The subfamily Eumeninae comprises more than 3900 described species and eumenine mitochondrial analyses are almost absent. In order to provide further evidence toward understanding the relationships within the subfamily, the characteristics of 54 eumenine mitogenomes were comparatively analyzed, among which 52 mitogenomes are newly annotated. Meanwhile, using both Maximum-likelihood (ML) and Bayesian inference (BI), comprehensive phylogenetic relationship in the subfamily were investigated based on two mitochondrial datasets.trnM which are highly similar, with 51.86% (Eumenes tripunctatus) to 90.65% (Pseumenes nigripectus) sequence identities, which is unique among the reported mitogenomes of the family Vespidae. Moreover, the translocation trnL1 upstream of nad1 is a common rearrangement event in all eumenine mitogenomes. The results of phylogenetic analyses support the paraphyly of the subfamily Eumeninae and the tribe Odynerini, respectively, and the monophyly of the tribe Eumenini, and verify that the tribe Zethini is a valid subfamily Zethinae. In this study, the relationships between some genera such as Allorhynchium and Pararrhynchium or the taxonomic status of the subgenera such as Eremodynerus and Dirhynchium are found to be confusing and there should be further inquiry with more samples.The subfamily Eumeninae plays a significant role in the biological control of agricultural pests. However, the characteristics of eumenine mitogenomes that are important molecular markers for phylogenetics are not clearly revealed. Here, 52 eumenine mitogenomes are newly sequenced and annotated, and the phylogenetic relationships of the subfamily are comprehensively analyzed based on 87 vespid mitogenomes. Through the comparative analysis of the 54 eumenine mitogenomes, the gene compositions of about one half of the 54 species match with ancestral insect mitogenome, and remaining others contain two  Zethus, Ischnocoelia, Elimus, Discoelius, and Protodiscoelius using vegetable matter for cell partition, and Psiliglossa and Raphiglossa using pith [Eumenes, Odynerus, and Synagris [Zethus, Calligaster, and Discoelius from the rest of his section ‘Euptéres’ of the ‘Eumhiens’ as the group ‘Zethites’ [The subfamily Eumeninae containing more than 3900 described species is the biggest of the family Vespidae (Hymenoptera). It is the primary lineage of the Vespidae , which ping pith ,5. Additing pith . Hence, Synagris . Later, ethites’ ,9. Thereethites’ , while Cethites’ . Recentlethites’ . Whetherabdominal-A, and RNA polymerase II) from 27 Vespidae species (containing 11 eumenine species), Hines et al. supported the division of Eumeninae into two separate monophyletic clades: “Zethinae” and “Eumeninae” [In the published research on phylogenetic relationships in the subfamily Eumeninae, some molecular data have been utilized. The first molecular study showed that the solitary Eumeninae was a sister taxon to the Polistinae + Vespinae cluster leveraged on nuclear 28S rDNA and mitochondrial 16S rDNA of 12 species from the family Vespidae including 3 eumenine species . Thereafmeninae” . Neithermeninae” . Then, Pmeninae” . So far,The mitogenome is a widely accepted molecular marker used in phylogenetic studies due to its maternal inheritance as well as the higher rate of nucleotide substitution compared with nuclear DNA ,17. To dThe 52 species of the subfamily Eumeninae, which were firstly identified at least to genus level by taxonomic specialists, were collected and stored in 95% ethanol at −20 °C in Chongqing Normal University, Chongqing, China . ThereafCOX1 and srRNA were amplified by standard PCR reactions and were used to identify mitogenome assemblies with at least 98% similarity sequences in BLAST [http://www.geneious.com/. Accessed date: 12 January 2022), which allowed for up to 2% mismatches, a maximum gap size of 3 bp, and a minimum overlap of 100 bp.The Illumina TruSeq library, containing an average size of 350 bp, was sequenced using the Illumina Hiseq 2500 platform at BerryGenomics . Then, high-quality reads  were used in de novo assembly with IDBA-UD by using the NGS QC Toolkit ,32. COX1in BLAST ,34. FinaKa) and synonymous (Ks) substitution ratio (Ka/Ks) of PCGs were calculated in DnaSP 5.0 [Annotation of the assembled mitochondrial sequences was identified using Clustal X 1.8 with homologous sequences against the publicly available Eumeninae mitogenomes . UnrecognaSP 5.0 ,40. ThennaSP 5.0 .Hylaeus dilatatus, Andrena cineraria, Megachile sculpturalis, and Apis cerana) were selected as outgroups , Polistinae (19 species), and Vespinae (11 species) downloaded from GenBank were selected as ingroups, and four species from Apoidea (utgroups . In totahttp://www.atgc-montpellier.fr/phyml/. Accessed date: 12 January 2022) and the node support values were evaluated via a bootstrap test with 100 replicates [Phylogenetic trees were inferred from two sets of data: (1) PCGR: 13 PCGs and 2 rRNAs; (2) PCG: 13 PCGs. Before the construction of trees, PartitionFinder version 2.1.1  was usedplicates . In addiplicates ,50. New Leptochilus sp.) to 23,251 bp (Rhynchium brunneum brunneum) and some of the entire A+T rich regions as well as three tRNA genes  were unable to be amplified in 23 mitogenomes (Subancistrocerus camicrus) to 84.7% (Eumenes pomiformis) which is similar to other hymenopteran mitogenomes [Pararrhynchium striatum) to 0.19 (Antepipona sp.)  .trnM duplications , the remaining being on the N-strand . In thisications .trnM genes which are highly similar, with 51.86% (Eumenes tripunctatus) to 90.65% (Pseumenes nigripectus) sequence identities (trnM0 and trnM1 are identified in the Amino Acid acceptor (AA) arm, TψC (T) arm, Variable (V) loop, Anticodon (AC) arm, and the dihydorouridine (DHU) arm  containing three trnM with 92–97% sequence identities and the genus Pachycephus (Hymenoptera: Cephidae) [trnL2 within the Eumeninae such as three regions of noncoding DNA containing four copies of trnL2 in Abispa ephippium [trnD, trnA, and trnE in the family Cephidae (Hymenoptera) and Trigonalyoidea (Hymenoptera), respectively [trnM may be one of the features to indicate whether a species belongs to the subfamily Eumeninae.Compared with other Vespidae, there are 26 in total in the 52 newly assembled mitogenomes of Eumeninae containing two entities . The subDHU) arm . The posephidae) ,53,54. Mphippium . Accordiectively ,53. TherAll the PCGs start with the typical ATA, ATG, or ATT codons and stop with the complete TAA or TAG or truncate TA- or T -- termination codons. The composition of PCGs is significantly biased toward adenine and thymine, with high A+T content from 75.9% to 84.4%, and the AT skews are always negative from −0.16 to −0.095 A. The A+The Relative Synonymous Codon Usage (RSCU) values of codons such as UUA, GUU which ended with A or U, are all greater than 1.3 and those ending with G or C are all less than 1 . The RSCKa/Ks is the ratio of the number of nonsynonymous substitutions per nonsynonymous site (Ka) to the number of synonymous substitutions per synonymous site (Ks), which could indicate something about the selective forces acting on the protein [Ka/Ks value of PCGs from eumenine mitogenomes, and the result shows that all the Ka/Ks of PCGs except ND4L are less than 1, which indicates that only ND4L is under a positive selection and evolves rapidly, and other PCGs are under a purifying selection. Moreover, the lowest Ka/Ks value of COX1 (0.11) indicates that it is conservative under environmental selection pressure and suitable for molecular barcoding  standard curve can indicate that the determinant of codon preference is mutation pressure or natural selection . Our res protein . Thus, warcoding .trnM and the positions of the two trnM are different, which means that the different mechanisms occurred in the gene rearrangement of Eumeninae. We investigated more rearrangement events of 54 eumenine mitogenomes and found that all eumenine mitogenomes contain a translocation trnL1 upstream of nad1 . The two concatenated nucleotides were subjected to Bayesian inference (BI) and maximum likelihood (ML) analyses, resulting in four trees where the positions of the four subfamilies are congruent  have been cited as exemplifying the critical evolutionary stages of subsocial and communal behavior which connects solitary and eusocial wasps because it is reported that some species of both Zethus and Calligaster construct their nests with plant material rather than the typical eumenine nest construction with mud [The results of substitution saturation show that Iss > Iss.c and and PCGR , which iongruent . In theswith mud ,67.Pseudozumia indosinensis belongs to clade VIII in ML trees with low bootstrap support value , while in BI trees it belongs to clade IX with high Bayesian posterior probability   . That thP = 1,1) . Therefois study . FurtherOreumenes + Delta) + (Katamenes + Eumenes) is strongly supported by all datasets in this study . Hermes et al. found that the genera Oreumenes, Delta, Katamenes, and Eumenes all belong to their clade 3 of Eumenini, and the genus Eumenes was recovered as a sister to the remaining taxa of Eumenini [Within the tribe Eumenini, the sister relationship of (Eumenini . The difAbispa) is a sister group to all remaining Eumeninae. Bank et al. reported that the genus Alastor (clade A) is inferred as a sister lineage to all remaining Eumeninae based on transcriptomes of 49 vespid wasps [Alastor, and Bank et al.’s study did not contain any species in the genus Abispa, whereas that of Piekarskis et al. containing both Abispa and Alastor, is consistent with the standpoint of Bank et al. [Leptochilus is inferred as a sister lineage to the genus Labus. In succession, the genus Symmorphus is an independent clade III and sister group to clades IV-X. In clades IV-X, there is a sister-group relationship between clades IV-V and VI-X. Within clades IV-V, clade IV is a sister group to clade V, while Jucancistrocerus (Jucancistrocerus) angustifrons and Jucancistrocerus (Eremodynerus) atrofasciatus are located at clades IV and V, respectively, which may support subgenera Eremodynerus being a valid genus [Antepipona + . Then, clade VII is a sister group to clades VIII-X, composed of Pararrhynchium and Allorhynchium, while Pararrhynchium striatum is located within the genus Allorhynchium. The misidentification of Pararrhynchium striatum is eliminated by the examination of specimens, so Pararrhynchium striatum should be transferred to the genus Allorhynchium, or these two genera are synonymized. Likewise, there is a sister relationship between clade VIII and clades IX-X, and the phylogenetic relationships of clade VIII are as follows: (Pareumenes + (Ectopioglossa + Pseumenes)). Finally, within these two clades IX and X, they are sisters to each other, and the phylogenetic relationships of clade IX are as follows: (Pseudozumia + (Euodynerus + Orancistrocerus)), and of clade X they are (Anterhynchium (Anterhynchium) + (Anterhynchium (Dirhynchium) + Rhynchium)). As the results show, with high Bayesian posterior probabilities (PP = 1), the subgenus Dirhynchium of Anterhynchium is more closely related to the genus Rhynchium than the nominate subgenus Anterhynchium, which means the subgenus Dirhynchium should be upgraded to a valid genus. Again, further investigation is needed.The tribe Odynerini is the biggest one within the subfamily Eumeninae . Here, wid wasps . Our stuk et al. ,15. In cid genus . Of courtrnM, which differs remarkably from the gene orders of other Vespidae. This study based on mitogenomes further supports previously proposed relationships among Vespidae [Eremodynerus and Dirhynchium as valid genera. Additionally, although Pararrhynchium striatum is proposed to be moved to Allorhynchium, it is possible that the relationship between these two genera is confused, which requires more species sampling and morphological characteristics to elucidate. Second, considering that only one limited mitogenome in some genera of Eumeninae, such as Abispa, Apodynerus, Leptochilus, Parancistrocerus, Paralepromenes, Pareumenes, Pseudozumia, and Subancistrocerus, is presented in our analyses, the taxonomic status of these genera may be unstable and uncertain. In the end, the relationships of these taxa in this study still need to be verified by morphological and biological information. Therefore, to further advance the research on the systematic relationships of the subfamily Eumeninae, more taxon sampling and information about the morphological characteristics, molecular data, and biological behaviors are needed.To sum up, the mitogenomes of Eumeninae are commonly found to contain two Vespidae ,14,68, e


Background: With recent advances in treatment, gastric metastases are increasingly becoming the subject of diagnostic imaging. On the other hand, it is difficult to detect gastric metastasis on CT finding images.Purpose: To characterize the CT findings of gastric metastasis and investigate its treatment method and natural history in patients.Materials and Methods: We retrospectively reviewed the CT findings of 15 patients diagnosed with gastric metastasis between April 2003 and December 2019 in our hospital. The location, size, and shape of the tumors on CT were evaluated. Moreover, their medical records, characteristics, complications, treatment options, and natural course were evaluated.Results: Of the 15 patients with gastric metastasis, 9 were male and 6 were female. The median age was 74 (55-87) years. Gastric metastasis was diagnosed simultaneously with primary cancer in five patients. In other patients, the median interval time from the date of primary cancer diagnosis to gastric metastasis diagnosis was 27 (10-259) months. CT findings revealed that the gastric metastasis had a median size of 18 (12-135) mm and was mainly located in the middle third of the stomach. In addition, most patients had a submucosal tumor (SMT) pattern, followed by diffuse wall thickness and polypoid patterns . The median time to death after gastric metastasis diagnosis was 112 (17-883) days.Conclusion: The SMT pattern in the middle third of the stomach is the characteristic CT finding of gastric metastasis. Malignant tumors rarely metastasize to the stomach, accounting for only 2.3%-5.9% of autopsy cases -2. SeverWith the recent development of treatment methods including chemotherapy, the number of long-term survivors of cancer with distant metastases is increasing, and the chances of gastric metastases being targeted for diagnostic imaging is increasing. On the other hand, symptoms of gastric metastasis are vague, and it is difficult to identify gastric metastasis on CT findings images. Early detection of gastric metastasis can lead to early treatment and improvement of quality of life. CT exam is widely utilized for surveillance of many types of malignancies and endoscopy is not usually performed except for cases with gastrointestinal manifestation. Therefore, CT is the initial modality to describe gastric metastasis. Therefore, it is important to organize CT imaging findings of gastric metastases. However, imaging findings of gastric metastasis have only been reported in case reports and need to be studied in a coherent number of cases -6.The purpose of this study is to characterize the CT findings of gastric metastasis and to investigate the treatment and natural history of this condition in patients.Our institutional review board approved this retrospective study and waived the requirement of informed consent from each patient. This study retrospectively reviewed the hospital’s information system and radiological information system and found 15 patients diagnosed with gastric metastasis between April 2003 and December 2019. Their medical records, characteristics, complications, treatment options, and natural course were evaluatedThe inclusion criteria were as follows: 1) age over 20 years, 2) a history of any cancer, and 3) a CT-detected gastric tumor. The exclusion criteria were the following: 1) a history of gastric cancer; 2) a history of gastric surgery such as total gastrectomy, distal gastrectomy, or proximal gastrectomy; 3) cases of direct invasion of cancer into the stomach; and 4) oral contrast-enhanced media in the stomach.CT techniqueAbdominal CT was performed using various scanners, such as the following: GE CT9800 , SIEMENS SOMATOM PLUS40 , PHILIPS Brilliance CT40, PHILIPS Brilliance CT64 , TOSHIBA Aquilion 16, TOSHIBA Aquilion ONE, TOSHIBA Aquilion CX , and Canon Aquilion ONE .For contrast-enhanced CT, 100-150 mL of iodinated contrast material was administered at 2-5 mL/s and scanning was performed with a bolus-tracking technique .An oral contrast medium was not used routinely. Whole-abdomen images were produced, showing varying section thickness depending on the period it was photographed: 10 mm, 2003-2004; 7 mm and 5 mm, 2006 onward. Abdominal CT images and soft-tissue window images were reconstructed by obtaining three cross-sectional images .Image interpretationTwo radiologists（S.T. and R.Y.）who had 14 and three years of experience, respectively, assessed the abdominal CT images independently using the Digital Imaging and Communications in Medicine (DICOM) viewer . Both were blinded to patients’ clinical information but were aware that each patient had gastric metastasis. They evaluated the following points: 1) Clinical findings of gastric metastasisThe date of the CT scan when gastric metastasis was first diagnosed was reviewed.2) CT findings of gastric metastasisTwo radiologists independently reviewed the abdominal CT images and determined the location, shape, and size of the tumor. The location was decided by dividing the stomach into three parts: upper third, middle third, and lower third. The shape was classified into the submucosal tumor (SMT) pattern, polyp or polypoid pattern, or diffuse wall thickness pattern -3 Figur. For theThe two radiologists independently evaluated the CT findings according to the given definitions. Disagreements were resolved through consensus. The size was decided by averaging the measurements made by these radiologists.Treatment options and clinical outcomes during follow-upThe hospital information system was retrospectively reviewed to evaluate the following aspects of the patient's treatment options:1) Clinical symptoms associated with gastric metastasis2) Treatment optionsAfter assessing the gastric metastasis diagnosis, we investigated the treatment options in each patient by analyzing the medical records. These options were conservative treatments such as best supportive care (BSC) and chemotherapy, and interventions such as endoscopic resection and surgery.3) Clinical outcomesPatient death or survival at the last follow-up was considered. In the case of death, the number of days from the date of diagnosis of gastric metastases to the date of death was counted.PatientsThe study patients consisted of nine males and six females, with a median age of 74 (55-87) years at diagnosis. Table Clinical findingsSymptoms associated with gastric metastasis were nonspecific. During gastric metastasis diagnosis, nine patients were asymptomatic, six had abdominal pain, and three had bleeding. Five patients were diagnosed with primary cancer and gastric metastasis simultaneously. Out of the 15 patients, 13 already had metastases to multiple organs during the diagnosis of gastric metastasis. The colon was the most common site of primary cancer (n=3). Other sites such as lung, diffuse large B-cell lymphoma (DLBCL), and pancreas accounted for two patients each, and the malignant melanoma, kidney, breast, esophagus, ovary, and bladder had one patient each. During the diagnosis of primary cancer, majority of the patients were already at stage IV (n=10); meanwhile, stages III, II, and I accounted for one, three, and one patients, respectively. This clinical staging was based on the TNM classification of the American Joint Committee on Cancer . The patCT and endoscopic findings of gastric metastasisTable Regarding tumor shape, CT detected an SMT pattern in most patients , followed by a diffuse wall thickness pattern in three (20.0%) patients, and a polypoid pattern in one (6.7%) patient. The contrast enhancement of the tumor was hypovascular, hypervascular, and moderate in nine (60%), one (6.7%), and five (33.3%) patients, respectively.Moreover, endoscopic findings showed an SMT pattern in nine (60%) patients, diffuse lesions in two (13.3%) patients, and a polyp pattern in one (6.7%) patient. Three patients did not undergo endoscopy. Endoscopic findings in patients who underwent endoscopy were consistent with CT findings. Additionally, six (33.3%) patients had gastric tumor ulcers, and two (13.3%) had tumor erosion.Treatment options and clinical outcomesAs for the treatment course, the majority of the patients received BSC (n=7); surgery, chemotherapy, and endoscopic treatment were provided to three, three, and two patients, respectively. The median survival time from the date of gastric metastasis diagnosis was 112 17-883) days. Only one patient, who had renal cell carcinoma (RCC), remained alive after endoscopic treatment. No recurrence of abdominal symptoms or melena was seen at five years of follow-up. However, we could not identify the outcomes of the three patients. Figure  days. OnThis study reviewed the CT imaging findings of 15 patients with gastric metastases diagnosed at our institution. The symptoms associated with gastric metastasis were nonspecific. The SMT pattern (73.3%) in the middle third of the stomach (73.3%) was the most recognized CT image pattern of gastric metastasis. The median tumor diameter was 18 mm. This CT finding was similar to the endoscopic finding. As for the treatment course, 47% of patients received BSC, while others chose surgery, chemotherapy, and endoscopic treatment. The median survival time from the date of gastric metastasis diagnosis was 112 days.In