Adopting a healthy lifestyle, including regular physical activity, is often part of interventions targeting childhood overweight and obesity. However, to properly inform the objectives of the intervention, reliable psychometric measures are needed to better understand children’s and their families necessities and characteristics.To evaluate the psychometric properties of the Physical Activity Parenting Practices questionnaire in a community sample of Portuguese parents of children aged 5–10, assess measurement invariance across children’s weight status, and construct validity.n = 125) completed the PAPP questionnaire 1 month later. Data analyses were performed using R’s lavaan (version 0.6–12) and psych (version 2.2.9) packages.Five hundred three parents completed the Portuguese version of the Physical Activity Parenting Practices (PAPP) questionnaire, a sociodemographic questionnaire, the Comprehensive Feeding Practices Questionnaire, and the Lifestyle Behavior Checklist. A subsample (r = .57 to r = .74.Confirmatory factor analyses revealed good psychometric properties for the PAPP’s single-factor Encouragement scale and the three-factor Discouragement scale. Configural, metric, and scalar invariance were found across parents of children with different weight statuses for both scales’ factor structures. Internal reliability ranged from α = .64 to α = .89, and test-retest reliability ranged from The constructs evaluated by PAPP questionnaire revealed adequate validity. The Portuguese version of the PAPP questionnaire is a reliable measure to assess relevant physical activity parenting practices, capable of differentiating the practices of parents with children of different weight statuses, and useful for both research and intervention purposes.The online version contains supplementary material available at 10.1186/s40359-023-01444-4. Childhood overweight (OW) and obesity (OB) are major public health challenges with an increasing prevalence worldwide over the last decades . The negOW/OB often results from an imbalance between energy consumption and expenditure and therefore can be prevented by adopting a healthy lifestyle, including regular physical activity (PA) . RegularChildhood OW/OB and related diseases are largely preventable . ParentsThe way specific parenting practices affect children’s engagement in PA requires further investigation and, in this regard, reliable and valid measures are crucial , 13. ValThe expert-informed PA parenting practices conceptual framework is empirically validated and developed to build a repository of relevant items to assess PA parenting practices . The catA conceptual framework was also developed in the context of child feeding practices . For thiThe Preschooler Physical Activity Parenting Practices (PAPP) is a self-report measure to identify practices used by parents to encourage and/or discourage pre-school children’s engagement in PA , 18. In In its original version , the meaA key concept related to parenting practices adopted by parents to manage children’s PA and feeding-related behaviors is parental self-efficacy. The use of ineffective parenting strategies is associated with low levels of parental self-efficacy , 22. ResThe purpose of the current study is to evaluate the psychometric properties of an adapted version of the PAPP questionnaire with parents of school-aged children. Specific objectives include: 1) assessing the factor structure of the PAPP scales in a community sample of parents of school-aged children; 2) testing measurement invariance of the PAPP scales’ factor structures across children’s weight status based on BMI z-scores ; and 3) evaluating the construct validity by assessing the association between PAPP scales’ factors and related constructs, namely parents’ feeding-related practices and parents’ self-efficacy. Considering the similarities between the PA and feeding practices’ conceptual frameworks, results are expected to reveal significant associations between practices categorized in each domain within the respective conceptual framework , 16. In M = 7.68, SD = 1.32) recruited from seven public school clusters in the North of Portugal, one of the regions with the highest prevalence of childhood OW/OB in the country [n = 428, 85.1%), in average 37.90 years old (SD = 5.58), with 11.54 years of schooling (SD = 3.90), and with a thin or normal weight status , as per their report. Most of the children  were enrolled in the second, third or fourth grades , and had a thin or normal weight status , as per their caregivers’ report. Further details on the sociodemographic characteristics of the sample are presented in Table SParticipants were 503 parents or caregivers of children aged 5 to 10  . School With the collaboration of the schoolteachers, 740 parents/caregivers were invited to participate in the study. Inclusion criteria were being a parent/caregiver of a child aged 5–10 years, and having basic language skills in Portuguese. All participants were informed about the study, and those who agreed to participate signed an informed consent form. Parents completed the printed assessment protocol during school evaluation meetings. Those who could not attend the evaluation meeting received the printed assessment protocol through their child’s classroom teacher, completed the questionnaires at home, and then returned the protocol in a sealed envelope to the research team through the teacher.SD = 8.72) after the first assessment wave. Data collection took place in 2019, from April to July.A total of 526 parents completed the printed assessment protocol . Only 503 were considered, as 23 questionnaires were returned blank, or were completed incorrectly. Even though the original study used a 2 weeks period for the test-restest reliability, in the current study, parents were invited to complete the PAPP again 1 month after the first assessment protocol. The longer period for the test-retest reliability evaluation was choosen given that in the measure’s instruction parents are asked to answer about their specific PA parenting practices over the last 30 days. If a shorter period was considered, the possibility of overestimating the temporal stability of the PAPP constructs had to be acknowledged. In addition, the literature on research methods also describes that test-retest reliability can be evaluated in intervals up to 4 weeks . A totalParents completed a sociodemographic questionnaire about the sex, age, education, height, and weight of their children, themselves and their partners. Children’s BMI z-scores were estimated according to the WHO reference . CaregivThe PAPP was translated into European Portuguese and adapted to be used with parents of school-aged children aged 5–10. Details on the translation and adaptation procedures are described elsewhere .The PAPP is a self-report questionnaire that evaluates the frequency of parental practices that encourage and discourage children’s engagement in PA . The enc2807 = 1363.12; p < .001; CFI = .91; TLI = 0.90; RMSEA = 0.04; SRMR = 0.05) and Cronbach’s alpha values ranged from .55 (Food as reward) to .87 (Monitoring).The CFPQ is a self-report instrument, that assesses specific parenting practices related to feeding, among parents of children aged between 18 months and 8 years . It was 2(154) = 533.01; p < .001; CFI = .90; TLI = .88; RMSEA = .070; SRMR = .073) and Cronbach’s alpha values ranged from .90  to .92 .The LBC , 31 is aConfirmatory factor analyses (CFA) were performed to evaluate the single-factor structure and the four-factor structure of the PAPP’s Encouragement and Discouragement scales, respectively. The dataset included missing data, which appeared to be missing completely at random (MCAR), as described in the results section. To deal with missing data, CFA were performed using the full information maximum likelihood estimation method. For model fit evaluation, CFI > = .95, TLI > = 0.95, RMSEA <= .06, and SRMR ≤ .10 were used as indicators of good fit to the data, CFI values from .90 to .94, TLI values from 0.90 to 0.94 and RMSEA values from .07 to .08 were used as indicators of acceptable fit , 33. AddMeasurement invariance for each factor structure was tested by performing CFA multigroup comparison according to children’s BMI z-score . Cross-group constraints were set, and the more restricted models compared with the less restricted ones , for conTo evaluate the factors’ reliability, Cronbach’s α values were obtained considering .70 or higher as indicative of an adequate reliability . ConvergM = 1.51%, SD = 5.45). A multiple regression analysis evaluating the sociodemographic and anthropometric characteristics of the children and parents as predictors of the percentage of missing values per participant was performed. Results  = 1.73, p = .054) showed that none of the variables in the dataset relate to the missing data, suggesting that the missingness pattern is completely at random (MCAR).The items’ descriptive statistics are presented in Table Sχ2 (90) = 594.08, CFI = .83, TLI = 0.80, RMSEA = .11, SRMR = .06, with standard factor loading values (SFL) ranging from .39 to .74. A second model was then tested (Model 2), including items residual covariance between six pairs of items. Model E2 revealed an acceptable model fit, χ2(84) = 323.28, CFI = .92, TLI = 0.90, RMSEA = .08, SRMR = .05  was tested with 15 items (Model 1) . The sinp < .05, **p < .01, ***p < .001.Standardized factor loadings, residual variance and residuals’ correlations for Model 2 – PAPP-E; *n = 125), revealing marginally acceptable fit (χ2(84) = 178.39, CFI = .84, TLI = 0.80, RMSEA = .10, SRMR = .07). The scores of the factor in each assessment wave were computed from the SFL and the correlation coefficient  revealed a temporal stability below appropriate for the Encouragement scale.The CFA was then replicated with the data from the second assessment wave (χ2(71) = 124.27, CFI = .98, TLI = 0.97, RMSEA = .04, SRMR = .04 (Table χ2(51) = 82.85, CFI = .99, TLI = 0.98, RMSEA = .04, SRMR = .04 (Table p < .001), as well as between Psychological Control and Safety Concerns . Reliability analysis yielded acceptable internal consistency for Promote Screen Time (α = .79) and Psychological Control (α = .73), and relatively low for Safety Concerns (α = .64). A CFA of the final model was performed with the data from the second assessment wave and revealed good fit to the data (χ2(51) = 68.26, CFI = .97, TLI = 0.96, RMSEA = .05, SRMR = .06). The test-retest reliability evaluation deemed acceptable temporal stability for the factors Promote Screen Time , Psychological Control  and Safety