A multifaceted crosstalk between brassinosteroid and gibberellin regulates the resistance of cucumber to Phytophthora melonis.

Cucumber plants are highly susceptible to the hemibiotroph oomycete Phytophthora melonis. However, the mechanism of resistance to cucumber blight remains poorly understood. Here, we demonstrated that cucumber plants with impairment in the biosynthesis of brassinosteroids (BRs) or gibberellins (GAs) were more susceptible to P. melonis. By contrast, increasing levels of endogenous BRs or exogenously application of 24-epibrassinolide enhanced the resistance of cucumber plants against P. melonis. Furthermore, we found that both knockout and overexpression of the BR biosynthesis gene CYP85A1 reduced the endogenous GA3 content compared with that of wild-type plants under the condition of inoculation with P. melonis, and the enhancement of disease resistance conferred by BR was inhibited in plants with silencing of the GA biosynthetic gene GA20ox1 or KAO. Together, these findings suggest that GA homeostasis is an essential factor mediating BRs-induced disease resistance. Moreover, BZR6, a key regulator of BR signaling, was found to physically interact with GA20ox1, thereby suppressing its transcription. Silencing of BZR6 promoted endogenous GA biosynthesis and compromised GA-mediated resistance. These findings reveal multifaceted crosstalk between BR and GA in response to pathogen infection, which can provide a new approach for genetically controlling P. melonis damage in cucumber production.

Comparison of clinical characteristics and disease burden of febrile seizures in children with and without COVID-19.

BACKGROUND: Febrile seizures (FS) are the most common seizure disorder in children and a common neurologic complication in children with coronavirus disease 2019 (COVID-19). This study aimed to identify differences in clinical characteristics and disease burden between FS with and without COVID-19. MATERIALS AND METHODS: We conducted a retrospective analysis of medical data at our hospital from December 2019 to July 2023, focusing on hospitalized patients under the age of 14 diagnosed with FS who underwent COVID-19 polymerase chain reaction (PCR) testing. Descriptive statistics and analysis of variance were employed to compare the COVID-19 and non-COVID-19 groups in terms of clinical characteristics and disease burden. RESULTS: A total of 514 patients were included, with 106 testing positive for COVID-19 and 408 testing negative. Patients with COVID-19 were older (34.87 ± 6.16 vs. 28.61 ± 11.35 months, P < 0.001) and had a higher proportion of males (79.2% vs. 62.3%, P = 0.001). The COVID-19 group had longer seizure durations (4.57 ± 4.38 vs. 3.22 ± 2.91 min, P = 0.006) and more complex FS (25.5% vs. 15.9%, P = 0.022). Laboratory tests showed lower lymphocyte counts in the COVID-19 group (1.87 ± 1.48 vs. 2.75 ± 1.51 × 103/µL, P < 0.001) and higher creatine kinase levels (158.49 ± 82.89 vs. 110.89 ± 56.11 U/L, P < 0.001). No significant differences were found in hospital costs, length of hospitalization, and intensive care unit admissions. CONCLUSION: Clinicians should be knowledgeable about the distinct clinical characteristics of FS in children with COVID-19. Despite distinct features, the prognosis remains favorable and does not require excessive intervention. Ongoing monitoring and research are needed to fully understand the impact of COVID-19 on FS and optimize management strategies.

Development and validation of health-oriented personal evaluation for the community-dwelling older person based on the International Classification of Functioning, Disability and Health.

