Development and validation of an interpretable machine learning model for predicting post-stroke epilepsy.

BACKGROUND: Epilepsy is a serious complication after an ischemic stroke. Although two studies have developed prediction model for post-stroke epilepsy (PSE), their accuracy remains insufficient, and their applicability to different populations is uncertain. With the rapid advancement of computer technology, machine learning (ML) offers new opportunities for creating more accurate prediction models. However, the potential of ML in predicting PSE is still not well understood. The purpose of this study was to develop prediction models for PSE among ischemic stroke patients. METHODS: Patients with ischemic stroke from two stroke centers were included in this retrospective cohort study. At the baseline level, 33 input variables were considered candidate features. The 2-year PSE prediction models in the derivation cohort were built using six ML algorithms. The predictive performance of these machine learning models required further appraisal and comparison with the reference model using the conventional triage classification information. The Shapley additive explanation (SHAP), based on fair profit allocation among many stakeholders according to their contributions, is used to interpret the predicted outcomes of the naive Bayes (NB) model. RESULTS: A total of 1977 patients were included to build the predictive model for PSE. The Boruta method identified NIHSS score, hospital length of stay, D-dimer level, and cortical involvement as the optimal features, with the receiver operating characteristic curves ranging from 0.709 to 0.849. An additional 870 patients were used to validate the ML and reference models. The NB model achieved the best performance among the PSE prediction models with an area under the receiver operating curve of 0.757. At the 20 % absolute risk threshold, the NB model also provided a sensitivity of 0.739 and a specificity of 0.720. The reference model had poor sensitivities of only 0.15 despite achieving a helpful AUC of 0.732. Furthermore, the SHAP method analysis demonstrated that a higher NIHSS score, longer hospital length of stay, higher D-dimer level, and cortical involvement were positive predictors of epilepsy after ischemic stroke. CONCLUSIONS: Our study confirmed the feasibility of applying the ML method to use easy-to-obtain variables for accurate prediction of PSE and provided improved strategies and effective resource allocation for high-risk patients. In addition, the SHAP method could improve model transparency and make it easier for clinicians to grasp the prediction model's reliability.

Circular RNA LMBR1 inhibits bladder cancer progression by enhancing expression of the protein ALDH1A3.

Background: Circular RNAs (circRNAs) have been identified as playing an integral role in the development of bladder cancer (BC). However, the mechanism by which circRNAs operate in the chemical carcinogenesis of BC remains unclear. Methods: To explore this mechanism, we used RNA high-throughput sequencing to identify differentially expressed circRNA in bladder epithelial cells and chemically induced malignant transformed BC cells. Subsequently, in vitro experiments were conducted to investigate the biological function and molecular mechanism of circLMBR1 in BC. Finally, animal experiments were conducted to examine the clinical relevance of circLMBR1 in vivo. Results: Our profiling of circular RNA expression during cellular malignant transformation induced by chemical carcinogens identified a subset of circRNAs associated with cell transformation. We verified that the expression of circLMBR1 in bladder epithelial malignant transformed cells was decreased compared with control cells, as well as in BC tissues and bladder cell lines. Furthermore, circLMBR1 was seen to inhibit the proliferation, invasion, and migration of BC cells both in vitro and in vivo. Mechanistically, circLMBR1 was found to exert its antitumor effect by binding to the protein ALDH1A3. Conclusions: Our findings have revealed that circLMBR1 inhibits the progression of BC cells by binding to ALDH1A3 and upregulating its expression. As such, circLMBR1 serves as a promising predictor of BC and may provide a novel therapeutic target for the treatment of BC.

Stromal-Like Cells Are Found in Peripheral Blood of Patients With Inflammatory Bowel Disease and Correlate With Immune Activation State.