Concerns .The test of the four-factor structure of the discouragement scale included 14 items (Model 3) and revealed good fit to the data, p < .05, **p < .01, ***p < .001.Standardized factor loadings, residual variance, and latent factors’ correlations for Model 4 – PAPP-D; *n = 278) vs. overweight/obese (n = 189). Configural, metric and scalar invariance were found between groups for encouragement and discouragement scales . In the adaptation of the questionnaire to parents of school-age children, the item related to the use of a stroller was discarded, and as a consequence the factor Promoting Inactivity was not included in the model because with only two items, the factor could not be estimated .The three-factor model structure kept the original items composition and presented acceptable reliability, with the exception of the factor Restriction for Safety Concerns, which revealed the lowest internal consistency. This may be consequence of the low SFL of item 31 (“How often do you let your child go outside to play around your home?”) which in turn, may be related with some heterogeneity of participants’ answers according to their area of residence and type of housing . These characteristics can potentially discourage PA parenting practices, especially for those living in urban areas, therefore future studies should explore how the area of residence and type of housing impact the child’s autonomous activity/play around their homes.The current study’s results also found configural, metric, and scalar invariance across parents of children of different weight statuses  for the factor structure of both PAPP scales. Such findings indicate that the parents assessed the constructs in the scales similarly, regardless of the weight status of their child. With these results, it can be ascertained that the PAPP, as an instrument, can distinguish the PA parenting practices of parents of children with different weight statuses. These findings show the utility of the questionnaire for research and intervention purposes.The study’s results also suggest the validity of the constructs assessed by the PAPP’s scales. Parents’ PA and feeding practices were found to be related, which is consistent with the research showing the importance of a balance between energy consumption and expenditure when adopting a healthy lifestyle . As expeConcerning parenting practices discouraging children’s engagement in PA, the findings suggest that the parents who use more often practices placed in the Neglect/Control domain of PA practices , such asThe associations between discouraging PA and inadequate feeding practices, framed within the Neglect/Control domain of PA practices  and the In the current study, discouraging PA practices were negatively related to parents’ confidence to deal with child’s lifestyle behavior problems. This is consistent with previous research suggesting that ineffective parenting strategies are linked to lower levels of parental self-confidence; e.g., parents who use psychological control practices related to PA and promote more screen time feel less confident when facing difficult lifestyle situations .Parents, as main caregivers, are responsible for most decisions related to children’s lifestyle. Practices regarding children’s PA and feeding are related, reflected in the pattern of care provided by the parents and, to some extent, characterize families’ lifestyles. The findings suggest that by promoting encouraging and preventing discouraging PA parenting practices, parents may adopt healthier, and reduce inadequate feeding practices, increasing their self-efficacy in dealing with children’s lifestyle behavior problems. Nevertheless, given the cross-sectional and correlational nature of the study, conclusions about the directionality of the associations cannot be drawn and should be focus of attention in future prospective research.The current study was the first to use a version of the PAPP adapted to evaluate PA parenting practices with parents or caregivers of school-aged children. Other strengths of the current study include the sample size, the rigorous procedures undertaken to ensure a distributed sample, and the analytic plan which included structural equation modelling. However, there are also some limitations. A first one relates to mothers being the main informants. Given the well-known influence of fathers over their children’s PA, the inclusion of more fathers as informants would be desirable to study measurement invariance across parents. A second limitation regards the use of self-report measures only. Future studies should collect data using other data collection methods , including multiple informants, and also assessing the characteristics of the neighborhood that can influence PA parenting practices .The Portuguese version of PAPP comprises a single-factor Encouragement scale and a three-factor Discouragement scale. Overall, the instrument revealed good psychometric properties in a Portuguese sample and seemed to be a reliable and valid measure to assess PA parenting practices among parents of children aged 5–10. The constructs assessed had the same meaning for parents, regardless of their children’s weight status. The PAPP construct validity was supported by its associations with parents’ feeding practices and parents’ confidence to address children’s lifestyle behaviors. The Portuguese version of the PAPP can thus be useful for both research and practice focusing on childhood OW/OB.Additional file 1 : Table S1. Sociodemographic characteristics of the sample (N = 503).Additional file 2 : Table S2. Descriptive statistics for each PAPP item (N=503).Additional file 3. STROBE Statement checklist of items that should be included in reports of cross-sectional studies.Additional file 4. Sampling strategy, recruitment process, and strategy to handle missing data.


Visceral obesity and insulin resistance contribute to developing cardiometabolic syndrome (MetS). We investigated the predictive abilities of lipid accumulation product (LAP), waist circumference‐triglyceride index (WTI), and triglyceride‐glucose (TyG) index for MetS screening among the general Ghanaian adults.The final prospective analysis included 4740 healthy adults aged 30–90 years from three communities comprising Ejisu, Konongo, and Ashanti Akim Agogo in Ghana. Self‐structured questionnaire pretested was used to collect sociodemographic, anthropometric, and clinical data. Blood samples were taken after fasting to measure glucose and lipid levels. LAP, WTI, and TyG were calculated from standard equations. MetS was defined by the International Diabetes Federation criteria. Receiver operating characteristic (ROC) curves and multivariable logistic regression were utilized to evaluate the potential of the three indices in identifying MetS.Of the 4740 participants, 39.7% had MetS. MetS was more common in females (50.3%) than in males (22.2%). Overall, LAP ≥ 27.52 yielded as the best index for MetS with the highest area under the ROC curve (AUC) (0.866). At cut‐off LAP point of ≥23.87 in males and ≥33.32 in females, an AUC of 0.951 and 0.790 was identified in MetS prediction, respectively. LAP was an independent risk measure of MetS for both males (45.6‐fold) and females (3.7‐fold) whereas TyG was an independent risk measure for females (3.7‐fold) only.MetS is increasing among the general adult population. LAP and TyG are important sex‐specific risk measures to screen for MetS among the general adult population in our cohort. Triglyceride‐glucose (TyG) and waist circumference‐triglyceride (WTI) indices are simple yet useful surrogate predictors of IR and have been shown as strong predictors for MetS in the Korean,Despite these novel findings and the usefulness of these measures in other populations, no study to the best of our knowledge, have simultaneously compared the value of these indices  for screening MetS among healthy Ghanaian adults. It is in light of this that this study aimed to explore the potential of these three easily calculated and cheap indices as predictors of MetS among the general Ghanaian adult population.22.1This was a cross‐sectional study carried out across multiple centers from January 2022 to September 2022. We enrolled participants from three communities namely, Ejisu, Konongo, and Asante‐Akim Agogo in the Ashanti Region, Ghana. Initially, cities were split into geographic zones, and then these zones were further divided into smaller units called primary sampling units. These units were randomly chosen for further sampling. The participants were evaluated using a standardized procedures that included in‐person interviews and clinical exams. These evaluations were conducted at the study centers and followed standard protocols.2.2n = 199), blood pressure (n = 44), fasting plasma glucose (n = 23), or lipid levels (n = 121) and those aged below 30 years and above 90 years (n = 432) were excluded from this study. The final analysis included a total of 4740 adults.A total of 5559 adults were initially recruited into the study. Healthy noninstitutionalized adults aged 30–90 years and residing in the Ejisu, Konongo, and Asante‐Akim Agogo communities were included in the study. Participants with known chronic illness and infections and were either attending medical check‐up or taking medications were excluded from the study. Other exclusion criteria were participants with missing data for anthropometric measurements (2.3α), 105 adults was the determined sample size. We extrapolated the population size to 4740 to increase the study's statistical power.With 7.4% MetS prevalence,2.4Approval was sought from the Committee on Human Research, Publication and Ethics (CHRPE) at the School of Medical Sciences of the Kwame Nkrumah University of Science and Technology (KNUST), Ghana and we obtained written consent from every participant before the study began.2.5Before recruiting participants, the purpose of the study was exaplained to them, and only those who consented to participate were included. A questionnaire was used to gather data on sociodemographic characteristics, including age and sex.2.6Trained nurses followed the American Heart Association (AHA) guidelines to measure blood pressure with a mercury sphygmomanometer and stethoscope.2.72.7.1(R) 400 plus Automated Chemistry Analyzer as per manufacturer's instructions (Fortress Diagnostics Ltd.). Low‐density lipoprotein cholesterol was estimated using the Friedewald formula.Blood samples of 5 mL were collected from participants following an overnight fast. The serum separator tube contained 4 mL, and the fluoride‐oxalate tube