BACKGROUND: The International Classification of Functioning, Disability and Health (ICF) offers a standardized international terminology to operationalize function management across multiple domains, but the summary score of the ICF qualifier scale provides limited information on the comparison of personal abilities and functioning difficulties. OBJECTIVES: To enhance the interpretative power of the ICF-based Health-oriented Personal Evaluation for the community-dwelling older person (iHOPE-OP) scale through the implementation of the item response theory (IRT) modelling. METHODS: This cross-sectional, multi-centre study administrated 161 ICF categories (58 on body functions, 15 on body structures, 60 on activities or participation and 28 on environmental factors) to evaluate the functional level of 338 older citizens (female = 158, male = 180) residing in community or supportive living facilities. The validation process encompassed assessing the IRT model fitness and evaluating the psychometric properties of the IRT-derived iHOPE-OP scale. RESULTS: The age of participants ranged from 60 to 94.57, with the mean age of 70. The analysis of non-parametric and parametric models revealed that the three-parameter logistic IRT model, with a dichotomous scoring principle, exhibited the best fit. The 53-item iHOPE-OP scale demonstrated high reliability (Cronbach's α = 0.9729, Guttman's lambda-2 = 0.9749, Molenaar-Sijtsma Statistic = 0.9803, latent class reliability coefficient = 0.9882). There was a good validity between person abilities and the Barthel Index (p < .001, r = .83), as well as instrumental activities of daily living (p < .001, r = .84). CONCLUSIONS: IRT methods generate the reliable and valid iHOPE-OP scale with the most discriminable and minimal items to represent the older person's functional performance at a comprehensive level. The use of the Wright map can aid in presby-functioning management by visualizing item difficulties and person abilities. IMPLICATIONS FOR PRACTICE: Considering the intricate and heterogeneous health status of older persons, a single functional assessment tool might not fulfil the need to fully understand the multifaceted health status. For use in conjunction with the IRT and ICF framework, the reliable and valid iHOPE-OP scale was developed and can be applied to capture presby-functioning. The Wright map depicts the distribution of item difficulties and person abilities on the same scale that facilitates person-centred goal setting and tailors intervention.

Transcutaneous auricular vagus nerve stimulation with task-oriented training improves upper extremity function in patients with subacute stroke: a randomized clinical trial.

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising brain stimulation modality in poststroke upper extremity rehabilitation. Although several studies have examined the safety and reliability of taVNS, the mechanisms underlying motor recovery in stroke patients remain unclear. Objectives: This study aimed to investigate the effects of taVNS paired with task-oriented training (TOT) on upper extremity function in patients with subacute stroke and explore the potential underlying mechanisms. Methods: In this double-blinded, randomized, controlled pilot trial, 40 patients with subacute stroke were randomly assigned to two groups: the VNS group (VG), receiving taVNS during TOT, and the Sham group (SG), receiving sham taVNS during TOT. The intervention was delivered 5 days per week for 4 weeks. Upper extremity function was measured using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), the Action Research Arm Test (ARAT). Activities of daily living were measured by the modified Barthel Index (MBI). Motor-evoked potentials (MEPs) were measured to evaluate cortical excitability. Assessments were administered at baseline and post-intervention. Additionally, the immediate effect of taVNS was detected using functional near-infrared spectroscopy (fNIRS) and heart rate variability (HRV) before intervention. Results: The VG showed significant improvements in upper extremity function (FMA-UE, ARAT) and activities of daily living (MBI) compared to the SG at post-intervention. Furthermore, the VG demonstrated a higher rate of elicited ipsilesional MEPs and a shorter latency of MEPs in the contralesional M1. In the VG, improvements in FMA-UE were significantly associated with reduced latency of contralesional MEPs. Additionally, fNIRS revealed increased activation in the contralesional prefrontal cortex and ipsilesional sensorimotor cortex in the VG in contrast to the SG. However, no significant between-group differences were found in HRV. Conclusion: The combination of taVNS with TOT effectively improves upper extremity function in patients with subacute stroke, potentially through modulating the bilateral cortex excitability to facilitate task-specific functional recovery.

Modeling blood metabolite homeostatic levels reduces sample heterogeneity across cohorts.