INTRODUCTION: Recent studies have identified a critical role of stromal-immune cell interactions in immunity and immune tolerance. Transcriptomic profiling has implicated stromal cells in immune-mediated disorders including the 2 common forms of inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC). Stromal-immune interactions may edify inflammatory state and the development of IBD-related complications such as fibrosis, yet the lack of protein markers has hampered studying stromal-immune perturbation. METHODS: In this study, we designed a 40-color spectral flow cytometry assay to characterize hematopoietic and nonhematopoietic cells in intestinal biopsies and matched blood samples from patients with CD or UC. RESULTS: We identified circulating stromal-like cells that are significantly more abundant in IBD blood samples than in healthy controls. Those cells expressed podoplanin (PDPN), a commonly used marker for fibroblasts, and they were associated with activated and memory T and B cells and altered natural killer cell, monocyte, and macrophage populations. PDPN + cells in the blood correlated with PDPN + cells in the colon. Principal component analysis distinctly separated healthy blood samples from IBD blood samples, with stromal-like cells and B-cell subtypes dominating the IBD signature; Pearson correlation detected an association between PDPN + stromal-like cells and B-cell populations in IBD blood and gut biopsies. DISCUSSION: These observations suggest that PDPN + cells in the blood may serve as a biomarker of IBD. Understanding the relationship between stromal cells and immune cells in the intestine and the blood may provide a window into disease pathogenesis and insight into therapeutic targets for IBD.

Response of Ionic Hydration Structure and Selective Transport Behavior to Aqueous Solution Chemistry during Nanofiltration.

The effect of aqueous solution chemistry on the ionic hydration structure and its corresponding nanofiltration (NF) selectivity is a research gap concerning ion-selective transport. In this study, the hydration distribution of two typical monovalent anions (Cl- and NO3-) under different aqueous solution chemical conditions and the corresponding transmembrane selectivity during NF were investigated by using in situ liquid time-of-flight secondary ion mass spectrometry in combination with molecular dynamics simulations. We demonstrate the inextricable link between the ion hydration structure and the pore steric effect and further find that ionic transmembrane transport can be regulated by breaking the balance between the hydrogen bond network (i.e., water-water) and ion hydration (i.e., ion-water) interactions of hydrated ion. For strongly hydrated (H2O)nCl- with more intense ion-water interactions, a higher salt concentration and coexisting ion competition led to a larger hydrated size and, thus, a higher ion rejection by the NF membrane, whereas weakly hydrated (H2O)nNO3- takes the reverse under the same conditions. Stronger OH--anion hydration competition resulted in a smaller hydrated size of (H2O)nCl- and (H2O)nNO3-, showing a lower observed average hydration number at pH 10.5. This study deepens the long-overlooked understanding of NF separation mechanisms, concerning the hydration structure.

Hospital-acquired infections as a risk factor for post-traumatic epilepsy: A registry-based cohort study.