contained 1 mL. After centrifugation, serum and plasma were stored at −80°C until assayed for FPG, HbA1C, TC, TG, and HDL‐C using the INTEGRA2.7.2Participants' weight (in kg) was measured using a bathroom scale (Zhongshan Camry Electronic Co. Ltd.) while wearing light clothing. To measure their height (in cm), a Seca 213 mobile stadiometer was used while they wore no shoes. Measuring tape was used to measure WC at the midpoint between the inferior angles of the ribs and the suprailiac crests. Hip circumference was measured at the widest point of the buttocks. Calculated indices included2.82.8.12) along with two of the following criteria: TG ≥ 150 mg/dL, low HDL‐C  or ongoing therapy for dyslipidaemia, BP ≥ 130/85 mmHg or ongoing therapy for hypertension, FPG ≥ 100 mg/dL or ongoing diabetes therapy.Metabolic syndrome was defined by IDF criteria2.8.2U‐test to evaluate differences between groups, while χ2 test was used to examine the relationship between sociodemographic characteristics  and MetS. Receiver operating characteristic (ROC) curves and multivariable logistic regression were utilized to assess the potential of all three indices in identifying MetS. The cut‐off values for the indices generated on the ROC curves analysis were stratified into high and low and logistics regression analysis were performed. All statistical results obtained were deemed significant at p < 0.05.Data was entered into Microsoft Excel 2016, and SPSS v26 (SPSS Inc.) and GraphPad Prism 8.0.1 (GraphPad LLC) were utilized for analysis. Categorical data were expressed as frequency (proportion). Continuous data were checked for normality using Kolmogorov–Smirnov test. Nonparametric data were expressed as median (interquartile range). Nonparametric data was analyzed with Mann–Whitney 33.1p < 0.0001). However, HDL‐C levels were significantly lower in MetS group than non‐MetS group. LDL‐C did not differ between the two groups. In addition, MetS group had significantly elevated anthropometric indices    males and 2938/4740 (62.0%) females were enrolled in the study. The female to male ratio for MetS prevalence was 4:1. The median age of participants was 55 years for the non‐MetS group and 57 years for the MetS group. Significantly higher median levels of FBS, HbA1c, TC, TG, VLDL‐C, coronary risk, SBP, and DBP were observed in subjects with MetS   of the participants were diagnosed with MetS. MetS and its components were more prevalent in females than males. Additionally, MetS varied significantly between male and female subjects. Of the individual MetS components, only central obesity and reduced HDL‐C differed between both sexes  whereas that between LAP and WTI was not significant. This shows that LAP was a stronger predictor for MetS than the other indices.For males, the AUC values for LAP and TyG were significantly different   Table .3.6After adjusting for age, males with LAP ≥ 23.87 were 45.6 times increased odds of having MetS compared to those with low LAP levels (<23.87).p = 0.007 versus aOR = 3.66 (1.10–12.23), p = 0.035.In the adjusted model for females, the higher risk group of LAP (LAP ≥ 33.12) and TyG (TyG ≥ 8.74) were at 3.7 times increased odds of having MetS compared to those in the lower risk group respectively, adjusted odds ratio (aOR) = 3.67 (1.42–9.54), LAP was the independent predictor for MetS in both males and females whereas TyG was the independent predictor of MetS in females only Table .4In this study, explored the potential of three easily calculated and cost‐effective obesity indices—LAP, WTI, and TyG index—as predictors of MetS among the Ghanaian healthy adult population. Among the healthy adult population, 39.7% were screened with MetS, being more prevalent in females (50.3%) compared to males (22.2%). Our study also revealed that LAP, WTI, and TyG could predict subjects with MetS per the ROC curve analysis: Their AUC values exceeded 0.70 in both sexes. LAP showed the highest diagnostic potential, followed by WTI, and then TyG. However, only LAP could independently predict MetS in both sexes after age was adjusted for in the multivariable logistic regression. TyG could independently predict MetS in females only. This suggests that LAP and TyG may be useful sex‐specific indices for MetS prediction.The current study found a significant proportion (39.7%) of the participants to have MetS. However, comparing the prevalence of MetS in different studies is difficult because of the varied definitions used in the literature. Compared to this current study, several studies conducted in different regions, such as the United States,Our study also reveals LAP as the best measure to discriminate MetS among the subjects as supported by our ROC analysis and logistic regression analysis: LAP showed the highest AUC of 0.951, 0.790, and 0.866 for males, females, and both sexes respectively; it could also independently predict MetS among the subjects in the adjusted logistic regression model. In this study, LAP proved “outstanding” (AUC ≥ 0.9) for MetS prediction in males but proved “excellent” (0.8 ≤ AUC < 0.9) in females per Homer and Lemeshow's criteriaFurthermore, the optimal cut‐off of LAP for predicting MetS in this study was ≥23.87 for males and ≥33.32 for females. Much higher cut‐off values of LAP were observed among the US adults ,Our next finding that TyG could be a better predictor of MetS in females only is supported by our ROC and logistic regression analysis: TyG yielded an AUC of 0.857, 0.761, and 0.794 for males, females, and both sexes, respectively; it could independently predict MetS among only female subjects in the adjusted logistic regression model. We found that TyG was “excellent” (0.8 ≤ AUC < 0.9) for MetS prediction in males but it was “acceptable” (0.7 ≤ AUC < 0.8) in females per Hosmer and Lemeshow's criteria for AUC. This signifies that TyG could be useful for MetS prediction in female subjects, though, weaker than LAP.TyG index has been linked to an increased risk of cardiovascular events.Our study revealed WTI as the least potent of all the three indices studied: it yielded an AUC of 0.893, 0.765, and 0.816 for males, females, and both sexes respectively but failed to independently predict MetS in both sexes after age was controlled.In contrast to our finding, Liu et al., who first proposed WTI found it to be closely related to MetS, with an “excellent” (0.8 ≤ AUC < 0.9) AUC for MetS prediction in both male and female Chinese population.An advantage of this study is that it is the first of its kind to be conducted in the Ghanaian population. This study had limitations noteworthy to mention. First, our study is a cross‐sectional study and as such conclusions may change over time. A future prospective study is required to evaluate how the present findings affect MetS. Second, only Ghanaians were recruited and so results may not apply to other nationalities. Finally, this study adopted IDF 2005 criteria for MetS diagnosis. Thus, whether other MetS criteria will yield reproducible results requires further investigation.In conclusion, we explored the potential of three easily calculated and cheap obesity and lipid‐related indices namely LAP, TyG, and WTI in identifying MetS in apparently healthy Ghanaian adults. LAP yielded as the best marker for MetS with the highest AUC and was an independent predictor of MetS in both males and females. However, TyG was an independent predictor of MetS in females only. MetS is becoming more common among the healthy adult population. LAP and TyG are important gender‐specific risk measures to screen for MetS among the apparently healthy population in our cohort.Enoch O. Anto: Conceptualization; Data curation; Investigation; Methodology; Project administration; Supervision; Writing—review and editing. Joseph Frimpong: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Writing—review and editing. Wina I. O. Boadu: Conceptualization; Investigation; Methodology; Supervision; Writing—review and editing. Emmanuel E. Korsah: Formal analysis; Investigation; Writing—original draft; Writing—review and editing. Valentine C. K. T. Tamakloe: Investigation; Software; Visualization; Writing—review and editing. Ezekiel Ansah: Data curation; Formal analysis; Software; Writing—original draft; Writing—review and editing. Stephen Opoku: Formal analysis; Methodology; Writing—original draft; Writing—review and editing. Emmanuel Acheampong: Investigation; Methodology; Resources; Writing—review and editing. Evans A. Asamoah: Formal analysis; Methodology; Writing—original draft; Writing—review and editing. Patience Nyarkoa: Methodology; Writing—review and editing. Eric Adua: Methodology; Writing—review and editing. Ebenezer Afrifa‐Yamoah: Investigation; Methodology; Supervision; Writing—review and editing. Max E. Annani‐Akollor: Methodology; Supervision; Writing—review and editing. Christian Obirikorang: Methodology; Supervision; Writing—review and editing.The authors declare no conflict of interest.The lead author Enoch Odame Anto affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned  have been explained.