Blood metabolite levels are affected by numerous factors, including preanalytical factors such as collection methods and geographical sites. These perturbations have caused deleterious consequences for many metabolomics studies and represent a major challenge in the metabolomics field. It is important to understand these factors and develop models to reduce their perturbations. However, to date, the lack of suitable mathematical models for blood metabolite levels under homeostasis has hindered progress. In this study, we develop quantitative models of blood metabolite levels in healthy adults based on multisite sample cohorts that mimic the current challenge. Five cohorts of samples obtained across four geographically distinct sites were investigated, focusing on approximately 50 metabolites that were quantified using 1H NMR spectroscopy. More than one-third of the variation in these metabolite profiles is due to cross-cohort variation. A dramatic reduction in the variation of metabolite levels (90%), especially their site-to-site variation (95%), was achieved by modeling each metabolite using demographic and clinical factors and especially other metabolites, as observed in the top principal components. The results also reveal that several metabolites contribute disproportionately to such variation, which could be explained by their association with biological pathways including biosynthesis and degradation. The study demonstrates an intriguing network effect of metabolites that can be utilized to better define homeostatic metabolite levels, which may have implications for improved health monitoring. As an example of the potential utility of the approach, we show that modeling gender-related metabolic differences retains the interesting variance while reducing unwanted (site-related) variance.

SIGNET: transcriptome-wide causal inference for gene regulatory networks.

Gene regulation plays an important role in understanding the mechanisms of human biology and diseases. However, inferring causal relationships between all genes is challenging due to the large number of genes in the transcriptome. Here, we present SIGNET (Statistical Inference on Gene Regulatory Networks), a flexible software package that reveals networks of causal regulation between genes built upon large-scale transcriptomic and genotypic data at the population level. Like Mendelian randomization, SIGNET uses genotypic variants as natural instrumental variables to establish such causal relationships but constructs a transcriptome-wide gene regulatory network with high confidence. SIGNET makes such a computationally heavy task feasible by deploying a well-designed statistical algorithm over a parallel computing environment. It also provides a user-friendly interface allowing for parameter tuning, efficient parallel computing scheduling, interactive network visualization, and confirmatory results retrieval. The Open source SIGNET software is freely available ( https://www.zstats.org/signet/ ).

Decision-making tree for surgical treatment in meningioma: a geriatric cohort study.

Controversies persist regarding the benefits of surgery in elderly patients with meningiomas. The objective of this study was to develop decision-making scale to clarify the necessity for surgical intervention and provide clinical consultation for this special population. This retrospective cohort study was conducted at a single center and included 478 elderly patients (≥ 65 years) who underwent meningioma resection. Follow-up was recorded to determine recurrence and mortality rates. Univariate and multivariate analyses were performed to identify significantly preoperative factors, and prognostic prediction models were developed with determined cutoff values for the prognostic index (PI). Model discrimination was evaluated using Kaplan-Meier curves based on the PI stratification, which categorized patients into low- and high-risk groups. A decision-making tree was then established based on the risk stratification from both models. Among all patients analyzed (n = 478), 62 (13.0%) experience recurrence and 47 (10.0%) died during the follow-up period. Significantly preoperative parameters from both models included advanced age, aCCI, recurrent tumor, motor cortex involvement, male sex, peritumoral edema, and tumor located in skull base (all P < 0.05). According to the classification of PI from the two models, the decision-making tree provided four recommendations that can be used for clinical consultation. Surgery is not recommended for patients assigned to the high-risk group in both models. Patients who meet the low-risk criteria in any model may undergo surgical intervention, but the final decision should depend on the surgeon's expertise.

Is brain invasion sufficient as a stand-alone criterion for grading atypical meningioma?