OBJECTIVE: Hospital-acquired infections are a common complication for patients with moderate or severe traumatic brain injury (TBI), contributing to morbidity and mortality. As infection-mediated immune responses can predispose towards epilepsy, we hypothesized that post-injury hospital-acquired infections increase the risk of post-traumatic epilepsy (PTE). METHODS: A retrospective cohort study of adults with moderate to severe TBI was conducted using data from the Victorian State Trauma Registry in Australia. Infections were identified from the International Statistical Classification of Diseases and Related Health Problems 10th Revision-Australian Modification (ICD-10-AM) codes, and diagnosis of PTE was determined by the Glasgow Outcome Scale - Extended questionnaire regarding epileptic fits at 24 months follow-up. RESULTS: Of all TBI patients (n = 15 152), 24% had evidence of having had any type of infection, with the most common being pneumonia, urinary tract, and respiratory infections. Of those who responded to the PTE question at 24 months (n = 1361), 11% had developed PTE. Univariable analysis found that the incidence of PTE was higher in patients who had any type of infection compared to patients without an infection (p < 0.001). After adjustment for covariates associated with both development of PTE and risk of infection, multivariable analysis found a solid association between infection and PTE (adjusted RR = 1.59; 95% CI: 1.11-2.28; p = 0.011). Having any type of complicating infection acquired during admission was also associated with poor GOSE outcomes at subsequent follow-ups (adjusted OR = 0.20; 95% CI: 0.11-0.35, p < 0.001). SIGNIFICANCE: These findings suggest that hospital-acquired infections contribute to PTE development after TBI. Future investigation into infections as a modifiable target to reduce poor outcomes after TBI is warranted. PLAIN LANGUAGE SUMMARY: Hospital-acquired infections are common in patients with traumatic brain injuries. A database study of adults with moderate or severe brain injuries in Australia examined whether these infections are associated with the development of epilepsy after a brain injury. 24% of patients had infections, with pneumonia and urinary tract infections being the most common. Of those surveyed 2 years after the injury, 11% developed post-traumatic epilepsy. Patients with infections had a significantly higher risk of epilepsy, even when accounting for other known risk factors, and infections were also linked to poor outcomes more broadly. The study suggests that preventing hospital-acquired infections could be a crucial target for improving outcomes after traumatic brain injuries.

Efficacy and safety of Chinese patent medicine combined with 5-aminosalicylic acid for patients with ulcerative colitis: A network meta-analysis of randomized controlled trials.

Objectives: Given the widespread use of Chinese patent medicines (CPMs) in combination with 5-aminosalicylic acid (5-ASA) for Ulcerative colitis (UC) patients, this study aimed to evaluate the efficacy and safety of nine CPMs combined with 5-ASA in the treatment of UC. Methods: A systematic literature search was conducted in eight databases from inception to May 2023 to identify eligible RCTs evaluating the effects of CPM combined with 5-ASA for the treatment of UC. The methodological quality of the included RCTs was assessed using the Cochrane risk of bias tool in Review Manager 5.4. The primary outcome of the meta-analysis was the overall response rate. The secondary outcomes included excellent rate, disease activity index (DAI), IL-6, IL-8, and TNF-α levels, mean platelet volume (MPV), fibrinogen (FIB) levels, recurrence rate, and adverse event rate. Network meta-analysis was performed using Review Manager 5.4 and Stata 15.0. Results: In total, 70 RCTs including 5973 patients and 10 treatment regimens were included. The combination of Kangfuxin Liquid (KFL) and 5-ASA showed the greatest efficacy in improving FIB levels and the overall response rate. Bupi Yichang Pill (BYP) combined with 5-ASA was associated with the fewest adverse events and the lowest recurrence rate. Hudi Enteric-coated Capsule (HEC) combined with 5-ASA ranked first in improving DAI. ZhiKang Capsule (ZKC), ChangYanNing Capsule (CYN), and Danshen Injection (DSI) combined with 5-ASA ranked first in improving IL-6, IL-10, and TNF-α levels, respectively. Shenling Baizhu Powder (SBP) combined with 5-ASA was associated with the highest excellent rate. Conclusions: CPM combined with 5-ASA may be more effective than 5-ASA alone for treating UC. Besides, CPM combined with 5-ASA could better reduce the recurrence rate and adverse event rate in UC patients. The current meta-analysis provides statistical evidence for clinical application.Systematic Review Registration: International Prospective Register of Systematic Reviews (PROSPERO), No. CRD42023433672.

In situ cleaning of foulants by gas scouring on the membrane-electrode in an electro-membrane bioreactor.