Drosophila. The underlying mechanism of how neural stem cells prevent premature nuclear Pros remains largely unknown. Here we identified that two pipsqueak family genes, distal antenna (dan) and distal antenna-related (danr), promote the proliferation of neural stem cells  in third instar larval brains. In the absence of Dan and Danr (dan/danr), the NBs produce fewer daughter cells with smaller lineage sizes. The larval brain NBs in dan/danr clones show premature accumulation of nuclear Prospero (Pros), which usually appears in the terminating NBs at early pupal stage. The premature nuclear Pros leads to NBs cell cycle defects and NB identities loss. Removal of Pros from dan/danr MARCM clones prevents lineage size shrinkage and rescues the loss of NB markers. We propose that the timing of nuclear Pros is after the downregulation of dan/danr in the wt terminating NBs. dan/danr and nuclear Pros are mutually exclusive in NBs. In addition, dan/danr are also required for the late temporal regulator, Grainyhead (Grh), in third instar larval brains. Our study uncovers the novel function of dan/danr in NBs cell fate maintenance. dan/danr antagonize nuclear Pros to prevent NBs aging in Drosophila larval brains.Neural stem cell aging is a fundamental question in neurogenesis. Premature nuclear Pros is considered as an indicator of early neural stem cell aging in  The following Gal4 lines used to analyze the gene expression patterns or to overexpress the genes in NBs: ase-Gal4, wor-Gal4 (Bloomington stock center). The UAS-CD8::GFP line (THJ0080) was used to label the cells. The balancer lines used in this paper were TM3sb/TM6B and Gla/Cyo (Bloomington stock center). FRT 42D and FRT 82B were used to induce clones in larval brains as controls.All fly stocks and crosses were maintained at 25°C. We used the following  danemS3 . We reco82B/TM6B  and pros2.2.Drosophila embryos were collected over a period about 6–8 h and then the embryos were kept at room temperature (RT). Heat-shock was conducted at around 24–30 h after larval hatching (ALH) at 37°C in water bath for between 30 min to 1 h as indicated. Dissection of the larval brains was conducted at the indicated time points  based on the corresponding genotypes, and then fixed for immunostaining.MARCM clones were generated according to the standard method . Once th2.3.Brains were fixed 15 min at 4% paraformaldehyde in 0.1 M HEPES pH 7.4. Antibody staining was performed according to the reported methods . The pri2.4.t-test and ordinary one-way ANOVA or 2way ANOVA test were performed to assess differences. A p value of <0.05 was considered statistically significant. Three replicates were conducted in each statistic group. All of the statistical details of experiments can be found in the figure panels and legends.Statistical analysis was performed in Graphpad Prism9. Data are presented as the mean ± SEM. Unpaired Student’s 3.3.1.dan and danr are Drosophila pipsqueak domain family genes and share highly conserved protein sequences . To explore the function of dan/danr in CNS development in larval brains, we generated dan/danr MARCM clones in NBs. Since type I NBs represent the majority of NBs in the central brain, we only focused on type I NB clones. We found the mutant NB lineages to be smaller in size than those of controls (dan/danr clone contained only 20 ± 7 (n = 13) cells whereas approximately 85 ± 13 (n = 14) cells were found in the controls at 96 h ALH  of the NBs in dan/danr MARCM clones presented with nuclear Pros at 96 h ALH, while no corresponding presence of Pros was observed in any of their counterparts in wt controls (n = 30). These observations suggest that lack of dan/danr leads to nuclear Pros accumulation in larval brain NBs.The observation of smaller lineages of ell fate . We foundanr NBs –C. Approdan/danr NBs during the development. dan/danr clones showed nuclear Pros in the NBs between 72 h to 120 h ALH, with a peak at 96 h ALH (n = 60) at 72 h ALH, 61% (n = 92) at 96 h ALH, and 26% (n = 69) at 120 h ALH  of NBs were labeled by Edu in dan/danr clones whereas the ratio of Edu positive NBs was almost 70% (n = 91) in the controls  compared to 68% (n = 51) in the controls (n = 92) in dan/danr clones but 82% (n = 102) in the controls (Previous studies have reported that NBs with nuclear Pros often exhibit cell cycle defects . To dete96 h ALH –E. Only controls . We notecontrols . At 120 controls .n = 95) were PH3 positive in dan/danr clones as compared with the controls  at 96 h ALH (dan/danr NBs being 46% (n = 95) at 72 h ALH, and 52% (n = 92) at 120 h ALH in dan/danr clones compared to 42% (n = 90) at 72 h ALH and 35% (n = 101) at 120 h ALH in the controls. Our Caspase-3 staining results also clarified that no apoptosis had occurred in the dan/danr clones  of the large cells in dan/danr MARCM clones were not labeled by anti-Ase at 72 h ALH (n = 61) of NBs were shown to be Ase negative at around 96 h ALH, with the percentage being 44% at 120 h AHL (n = 76) . This observation suggests that the NBs had gradually lost their NB identity in dan/danr mutant clones. Meanwhile, Dpn immunofluorescence staining showed a similar tendency in that the ratio of Dpn negative NBs increased from 72 h ALH to 120 h ALH in dan/danr clones (NB terminating features include the presence of nuclear Pros and the loss of NB markers . We exam72 h ALH –D. This 72 h ALH . About 1(n = 76) . Howeverr clones –C,E.3.5.dan/danr clones with Ase and Pros at different time points. The ratios of nuclear Pros and Ase double positive NBs increased from 72 h to 96 h ALH (n = 57) to 58% (n = 76), respectively. This suggests that the appearance of nuclear Pros occurs earlier than the disappearance of Ase expression. It is known that heat-shock induced overexpression of Pros in wt NBs leads to nuclear Pros accumulation  showed Ase positive in pros/dan/danr triple mutant clones, whereas there were about 82% (n = 43) NBs showing Ase positive in their dan/danr double mutant counterparts (n = 30) exhibited Dpn expression in pros/dan/danr clones, while only 82% (n = 37) NBs showed Dpn in the dan/danr NB clones (pros/dan/danr NB were larger than those of dan/danr clones (n = 11) cells in each pros/dan/danr clone, whereas only 17 ± 8 (n = 9) cells in each of the dan/danr clones (p = 0.009)  . These o3.6.dan/danr at the early pupal stage when nuclear Pros appears in NBs prior to their termination. We firstly performed Dan/Danr and Pros double labeling in the wt third instar larval brains and found that Dan/Danr were present in the NB nuclei and that no nuclear Pros was detectable  of the dan/danr NBs failed to express Grh at 96 h ALH  of the NBs exhibited smaller cell sizes (< 8 μm) and about 29% (n = 79) of the NBs showed nuclear Pros in grh MARCM clones at 96 h ALH (dan/danr NBs showed that about 24% (n = 81) of NBs displayed smaller cell sizes (< 8 μm) in dan/danr clones at 96 h ALH  Pros accumulation in nuclei; (ii) loss of NB markers (Ase and Dpn); and (iii) cell cycle alteration. Among these, NB molecular marker loss and cell cycle alteration are the consequence of the presence of nuclear Pros in  and Dpn . Our datgression . Thus, wdan/danr mutant NBs and the overexpression of Pros in wt NBs results in the detection of nuclear Pros and suppression of Dan/Danr. These observations suggest that Dan/Danr and nuclear Pros appear to antagonize each other and are mutually exclusive in NBs.At the larval stage, Dan/Danr are mainly expressed in NBs while nuclear Pros remains undetected. At the early pupal stage, Dan/Danr are decreased in NBs, just at the time point that Pros signals begin to present themselves in the nuclei of the NBs. In our confocal images, Dan/Danr positive NBs failed to show nuclear Pros signals, and vice versa. Premature nuclear Pros is only detected in dan/danr and nuclear Pros, we checked RanGAP expression in dan/danr NBs. We discovered that Dan/Danr is expressed in rangap NBs in the larval brains. While in dan/danr NBs, the RanGAP was absent  might be involved in this process.Our previous study reported that the lack of RanGap facilitates nuclear Pros accumulation in NBs . In ordes absent . We propgrh MARCM clones, about 60% of the NBs exhibited smaller cell sizes. The Grh expression partially depends on Dan/Danr. In dan/danr clones, the ratio of Grh negative NBs is about 26%. This coincides with the percentage of NBs displaying smaller cell sizes. This may reflect that Grh operates genetically downstream of Dan/Danr and acts to prevent NB cell size shrinkage.Grh is a late temporal regulatory factor and acts to prevent premature termination of NBs . We showIn conclusion, our study demonstrates a novel function of pipsqueak domain transcription factors Dan/Danr in NBs fate maintenance in the third instar larval brains . In the The original contributions presented in the study are included in the article/HA, YX, and YC conceived the idea of the project and designed the experiments. HA performed the experiments contributed to data analysis. YY, XR, and MZ conducted the genetic experiments. FZ, HZ, and RS generated the antibodies. YB and TL contributed to project discussion and coordination. HA wrote the initial manuscript. YX revised the manuscript. All authors read and approved the final manuscript.This work was funded by the Chinese National Natural Science Foundation (32000506), The Youth Innovation Team of Shaanxi Universities, and the Natural Science Special Project of Shaanxi Education Department (18JK0919).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.


Background: After introducing Covid‐19 vaccines, a few side effects were reported, pityriasis rosea being one of them. Therefore, this study will systematically review its manifestation afteradministration.Methods: Databases were searched, covering a timeline from December 1, 2019 to February 28, 2022. Data were independently extracted and accessed for bias. SPSS statistical software version 25 was used for appropriate inferential statistics. Results: Thirty‐one studies were included for data extraction after screening following the eligibility criteria. A total of 111 people were identified to have developed pityriasis rosea or pityriasis rosea‐like eruptions after vaccination, out of which 36 (55.38%) were female. The average age of incidence was calculated to be 44.92 years, and 63 (62.37%) people presented after administration of the first dose. It was found popularly in the trunk area, either asymptomatically or with mild symptoms. Meantime the onset, was 8.58 days, and meantime it took to recover, was 6.44 weeks. Conclusion: The association between pityriasis rosea and pityriasis rosea‐like eruptions after Covid‐19 vaccines was established, but given the scarcity of studies, there is a need to conduct different clinical trials to confirm this association further and study the etiology and mechanism of the disease. Immune response to SARS‐CoV‐2 mRNA vaccine. Common morphological presentation for PR, in about 80% of the patients, was of a “herald patch”; 2−10 cm oval, salmon‐colored plaques, known to be like a “Christmas tree” pattern along the cleavage lines.Since PR is a rare disease, there is very scarce and scattered literature available on it. Hence it is essential to systematically review it while highlighting its clinical and diagnostic histological features and appropriate treatment options, prompt diagnosis, and treatment. It can also aid in avoiding costly and unnecessary investigations. Furthermore, at devastating times like these, where scientists worldwide are urging people to get vaccinated to combat the SARS‐CoV‐2 virus and impede its viral transmission, it is crucial to study the possible cutaneous side effects of vaccination. Such findings on the degree of awareness can help address this concern against getting vaccinated and counsel people accordingly to reduce vaccine hesitancy. Hence this study is being conducted to study the prevalence of PR, and pityriasis rosea‐like eruptions (PRLE) in individuals who have been vaccinated against Covid‐19.2Extensive literature research was performed using the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) guidelines.2.1We implemented the