OBJECTIVE: Despite the controversy surrounding brain invasion (BI) as the sole indicator used to diagnose atypical meningioma, this criterion was still incorporated in the 2021 WHO classification scheme. In this study, the authors investigated the reproducibility of this prognostic effect and the impact of BI on the prognosis in otherwise benign meningioma (benign meningioma with BI). METHODS: Patients (n = 1006) with a pathological diagnosis of benign or atypical meningioma according to the latest WHO classification criteria were enrolled in this study. In patients with atypical meningioma, the cases were further categorized as benign meningioma with BI and classical atypical meningioma. Clinical, pathological, and follow-up data were collected. Kaplan-Meier curves were compared with a log-rank test, and univariate and multivariate analyses were performed. RESULTS: The study patient cohort included 282 (28.0%) individuals who were pathologically confirmed as having BI among all 1006 patients with benign or atypical meningioma. A significant difference in recurrence-free survival was observed between patients who had benign meningioma with BI and those who had classical atypical meningioma (p < 0.001), as well as between patients with benign meningiomas and those without BI (p = 0.003). Multivariate Cox analysis indicated that BI was independently associated with increased risk of relapse in the entire population (HR 1.46, 95% CI 1.01-2.12, p = 0.049) and in the atypical meningioma subcohort (HR 2.21, 95% CI 1.32-3.71, p = 0.003), as well as the benign meningioma with and without BI subcohorts (HR 1.89, 95% CI 1.01-3.56, p = 0.049). Moreover, patients with classical atypical meningiomas had a risk of relapse four times higher than those who had benign meningioma with BI (p < 0.001). CONCLUSIONS: The findings demonstrate that benign meningioma with BI typically has an intermediate prognosis and can be differentiated from benign meningioma and classical atypical meningioma, which suggests that the importance of the diagnostic effect of BI is insufficiently accounted for in grading of atypical meningioma. Increased emphasis on the presence of BI in patients with atypical meningioma may be helpful in postsurgical decision-making and facilitating improvements in individual therapy.

SIGNET: Transcriptome-wide Causal Inference for Gene Regulatory Networks.

Gene regulation plays an important role in understanding the mechanisms of human biology and diseases. However, inferring causal relationships between all genes is challenging due to the large number of genes in the transcriptome. Here, we present SIGNET (Statistical Inference on Gene Regulatory Networks), a flexible software package that reveals networks of causal regulation between genes built upon large-scale transcriptomic and genotypic data at the population level. Like Mendelian randomization, SIGNET uses genotypic variants as natural instrumental variables to establish such causal relationships but constructs a transcriptome-wide gene regulatory network with high confidence. SIGNET makes such a computationally heavy task feasible by deploying a well-designed statistical algorithm over a parallel computing environment. It also provides a user-friendly interface allowing for parameter tuning, efficient parallel computing scheduling, interactive network visualization, and confirmatory results retrieval. The Open source SIGNET software is freely available (https://www.zstats.org/signet/).

Network analysis of internet addiction and sleep disturbance symptoms.

BACKGROUND: Internet addiction (IA) is a behavioral addiction to problematic internet use. IA is associated with poorer sleep quality. Few studies to date, however, have explored the interactions between symptoms of IA and symptoms of sleep disturbance. This study uses network analysis to identify bridge symptoms by analyzing these interactions in a large sample of students. METHOD: We recruited 1977 university students to participate in our study. Each student completed the Internet Addiction Test (IAT) and the Pittsburgh Sleep Quality Index (PSQI). We used these collected data for network analysis to identify the bridge symptoms in the IAT-PSQI network by calculating the bridge centrality. Furthermore, the closest symptom connected with the bridge symptom was found to identify the comorbidity mechanisms. RESULTS: The core symptom of IA and the sleep disturbance network was "I08" (Study efficiency suffers due to internet use). The bridge symptoms between IA and sleep disturbance were "I14" (Surfing the internet late instead of sleeping), "P_DD" (Daytime dysfunction), and "I02" (Spending much time online instead of socializing in real life). Among the symptoms, "I14" had the highest bridge centrality. The edge connecting nodes "I14" and "P_SDu" (Sleep duration) had the strongest weight (0.102) around all the symptoms of sleep disturbance. Nodes "I14" and "I15" (Thinking about online shopping, games, social networking, and other network activities when unable to access the internet) had the strongest weight (0.181), connecting all the symptoms of IA. CONCLUSIONS: IA leads to poorer sleep quality, most likely by shortening sleep duration. Preoccupation with and craving the internet while being offline may lead to this situation. Healthy sleep habits should be learned, and craving may be a good point at which to treat the symptoms of IA and sleep disturbance.

Comparison of temporal-to-frontal horn shunt and ventriculo-peritoneal shunt for treatment of trapped temporal horn: a retrospective cohort study.