Low-maintenance membrane cleaning is essential for the stable operation of membrane bioreactors. This work proposes an in-situ electrical-cleaning method using an electro-MBR. When the applied bias was transiently increased, the membrane flux recovered rapidly because of the scouring effect from gas evolution reactions. The exfoliation of the cake layer induced by gas scouring played a major role in mitigating membrane fouling, recovering the transmembrane pressure (TMP) by 88.6 % under optimal conditions. Membrane modules did not require replacement during the operation period due to the efficacy of electrical cleaning, with the TMP varying between 37.5 % and 62.5 % of the ultimate pressure requiring change of the membrane modules. Despite the increase in power consumption of 0.66 Wh·m-3 due to the additional applied bias, there was no need for chemical additives or manual maintenance. Therefore, the electrical cleaning method enhanced the service life and reduced the maintenance costs of the electro-MBR.

SOX9 is regulated by AURKA in response to Helicobacter pylori infection via EIF4E-mediated cap-dependent translation.

Helicobacter pylori (H. pylori) infection is the main risk factor for gastric cancer. The SRY-Box Transcription Factor 9 (SOX9) serves as a marker of stomach stem cells. We detected strong associations between AURKA and SOX9 expression levels in gastric cancers. Utilizing in vitro and in vivo mouse models, we demonstrated that H. pylori infection induced elevated levels of both AURKA and SOX9 proteins. Notably, the SOX9 protein and transcription activity levels were dependent on AURKA expression. AURKA knockdown led to a reduction in the number and size of gastric gland organoids. Conditional knockout of AURKA in mice resulted in a decrease in SOX9 baseline level in AURKA-knockout gastric glands, accompanied by diminished SOX9 induction following H. pylori infection. We found an AURKA-dependent increase in EIF4E and cap-dependent translation with an AURKA-EIF4E-dependent increase in SOX9 polysomal RNA levels. Immunoprecipitation assays demonstrated binding of AURKA to EIF4E with a decrease in EIF4E ubiquitination. Immunohistochemistry analysis on tissue arrays revealed moderate to strong immunostaining of AURKA and SOX9 with a significant correlation in gastric cancer tissues. These findings elucidate the mechanistic role of AURKA in regulating SOX9 levels via cap-dependent translation in response to H. pylori infection in gastric tumorigenesis.

Australian Headache Epidemiology Data (AHEAD): a pilot study to assess sampling and engagement methodology for a nationwide population-based survey.

BACKGROUND: There are no robust population-based Australian data on prevalence and attributed burden of migraine and medication-overuse headache (MOH) data. In this pilot cross-sectional study, we aimed to capture the participation rate, preferred response method, and acceptability of self-report questionnaires to inform the conduct of a future nationwide migraine/MOH epidemiological study. METHODS: We developed a self-report questionnaire, available in hard-copy and online, including modules from the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire, the Eq. 5D (quality of life), and enquiry into treatment gaps. Study invitations were mailed to 20,000 randomly selected households across Australia's two most populous states. The household member who most recently had a birthday and was aged ≥ 18 years was invited to participate, and could do so by returning a hard-copy questionnaire via reply-paid mail, or by entering responses directly into an online platform. RESULTS: The participation rate was 5.0% (N = 1,000). Participants' median age was 60 years (IQR 44-71 years), and 64.7% (n = 647) were female. Significantly more responses were received from areas with relatively older populations and middle-level socioeconomic status. Hard copy was the more commonly chosen response method (n = 736). Females and younger respondents were significantly more likely to respond online than via hard-copy. CONCLUSIONS: This pilot study indicates that alternative methodology is needed to achieve satisfactory engagement in a future nationwide migraine/MOH epidemiological study, for example through inclusion of migraine screening questions in well-resourced, interview-based national health surveys that are conducted regularly by government agencies. Meanwhile, additional future research directions include defining and addressing treatment gaps to improve migraine awareness, and minimise under-diagnosis and under-treatment.

Improving physical movement during stroke rehabilitation: investigating associations between sleep measured by wearable actigraphy technology, fatigue, and key biomarkers.