previous reports of endoscopic findings, gastric metastases often showed gastric cancer-like lesions or SMT patterns , 9-12. IIn several reports on endoscopic findings, gastric metastases were often located in the middle or upper third of the stomach , 10-12. In this study, gastric metastases often showed SMT patterns in the middle third of the stomach on CT. Although the detailed mechanism is unknown, it was expected that the blood flow control of the stomach is involved. The possibility of gastric metastasis may need to be considered, especially when the above findings are seen on CT in cancer-bearing patients. Early intervention may reduce the disadvantages to the patient, such as hemorrhagic events.According to a previous report that analyzed the clinical characteristics and examined the prognosis of gastrointestinal metastasis of lung cancer , the meaThe follow-up of malignant tumors with CT is one of the most used methods. Early detection of gastric metastases with CT would improve the patient's quality of life. It would also predict prognosis and have a significant impact on the response. Therefore, it is important to evaluate the features of CT findings.This study has some limitations. It is a retrospective, single-center study, has a small sample size, and included some patients with no endoscopic or pathological findings. Therefore, future studies should collect a large number of cases at multiple centers and positively consider the clinical course, treatment, and prognosis.In this study, two radiologists reviewed the characteristics of CT imaging findings of gastric metastases in 15 cases experienced at our hospital. As a result, in many cases, lesions were found in the middle third of stomach, and the shape was SMT pattern. This may be a CT imaging finding characteristic of gastric metastasis. This was also reported in a study on the findings of gastric metastases on endoscopy. CT is widely used in the follow-up of cancer patients, and we believe that it is necessary to consider gastric metastasis when the above findings are observed. This study was conducted at a single institution and the number of cases is small, further studies with more cases are needed to confirm our findings.


We provide an overview of diagnostic features and present a framework for arriving at an adequate diagnosis, consisting of the use of the SEE-FIM grossing protocol, evaluation by a subspecialized gynecopathologist, rational use of immunohistochemical staining, and obtaining a second opinion from a colleague.Our understanding of the oncogenesis of high-grade serous cancer of the ovary and its precursor lesions, such as serous tubal intraepithelial carcinoma (STIC), has significantly increased over the last decades. Adequate and reproducible diagnosis of these precursor lesions is important. Diagnosing STIC can have prognostic consequences and is an absolute requirement for safely offering alternative risk reducing strategies, such as risk reducing salpingectomy with delayed oophorectomy. However, diagnosing STIC is a challenging task, possessing only moderate reproducibility. In this review and meta-analysis, we look at how pathologists come to a diagnosis of STIC. We performed a literature search identifying 39 studies on risk reducing salpingo-oophorectomy in women with a known BRCA1/2 PV, collectively reporting on 6833 patients. We found a pooled estimated proportion of STIC of 2.8% . We focused on reported grossing protocols, morphological criteria, level of pathologist training, and the use of immunohistochemistry. The most commonly mentioned morphological characteristics of STIC are (1) loss of cell polarity, (2) nuclear pleomorphism, (3) high nuclear to cytoplasmic ratio, (4) mitotic activity, (5) pseudostratification, and (6) prominent nucleoli. The difference in reported incidence of STIC between studies who totally embedded all specimens and those who did not was 3.2%  versus 1.7%  (The online version contains supplementary material available at 10.1007/s00428-021-03244-w. BRCA1/2 pathogenic variant (PV), who have a life-time risk of 16–44% to develop EOC [Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. The most common histological subtype of EOC is high-grade serous carcinoma (HGSC), which is accountable for the majority of EOC deaths , 2. HGSCelop EOC , 6.TP53 mutations in STIC lesions and in concomitant HGSC provides evidence for a clonal relationship [TP53 mutations, but lack the full cytomorphological and immunophenotypical features of STIC. Sometimes these lesions are grouped together as early serous proliferations (ESP). When these ESP present in an isolated status, no substantial malignant potential has been objectified so far [Our understanding of the pathogenesis of HGSC has greatly improved over the last few decades. Convincing evidence for a precursor lesion, originating in the fallopian tubes, has been found. This precursor lesion is most commonly referred to as serous tubal intraepithelial carcinoma (STIC). Correspondence between tionship . Moreovetionship . Other ad so far . ExampleWith the discovery that precursor lesions to HGSC originate in the fallopian tube, possible alternative preventive strategies for woman at an increased risk of developing HGSC emerge. Such strategies, consisting of a salpingectomy with delayed oophorectomy are currently being studied . To alsoSTIC diagnosis is very rare for women undergoing salpingectomy for benign indications, (< 0.01%) . In contOn the individual patient level, the detection of STIC is important, because it can have implications on prognosis. For example, in the case of RRSO, STIC is related to an increased risk of HGSC of the peritoneum , 17. So Multiple efforts to improve STIC detection have been initiated over the years. Grossing protocols, such as the “Sectioning and Extensively Examining the FIMbriated end” (SEE-FIM) have been developed . Next toBRCA1/2-PV carriers, we limited ourselves to these studies.Our objective is to set up a systematic review to provide an overview of current practices in the pathological diagnosis “STIC.” We will cover the use of grossing protocols, morphological criteria, training level of the pathologist, and the use of immunohistochemical stains (IHC). Because STIC and its diagnostic approach are commonly best described in studies on RRSO from , with search terms for BRCA, risk-reducing surgery, and pathological outcome. Three independent researchers (JBo/MSt/JHe) first screened the studies by title and abstract and secondly by full text. Each study was assessed by at least 2 researchers. Discrepancies were resolved by discussion or consultation of a third researcher (MSi). The review was performed in concordance with a protocol registered in PROSPERO (CRD42020120728). The search protocol is provided in the supplementary appendix.A literature search strategy was designed for Embase, Medline, and Cochrane (CENTRAL) from inception until 1 September 2020BRCA1/2 PV carriers, aimed at defining the incidence or describing the histopathological characteristics of ovaries and fallopian tubes, were considered eligible for inclusion. Though STIC is also reported in women without a known BRCA1/2 PV, the incidence in this group is low. As the incidence rates will be used to compare the effectiveness of various diagnostic features, this group might form a bias and was therefore excluded. For studies containing only summarized results for BRCA1/2-PV carriers, authors were asked to provide the subgroup data. Articles were excluded if these data remained unavailable. Articles written in another language than English or Dutch, conference abstracts, case reports, and review articles were also excluded.All studies describing the pathology results of a risk-reducing salpingo-oophorectomy, performed among The primary outcomes recorded were incidence of STIC, morphological characteristics, the use of grossing protocols, the use and role of IHC, and whether a subspecialized gynecopathologist assessed the pathology specimens. Secondary outcomes included the incidence of invasive carcinomas hyperplasia, atypia, p53-signatures, and STIL. Sensitivity analyses were performed on the method by which tissue was embedded , whether a subspecialized gynecological pathologist made the pathological assessment (yes/no/unknown) and on the use of IHC (yes/no/unknown). The authors were contacted in case of missing data or inconsistencies.The methodological quality was independently assessed by two review authors (JBo/MSt) according to the standardized quality assessment tool for observational cohort and cross-sectional studies of the National Heart, Lung and Blood institute (NIH). Disagreements were resolved by discussion of consultation of a third review author (MSi).A language and environment for statistical computing; R Foundation for Statistical Computing, Vienna, Austria, version 4.0.4, packages “meta” and “dplyr”).For the statistical analysis, with random effect models, and plots, we used R  , 31, 33.p = 0.92)  used, and five studies do not report on the use of a specific grossing protocol. The incidence of STIC in studies applying the SEE-FIM protocol was 2.8% , while an incidence of 2.7%  was found in studies without the SEE-FIM protocol (p = 0.24)  and 1.7%  was found , followed by nuclear pleomorphism/atypia (13/19), high nuclear to cytoplasmic ratio (13/19), mitotic activity  pseudostratification (10/19), prominent nucleoli (10/19), loss of ciliated cells (8 /19), detachment of cells from the surface (3/19), apoptotic bodies (1/19), and abnormal chromatin (1/19). The described morphological criteria used for identifying STIC are shown in Fig. p = 0.34)  gynecopathologist in 25 out of 39 studies. Of the remaining studies, one reported that a general pathologist analyzed the specimens, and 13 studies did not report on this feature. The studies with a reported subspecialized gynecopathologist had a STIC incidence of 3.1% , compared to an incidence of 2.3%  for the other studies .  