSM on work and activity impairments could be through overall symptom improvement, in particular, reduction related to abdominal pain/discomfort ,9,31, psThis study extends our previous evidence by reporting that the positive impacts of the CSM intervention on overall work-productivity loss for adults with IBS are primarily through improving presenteeism, but not absenteeism. Due to a lack of model convergence, we are unable to determine if the intervention had a benefit for daily absenteeism. At baseline, only 7.2% of our employed/student participants reported absenteeism (days of work missed) on daily diaries. As such, our study may have been underpowered to detect modest changes in absenteeism with daily diaries. The rate of WPAI-IBS absenteeism in this study sample (24.3%) is comparable with the previous findings of about 20~24.3% of IBS populations reporting any hours missed from work due to IBS ,20. Of nWe also examined the correlations between daily diary and WPAI-IBS measures of work productivity and work impairment. Our correlational analysis showed, at baseline, that prospective diary and retrospective WPAI-IBS measures were significantly positively correlated; however, the diary and retrospective measures of absenteeism had low correlations. Additionally, at baseline, only 7.2% of participants reported absenteeism (days of work missed) on daily diaries, whereas 24.3% reported absenteeism on the WPAI-IBS (hours of work missed). These discrepancies in the findings could be attributed to the different measurement constructs of absenteeism between the diary and WPAI-IBS measures. That is, the WPAI-IBS captures absenteeism by using both hours missed and the entire workday, while the diary uses a single item, “missed workday”. A higher rate of absenteeism was reported on the WPAI-IBS measure than on the daily diaries, and this may suggest that missed work hours is more likely occurring than taking a whole day of leave for persons with IBS. The different types of data-collection methods may also explain these discrepancies. Prospective diaries have been preferred to retrospective reports for collection of daily health-behavior data, due to the shorter recall periods ,34. The This study has several limitations. This secondary data analysis is limited to the data collected in an RCT study that did not focus on work- and activity-related impairment as the primary outcomes. Thus, employment status was not an eligibility criteria for the parent RCT study, and it was not taken into account in a randomization procedure, although the differences between the CSM and UC groups remained non-significant in daily dairy and WPAI-IBS outcomes at baseline. Given that only 7.2% of participants  reporting days absent in our community-recruited sample and the model was unable to converge, this secondary analysis is unable to determine the effect of CSM intervention on absenteeism with daily diaries. Additional replication in more diverse IBS samples with days absent is warranted. This study showed that the effects of CSM on presenteeism, work productivity loss and activity impairment were small to medium based on statistical significance ; howeverIn conclusion, a CBT-based CSM intervention was more effective in reducing presenteeism, overall work productivity loss and activity impairments compared to usual care for adult IBS patients, especially for those with greater baseline work and activity impairments. Therefore, individuals with IBS reporting work- and activity-related impairment can be encouraged that a comprehensive self-management not only reduces symptoms but also influences work productivity and activity impairment. It is important that future RCTs assess the impact of interventions not only on proximal outcomes of symptom management but also on more distal outcomes related to work and activity impairment. Further, we recommend clinicians and researchers assess hours absent and presenteeism, as well as prospective daily diaries instead of single-time retrospective questionnaires to evaluate the impact of IBS on work-related outcomes. Future studies are warranted to recruit larger and diverse samples to understand the CSM intervention mechanism leading to work and activity improvement.