BACKGROUND: Sleep disturbance and fatigue are common in individuals undergoing inpatient rehabilitation following stroke. Understanding the relationships between sleep, fatigue, motor performance, and key biomarkers of inflammation and neuroplasticity could provide valuable insight into stroke recovery, possibly leading to personalized rehabilitation strategies. This study aimed to investigate the influence of sleep quality on motor function following stroke utilizing wearable technology to obtain objective sleep measurements. Additionally, we aimed to determine if there were relationships between sleep, fatigue, and motor function. Lastly, the study aimed to determine if salivary biomarkers of stress, inflammation, and neuroplasticity were associated with motor function or fatigue post-stroke. METHODS: Eighteen individuals who experienced a stroke and were undergoing inpatient rehabilitation participated in a cross-sectional observational study. Following consent, participants completed questionnaires to assess sleep patterns, fatigue, and quality of life. Objective sleep was measured throughout one night using the wearable Philips Actiwatch. Upper limb motor performance was assessed on the following day and saliva was collected for biomarker analysis. Correlation analyses were performed to assess the relationships between variables. RESULTS: Participants reported poor sleep quality, frequent awakenings, and difficulties falling asleep following stroke. We identified a significant negative relationship between fatigue severity and both sleep quality (r=-0.539, p = 0.021) and participants experience of awakening from sleep (r=-0.656, p = 0.003). A significant positive relationship was found between grip strength on the non-hemiplegic limb and salivary gene expression of Brain-derived Neurotrophic Factor (r = 0.606, p = 0.028), as well as a significant negative relationship between grip strength on the hemiplegic side and salivary gene expression of C-reactive Protein (r=-0.556, p = 0.048). CONCLUSION: The findings of this study emphasize the importance of considering sleep quality, fatigue, and biomarkers in stroke rehabilitation to optimize recovery and that interventions may need to be tailored to the individual. Future longitudinal studies are required to explore these relationships over time. Integrating wearable technology for sleep and biomarker analysis can enhance monitoring and prediction of outcomes following stroke, ultimately improving rehabilitation strategies and patient outcomes.

Trends and disparities in the prevalence of physical activity among US adults with epilepsy, 2010-2022.

BACKGROUND: Physical activity may be associated with health benefits for people with epilepsy. It remains unclear how the prevalence of physical activity has changed at a national level over the years and whether this prevalence varies between subgroups. METHODS: The National Health and Interview Survey, which was conducted from 2010 to 2017 and again in 2022, was used for our nationally representative study. This study explored the trends and disparities in meeting physical activity guidelines among US individuals with epilepsy and non-epilepsy adults. RESULTS: The prevalence of adults with epilepsy meeting physical activity guidelines was consistently lower and remained unchanged compared to those without epilepsy. Among the population with epilepsy, the prevalence of aerobic physical activity was 38.1 % (95 % CI, 32.6 %-43.5 %) in 2010 and 39.0 % (95 % CI, 33.4 %-44.7 %) in 2017 (P for trend = 0.84), and remained unchanged in 2022 (39.1 %). For muscle-strength training, the prevalence was 17.5 % (95 % CI, 13.3 %-21.7 %) in 2010 and 18.8 % (95 % CI, 14.8 %-22.8 %) in 2017 (P for trend = 0.82). The prevalence for both activities combined was 12.4 % (95 % CI, 8.7 %-16.2 %) in 2010 and 16.6 % (95 % CI, 12.8 %-20.5 %) in 2017 (P for trend = 0.26). The prevalence of aerobic physical activity varied by educational attainment, body mass index, comorbid conditions, alcohol-drinking status, and epilepsy status. CONCLUSION: This study suggests that the adherence rate to meeting physical activity guidelines among US adults with epilepsy was at a low level and had not improved over time. This finding highlights the need for additional nationwide efforts to promote physical activity in the US population with epilepsy.

Early Access to First-Seizure Clinics, Subsequent Outcomes, and Factors Associated With Attendance.