loss of polarity, (2) nuclear pleomorphism/atypia, (3) high nuclear to cytoplasmic ratio, (4) mitotic activity, (5) pseudostratification, and (6) prominent nucleoli. These criteria were all mentioned by more than half of the studies commenting on morphology. Whether these criteria were equally weighted and if these criteria are a prerequisite for diagnosing STIC remains unclear in these articles.k) score of 0.333 [k-score of 0.39 amongst five pathologists [Fallopian tube tissue consists of stromal components which are lined by a predominantly single layer of secretory, ciliated, and intercalated cells. Recognizing epithelium as being aberrant is a cornerstone in the diagnostic process of STIC. However, standardized morphological criteria for STIC are lacking. Moreover, inter observer variability for recognizing aberrant fallopian tube epithelium is found to be high in multiple studies. Carlson et al. asked six pathologists and six pathology trainees to review a total of 30 cases, containing 14 STIC lesions. The majority agreed on 9 out of these 14 cases, leading to a minimal reproducibility, with a kappa  was better than that amongst trainees (k = 0.253) [The importance of proper training was demonstrated in the difference between trainees and pathologist in Carlson’s study, whereby the agreement between experienced pathologist (= 0.253) . In addi= 0.253) , 66. EveAdditional IHC staining is often used in diagnosing STIC, most notably p53 and Ki-67. Twenty-one studies mention the use of IHC; however, the remaining studies often did not comment on this. No difference in STIC incidence was found between the group that describes the use of IHC and the one that does not. However, this does not necessarily mean that IHC would not be of added value. IHC stainings might influence the incidence in two ways. On the one hand, IHC may lead to downgrading of cases, e.g., from STIC to STIL. On the other hand, more lesions might be identified due to increased sensitivity. As a result, a comparable incidence may be found regardless of the use of IHC.How these stains are interpreted, either being a prerequisite or a supportive tool, often remains unclear in the articles. Though these stains can indeed prove helpful, we must be aware of how to interpret these stains. Previously suggested diagnostic algorithms often strongly rely on IHC. For example, Visvanathan et al. developed a model based on a combination of morphological suspicion of STIC and the results of p53 and Ki-67 stains . LesionsTP53 has been shown to be mutated in approximately half of all human cancers, in 96.7% of HGSC and in approximately 92% of STIC, tested with TP53 sequencing [TP53 mutations is the gold standard. However, this is costly, labour intensive, and not always available. IHC can therefore indeed be an attractive substitute for molecular testing. The p53 stain is usually considered to be aberrant, when more than 75% of the nuclei, in a region of at least 12 epithelial cells, show an increased expression, or if there is an complete absence of staining [The tumour suppressor gene quencing , 70, 71.staining , 62. Kuhstaining . This inAdditionally, Ki-67 can also play a supportive role in diagnosing STIC; however, the extent to which it can help to distinguish STIC from STIL or reactive lesions remains debatable. Ki-67 is a non-specific proliferation marker. An increased proliferative activity is usually defined as an overall Ki-67 expression of more than 10% of cells, but alternative systems, whereby the maximum proliferative index within a part of the lesion is taken, have also been proposed , 69 One The strength of this review lies in the large number of inclusions, with 39 studies, accounting for a total of 6833 patients. To our knowledge, it is also the first time that these diagnostic features have all been considered in one review. The limitations of this study are found in the predominantly retrospective nature of these studies and the moderate heterogeneity . VaryingAccurate and reproducible STIC diagnosis is important, both for individual patient care and for better understanding the oncogenesis of HGSC, but remains a challenging task. The diagnostic process can be broken down into several steps, which are highlighted in Fig. We believe that a good grossing protocol, evaluation by a subspecialized pathologist, rational use of immunohistochemical staining, and a low threshold for consultation with a colleague are the building blocks for a proper diagnostic approach toward STIC. Pathologists and clinicians alike should thereby be aware of the sliding scale in various other aberrant lesions, such as STIL and p53 signatures, and the challenges that occur when classifying them. Further standardization of the morphological criteria of STIC, a common approach in the diagnosis of other aberrant lesions in the fallopian tube and a better understanding of their clinical implications is needed.Supplementary file1 (PDF 806 KB)Below is the link to the electronic supplementary material.


Since 5 years ago, an increasing number of studies have found that SYTs also played important roles in the occurrence and development of lung cancer, gastric cancer, colon cancer, and other cancers. Down-regulation of SYTs inhibited cell proliferation, migration, and invasion of cancer cells, but promoted cell apoptosis. Growth of peritoneal nodules is inhibited and survival is prolonged in mice administrated with siSYTs intraperitoneally. Therefore, most studies have found SYTs serve as an oncogene after overexpression and may become potential prognostic biomarkers for multiple cancers. This article provides an overview of recent studies that focus on SYT family members’ roles in cancers and highlights the advances that have been achieved.With the continuous development of bioinformatics and public database, more and more genes that play a role in cancers have been discovered. Synaptotagmins (SYTs) are abundant, evolutionarily conserved integral membrane proteins composed of a short N-terminus, a variable linker domain, a single transmembrane domain, and two C2 domains, and they constitute a family of 17 isoforms. The synaptotagmin family members are known to regulate calcium-dependent membrane fusion events. Some SYTs play roles in hormone secretion or neurotransmitter release or both, and much evidence supports SYTs as Ca SYT1–3, 5–7, and 9 have C2 domains, while the others do not (Synaptotagmins (SYTs) are a family of membrane-trafficking proteins composed of a short N-terminus, a variable linker domain, a single transmembrane domain, and two C2 domains (C2A and C2B domains) . The C2 s do not  , and adverse prognostic characteristics. Knockdown of SYT7 suppressed the proliferation of GC cells and attenuated the invasion, migration, and adhesion ability of cancer . It has in vitro, including promoting proliferation, invasion, and migration, but inhibiting apoptosis of cancer cells. It was also demonstrated that shSYT7 significantly blocked the growth of NSCLC tumor cells in a xenograft model. The expression of Vimentin and N-cadherin in cultured cells was decreased after the knockdown of SYT7, while E-cadherin levels increased , and its high expression was positively correlated with T stage and tumor differentiation. Patients with lower SYT7 expression had longer survival than those with higher expression . Liu et ncreased . The aboncreased .in vitro with time independence. Furthermore, knockdown of SYT7 could also increase cell apoptosis rates, induce cell cycle arrest with a decreased proportion of S phase and increased G2 phase, and inhibit the invasion and migration capability . The 40-kDa form was present in the cytosol in the brain, in clonal beta-cells, and in PC12 cells, while the 50-kDa form was localized in very typical clusters. Further research found that SYT8 is not a Cane cells . There aRT1 axis .High expression scores of the dual-marker expression panel (MAGED2 and SYT8) were significantly correlated with higher tumor stage, more lymph node or peritoneal metastasis, and more vascular invasion. Moreover, compared with single markers, the C-index of the combination panel was obviously higher. Patients with GC can be precisely stratified into high, intermediate and low risk by this dual-marker predictive signature after gastrectomy . The autFinally, it may be concluded that SYT8 may serve as an oncogene in pancreatic cancer and GC. The underlying mechanism in pancreatic cancer could be involved in TNNI2/ERRα/SIRT1 signaling pathway.in vitro showed that knockdown of SYT12 inhibited cell colony formation, proliferation, migration, and invasion ability of PTC cell lines, but accelerated the process of apoptosis -derived cell lines and primary OSCC tissues. Knockdown of SYT12 in OSCC inhibited cellular proliferation, invasion, and migration and arrested the cell cycle in G1 phase. Meanwhile, L-dopa , which has been approved for Parkinson’s disease, could reduce cellular SYT12 expression, allowing cells to acquire a cellular phenotype similar to SYT12 knockdown. Therefore, L-dopa is expected to become a new drug for the clinical therapy of OSCC by regulating the expression level of SYT12 . Analysif PIK3R3 .via the PI3K/AKT/mTOR axis.To summarize, SYT12 may serve as an oncogene in PTC, OSCC, and LUAD. High expression of SYT12 predicted poor prognosis in LUAD. The underlying mechanism in LUAD could be involved in signaling P = 0.0246, HR = 3.69, 95% CI = 1.18–12.74) (SYT13 locates at human chromosome 11p11.2 and encodes a predicted single-pass 47-kDa transmembrane protein . SYT13 a8–12.74) . Kanda e8–12.74) .In vitro experiments showed that silencing of SYT13 could depress the activity of the CRC cell lines RKO and HCT116, including proliferation, colony formation, invasion, and migration. In vivo assays also showed the role of SYT13 in promoting tumor growth. In addition, after SYT13 knockdown, N-cadherin, Vimentin, and Snail expression were all inhibited, suggesting that downregulation of SYT13 may inhibit the occurrence of EMT  To develop SYT-targeted therapy, the dose, route, frequency, and duration of administration of siSYTs or inhibitors should be optimized. In addition, the existence of a synergistic effect of siSYTs in combination with existing chemotherapeutic agents also needs to be confirmed. Through the above research, we will obtain a better understanding of the functions of the SYTs and may find a new target for anticancer therapy.Although the results from previous studies appear to be promising, supporting evidence of SYTs as a tumor marker is still lacking since most studies were retrospective. In the future, large-scale prospective studies are needed to further assess the value of SYTs in the diagnosis and prognostic prediction. We suggest the following for further research: (1) At present, we still do not understand the mechanism by which SYTs affect the occurrence and development of cancer. More work is required to elucidate the proteins and pathways that interact with SYTs to promote tumor growth and metastasis for further understanding of the biological functions of SYTs in cancers. (2) With the continuous improvement of public databases, more and more tumor markers or potential prognostic biomarkers have been discovered –58. For In the past 5 years, an increasing number of studies have demonstrated that SYTs play important roles in the occurrence and development of cancers. At present, most studies have shown that SYTs serve as oncogenes after overexpression. Downregulation of SYTs can inhibit the proliferation, migration, and invasion of cancer cells, but promote apoptosis. Through more in-depth research, SYTs may become a new target for the treatment of tumor diseases in the future.HS and NX searched the literature for recent advances in the field. HS wrote the manuscript. KW designed the study and edited and revised the manuscript. All authors approved the final version to be published.