Boolean (and/or) logic using the following set of Mesh terms; “Covid‐19,” “SARS‐CoV‐2,” “vaccination,” “immunization,” “side effects,” “cutaneous reactions, “and “Pityriasis Rosea” over the following authoritative databases: PubMed, Science Direct, Google Scholar, Cochrane Library, and Directory of Open Access Journals. Additionally, MedRxiv and BioRxiv were searched to identify preprinted studies, covering a timeline of December 1, 2019 to February 28, 2022. The search strategy used in each database is provided in Supporting Information: Table 2.2One thousand six hundred twenty‐nine studies were identified after a literature search, and 1081 of them were excluded due to duplication using Endnote. Two screening stages were conducted by two authors separately; I. K. and A. A., and a third author; S. S. T., resolved any disagreements. In the first stage, the abstracts and titles of the remaining 548 reports were individually screened to filter out studies relevant to our research question, which were 84. Furthermore, in the second stage, any human and observational study was selected, including case series, case reports, cohort, and cross‐sectional studies. Review articles, responses, and commentaries were excluded, 49 in number. After individually screening the full‐text links, 31 studies were finalized that met the eligibility criteria and were used for data extraction and synthesis.2.3To avoid selection bias, inclusion criteria were set up for the target population to contain participants that: (1) have received at least one dose of the following Covid‐19 vaccination: mRNA (Moderna BNT162b2 and Pfizer BioNTech BNT162b2), Adenovirus vectored , Inactivated , Recombinant subunit , and DNA (INO‐4800 Inovio); (2) people diagnosed with PR and PR‐LE in the study irrespective of the diagnostic criteria; (3) are of age 18 or above; (4) male or/and female. Studies were excluded if participants; (1) had a history of PR and PR‐LE before presentation; (2) had been previously or recently tested positive for covid‐19; (3) had any comorbidities or autoimmune/systemic disease; (4) were on any immunosuppressive drug; (5) currently have any other viral disease.2.4Two investigators independently scanned the 31 potential studies. The following data were extracted: Title, author names, study design, year of publication, sample size, age, and gender  of patients, name, and dose of vaccines administered, distribution, and time of onset of the cutaneous reaction after any dose of vaccination, morphological, its histological and clinical features, treatment prescribed, and days taken to recover. Discrepancies, if any, were settled by a third author.p‐value of <.05 considered significant and a 95% CI, was used for appropriate inferential statistics. Descriptive data were analyzed and presented as frequency/percentage, and continuous data were reported as mean with standard deviation. Finally, qualitative data were combined and analyzed to conclude the findings.Data extracted was then organized systematically in a shared excel spreadsheet, categorized according to a standardized data extraction form. SPSS statistical software Version 25, with a 2.5Appropriate quality assessment tools for case study/series and observational studies developed by the National Heart, Lung, and Brain Institute and Research Triangle Institute International were used to evaluate internal validity and remove the risk of bias. (13) Two authors independently assessed the quality of selected articles; A. A. E., and A. M. S., as shown in Supporting Information: Tables 3Of the final chosen 31 studies, 27 (87.10%) were case reports and series, and 4 (12.90%) were identified as cohort studies.3.1n = 23, 21.49%), AstraZeneca; AZD1222 Vaxzevria, , Bharat Biotech; SARS‐CoV‐2 Vaccine, Inactivated (Vero Cell)/COVAXIN , Sinopharm; SARS‐CoV‐2 Vaccine (Vero Cell), Inactivated (lnCoV) , Johnson and Johnson; Ad26.COV2.S , while 4 of them were unknown  cases. Twenty‐nine (44.62%) patients were male, while the gender of 46 from 111 people had not been specified in the studies. The average age of incidence was calculated to be 44.92 years. The age of 32 participants was not recorded. Of 101 cases with a specified number of vaccination doses administered before presentation, 63 (62.37%) comprised the first dose, and 38 (37.62%) accounted for the onset after the second dose. Studies included the manifestation of different kinds of vaccines manufactured by different companies. People predominantly reported to have received the mRNA vaccine; of Pfizer; BioNTech BNT162b2, in 38 cases (35.51%), and of Moderna; mRNA‐1273 in 27 patients (25.23%) before exhibiting the symptoms of the cutaneous reaction. Two (1.86%) other mRNA vaccines were found, but the pharmaceutical company was not identified. Other vaccines included manufacturers Sinovac; COVID‐19 Vaccine (Vero Cell), Inactivated/CoronaVac,  patients. Thirty‐seven (72.54%) people were given antihistamines. Other treatments advised were antibiotics (1.96%) and antivirals (3.92%), namely Doxycycline and Valaciclovir or Ganciclovir. These findings are portrayed in Table 9% patien3.3Thirty‐nine participants failed to report the morphological features. Six (8.33%) out of the remaining 72 people specifically presented as atypical PR with vesicular lesions in 5 and herald patches in only 3 of them. The appearance of the rash of 34 (37.22%) out of 72 people surfaced like a typical “herald patch.” In 36 cases (50.00%), lesions presented as “Christmas tree appearance,” 8 (10.53%) patients were also found to have developed collarette scales. In addition, 26 studies reported histological findings, of which common were parakeratosis (26.92%), spongiosis (59.25%), extravasated red blood cells (23.07%), and perivascular lymphocytic infiltrates (26.92%). These principal characteristics of each case were synthesized and summarized in Table 3.4n = 13, 40.62%), back , and abdomen . Only a few associated symptoms were noticed, which included itch , fever , myalgia , asthenia , headache . Twelve out of 16 people did not experience symptoms (75%). Table The distribution of the rashes was calculated to be most common in the trunk, 28 cases (87.5%) of the 32 cases with this data, which extended to proximal extremities . This may be because they have a more active immune response as compared to the other age groups. Peripheral dendritic cells, along with CD4+, CD8+, and T‐cells, linearly decrease as we grow older. The pediatric population has been found to have a noticeable increase in cytokines, especially IL‐6, IFN‐γ, and IL‐10. This can also help justify their severe immune response to the covid‐19 infection.Significant triggers other than autoimmunity for PR can be bacterial, viral, environmental factors like seasonal change, atopy, stress, or drugs such as ACE inhibitors, like captopril, Allopurinol, hydrochlorothiazide, barbiturates, nimesulide, and metronidazole.In this review, cases displayed and summarized a wide set of morphological features, typically appearing as a herald patch localized in the trunk initially, then spreading to other areas to mimic a pine tree. Atypical PR has unusual characteristics like some cases displayed vesicular or purpuric large but fewer patches in number as a coalescent, with an unconventional distribution like in the axilla, groin, limbs, and rarely face and neck, with trunk spared.A study shows that 75% of people with herald patch present with symptoms like headache, insomnia, irritability, and mostly fatigue, but our review was not suggestive of this. The patients were mainly asymptomatic, and symptoms reported in our studies were itch, fever, myalgia, asthenia, and headache.l‐lysine, taken 3 g in the first 3 days, then 500 m for the next 30 days as a maintenance dose. l‐Lysine targets the intestines and kidneys to increase l‐Arginine excretion, interfering in protein synthesis and viral replication.Even though PR is a self‐limiting reaction, drugs for symptomatic treatment and relief were prescribed, like mometasone furoate for the itch.Reactivation of PR was reported in one of our cases with the follow‐up data. It was presented after 4 days of administering the second dose of the CoronaVac vaccine. The lesions were similar, but they were self‐resolved, and the duration was shorter than the first occurrence, 1 week.4.1Our systematic review has a few limitations. Many participant studies had information bias, as many key study variables were missing from existing reports, affecting the quality of our review. Biopsies were not performed in some cases, which led to inadequate histological knowledge. There was a lack of follow‐up in a few records, because of which we could not determine the actual effectiveness of the treatment prescribed. Since the studies chosen for data extraction reported cases from different races and backgrounds, there were variations in characteristics reported of PR and PR‐LE; for example, the findings were presented according to each patient's skin color and texture, which is why one specific diagnostic criterion could not be used. Despite the vigorous screening process, our review was limited in generalizability, as the data available in the selected studies and the sample size was small and could only be applied to a narrow population.5In conclusion, this review summarized the manifestation and characteristics of PR/PR‐LE reported in a significant number of people after the administration of the Covid‐19 vaccination, hence establishing a positive association. Our study supports the reaction to be mild, presenting as mostly asymptomatic (75%) or with minor symptoms (25%). Its prompt treatment has also reported safe and effective treatment options, including corticosteroids and acyclovir. This can help improve knowledge and perception regarding such side effects of the Covid‐19 vaccine and avert people from discouraging vaccination. Further in‐depth studies and clinical trials should be conducted to confirm the association further and fully understand the path‐etiology of the reaction, which can also allow them to improve their vaccine‐making strategies.Iman Khan and Ahmed A. Elsanousi conceptualized the study and did formal analysis. Amena M. Shareef and Sameer S. Tebha contributed in methodology and project administration. Aabiya Arif and Sana Gul took part in investigation and software. All authors equally participated in writing of the original draft, reviewing, and editing it. All authors have read and approved the final manuscript.The authors declare no conflict of interest.Supporting information.Click here for additional data file.