Importance: First-seizure clinics (FSCs) aim to deliver prompt specialist care to patients with new-onset undifferentiated seizure events. Objective: To determine whether FSC attendance and time to FSC are associated with subsequent health care utilization and mortality and to investigate factors associated with FSC nonattendance. Design, Setting, and Participants: This was a record-linkage, retrospective, cohort study of patients who booked appointments at 2 FSCs between 2007 and 2018. Patients' records were linked to state-wide administrative databases between 2000 and 2021. The setting comprised the FSCs of 2 major metropolitan public hospitals in Melbourne, Australia, providing national inpatient and outpatient adult epilepsy services. Of patients who booked appointments at the FSCs, those who were successfully linked for analysis were included in the study. Patients who recorded only canceled appointments were excluded from analysis of outcomes. Study data were analyzed from January 2000 to December 2021. Exposure: FSC attendance. Main Outcomes and Measures: Subsequent all-cause and seizure-related emergency department (ED) presentations and hospital admissions. Results: Of 10 162 patients with appointments at FSCs, 9392 were linked for analysis, with mean (SD) follow-up time 6.9 (2.8) years after FSC referral. A total of 703 patients were excluded. Among 9392 linked patients, 5398 were male (57.5%; mean [SD] age, 59.7 [11.2] years). FSC attendance was associated with reduced subsequent all-cause emergency presentations (adjusted incidence rate ratio [aIRR], 0.72; 95% CI, 0.66-0.79) and all-cause hospitalization (aIRR, 0.81; 95% CI, 0.75-0.88). Those who attended at the first-scheduled appointment, compared with those who attended only a rescheduled, delayed appointment, had reduced subsequent all-cause emergency presentations (aIRR, 0.83; 95% CI, 0.76-0.91), all-cause hospitalization (aIRR, 0.71; 95% CI, 0.65-0.79), seizure-related presentations (aIRR, 0.40; 95% CI, 0.33-0.49), and mortality (hazard ratio, 0.82; 95% CI, 0.69-0.98). Male sex was associated with nonattendance (adjusted relative risk [aRR], 1.12; 95% CI, 1.03-1.22), as were injury at emergency presentation (aRR, 1.12; 95% CI, 1.01-1.24), psychiatric comorbidity (aRR, 1.68; 95% CI, 1.55-1.81), previous seizure-related presentations (aRR, 1.35; 95% CI, 1.22-1.49), and delays (>14 days) between FSC referral and appointment (aRR, 1.35; 95% CI, 1.18-1.54). Hospitalization at referral was associated with reduced nonattendance (aRR, 0.80; 95% CI, 0.72-0.90), as were non-English language preference (aRR, 0.81; 95% CI, 0.69-0.94), distance greater than 6 mi from home to clinic (aRR, 0.85; 95% CI, 0.76-0.95), and physical comorbidity (aRR, 0.80; 95% CI, 0.72-0.89). Conclusions and Relevance: Results of this cohort study suggest that FSC attendance, particularly early attendance, was associated with reduced rates of subsequent hospital utilization. This knowledge may support adequately resourcing FSCs to improve equitable, timely access. Future study directions include assessing interventions that may support FSC attendance for at-risk groups.

Enterprise stents for the treatment of symptomatic non-acute intracranial artery stenosis disease: safety and efficiency evaluation.