Prior research has found that experiences with violence in the U.S. differ across individual demographic characteristics, including race, gender, and sexual orientation. However, peer reviewed studies have yet to examine the relationship between the intersections of race, gender, and sexual orientation, victimization risk, and characteristics of victimization.We use data from three years (2017–2019) of the National Crime Victimization Survey, the primary source of information on criminal victimization in the United States, to examine victimization at the intersection of sexual orientation, gender, and race/ethnicity. We test whether non-Hispanic Black, Hispanic, and non-Hispanic White sexual and gender minority (SGM) persons aged 16 or over are victimized at greater rates than their non-SGM counterparts and assess whether there are differences between sexual minority females and males of each racial group. We further document characteristics of victimization such as reporting to the police by SGM status and race or ethnicity.OR] = 3.3, 90% CI [CI] = 1.36, 5.16; Hispanic OR = 4.5, CI = 2.25, 6.71; non-Hispanic White OR = 4.8, CI = 2.25, 6.71). However, sexual orientation disparities are statistically distinguishable for lesbian or bisexual (LB) non-Hispanic White and Hispanic females but not for non-Hispanic Black LB females. Among LB females, the overall differences in victimization were primarily driven by bisexual respondents. We further find racial and ethnic differences among SGM victims in the likelihood of having the victimization reported to the police, in the utilization of community (non-police) resources, and in other aspects of victimization experiences, such as whether arrests occurred or in the suspicion that the violent incident was a hate crime.We find that SGMs are disproportionately more likely to be victims of violent crime than non-SGM people, and these disparities are present across the assessed racial and ethnic groups (non-Hispanic Black odds ratio [Our findings raise indicate a complex picture of how sexual orientation, gender identity, sex, and race and ethnicity interact in victimizations and their characteristics that should be further explored. Prior research suggests that experiences with violence differ across gender, race, and ethnicity in the United States. Women tend to have higher rates of victimization than men; Black or African American persons historically have higher risk of victimization than non-Hispanic White people . For decAcross studies of victimization disparities, findings show that minority or subjugated groups  tend to experience victimization at higher rates than dominant social groups, such as White, cisgender men, and heterosexual people , 2, 4–6.With some exceptions , most reTheoretical work on the impact of belonging to multiple marginalized social statuses, particularly among LGBT youth of color, indicate that being in two or more stigmatized social groups may produce compounded threats to victimization ; howeverThe National Crime Victimization Survey (NCVS) is a stratified, multi-stage cluster sample of households in the United States that surveys individuals aged 12 years and older. The US Census Bureau administers the NCVS for the Bureau of Justice Statistics. The purpose of the NCVS is to document the prevalence and characteristics of violent and property crimes in the U.S., regardless of whether such experiences were reported to the police. Data collection for the NCVS is performed on a continuous basis, with households probabilistically selected, recruited and empaneled for 3.5 years and interviewed at 6-month intervals. The sampling frame includes group quarters, such as dormitories, but excludes military base housing and institutional settings . Households are sampled and recruited monthly, with one-seventh of the empaneled households rolling off and being replaced by a new sample of households.Once a household is sampled, all eligible respondents 12-year-old or older are interviewed. From 2017 to 2019 NCVS respondents aged 16-year-old or older were asked three questions relating to their sexual and gender identities. Thus, the sample for the current study includes individuals 16-year-old or older.The US Census Bureau field representatives conduct the interviews either in person or over the telephone. Usually, the first survey is conducted in person while the follow-up surveys are conducted via telephone. The 2017 NCVS contains 145,508 household interviews and 239,541 individual interviews, representing 76% of eligible households and an individual response rate 84% . The 201The NCVS public-use files are available for download in the National Archive of Criminal Justice Data hosted by the Inter-University Consortium for Political and Social Research at the University of Michigan. Since the current analyses are a secondary analysis of publicly available survey data, the study is not considered human subjects research for ethical review purposes and is exempt from human subjects’ review, and the researchers did not engage in primary data collection and thus did not obtain consent.n = 3,737) were gay, 0.3% (n = 799) were bisexual, 95.8%  were straight, and 2.3%  responded as something else, do not know, or refused to answer this question. Of women in the pooled sample, 1.1%  were lesbian, 1.0%  were bisexual, 95.5%  were straight, and 2.5%  responded as something else, do not know, or refused to answer this question.Sexual orientation can be measured in surveys by asking about people’s sexual identities, behaviors, and/or attractions. In the NCVS, sexual identity was measured by asking, “Which of the following best represents how you think of yourself?” with the following response options, “lesbian or gay,” “straight, that is, not lesbian or gay,” “bisexual,” “something else,” or “I don’t know the answer” (variable name: V3084). Of men in the pooled sample, 1.6% (n = 535) were categorized as transgender and 99.9%  as cisgender.Gender identity was measured via a two-step procedure, where respondents are asked their sex assigned at birth and then asked their current gender identity . In the Sexual and gender identity measures were included in the survey after pre-implementation cognitive checks and during implementation checks such as focus groups, interviewer trainings, interviews with interviewers, and cognitive testing, which evaluated how the inclusion of these measures would affect overall data quality of the NCVS , 23.n = 10,533) were SGMs, 94.8%  were non-SGMs, and 3.1%  were Unknown/Other.For the aims of this study, we categorized respondents as a SGM if they either identified as lesbian, gay, or bisexual or if they were categorized as transgender. We categorized respondents as non-SGM if they identified as straight and were classified as cisgender. Respondents who identified as “something else” in the sexual orientation question or “none of these” in the gender identity question but otherwise were not an SGM, were categorized separately from non-SGMs and SGMs as “Unknown/Other.” We report results for this group in The NCVS measures the race of respondents with the following question and response options, “Please choose one or more races that you consider yourself to be: “White,” “Black or African American,” “American Indian or Alaska Native,” “Asian,”, or “Native Hawaiian or Other Pacific Islander.” The person-level file contains a summary measure of race including whether and what multiple categories of race were selected (variable name: V3023A).n = 388,359), non-Hispanic Black inclusive of multiracial or biracial persons , Hispanic , and other race or multiracial . For sample size purposes, we restrict our analyses to non-Hispanic White, non-Hispanic Black, and Hispanic respondents. Our decision to categorize multiracial or biracial non-Hispanic Black respondents as Black is to create an inclusive category reflecting an experience of potentially being perceived as Black. Research shows that the experience of blackness and anti-black prejudice are, in part, a function of other people’s perceptions of one’s race and that many black multiracial people describe experiences of social treatment aligned with monoracial black people’s reports  = 1.34, 5.16; Hispanic OR = 4.5, CI = 2.25, 6.71; White OR = 4.8, CI = 2.80, 6.76). However, the patterns of SGM differences in victimization are not the same in each racialized group for each subtype of violent victimization . Among Hispanic and White respondents, SGMs had higher victimization rates than non-SGMs in simple assaults , but these rates were not significant between Black SGMs and non-SGMs . With regard to serious violent victimizations, SGMs have higher rates than non-SGMs within each racialized group  and serious victimizations involving injury . However, the serious violence involving injury victimization rate is based on fewer than the observations for Black SGMs, and should not be considered a reliable estimate.We report victimization rates for select types of crime by race or ethnicity  and diffOR = 4.1, CI = 1.35, 6.85; Hispanic OR = 5.4, CI = 1.44, 9.41; White OR = 4.5, CI = 3.03, 6.06). Hispanic and White SGMs had higher rates of violent victimizations than non-SGMs involving strangers , but this was not significant between Black SGMs and non-SGMs . We find that among White and Hispanic populations, significant disparities exist between SGMs and non-SGMs in well-known and stranger violent victimization rates. We also find among Black populations there are significant disparities between SGMs and non-SGMs in victimization rates when the perpetrator is well-known to the victim.Victimization rates by victim-offender relationship are also reported  and diffOR = 2.2, CI = 1.46, 2.87) but not for Black males  and Hispanic males . However, the difference in victimization rates between LGB and straight males among White and Black men were significant  and Hispanic females  but not for Black females .Among females, White and Hispanic LB females have higher violent victimization rates than Black LB females. Significant disparities between LB females and straight females are present among White females , 175.8 , 201.1  victimizations per 1,000 people for Black, Hispanic, and White bisexual females, respectively. This resulted in significant disparities between bisexual females and straight females for Hispanic females  and White females  but not for Black females . Due to sample size limitations, analyses could not be performed for other LGB subgroups  by sex and race/ethnicity.Among LB females, the overall differences in victimization rates were primarily driven by bisexual respondents. The rates of violent victimization for bisexual females were 133.3 , but they were more likely to access professional help for feelings associated with the crime . When an incident was reported to police, Black , Hispanic , and White  SGM respondents were less likely to indicate that the perpetrator was arrested than their non-SGM peers. Only White SGM respondents were more likely to suspect the incident was a hate crime compared to their non-SGM counterparts .We tested for