New-onset atrial fibrillation (NOAF) is associated with worse prognostic outcomes in cases diagnosed with ST-segment elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention (PCI). The triglyceride-glucose (TyG) index, as a credible and convenient marker of insulin resistance, has been shown to be predictive of outcomes for STEMI patients following revascularization. The association between TyG index and NOAF among STEMI patients following PCI, however, has not been established to date.To assess the utility of the TyG index as a predictor of NOAF incidence in STEMI patients following PCI, and to assess the relationship between NOAF and long-term all-cause mortality.This retrospective cohort research enrolled 549 STEMI patients that had undergone PCI, with these patients being clustered into the NOAF group and sinus rhythm (SR) group. The predictive relevance of TyG index was evaluated through logistic regression analyses and the receiver operating characteristic (ROC) curve. Kaplan-Meier curve was employed to explore differences in the long-term all-cause mortality between the NOAF and SR group.P = 0.014], with ROC curve analyses further supporting the predictive value of this parameter, which exhibited an area under ROC curve of 0.758 . All-cause mortality rates were greater for patients in the NOAF group in comparison with the SR group over a median 35-month follow-up period (log-rank P = 0.002).NOAF occurred in 7.7% of the enrolled STEMI patients after PCI. After multivariate logistic regression analysis, the TyG index was found to be an independent predictor of NOAF [odds ratio (OR): 8.884, 95% confidence interval (CI): 1.570–50.265, The TyG index exhibits values as an independent predictor of NOAF during hospitalization, which indicated a poorer prognosis after a relatively long-term follow-up. One of the most frequent complications that affects an estimated 5–11% of ST-segment elevation myocardial infarction (STEMI) cases following percutaneous coronary intervention (PCI) is new-onset atrial fibrillation (NOAF) . NOAF inInsulin resistance (IR), as a metabolic disorder in which the normal utilization of glucose by the body is disrupted, resulting in altered lipid processing and reduced glycogen synthesis, has been closely linked to the onset of cardiovascular disease (CVD) . A recenA hyperinsulinemic-euglycemic clamp remains the benchmark test for IR at present, but it is a complex and dangerous procedure that is rarely implemented in the clinic . In addiFor the present study, 709 consecutive STEMI patients > 18 years old who had been admitted to the Yijishan hospital department of cardiology between February 2016 and February 2020 were retrospectively enrolled. Patients were diagnosed with STEMI as per the European Society of Cardiology standard  they undData regarding patient demographics, clinical data, electrocardiogram (ECG) results, laboratory parameters, angiographic and echocardiography findings, duration of hospitalization, and in-hospital outcomes were obtained from electronic medical records. Blood routine examination, such as white blood cell (WBC), neutrophil, hemoglobin, platelet, was measured with the Mindray BC-5380 hematology analyzer using the manufacturer recommended reagents. An automated biochemistry analyzer  was used to assess TG and FPG values in overnight fasting blood samples collected from the cubital vein of each patient within 12–24 h post-symptom onset. TyG index values were evaluated as follows: ln [fasting TG (mg/dL) × FPG (mg/dL)/2] . The estThe diagnosis of AF was complied with the consensus guidelines . TelemetAnalyzed patient outcomes included in-hospital mortality, cardiogenic shock, pulmonary edema, post-PCI ventricular tachycardia, intra-aortic ballon pump (IABP) implantation, stroke and long-term all-cause mortality. Patients' follow-up outcomes were collected from patient medical records or telephone-based interviews. June 16, 2021 was the end time point of follow-up.t-tests or Mann-Whitney U-tests, while categorical variables were compared via Fisher's exact analysis or chi-squared tests. Multivariate logistic regression analysis was performed incorporating significant variables from univariate analyses (P < 0.1) in an effort to identify independent predictors of NOAF. The curve of receiver operating characteristic (ROC) was implemented to gauge the value of the TyG index as a predictor of NOAF incidence. Youden's index was used to select an appropriate TyG index cut-off value. All-cause mortality rates were compared between patients with and without NOAF using Kaplan-Meier curves. SPSS 23.0 (IBM) was used to analyze all data, with P < 0.05 as the threshold of significance.The Kolmogorov-Smirnov assessment was employed to evaluate whether data were normally distributed. Those obtained results that were normally distributed were given as means ± standard deviation (SD), while they were otherwise reported as medians with interquartile ranges. Continuous data were scrutinized via Student's In sum, 549 contributors were enrolled in this research and separated into NOAF and sinus rhythm (SR) groups, with NOAF patients accounting for 7.7% (42/549) of the overall cohort. Patient baseline characteristics are compiled in Substantial discrepancies were observed between the NOAF and SR groups in relation to white blood cell (WBC), neutrophil, hemoglobin, platelet, glucose, triglyceride, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), eGFR, and TyG index values, while albumin, uric acid, peak creatine kinase (CK) and total cholesterol levels did not differ between these groups. Specifically, WBC, neutrophil, glucose, triglyceride, and TyG index were higher in NOAF patients relative to SR patients, whereas platelet and hemoglobin levels, and the values of eGFR were decreased in individuals exhibiting NOAF. Coronary angiography and echocardiography analyses revealed that patients in the NOAF group exhibited worse cardiac function and a larger left atrial diameter. No differences in SYNTAX scores, stent length, culprit vessels, or TIMI flow grade <3 prior to PCI were detected when