Right atrial masses in dogs are commonly diagnosed as malignant tumors. This report describes a dog with a right atrial mass that appeared after successful electrical cardioversion of atrial fibrillation and resolved with antithrombotic treatment. A 9‐year‐old mastiff was presented for acute vomiting, and occasional cough of several weeks' duration. Ultrasonographic and radiographic examinations of the abdomen and chest identified mechanical ileus, as well as pleural effusion and pulmonary edema, respectively. Echocardiography indicated a dilated cardiomyopathy phenotype. During anesthetic induction for laparotomy, atrial fibrillation developed. Electrical cardioversion successfully restored sinus rhythm. An echocardiogram performed 2 weeks later disclosed a right atrial mass, which had not been apparent before cardioversion. Repeat echocardiography after 2 months of clopidogrel and enoxaparin treatment failed to detect the mass. Intra‐atrial thrombus formation is possible after successful cardioversion of atrial fibrillation and should be considered as a differential diagnosis for echocardiographically detected atrial masses. The dog had vomited 4 to 5 times after eating, which began the night before presentation. In addition, a single episode of collapse 6 weeks earlier was reported. Finally, the owner mentioned occasional cough, which started 3 weeks earlier. Current medications were PO carprofen (2.2 mg/kg q12h) and PO glucosamine with chondroitin sulfate for chronic arthritis. The dog had a history of 3 previous gastrointestinal foreign body surgeries—an enterotomy, a gastrotomy, and resection of approximately 60 cm of jejunum because of extensive adhesions, 3 years before the current presentation.Abdominal radiographs completed by the primary care veterinarian showed signs of mechanical ileus as evidenced by radiodense intestinal foreign material with extensive intestinal gas formation. The dog was referred to a specialist center where physical examination disclosed muffled heart sounds as a new finding. A point‐of‐care thoracic ultrasound examination identified a moderate volume of pleural effusion, subjective cardiomegaly, and suspected left ventricular systolic dysfunction. The dog was referred to our institution for evaluation of the heart and the pleural effusion as well as to address the mechanical ileus.At presentation, the dog was bright, alert, and responsive with a body condition score of 3/9 and moderate muscular atrophy. Rectal temperature was 38.2°C. Continuous panting with mildly increased respiratory effort was noted. Femoral pulse quality was fair, regular, with a frequency of 168/min. Mucous membranes were pink with capillary refill time of <2 seconds. Cardiac auscultation identified a grade 3/6 left apical systolic murmur. Thoracic auscultation identified decreased lung sounds ventrally. Deep abdominal palpation detected a soft abdomen and mild discomfort.After placement of an IV catheter, an echocardiogram, blood tests, thoracic and abdominal radiographs, thoracocentesis, and abdominocentesis with laboratory fluid analysis were performed.Blood tests identified mild hypoproteinemia , mild hypoalbuminemia , mild hyponatremia , mild hyperchloremia , and a mildly increased creatine kinase activity . The pH, bicarbonate, potassium, magnesium, calcium, phosphate, glucose, lactate, creatinine, urea, cholesterol, iron, and bilirubin concentrations, and liver enzyme activities, as well as CBC were within the RI.Abdominal radiographs confirmed mechanical intestinal obstruction caused by radiodense foreign material. Thoracic radiographs showed pleural effusion and signs of pulmonary edema, consistent with congestive heart failure, and no apparent lung metastases.Echocardiography indicated a dilated cardiomyopathy phenotype with biventricular enlargement. Moderate pleural and no pericardial effusion was noted. Moderate left ventricular eccentric hypertrophy and moderate systolic dysfunction was noted with a normalized left ventricular diastolic internal dimension of 1.93  and a systolic dimension of 1.15  with a fractional shortening of 19% . The left atrium was moderately dilated with a left atrial‐to‐aortic ratio of 1.95 . There was a severe, centrally directed jet of mitral valve insufficiency, suspected to be caused by annular dilatation secondary to eccentric left ventricular hypertrophy. The mitral valve leaflets were mildly thickened and mitral inflow was associated with a restrictive filling pattern. The right atrium and ventricle were subjectively mildly dilated. Mild tricuspid valve insufficiency was present. The great vessels showed no abnormalities. No overt cardiac masses were visualized and trace peritoneal effusion was observed. The hepatic veins were moderately dilated, and the caudal vena cava showed decreased respiratory variation in diameter. Simultaneous ECG showed sinus rhythm with a single ventricular premature complex.Under ultrasound guidance, thoracocentesis and abdominocentesis were performed and fluid samples were submitted for laboratory examination. Both samples were compatible with modified transudate without apparent neoplastic cells, infectious agents, or signs of inflammation. Carprofen was discontinued, and furosemide (2 mg/kg IV q8h), pimobendan (0.27 mg/kg PO q12h), and maropitant (1 mg/kg IV q24h) were started.An emergency laparotomy was performed to treat the intestinal obstruction. Before anesthetic induction, methadone (0.2 mg/kg IV), fentanyl (2.5 μg/kg IV), midazolam (0.3 mg/kg IV), and lidocaine (2 mg/kg IV) were administered for sedation. Anesthesia was induced with fentanyl (4 μg/kg IV), midazolam (0.12 mg/kg IV), and etomidate (0.1 mg/kg IV). After endotracheal intubation, anesthesia was maintained with inhaled isoflurane and IV fentanyl (0.1 μg/kg/min continuous rate infusion). During anesthesia, dopamine (5 μg/kg/min), lidocaine (50 μg/kg/min), and dobutamine (2.5 μg/kg/min) were administered. At anesthetic induction, sinus rhythm spontaneously converted into atrial fibrillation with a ventricular response rate of 60 beats per minute. At the same time, arterial blood pressure (measured invasively) decreased from 125/98  mmHg to 68/35  mmHg. Atrial fibrillation appeared approximately 35 minutes after the lidocaine bolus. The dog was given magnesium chloride  and potassium chloride (10 mEq at a rate of 0.25 mEq/kg/min IV). The dog was placed in dorsal recumbency, and the thorax shaved on both sides. Electrocardiographic leads from the defibrillator device were attached to the dog's skin, lead II was selected, and synchronization mode was switched on to identify native QRS complexes. A single shock of 75 J (1.3 J/kg) was delivered with immediate restoration of sinus rhythm. Systemic arterial blood pressure increased to 112/72  mmHg. After administration of prophylactic antibiotics  the dog was transferred to the operating room. During a midline laparotomy, an intraluminal foreign body was located at the level of the mid‐jejunum at the site of the previous resection and anastomosis with no evidence of hyperemia or damage to serosa or blood supply. Mild adhesions were present at the site of the previous anastomosis, but there was no evidence of perforation or intestinal necrosis. The obstructive foreign material, which appeared to be 2 rocks, was removed. Recovery from anesthesia was uneventful. The mean systemic blood pressure during the procedure varied between 65 and 81 mmHg. The dog was hospitalized overnight on continuous ECG, fluid treatment, fentanyl (2‐5 μg/kg/h IV), metoclopramide (1 mg/kg/day), gabapentin (6 mg/kg PO q8h), and amantadine (4 mg/kg PO q8h). Surface ECG showed sinus rhythm with occasional ventricular premature complexes throughout the day. Two days after surgery, the dog was discharged from the hospital and a re‐evaluation was planned for 2 weeks later. Oral pimobendan (0.3 mg/kg q12h) and furosemide (1 mg/kg q12h) were prescribed.Echocardiographic examination performed 2 weeks after laparotomy had comparable findings to the preoperative echocardiogram with the exception that no pleural or abdominal effusion was noted. However, an elongated soft tissue mass with a rounded surface and uniform echogenicity was detected in the right atrial lumen attached to the dorsal atrial wall Figures  and 2. TEchocardiography 1 week after starting clopidogrel showed a reduction in the size of the mass 1.8 cm × 2 cm). Enoxaparin was prescribed to be administered as injections by the owner at home . Recheck echocardiography 1 week later showed further decrease in the size of the mass (1.3 cm × 1.7 cm). Echocardiography 2 months after initial detection of the right atrial mass indicated resolution of the thrombus (Figure  cm. Enox3We documented right atrial thrombus formation in a dog after successful electrical cardioversion for atrial fibrillation. In humans, atrial thrombus formation is a well‐recognized complication of cardioversion, occurring in cases of successful cardioversion of atrial fibrillation or atrial flutter.Right atrial thrombus in a dog with atrial fibrillation has not been reported previously. In humans with atrial fibrillation, right atrial thrombus formation is very rare and, if it occurs, is typically localized in the atrial appendage.Differentiating a malignant tumor from a thrombus by echocardiography alone can be very difficult, if not impossible, especially if the mass is attached to the atrial wall. Ultrasound‐guided fine needle aspiration biopsy to sample the mass for cytologic examination would not only carry a high risk of inducing arrhythmias and intrapericardial hemorrhage, but it would likely not be able to differentiate thrombus from hemangiosarcoma. In our case, serum cardiac troponin I concentration was measured, because increased concentrations of this cardiac biomarker have been reported in dogs with cardiac hemangiosarcoma.Because of the acute onset of atrial fibrillation in the present case, there was no time for pretreating the dog with amiodarone.To establish the incidence of atrial thrombus formation in dogs after electrical cardioversion, screening echocardiography could be considered within 2 days after successful cardioversion of atrial fibrillation or flutter in future cases.We conclude that a right atrial thrombus can develop in dogs with atrial fibrillation after successful electrical cardioversion. Because a thrombus can be treated successfully, as opposed to a cardiac hemangiosarcoma, it is important to include this condition on the differential diagnosis, although it is rare.Authors declare no conflict of interest.Authors declare no off‐label use of antimicrobials.Authors declare no IACUC or other approval was needed.Authors declare human ethics approval was not needed for this study.