differences based on SGM status on characteristics of violent victimization reports within each racial group . There wThis study is among the first to use population-based data to examine criminal victimization—including simple violent victimizations, serious violent victimizations, and serious violent victimizations that involve injuries—among sexual and gender minorities at the intersection of race/ethnicity and sex. This study replicates prior research showing that SGMs have higher victimization rates than non-SGMs and extends prior work –6 by demOverall, there were notable differences in patterns of LGB-related differences in victimization rates at the intersection of sex and race. Among White respondents, the differences in violent victimization rates were significantly different by sex, with LGB White males and females reporting higher rates than their non-LGB counterparts. However, among Hispanic respondents, the LGB to non-LGB differences in victimization rates were only significant for females; among Black respondents, the rate differences were significant only for males. It is unclear what accounts for these differential rates of victimization at the intersection of sex, race and LGB identification. Regarding experiences with victimization among Black respondents, it could be that the overall higher rates of serious types of victimization among Black SGM people is driven by the experiences of Black LGB males. Similarly, it is possible that the overall high rates of victimization among SGM Hispanic respondents may be driven by higher rates among LGB females. For example, one study of sex and race differences in types of victimization showed that Black males had the highest levels of violent victimization and Hispanic females were highly likely to experience minor forms of victimization persistently across their lifespans . Future For this study, we combined subgroups of SGM people  and collapsed potentially important subtypes of victimization by people who are well-known to the respondent  which may have masked important intersections of experiences, such as rates of intimate partner violence among Black transgender women compared to all other groups see e.g. , 31. ForThere were racial differences in the relationship between SGM status and victimization characteristics. Namely, SGM Black respondents were the least likely to report victimization incidents to the police than their non-SGM counterparts. General population research has shown that Black women are more likely than White women to report intimate partner violence to the police despite existing highly strained relationships between Black communities and police departments, possibly as a function of the severity of violence being experienced . It is rOur study contributes to understanding how multiple social status categories may result in unique victimization rates and experiences. To understand this, we examined victimization rates between sexual and gender identity groups within the three largest racial/ethnic categories in the U.S. Due to the quantitative nature of the data and that the surveys are not designed to assess subgroup specific factors relevant to victimization at related to combinations of gender, race/ethnic and SGM groups, we are limited in describing the intersectional pathways that lead to such experiences [e.g. as discussed in S1 Appendix(DOCX)Click here for additional data file.S2 Appendix(DOCX)Click here for additional data file.


Epilepsy is a chronic brain disease that recurs during childhood, and more than half of adult epilepsy originates from childhood. Studies suggested that immunoglobulin G (IgG) glycosylation are closely related to neurological diseases. Here we analyzed the characteristics of the immunoglobulin glycosylation profile of children with epilepsy.Patients were recruited in Taian, Shandong Province from December 2019 to March 2020. Serum IgG glycome composition was analyzed by hydrophilic interaction liquid chromatography with ultra-high-performance liquid chromatography approach.The proportion of fucosylated glycans in total IgG glycans was 93.72% in the epilepsy patients, which was significantly lower than that in the control group (94.94%). A lower level of total monogalactosylated and digalactosylated glycans were observed in the epilepsy patients group (30.76 and 40.14%) than that in the controls (36.17 and 42.69%). There was no significant difference between the two groups in bisected GlcNAc glycans and sialylated glycans.The decrease of core fucosylation and galactosylation may promote the inflammatory reaction of the body and participate in the occurrence of epilepsy in children. Epilepsy is a chronic brain disease characterized by repetitive, paroxysmal and transient central nervous system dysfunction caused by excessive discharge of brain neurons . It has Due to the complex pathogenesis of epilepsy, different types of epilepsy have different symptoms and characteristics. Studies have shown that the accumulation of immune inflammatory damage may be the core mechanism of epilepsy . Immune N-glycosylation modification site on Asn297 in the constant region of IgG , which constitutes 10–20% of plasma proteins, plays an important role in the immune system to recognize and clear foreign antigens and pathogens . There in of IgG . N-glycofunction . The stafunction . Changesdiseases . AlthougFrom December 2019 to March 2020, we recruited epilepsy patients in Taian, Shandong Province, China, who fulfilled the International League against Epilepsy classification criteria  for ChilAll healthy children must meet the following inclusion and exclusion criteria: (1) no history of any drugs using in the past 2 weeks; (2) aged 1 to 14 years; (3) no cardiovascular illness, autoimmune disease, tumor, or infectious disease; (4) no symptoms such as fever; and (5) being treated for other mental diseases such as autism were excluded. All study participants provided written informed consent. The study was approved by the Ethics Committee of Tai’an Maternal and Child Health Hospital and was conducted in line with the Declaration of Helsinki.N-glycans release, labeling, and detection were executed as described previously  into 24 glycan peaks (GPs), according to our previous descriptions . The glycans were released with 2 units of PNGase F in 10 μL 5× PBS and incubated at 37°C for 20 h. Then, the incubated samples were evaporated in a vapor dryer . Right after the completion of this step, released glycans were labeled with 35 μL 2-AB fluorescent labeling mixture, included 2-AB , acetic acid , sodium cyanoborohydride , and dimethyl sulfoxide  at 65°C for 3 h and then purified, washed, and eluted using hydrophilic interaction liquid chromatography solid phase extraction. Finally, labeled IgG riptions . The ACQeviously . Statistp values reported were two-tailed. A p value of less than 0.05 was considered of statistical significance.Normal distribution of all analysis results was checked using the Kolmogorov-Smirnov test. Continuous variables underlying the abnormal distribution were represented as the medians (interquartile ranges). The difference of continuous variables between two groups was tested using the Wilcoxon rank-sum test. Statistical analyses were conducted using IBM SPSS statistical software, version 25.0 for Windows . All Clinical characteristics of the study are summarized in N glycan profiles were analyzed by hydrophilic interaction liquid chromatography with ultra-high-performance liquid chromatography (HILIC-UPLC), where 24 initial GPs (GP1–GP24) were obtained from each chromatogram. The differences of directly measured (GP1–GP24) and derived glycan compositions between epilepsy patients and healthy controls for the Chinese children were shown in Immunoglobulin G-We further calculated the derived glycans traits using the measurement data of the initial GPs, which consist of core fucosylation, bisecting GlcNAc, agalactosylation, monogalactosylation, digalactosylation trait, sialylation traits, and Gal-ratio traits . As listAs shown in With regard to galactosylation, the decrease of GP7, GP8, GP9, GP10, GP12, GP14, GP15, G2, and G1 were identified in the epilepsy patients . TherefoThe proportion of agalactosylated glycans in total IgG glycans was 29.04% in the epilepsy patients, which was significantly higher than that in the control group (20.63%). Meanwhile, a lower level of total monogalactosylated and digalactosylated glycans were observed in the epilepsy patients group (30.76 and 40.14%) than that in the controls  were higher in the epilepsy patients . NonetheN-glycan profile and investigated the disparate points of the IgG glycome in identifying individuals with epilepsy children using a case–control epidemiological approach.Whereas studies on glycosylation of human serum IgG as well as nervous system diseases such as Alzheimer’s disease are abundant, IgG glycosylation of epilepsy has been less studied. Particularly in epilepsy, to our knowledge, this is the first study that presents the This study aimed to identify changes in the peripheral serum IgG glycome of children with epilepsy that could represent an interphenotype of the disorder: a link between the genome, the environment, and the disease phenotype. Indeed, this study found that children with epilepsy had a different IgG glycosylation profile than controls.N-glycan structure and a core fucosylated N-glycan structure, as well as an increased relative abundance of a core fucosylated N-glycan structure, a bisected GlcNAc N-glycan structure and a high-mannitose N-glycan structure (GP5).Observing our classification model, individuals with epilepsy had a reduced relative abundance of GP7, GP8, GP9, GP10, GP12, GP14, GP15, GP16, and GP21, and an increased relative abundance of GP1, GP2, GP3, GP4, GP5, GP11, and GP13. Specifically, the model demonstrated that the presence of epilepsy pathology was predominantly explained with a reduced relative abundance of a galactose Epilepsy, as the third common chronic brain disease, is characterized by long-term susceptibility to seizures . NumerouThe Fc segment of Ig G is modified by glycosylation to mediate complement activation, antibody-dependent cell-mediated cytotoxicity (ADCC), etc., thereby regulating inflammation, affecting the body’s pro-inflammatory or anti-inflammatory effects, and then affecting diseases . The corThe deletion or reduction of galactosylated glycan at the end of IgG makes Ig G exposed at the end of sugar chain to acetylglucosamine, which is not easy to be cleared by phagocytes, leading to the decrease of binding force between antibody and FcγRIIB, activating complement and promoting the occurrence and development of inflammation . We founN-glycans was related to autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis  was higher than in healthy children; lack of nogalactosylation can activate the complement system and promote the occurrence of inflammatory response, reduce IgG anti-inflammatory response, and contribute to the pathogenesis of epilepsy. In summary, this study provides new insights into the pathogenesis of epilepsy in children, although further studies are needed.In conclusion, we presented the The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/The studies involving human participants were reviewed and approved by the Ethics Committee of the Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, China. The ethics approval was given in compliance with the Declaration of Helsinki. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.JL and GW contributed to the study concept and design. FS, HJ, MW, PL, and LJ contributed to the acquisition of subjects and/or data. YL, XC, and HZ contributed to the analysis and interpretation of data. JL, YL, LJ, and XC contributed to the preparation of the manuscript. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Maize is one of the most important crops for human and animal consumption and contains a chemical arsenal essential for survival: flavonoids. Moreover, flavonoids are well known for their beneficial effects on human health. In this review, we decided to organize the information about maize flavonoids into three sections. In the first section, we include updated information about the enzymatic pathway of maize flavonoids. We describe a total of twenty-one genes for the flavonoid pathway of maize. The first three genes participate in the general phenylpropanoid pathway. Four genes are common biosynthetic early genes for flavonoids, and fourteen are specific genes for the flavonoid subgroups, the anthocyanins, and flavone C-glycosides. The second section explains the tissue accumulation and regulation of flavonoids by environmental factors affecting the expression of the MYB-bHLH-WD40 (MBW) transcriptional complex. The study of transcription factors of the MBW complex is fundamental for understanding how the flavonoid profiles generate a palette of colors in the plant tissues. Finally, we also include an update of the biological activities of C3G, the major maize anthocyanin, including anticancer, antidiabetic, and antioxidant effects, among others. This review intends to disclose and integrate the existing knowledge regarding maize flavonoid pigmentation and its relevance in the human health sector. The comprehension of the maize flavonoid pathways is necessary not only for plant breeders that want to develop new pigmented maize varieties with better nutraceutical properties but also for any health and food scientists working with phenolic compounds. The diversity in the palette of color in maize seeds correlates with differences in the pigment, including carotenoids and flavonoids. We will deepen into these aspects to explain the impressive correlation between plant color, plant survival, and human health.Zea mays L.), flavonoids act as deterrents against herbivores, regulate pollen development, and also have defensive roles against UV-B radiation . Mu. MuZmCHSnd whip1 ,34. Indeflavones ,35. Meanlic acid .O to its α,β-unsaturated carbonyl  or triploid (endosperm) tissues increases the cyanidin-base anthocyanins  accumulation in salmon-colored silks . Th. Th44]. interval ,47. The interval . If therinterval . ZmDFR in the diversification of flavonoids is further exemplified by its interaction with multiple transcription factors . Th. Th53]. ocyanins . bz2 gene, a GST type III, is supposed to label the anthocyanin to be recognized by a vacuolar glutathione pump, and then the labeled anthocyanin is transported into the vacuolar lumen . Th. Th92].  earworm ,43. This[ZmRHS1) . The genWe will focus in this section on the genetic regulation of the two flavonoid subgroups in maize with the most relevance to the scientific community: anthocyanins and C-glycosylated flavonoids. Maize has been and continues to be a model organism for studying the genetics of anthocyanin accumulation and its regulation in plants. Therefore, most of the information generated on flavonoid regulation has been focused on one subgroup, and we will also focus primarily on anthocyanins. Flavonoid regulation must be related to the role of the MYB family transcription factors and, in the particular case of anthocyanins, the function of the MBW transcriptional complex . This seIn c1 (ZmMYB1) and pl1 (ZmMYB2), and the second couple is p1 (ZmMYB3) and p2 (ZmMYB55) [We begin this section by explaining the R2R3-MYB genes involved in anthocyanin biosynthesis . A comprZmMYB55) ,97,98.c1 and pl1 genes regulate the accumulation of anthocyanins [p1 and p2 accumulate 3-deoxyflavonoids, flavones, and phlobaphenes, without bHLH and WD40 proteins [p1 expression is performed in pericarp, cob, and tassel glumes, whereas p2 expression controls the accumulation of anthocyanins of anthers, and both genes produce the salmon-colored silks to repel corn earworm [p1 on the accumulation of phlobaphenes correlates with an augmented thickness of the pericarp and lower mycotoxin levels [The ocyanins ,105 by uocyanins . The forocyanins , and theocyanins . These Mocyanins . Howeverproteins ,43,109.  earworm ,111. Then levels . ZmbHLH gene sequences [r1 gene (ZmbHLH1) due to the observed effects of its diverse alleles, with multiple isoforms, on the regulation of anthocyanin pigmentation in anthers, scutellum, and the aleurone layer of endosperm [b1 gene (ZmbHLH2) modulates pigment accumulation in vegetative tissue, including the pericarp kernel, as in the case of the high-altitude purple maize varieties [The second member of the MBW complex is from the bHLH family. In the GRASSIUS database, there are a total of 175 sequences for maize. However, a recent genome-wide analysis for the bHLH family in maize found up to 208 equences . The firndosperm ,113,114.arieties ,116. in1 gene represents a classical gene that was supposed to express a bHLH protein. However, the genome-wide analysis of Zhang and collaborators did not identify it as a member of the bHLH family [a3 is known for negatively regulating the expression of b1 if a dominant A3 allele is present; however, aside from its genomic location, little is known about its mechanism and gene product [The H family . The domH family . The proH family . The loc product . pac1 gene that produces a protein with a WD40 repeat (WDR) motif that enables its capacity for DNA interaction [The third member of the MBW complex is the eraction . Mutantseraction ,118.Z. mays (Petunia and Arabidopsis [ZmPAL (8-fold) and ZmCHS (50-fold), but also those of anthocyanin biosynthetic and regulatory genes (up to 7- to 10-fold) [r1  and c1 and induces the accumulation of anthocyanins in the aleurone and scutella during seed maturation and germination, respectively [pl1 and r1 increases in seedlings under ultraviolet, blue, and white light treatments compared to that of the null alleles [Different environmental stimuli may influence the regulatory activities of MBW complexes, such as light, temperature, water/nutrient deficiencies, and other internal stimuli related to changes in hormone levels . UnfortuZ. mays  but focubidopsis . However10-fold) . Similarectively . Moreove alleles ,125. vp1 mutation, the embryo does not become dormant, and there is a suppression of anthocyanin pigmentation in the aleurone [Bemisia tabaci (Genn.)) infestation induced a strong response against drought stress in maize, enhancing the expression of jasmonic acid (JA) and anthocyanin biosynthetic genes in the roots and leaves of seedlings [Both light and temperature induction of anthocyanins require the co-supply of sucrose or other sugars . This sualeurone . Contraraleurone . Cytokinaleurone ,127. Whieedlings . The application of S-methylmethionine (SMM), a treatment to induce stress tolerance in plants, also stimulates the concentration of anthocyanins in maize seedlings and stems ,132. Theb1 [r1 [p1 [pl1 [Another well-studied mechanism of regulation for the members of the MBW complex is the phenomenon of paramutation . Paramutb1 , r1 [102 [r1 [p1 , and pl1[p1 [pl1 . These g[p1 [pl1 .mop1 gene, which codes for an RNA-dependent RNA polymerase that is necessary to epigenetically silence a paramutable allele [p1 of high-altitude landraces compared to inbred lines and induces higher expression of p1 on leaves, enhancing the plant capacity to overcome the photo-oxidative stress related to high altitudes [This production of siRNA depends on the e allele . The mece allele . Externaltitudes . Daucus carota) or sea buckthorn (Hippophae rhamnoides) indicates that the MYB mRNA is not degraded by miRNA [Arabidopsis thaliana, the expression of non-coding RNAs favors anthocyanin expression under abiotic stresses, such as phosphate or nitrogen deficiency [Other recently studied mechanisms of flavonoid regulation are those mediated by non-coding RNAs. Although this information is limited to maize, data obtained from another species may suggest a similar regulation mechanism. For example, the expression of long non-coding RNA in carrot , and they are the most abundant flavonoids present in pigmented maize varieties. Previously, we have reviewed and discussed the myriad of positive effects attributed to anthocyanin-enriched extracts, which include antioxidative, antimicrobial, antifungal, antihyperglycemic, antitumoral, and anti-inflammatory activities . CyanidiThe flavonoid profile corresponds to a specific allele combination that dictates which compounds will be present in the tissue. However, the environmental factors are the ones that deliver signals, through phytohormones, regulating their concentration. Those factors have an impact not only on the survival of the plant but also on food science in terms of nutritional value and health benefits. pr1. Considering the importance of maize anthocyanin genetics in producing a better pigmented maize variety, maize should be selected according to the intended food processes. For example, selecting deep-colored grains with pigmentation in the pericarp  is not adequate when the food product requires a nixtamalization process to obtain maize dough. In fact, seeds for red or purple maize dough differ only in the gene Recessive alleles or new mutations in genes controlling the upregulation of the enzymatic machinery or initial enzymatic steps of a flavonoid pathway produce colorless tissue. Thus, this allows the inclusion of other chemical pigments, such as carotenoids or chlorophylls, to be responsible for the tissue color instead of flavonoids. In addition, maize has a natural capacity to produce grain enriched with anthocyanins, but consumers normally prefer to consume maize without anthocyanins. For centuries, white or yellow seeds have seemed to be more appealing to human populations worldwide, except in some places that grow and conserve the pigmented maize landraces. Previous health research has demonstrated the effectiveness of anthocyanin consumption in preventing or managing diseases related to oxidative stress, although more studies are needed to confirm some proposed action mechanisms of flavonoids in human health.In this review, we have provided updated information regarding colorful phytochemicals, including anthocyanins, which exert first a physiological role in the plant but may also trigger diverse biological responses with the potential to improve human health.