comparing the NOAF and SR groups .NOAF patients exhibited significantly increased rates of in-hospital mortality, cardiogenic shock, pulmonary edema, IABP implantation, and post-PCI ventricular tachycardia as compared to SR patients, in addition to exhibiting a longer average duration of hospitalization .In univariate logistic regression analyses, age, hypertension, DM, a Killip class ≥II, BMI, hemoglobin, WBC, neutrophil, platelet, glucose, total cholesterol, triglyceride, TyG index, HDL-c, LDL-c, eGFR, stent length, SYNTAX score, left atrium diameter, and left ventricular ejection fraction values were all identified as predictors of NOAF incidence among STEMI cases following PCI. Of these, a multivariate regression analysis revealed age, TyG index, and eGFR levels to be independent predictors of NOAF incidence in this patient population .P < 0.001].A ROC curve of the TyG index for the prediction of NOAF in STEMI patients following PCI had been displayed in Next, patients were separated into cohorts with low or high TyG index values based on a TyG index cut-off value derived from an ROC analysis. On average, cases with a high TyG index were younger, more likely to be female, had higher DM incidence rates, and exhibited higher WBC, neutrophil, hemoglobin, glucose, total cholesterol, triglyceride, and albumin levels and left atrial diameter values as compared to cases with a low TyG index value. NOAF incidence and in-hospital mortality rates were also greater among cases with a high TyG index .P = 0.002, Long-term outcome data were available for 528 patients, while 21 patients experienced in-hospital mortality. Over a median 35-month follow-up period, the rate of all-cause mortality in the NOAF and SR group was 19.4 and 6.5%, respectively, with the rate being substantially greater in the NOAF group (log-rank Herein, the TyG index was utilized as a surrogate biomarker for IR status in an effort to clarify the utility of IR as a predictor of NOAF in STEMI patients after PCI. Overall, these analyses confirmed that the TyG index offers value as an independent risk factor associated with post-PCI NOAF occurrence among STEMI patients, in addition to revealing that long-term all-cause mortality among NOAF patients were higher than those for SR patients. This study is the first to our knowledge to have demonstrated the value of the TyG index as a tool for gauging the risk of NOAF incidence among STEMI patients that have undergone PCI.NOAF is a relatively common outcome observed after PCI in STEMI patients. We found that 7.7% of the STEMI patients in our study cohort developed NOAF during hospitalization, consistent with previously reported rates of AF development for similar patient populations , 2. PrioRecent researches explain that the TyG index is positively associated with metabolic risk factors and cardiovascular outcomes in different patient populations. For example, an analysis of 5,014 cases in the Vascular Metabolic CUN cohort revealed that elevated values of TyG index had been correlated with higher odds of CVD onset over a 10-year follow-up period . Zhao etThe TyG index is a composite metric that incorporates TG and FDP in an effort to provide an easily measured indicator of patient IR status. While the hyperinsulinemic-euglycemic clamp approach remains the benchmark means of assessing IR, it entails significant risk and complexity that render it unsuitable for routine clinical use . The HOMThe exact mechanistic basis for the correlation between the TyG index and AF development remains to be fully elucidated. Given that the TyG index serves as a surrogate for IR, this may underlie its association with NOAF in the present patient cohort. IR is a complex metabolic disorder in which tissues and organs exhibit impaired glucose uptake and/or utilization together with abnormal lipolysis owing to dysfunctional insulin signaling, ultimately resulting in compensatory hyperinsulinemia , 33. IR There are multiple important clinical implications to these results. First, the TyG index is a convenient, easy to measure biochemical indicator that is ideally suited to use in routine clinical practice, thus enabling the efficient identification of patients at a high risk of NOAF incidence. By determining which patients are most likely to suffer from this adverse outcome, it may be possible to provide them with better individualized care such as prolonged ECG monitoring during hospitalization. Moreover, our results have the potential to expand current understanding regarding the pathological mechanisms underlying NOAF, thus suggesting potential avenues for the inhibition of this condition.Several Limitations need to be taken into consideration in present study. For one, this was a single-center study focused solely on Chinese participants, thus limiting the degree to which these results can be generalized. Moreover, this was a retrospective analysis with a limited sample size, thus might limit a sound statistical analysis. All risk factors with the potential to influence IR, including hypertension or diabetes medications, dietary habits and lifestyle characteristics, were not assessed. The result was inherently susceptible to selection bias. Future large-scale prospective research is thus critical to validate and expand our result. In addition, the lack of fasting insulin levels and HOMA-IR may be another limitation. Lastly, TyG index values were only assessed at the time of hospitalization, and whether TyG index values during follow-up offer valuable insight into IR status remains to be established.In summary, the TyG index represents an independent predictor of NOAF during hospitalization. Moreover, the patients with NOAF during hospitalization had worse prognosis after discharge.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Ethics Committee of Yijishan Hospital, Wannan Medical College. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.YL designed the subject and wrote the manuscript. QF, JL, and LJ collected the data for the article. CF and ST analyzed the data and reviewed the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.