As a localized hydrocephalus, trapped temporal horn (TTH) can be effectively resolved via cerebrospinal fluid shunting. In addition to conventional ventriculo-peritoneal shunt (VPS), temporal-to-frontal horn shunt (TFHS) has been described as a less complex and invasive procedure with promising results; however, there is limited data comparing VPS to TFHS regarding patient outcomes. This study aims to compare TFHS versus VPS for treatment of TTH. We conducted a comparative cohort study with patients undergoing TFHS or VPS for TTH after surgery of trigonal or peritrigonal tumors between 2012 and 2021. The primary outcome was revision rates at 30-day, 6-month, and 1-year. Secondary outcomes included operative duration, postoperative pain, hospital stay, overdrainage, and cost for shunt placement and revision. A total of 24 patients included, with 13 (54.2%) patients receiving TFHS and 11 (45.8%) receiving VPS. Both cohorts shared similar baseline characteristics. There were no significant differences between TFHS and VPS in 30-day (7.7% vs 9.1%, p > 0.99), 6-month (7.7% vs 18.2%, p = 0.576), or 1-year (8.3% vs 18.2%, p = 0.590) revision rates. There were no significant differences in terms of operative duration (93.5 ± 24.1 vs 90.5 ± 29.6 min, p = 0.744), surgical site pain (0 vs 18.2%, p = 0.199), or postoperative length of stay (4.8 ± 2.6 vs 6.9 ± 4.0 days, p = 0.157) between the two groups. For the TFHS cohort, no patient experienced shunt related overdrainage, and there was a trend towards fewer overdrainage (0% vs 27.3%, p = 0.082) compared with VPS. TFHS offered significant reduction in cost for initial shunt (¥20,417 vs ¥33,314, p = 0.030) and total costs for shunt and revision (¥21,602 vs ¥43,196, p = 0.006) compared to VPS. As a technique of valveless shunt and without abdominal incision, TFHS is cosmetic, cost-effective, and completely free of overdrainage with similar revision rates as compared with VPS.

Haemophilia item bank based on International Classification of Functioning, Disability and Health: a systematic review.

BACKGROUND AND OBJECTIVES: Haemophilia comprises a continuum of blood disorders that often include joint and muscular dysfunction, which may lead to a constellation of activity limitations and participation restrictions. However, there is scant research incorporating functional assessment scales into the common language provided by the International Classification of Functioning, Disability and Health (ICF). This study aims to identify the ICF categories to include in an item bank of functioning aspects relevant for haemophilia. DESIGN AND METHODS: A systematic search was carried out in July 2021 based on the PubMed MEDLINE, CLINICAL, and Cochrane databases for qualified articles, investigating haemophilia-specific scales and the scales recommended by the World Federation of Haemophilia (WFH) linked to ICF categories between 2001 and 2021. Well-trained healthcare professionals in the haemophilia field and ICF evaluation conducted group discussions to determine the ICF items for haemophilia. RESULTS: A total of 112 out of 176 items measuring function were collected for the haemophilia ICF item bank, including 32 items for body function (b), 45 items for activity and participation (d), 27 items for environmental factors (e), and 8 items for body structure(s). INTERPRETATION AND CONCLUSIONS: We recommend that future haemophilia research use the haemophilia-specific ICF item bank, which could capture a whole spectrum of functional measurements and facilitate multidisciplinary and worldwide communication. This study also indicates that further development and analysis of the psychometric properties of the 112 haemophilia-related ICF items is warranted.

Comprehensive Analysis of Major Latex-Like Protein Family Genes in Cucumber (Cucumis sativus L.) and Their Potential Roles in Phytophthora Blight Resistance.

Major latex-like proteins (MLPs) play crucial roles in abiotic and biotic stresses. However, little was known about this gene family in cucumbers. In this study, a total of 37 putative cucumber MLP genes were identified on a genome-wide level and classified into three groups by sequence homologous comparison with Arabidopsis thaliana. Chromosome mapping suggested that only tandem duplication occurred in evolution. The multiple regulatory cis-elements related to stress, hormone, light and growth response were found in the promoter region of these CsMLP genes, indicating that CsMLPs might be widely involved in the process of plant growth, development and various stress conditions. Transcriptome analysis indicated a strong reprogramming of MLPs expression in response to Phytophthora melonis infection in cucumber. Knockdown of CsMLP1 reduced the P. melonis tolerance, while transient overexpression of CsMLP1 improved disease tolerance in cucumber. Conversely, the silence of CsMLP5 decreased the lesion area caused by P. melonis in the cotyledons, and overexpression of CsMLP5 promoted lesion expansion. Taken together, our results provide a comprehensive basis for further mining the function of CsMLP members and will also be significant for elucidating the evolutionary relationship in cucumber.