This study aimed to evaluate the predictive value of systemic inflammation response index (SIRI) in primary gastrointestinal diffuse large B‐cell lymphoma (PGI‐DLBCL) patients and establish a highly discriminating risk prediction model.n = 102) and a validation set (n = 51). Univariate and multivariate Cox regression analyses were conducted to examine the significance of variables on overall survival (OS) and progression‐free survival (PFS). An inflammation‐covered score system was established according to the multivariate results.This retrospective analysis included 153 PGI‐DCBCL patients diagnosed between 2011 and 2021. These patients were divided into a training set (p < 0.001) was significantly associated with poorer survival and identified as an independent prognostic factor. Compared with NCCN‐IPI, the prognostic and discriminatory capability of the novel model SIRI‐PI showed a more precise high‐risk assessment with a higher area under the curve (AUC) (0.916 vs 0.835) and C‐index (0.912 vs 0.836) for OS in the training cohort, and similar results were obtained in the validation cohort. Moreover, SIRI‐PI also showed good discriminative power for efficacy assessment. This new model identified patients at risk of developing severe gastrointestinal complications following chemotherapy.The presence of high pretreatment SIRI (≥1.34, The results of this analysis suggested that the pretreatment SIRI may be a potential candidate for identifying patients with a poor prognosis. And we established and validated a better‐performing clinical model, which facilitated the prognostic stratification of PGI‐DLBCL patients and can serve as a reference for clinical decision‐making. SIRI, a reproducible and easily accessible hallmark, is considered a potent and independent prognostic indicator in our study. Compared to the NCCN‐IPI, the SIRI‐PI presents good performance, which could aid in appropriate decision‐making and provide added value for categorizing high‐risk patients and those with severe complications.  By incorporating the SIRI and NCCN‐IPI, this predictive tool may help distinguish high‐risk patients and assist in implementing appropriate clinical decisions.22.1We retrospectively evaluated the clinical characteristics and follow‐up data of 153 patients with PGI‐DLBCL  newly diagnosed at Shandong Provincial Hospital between January 2011 and February 2022. All patients recruited met the following criteria: (1) pathologically diagnosed as gastrointestinal DLBCL, (2) no previous chemotherapy or immunotherapy treatment, (3) no previous history of malignancy or immunosuppression, (4) receiving CHOP‐based therapies, and (5) with a complete series of clinical information and follow‐up data. In all cohorts, data included patients' age, gender, primary site, germinal center B‐cell‐like (GCB) versus non‐GCB, systemic B symptoms, Ann Arbor stage (I‐IV), Eastern Cooperative Oncology Group (ECOG) performance status (PS), involvement of extranodal sites, NCCN‐IPI, serum lactate dehydrogenase (LDH), Alb, prognostic nutritional index (PNI), β2‐microglobulin (β2‐MG), NLR, LMR, PLR, SII, and SIRI. All these laboratory parameters were extracted from serum ≤3 days before the first chemotherapy or immunochemotherapy treatment. Furthermore, a cohort of 8301 patients diagnosed with PGI‐DLBCL between 2000 and 2018 was obtained from the SEER database. Overall survival (OS), the primary endpoint, was defined as the period from diagnosis to death from any cause or the last follow‐up time. Progression‐free survival (PFS) was determined as the period from the diagnosis to the earliest death, disease recurrence, or disease progression.2.23.SII is described as (P × N)/L, where P, N, and L represent platelet, neutrophil, and lymphocyte counts, respectively. SIRI is calculated as neutrophil × monocyte/lymphocyte (N × M/L). PNI is estimated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count/mmSevere postchemotherapy GICs include gastrointestinal bleeding (GIB), obstruction (GIO), and perforation (GIP), which can be identified by clinical testing, imaging, or surgery. Specifically, severe GIB was outlined as a bleeding episode such as hematemesis, melena, and/or bloody stools.2.3n = 102) and a validation cohort (n = 51) based on a 2:1 ratio. The multivariate Cox proportional hazard regression analyzed clinical characteristics associated with survival, inflammatory markers, and the components of NCCN‐IPI. Owing to the multivariate results, a new multiparameter prognostic model was constructed by the integration of the NCCN‐IPI and SIRI. The prognostic performance and discriminatory power of two risk score models were measured by area under the curve (AUC), which was derived from the receiver operating characteristic (ROC) curve, and Harrell's C‐index. We also calculated the integrated discrimination improvement (IDI), the continuous version of the net reclassification improvement (NRI),The recruited patients were randomly assigned to a training cohort  was used to assess the net clinical benefit of the models. Survival analyses were performed using Cox regression and the log‐rank test. If the log‐rank test was not applicable for some survival plots, we performed a landmark analysis. The weights were calculated in accordance with the respective β coefficients from the multivariable analysis.p < 0.05 was regarded as statistically significant, and hazard ratios (HRs) were estimated with 95% confidence intervals (95% CIs).SPSS 25.0 and R software 4.1.2 were used to conduct the statistical analyses and draw figures. Clinical data were gathered using SEER*Stat software (version 8.3.6). Baseline clinical features were assessed by the Chi‐squared test or Fisher's exact test for categorical variables. The unpaired 33.1An initial cohort of 201 patients in our center and 8301 patients in the SEER database with PGI‐DLBCL were enrolled in this study. Table SThe flow chart in Figure S3.2p < 0.05).The predictive values of inflammatory indices  were evaluated by the ROC curves Figure S. Accordip = 0.026), B symptoms , and LDH > ULN . Moreover, SIRI ≥1.34 , B symptoms , and LDH > ULN  emerged as the indicators for considerably inferior PFS times.In univariate regression analysis, the significant variables for OS and PFS comprised extranodal sites, LDH, B symptoms, NLR, LMR, SII, and SIRI Figure . Accordi3.3β coefficients compared with the effect of an elevated LDH level (>ULN) in the multivariate analysis of OS. This established an integrated scoring model with a maximum of 10 points  allowed us to predict clinical outcomes effectively and could enrich the current stratification. The novel model (SIRI‐PI) may suggest greater predictive accuracy than the NCCN‐IPI alone. Patients with SIRI ≥1.34 were allocated two points as a risk factor calculated in terms of the C‐index (0.912 vs 0.836) were superior based on the SIRI‐PI in the training set, indicative of good discrimination  in discrimination  for IDI and 0.723 (95% CI: 0.480–0.936) for NRI, respectively. The IDI was 0.26, indicating a 26% relative improvement in the discrimination slope with the addition of the SIRI.3.4n = 153). Overall, the objective response rate in PGI‐DLBCL patients was 65.5%, with 49 (43.4%) complete responses (CR) and 25 (22.1%) partial responses (PR). Fourteen (12.4%) patients had stable disease (SD), and 25 (22.1%) patients had progressive disease (PD) at the first radiographic assessment. According to the SIRI‐PI model, 113 patients were divided into two groups: the low/low‐intermediate cohort and the high/high‐intermediate cohort. Concerning the efficacy outcomes, both cohorts presented distinct and disparate efficacy outcomes in terms of radiation tumor response (p = 0.003) and disease control (p = 0.001), suggesting good predictive power for clinical applications when assessing efficacy  of patients, including GIO in 7.8% (12/153), GIB in 3.3% (5/153), and only one patient (0.7%) was recorded for GIP  extracted from serum and, thereby, allows better assessment of inflammatory responses associated with tumorigenesis and progression. Likewise, contrasted with single‐cell components, the consolidated SIRI is less likely to be affected in diverse clinical settings: infections, impaired liver function, fluid retention, and dehydration. Some studies demonstrated that platelets were a helpful factor in predicting dismal results and could improve the predictive ability of IPI in patients with DLBCL.C‐index than the NCCN‐IPI. Namely, the prognostic model delivered superior prognostication and risk evaluation of oncologic outcomes. Also, our model is related to survival and achieving disease control (response or stabilization). As a result, it may define patients with a poor prognosis and predict poorly responding patients, allowing for more appropriate and efficient treatments for those with PGI‐BLBCL. It is prudent to interpret the results of our study according to the newly established model, for it is supposed to be of additional value in guiding the appropriate treatment for PGI‐DLBCL patients rather than replacing NCCN‐IPI in practice.Presently, the NCCN‐IPI, as an enhanced IPI score, has been widely utilized for the stratification of DLBCL. Nonetheless, due to a lack of consideration for the role that adaptive immunity and the tumor microenvironment play in the pathogenesis of lymphoma, this stratification tool cannot well differentiate high‐risk populations when taking rituximab‐based therapies. The model established by combining the SIRI and NCCN‐IPI can predict the survival of PGI‐DLBCL patients more effectively, as it could yield a better ROC curve and Perforation, massive bleeding, and obstruction are potentially life‐threatening complications of lymphomas involving the gastrointestinal tract and result in considerable morbidity, which requires timely identification and treatment.Given the nature of retrospective and single‐center analysis, the findings of this study were accompanied by a few limitations. First, we might have been subject to potential selection bias in data collection. Second, according to the limited number of enrolled patients and the deficiency of external validation of this model, our analyses should rather be considered exploratory than confirmatory. Third, there might be overlap between high SIRI and other high‐risk factors, such as B symptoms and higher LDH. Further analyses should take into account these high‐risk characteristics collectively since they may be associated with the patients' inflammatory state. Lastly, as a single‐center study, it is anticipated that our results demand to be confirmed in a larger cohort of patients to demonstrate the generalizability of our model and be explored in distinct clinical settings. Despite differences in patient race, there was no significant difference in the distribution of baseline data such as sex, primary site, B symptoms, and whether surgery was performed or not in our database and the SEER database, which may provide the possibility for the application of this prognostic model. Nevertheless, the prognostic model needs further verification due to a higher portion of patients with stage III‐IV and younger patients in our research.5Overall, SIRI, a reproducible and easily accessible hallmark, is considered a potent and independent prognostic indicator in our study. Compared to the NCCN‐IPI, the SIRI‐PI presents good performance, which could aid in appropriate decision‐making and provide added value for categorizing high‐risk patients and those with severe complications.Yurou Chu: Data curation (lead); formal analysis (lead); investigation ; writing – original draft (lead). Yingyue Liu: Data curation . Yujie Jiang: Data curation . Xueling Ge: Data curation . Dai Yuan: Formal analysis (supporting). Mei Ding: Data curation . Huiting Qu: Formal analysis (supporting). Fang Liu: Writing – review and editing (supporting). Xiangxiang Zhou: Writing – review and editing . Xin Wang: Writing – review and editing .This study was supported by National Natural Science Foundation ; Key Research and Development Program of Shandong Province (2018CXGC1213); Development Project of Youth Innovation Teams in Colleges and Universities of Shandong Province (2020KJL006); China Postdoctoral Science Foundation ; Translational Research Grant of NCRCH ; Shandong Provincial Natural Science Foundation (ZR2021YQ51); Technology Development Project of Jinan City (no. 202134034); Taishan Scholars Program of Shandong Province; Shandong Provincial Engineering Research Center of Lymphoma; and Academic Promotion Programme of Shandong First Medical University .The authors have no relevant conflicts.The study was conducted in accordance with the Declaration of Helsinki. This study was approved by the Medical Ethical Committee of Shandong Provincial Hospital Affiliated to Shandong University. And informed consent was waived because of its retrospective nature.Data S1.Click here for additional data file.