Background: Pilomatrix carcinoma (PC) is a rare skin tumor arising from hair follicle matrix cells. It is locally aggressive with a high rate of local recurrence after surgical excision. Few cases in the literature have been described and the management is not well defined. Objectives: The aim of this study was to present two cases of PC located on the head and review the relevant literature about epidemiology, clinical and dermoscopic evaluation, characteristics of local and distant metastases, local recurrence rate and management of this rare skin tumor. Methods: We consulted databases from PubMed, Research Gate and Google Scholar, from January 2012 to November 2022. We reviewed the literature and reported two additional cases. Results: We selected 52 tumors in middle-aged to older patients located mostly on the head. Dermoscopy evaluation was rarely performed in the pre-operative diagnostic setting. The most definitive treatment was wide local excision, but local recurrences were common. In total, we observed 11 cases of recurrences and 9 patients with locoregional or distant metastases. Four patients received adjuvant radiotherapy, two patients needed chemotherapy and local cancer therapy and one patient received radiochemotherapy. Conclusion: Our reports and the review of the literature can provide a better awareness and management of this rare tumor. Pilomatrix carcinoma (PC) is a rare skin tumor arising from hair follicle matrix cells and it is most frequently located on the head and neck region of male patients (fifth to seventh decades) . PC corrPC usually presents as a rapidly growing nodular lesion and dermoscopy may be helpful for improving its recognition, even if the diagnosis of malignancy is based on histological examination.Few cases in the literature have been described and the management is not well defined. To better describe the epidemiologic characteristics, clinical features, therapeutic options and follow-up of this rare tumor, we reviewed the literature and reported two additional cases.The aim of this study was to present two cases of PC located on the head and to review the literature evaluating epidemiology , clinical and dermoscopic evaluation, characteristics of local and distant metastases, local recurrence rate and management (follow-up and treatment) of this rare tumor.We found the relevant literature by searching different databases: PubMed, Research Gate and Google Scholar. We used the following combination of key words: “pilomatrix carcinoma”, “pilomatrical carcinoma”, “malignant pilomatricoma”, from January 2012 to November 2022. In total, 48 papers were identified. Inclusion criteria were systematic review or meta-analysis of randomized controlled trials, review, retrospective comparative reviews/studies and case series. Exclusion criteria were laboratory studies and non-English translated articles. A wide review of the bibliography of each of the selected articles was performed. In total, 37 papers met our inclusion criteria, including 1 review ,36,37,38We present two cases of a PC on the head.The first patient, a 54-year-old man, arrived for consultation in our department for a fast-growing asymptomatic nodule localized in the left supraorbital area. Clinical examination revealed a solitary, reddish, firm raised nodule, 12 mm in diameter without locoregional lymphadenopathy a. DermosThe second case concerns an otherwise healthy 65-year-old women with an asymptomatic erythematous, firm, 14 mm in diameter nodule located on the left preauricular area a. DermosIn the last 10 years (from 2012 to 2022), 52 cases of PC have been described in the literature, making this tumor very rare. There was a male predominance with 29 male patients (55.8%) compared to 23 female patients (44.2%) . Age at presentation ranged from 8 months to 87 years . Lesions occurred most in the sixth and seventh decades (52%) .N = 32/52, 62%), followed by the upper extremity  trunk , lower extremity , neck  and genitalia . No patient had multiple lesions . Tumor diameters ranged from 0.5 to 15 cm . Rapid growth, either of new lesion or stable lesion from several months was the most frequent motivation for biopsy and diagnosis .Locoregional or distant metastases occurred in nine patients 17%) [% 7,16,1,22,34. TNew findings showed that metastases occurred in six patients with previously treated PC ,16,18,22Dermoscopic examination was reported in only three patients ,27,32. TAll 52 patients had a histological diagnosis of PC. A first incisional biopsy was performed in five lesions of the head and upper extremities (10%), followed by a wide local excision. Only one patient died before re-excision .In total, a wide local excision was reported for 32 lesions (62%). Mohs micrographic surgery (MMS) was chosen for four tumors ,20,21,23Eckhoff et al. excised the lesion and left the skin defect uncovered pending final pathology, then they re-excised after 12 days to obtain 5 mm margins and subsequently cover the skin with a graft . The patIn total, 13 PCs were simply excised, without reported margins of excision and one case was first excised and then re-excised to obtain 2 mm safety margin after diagnosis . In two Due to lymph node infiltration, one patient experienced a neck dissection ; insteadTwo patients needed chemotherapy (CT) and local cancer therapy ,34 and oRadiochemotherapy was performed in case of extensive local invasion and metastasis: first line CT therapy with 5-Fluorouracil and cisplatin, second line with gemcitabine and taxotere, third line with irinotecan and bevacizumab, fourth line with cyclophosphamide and vinblastine . A summaN = 11/52, 21%), at an average of 6 months after surgery (range 2 to 16 months) [N = 6/52, 6%), one case 2 months after surgery (the other one not reported) and 6 lesions simply excised recurred at an average of 6 months . One patient, with malignant PC with involvement of the base and margins of the specimen, refused radiotherapy post-surgery and presented recurrence and fatal metastasis after 16 months from diagnosis [In total 11 cases of recurrences were observed N = 11/5, 21%, at months) ,24,29,31N = 6/52, 12%) [N = 41/52, 79%) had a regular follow-up (range from one month to eight years), receiving biannual dermatologic visits and in some cases also had a radiological examination. The follow-up imaging procedures used were chest radiography [Follow-up information was not reported in six cases 52, 12%) ,25,32,352, 12% ,2iography ,31, CT siography , 18F-FDGiography , alternaiography , and radiography .One patient was lost to follow-up . Four paCharacteristics of the 52 cases of PC in the recent literature (2012–2022) are reported in In the literature, benign pilomatricoma shows a female predilection and occurs usually in children and young adults with a small peak of onset in the elderly , whereasEven if multiple pilomatricomas have been associated with some particular disease including Turner syndrome, Gardner syndrome, myotonic dystrophy, Steinert disease and sarcoidosis , we did Clinically, PC shares some features with pilomatricoma, in fact it is a firm asymptomatic nodule typically found in the head and neck area, but unlike the benign variant, PC frequently shows a rapid growth ,7. In prDermoscopy evaluation was rarely performed/reported in pre-operative diagnostic settings although it is a useful tool in the context of a rare and difficult to suspect tumor. The most frequent dermoscopic characteristics were purple/blue background with white/yellow blotches, irregularly-shaped telangiectasias, arborized vessels and focal ulceration. White/yellowish blotches can also be found in pilomatricoma because of the presence of calcifications and cornified substance, instead ulceration is rarely found in pilomatricoma and the arborizing vessels have never been observed in this benign tumor . Unlike Wide local excision was the most frequent therapeutic option due to the relative high recurrence rate reported in the literature . RadicalIn previous studies, distant metastases were uncommon and occurred in 10–13% of cases ,40. In tFurthermore, we observed three deaths resulting directly or indirectly from PC invasion.Adjuvant RT was used to treat local recurrence and metastatic disease and it was also recommended due to one close margin, after multidisciplinary discussion.Although some authors considered CT and RT to be not effective in disease control ,41,42, iFollow-up information was not reported in all cases, but the majority of patients received regular clinical examination. There are no well-defined recommendations for follow-up; however, the patients should be closely monitored with ultrasound and other imaging examinations if necessary. The role and the type of follow-up imaging are still unclear, it depends on the patient history and the clinical examination.PC is a rare skin tumor arising from hair follicle matrix cells. It is a lesion with non-specific features and dermoscopy evaluation can be helpful for improving the clinical suspicion. The excision of doubtful nodular lesions is mandatory especially in adults, because PC carcinoma has not only a strong tendency to recur locally, but it can also metastasize. However due to its rarity, there are no well-defined guidelines for the management. A complete surgical excision with clear margins is the best therapeutic option and a regular follow-up is recommended overall.These two case reports and the review of the literature can give a better awareness and management of this rare tumor.