ICF-Based simple scale for children with cerebral palsy: Application of Mokken scale analysis and Rasch modeling.

Children with cerebral palsy (CP) are faced with long-term dysfunction. The International Classification of Functioning, Disability and Health for Children and Youth (ICF-CY) has been proposed but the complicated procedure limits the feasibility of clinical application and the exploration of health degrees. This study was aimed to establish a Mokken scale based on the ICF-CY for CP, and then to estimate psychometric properties through the derived Rasch model. 150 children with CP were assessed by the categories of "b" and "d" components in the core set. The binarized data was screened by the Mokken scale analysis and utilized for generating a reliable Rasch model. The validity of the final model was checked by the correlation between person ability, Gross Motor Function Classification System (GMFCS) and total scores. Using the Mokken scale to guide Rasch modeling, we can parameterize the properties of ICF-CY and realize the simple assessment of person abilities for children with CP.

Activity and participation in haemophiliacs: Item response modelling based on international classification of functioning, disability and health.

BACKGROUND AND OBJECTIVES: There is scant research investigating the user-friendly functional assessment tool conceptualized by the International Classification of Functioning, Disability and Health (ICF) among persons with haemophilia (PWH). This study aims to accomplish two goals: (1) quantifying comprehensive functioning measures of haemophilia through Item Response Theory (IRT); (2) discussing patient-centred care based on the Wright map of personal ability and item difficulty. METHODS: A cross-sectional study was carried out in 70 PWH (mean age, 33.09 ± 11.04) via convenience sampling. All patients completed the 45 ICF categories of haemophilic-specific activity and participation. Psychometric properties of the categories were examined using Mokken scale analysis and parametric item response modelling. RESULTS: We extracted a unidimensional scale with 31 categories, and constructed a Rasch model with good fitness. The Cronbach's α of the scale was .9713, with the Guttman's λ2  = .9730, Molenaar Sijtsma ρ = .9802, and latent class reliability coefficient = .9769, indicating great internal reliability. The estimated individual social competence by the Rasch model was highly related to the index score of the three-level EuroQol five-dimensional questionnaire (EQ-5D-3L) (p < .001, r = .62), and had a moderate correlation (p < .001, r = .54) with the score of Haemophilia Activities List (HAL). CONCLUSIONS: The ICF scale of haemophilic activity and participation with 31 categories (HAPPY-ICF) has good construct validity and internal consistency. The person-item threshold distribution map might be helpful in research and clinical practices for patient-oriented care.

Integrated genomic analysis identifies novel low-frequency cis-regulatory variant rs2279658 associated with VSD risk in Chinese children.

VSD combined with other cardiac or extracardiac malformations (defined as "complex VSD" by us) is one of the major causes of perinatal morbidity and mortality. Functional non-coding SNPs (cis-regulatory SNPs) have not been systematically studied in CHDs, including complex VSD. Here we report an exome-wide association analysis using WES data of 60 PA/VSD cases, 20 TOF cases and 100 controls in Chinese children. We identify 93 low-frequency non-coding SNPs associated with complex VSD risk. A functional genomics pipeline integrating ATAC-seq, ChIP-seq and promoter CHi-C recognizes the rs2279658 variant as a candidate cis-regulatory SNP. Specifically, rs2279658 resides in a cardiac-specific enhancer bound by FOXH1 and PITX2, and would abrogate binding of these two transcription factors to the identified enhancer during cardiac morphogenesis. COQ2 and FAM175A are predicted to be target genes for "rs2279658-FOXH1 or PITX2" pairs in the heart. These findings highlight the importance of cis-regulatory SNPs in the pathogenesis of complex VSD and broaden our understanding of this disease.