Temporal lobe epilepsy is a neurological network disease in which genetics played a greater role than previously appreciated. This study aimed to explore shared functional network abnormalities in patients with sporadic temporal lobe epilepsy and their unaffected siblings.Fifty‐eight patients with sporadic temporal lobe epilepsy, 13 unaffected siblings, and 30 healthy controls participated in this cross‐sectional study. We examined the task‐based whole‐brain functional network topology and the effective functional connectivity between networks identified by group‐independent component analysis.p < 0.05, false discovery rate‐corrected). The effective network connectivity from the ventral attention network to the limbic system was impaired . These features had higher prevalence in unaffected siblings than in normal population and was not correlated with disease burden. In addition, topological abnormalities had a high intraclass correlation between patients and their siblings.We observed increased global efficiency, decreased clustering coefficiency, and decreased small‐worldness in patients and siblings (Patients with temporal lobe epilepsy and their unaffected siblings showed shared topological functional disturbance and the effective functional network connectivity impairment. These abnormalities may contribute to the pathogenesis that promotes the susceptibility of seizures and language decline in temporal lobe epilepsy. Patients with temporal lobe epilepsy and their unaffected siblings showed shared topological disturbance of whole‐brain functional network and the effective functional network connectivity impairment between the ventral attention network and the limbic system. These abnormalities were potential endophenotype candidates and may contribute to the pathogenesis that promotes the susceptibility of seizures and language decline in temporal lobe epilepsy. Functional brain network topology modulated the threshold for seizure propagation,While resting‐state functional MRI focuses primarily on the spontaneous activities in rest, task‐based functional MRI (tb‐fMRI) provides direct information for language impairment.With a well‐tested Chinese character verbal fluency task,22.1From December 2018 to January 2021, we sequentially recruited 58 patients with sporadic TLE from the Department of Neurology, Xiangya Hospital. Patients visited our institution due to recent seizures. We identified 30 patients with HS :right TLE (RTLE) = 13:17) and 28 patients without HS . The clinical semiology, electroencephalography, and MRI evidence were evaluated by two experienced epileptologists (BX and LL) to diagnose and lateralize TLE.http://niftyweb.cs.ucl.ac.uk/program.php?p=HIPPOSEG),All subjects routinely underwent T2WI, T2WI fluid‐attenuated inversion recovery, and 3DT1 sequences, which were visually assessed by experienced neuroimagers to diagnose HS or other potential structural abnormalities. The hippocampi of subjects were segmented by Hipposeg, an automatic online hippocampal segmentation algorithm developed for TLE, to calculate the hippocampal volume ,2.3With a Siemens MAGNETOM Prisma 3.0T MR scanner and standard head coils at the MRI center of Xiangya Hospital, MRI images were collected, including the whole‐brain structural images obtained using a magnetization‐prepared rapid acquisition with gradient echo sequence , and the whole‐brain blood oxygenation level‐dependent (BOLD) signals provided by a gradient echo planar T2‐weighted sequence .A previously described and well‐tested Chinese character verbal fluency task2.4https://www.fil.ion.ucl.ac.uk/spm/). The preprocessing pipeline includes realignment, coregistration, segmentation, normalization to the Montreal Neurological Institute (MNI) space, and spatial smoothing (6 mm).Imaging data were preprocessed with the Statistical Parametric Mapping 12 software (2.5http://www.nitrc.org/projects/conn) to conduct two different types of functional connectivity analysis with our tb‐fMRI data. Task‐based functional connectivity (tb‐FC) analyzed the functional connections during tasks. By regressing out task‐specific signals, the task residual‐functional connectivity (tr‐FC) approach extracted resting‐state functional connectivity from tb‐fMRI data.We used toolbox CONN v.20.bThe image data of every subject were parcellated into 272 regions of interest (ROI), including 210 cortical region, 36 subcortical regions,rand)/(APL/APLrand). Both GE and APL reflect the integration level of the network, and the CC measures the segregation level of the network. The property of healthy brains accords with a small‐world organization, characterized by relatively higher CC and lower APL than that of a random network. CCrand and APLrand are the CC and APL of equivalent random networks. The theoretical values are:A generalized linear model (GLM) with bivariate‐correlationTo investigate the between‐group differences across different connection densities, we computed the area under curve (AUC), which provided an overall scalar value integrating differences under all densities.2.627,28,43 ICs were labeled by the dice coefficient of spatial overlap and visual assessment.p < 0.05.The toolbox CONN v.20.b was used to conduct group‐ICA and post hoc eFNC.2.7https://www.ibm.com/products/spss‐statistics) for statistical analysis. Kolmogorov–Smirnov test was used to assess data distribution. Data without a normal distribution or homogeneity of variance would be compared between groups with nonparametric approach. When comparing qualitative variables, we used Kruskal–Wallis H‐test, ANCOVA, Quade nonparametric ANCOVA and post hoc pairwise comparisons, or Mann–Whitney U test when applicable. Considering the difference in sample size, we additionally reported the effect sizes.We used the IBM SPSS Statistics 23  curve analysis,We employed the functional network parameters in the logistic regression and ROC curve analysis to discriminate siblings from healthy controls. High discriminative accuracy indicates that siblings have higher prevalence of functional network abnormalities than the normal population.We investigated the relation between endophenotype candidates and language test scores. To assess the impact of disease severity and psychiatric comorbidity, we additionally evaluated the correlation of endophenotype candidates with SAS, SDS, age of onset (AOO), disease duration, seizure frequency, and the number of antiseizure medications (ASMs) in patients.To assess the heritability of potential endophenotypes, we calculated the ICC of graph theory metrics and eFNC between patient‐sibling pairs.2.8.2Patients were divided into two groups according to HS and NHS. There were seven unaffected siblings of patients with TLE‐HS (Sib‐HS), and six unaffected siblings of patients with TLE‐NHS (Sib‐NHS). We explored the difference between HC, two patient groups, and two sibling groups.Besides, differences within LTLE and RTLE subgroups were explored to address the laterality effect.33.1p = 0.008, FDR‐corrected; F = 9.55, η2 = 0.089) and siblings . Patients had higher anxiety level than HC  and siblings , and higher depression level than HC . The HC group outperformed patients in VFP  and BN . Details of demographic and clinical data were listed in Table No significant group difference of age, sex, or educational level was noted. But HC performed better in MoCA than patients , lower CC , and lower σ . Though the difference was not statistically significant, siblings showed the same but milder abnormality as patients.On the overall scale Figure , patientThe group difference of functional connectivity topology under specific densities was presented in Figure 3.3p = 0.005, FDR‐corrected; F = 10.85; η2 = 0.103), lower CC , and lower σ  in comparison with HC. Compared to HC, siblings also had higher GE  and lower CC .On the overall scale Figure , patientThe group difference of functional connectivity topology under specific densities was presented in Figure 3.4The group‐ICA successfully separated the DMN, limbic system, ventral attention network (VAN), and other task‐related networks. The detailed labeling and presenting of all 20 ICs are listed in Figure p < 0.05, FDR‐corrected; F = 14.01; η2 = 0.230; Figure p < 0.001, FDR‐corrected; F = 16.62; η2 = 0.150) and patients  compared to HC  to the IC 17 (limbic system) was significantly different across the three groups  and the eFNC from the VAN to the limbic system  reached high accuracy when discriminating siblings from HC. The combination of two methods had an AUC = 0.813, 95% CI = 0.672–0.954 . Stronger connectivity between the VAN and the limbic system was correlated with higher VFP scores .Graph theory metrics or eFNC were not correlated with disease burden , or number of ASMs  and siblings . In addition, the eFNC strength was not correlated with SAS or SDS in the patients .Since the limbic system is related to psychiatric comorbidity, we examined the group difference of eFNC after controlling for SAS and SDS scores. HC presented stronger functional connectivity compared to patients (3.5.5p > 0.8).Since patients and siblings presented lower MoCA scores compared to HC, we calculated the partial correlation between MoCA scores and functional statistics. The MoCA score was not correlated with functional network connectivity and graph statistics (4With a Chinese character version of verbal fluency task, we observed shared functional network abnormalities in patients with TLE and their unaffected siblings. The topological disturbance and network‐level impairment, especially the eFNC from the VAN to the limbic system, could be considered functional endophenotypes that might contribute to the susceptibility of seizures and cognitive decline in TLE.Verbal fluency decline is a common deficit in TLE. A Chinese character verbal fluency task mobilizes orthographic, tonal, phonological, and semantic processing procedures.By exploring the graph theory metrics, we observed a less small‐world and more random topology in patients with TLE and their unaffected siblings. A small‐world network balances information local processing and global transferring, with economical energy cost.In addition, we explored the eFNC between networks identified by group‐ICA. In patients and their unaffected siblings, we observed reduced connectivity from the VAN to limbic system. The VAN served to regulate one's attention when unexpected stimuli appeared during a task.The genetic background of seizure and cognitive decline in TLE is a topic of ongoing debate. While structural abnormalities connected directly to the genotype that influence cortex development, functional disturbances lie closer to seizure generation and spreading, representing an essential step from genotype to phenotype.We conducted sensitivity analyses in subgroups to explore the effect of HS and lesion laterality. Patients with HS and their siblings presented more severe topological disturbance compared to patients without HS and their siblings. This observation not only further supported the heritability of network topology but also suggested that HS was related to whole‐brain network topology. A possible explanation is that HS is a protruding phenotype of genetic factors that affect whole‐brain development.There are limitations. First, our cohort of siblings was relatively small. Hence, we collected clinical details and applied well‐established and robust methods. Even though the power of analyses for unaffected siblings was lowered by the small sample size, we still observed significant differences between siblings and healthy controls, suggesting our results are reliable. Further sensitivity analyses also verified that the functional network abnormalities are promising endophenotypes. Still, the results may not be representative, and a larger cohort of unaffected siblings would benefit future studies. Second, some patients had HS despite normal hippocampal volume and MRI signal.In conclusion, we observed shared whole‐brain functional network topological disruption and impaired eFNC from the VAN to the limbic system in patients with TLE and their unaffected siblings. The functional disturbance could be considered endophenotypes that precede and even promote seizure susceptibility and cognitive decline in TLE. These imaging traits could be applied as predictors for seizure onset and language decline in future prospective studies. Our findings would also benefit future genetic searching aimed for common variants in TLE.Kangrun Wang designed and conceptualized study, played a role in the acquisition of data, analyzed the data and functional connectivity, and drafted the manuscript. Fangfang Xie designed and conceptualized study, analyzed the data, major role in the acquisition of data, and drafted the manuscript. Charong Liu, Ge Wang, and Min Zhang analyzed the data and played a role in the acquisition of data. Jialinzi He and Langzi Tan set the parameters of the task and played a role in the acquisition of data. Haiyun Tang played a role in the acquisition of data. Fenghua Chen and Bo Xiao designed and conceptualized study. Yanmin Song supervised the study, played a role in the acquisition of data, and revised the final manuscript. Lili Long designed and conceptualized the study, supervised the study, and revised the final manuscript.The authors declare that they have no conflict of interest.Written informed consent was obtained from all participants.Appendix S1Click here for additional data file.