BACKGROUND: Enterprise stent was approved for the treatment of wide-necked intracranial aneurysms. However, it has been widely used in the endovascular treatment of intracranial artery stenosis, which is still controversial. The purpose of this study was to evaluate the safety and efficiency of the Enterprise stent in the endovascular treatment of intracranial artery stenosis disease. METHODS: We conducted a retrospective case series of 107 patients with intracranial artery stenosis who received Enterprise stent implantation at Nanjing Drum Tower Hospital from January 2020 to December 2022. The rates of recanalization, perioperative complications, in-stent restenosis at 3-12 months and stroke recurrence were assessed for endovascular treatment. RESULTS: A total of 107 individuals were included in this study, 88 were followed up, and 19 (17.8%) patients were lost to follow-up. The operation success rate was 100%, During the procedure,4（3.7%）patients had vasospasm, and 2(1.9%) patients showed symptomatic bleeding. The overall perioperative complication rate was 5.6%, including 2.8% distal artery embolism, 0.9% in-stent thrombosis, and 1.9% symptomatic bleeding. 88 (82.2%) patients were followed up from 3 to 12 months, of whom 12 (13.6%) had in-stent restenosis, 4 (4.7%) recurrent strokes and 2 died of pulmonary infection caused by COVID-19. Patients were divided into 3 groups according to the cerebral artery, including the middle cerebral artery group, internal carotid artery group, and vertebrobasilar artery group. CONCLUSIONS: In this study, the placement of the Enterprise stent in patients with symptomatic non-acute intracranial stenosis was successful. However, the occurrence of periprocedural and long-term complications after stenting remains of high concern.

Correlation between risk factors of cognitive dysfunction and blood pressure variability after acute ischemic stroke in northwest Shanghai.

Abstract：Objective: To explore the relationship between risk factors of cognitive dysfunction and blood pressure variability after acute ischemic stroke in northwest Shanghai to establish a model for early identification of high-risk groups of cognitive dysfunction and formulation of more targeted prevention and treatment measures. Methods: Spearman test was used to evaluate the correlation between blood pressure variability and Montreal Cognitive Assessment (MoCA) score in patients with acute ischemic stroke and the partial regression coefficient model was constructed based on the above independent risk factors, and the receiver operating characteristic (ROC) curve was described to analyze the relevant independent risk factors. Results: ROC curve analysis results showed that the clinical prediction model was significantly more effective than a single factor in predicting the risk of cognitive impairment after acute ischemic stroke in northwest Shanghai（P < 0.05）. Conclusion: Cognitive dysfunction after acute ischemic stroke was closely related to high Homocysteine (Hcy) levels, high standard deviation of systolic blood pressure, previous infarction history and infarction of cognitive function area in northwest Shanghai. The prediction model based on the above factors showed satisfactory value in predicting of cognitive dysfunction risk after acute ischemic stroke and there was also the correlation between cognitive function and blood pressure variability.

Association of Localizing 18F-FDG-PET Hypometabolism and Outcome Following Epilepsy Surgery: Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Although commonly used in the evaluation of patients for epilepsy surgery, the association between the detection of localizing 18fluorine fluorodeoxyglucose PET (18F-FDG-PET) hypometabolism and epilepsy surgery outcome is uncertain. We conducted a systematic review and meta-analysis to determine whether localizing 18F-FDG-PET hypometabolism is associated with favorable outcome after epilepsy surgery. METHODS: A systematic literature search was undertaken. Eligible publications included evaluation with 18F-FDG-PET before epilepsy surgery, with ≥10 participants, and those that reported surgical outcome at ≥12 months. Random-effects meta-analysis was used to calculate the odds of achieving a favorable outcome, defined as Engel class I, International League Against Epilepsy class 1-2, or seizure-free, with localizing 18F-FDG-PET hypometabolism, defined as concordant with the epilepsy surgery resection zone. Meta-regression was used to characterize sources of heterogeneity. RESULTS: The database search identified 8,916 studies, of which 98 were included (total patients n = 4,104). Localizing 18F-FDG-PET hypometabolism was associated with favorable outcome after epilepsy surgery for all patients with odds ratio (OR) 2.68 (95% CI 2.08-3.45). Subgroup analysis yielded similar findings for those with (OR 2.64, 95% CI 1.54-4.52) and without epileptogenic lesion detected on MRI (OR 2.49, 95% CI 1.80-3.44). Concordance with EEG (OR 2.34, 95% CI 1.43-3.83), MRI (OR 1.69, 95% CI 1.19-2.40), and triple concordance with both (OR 2.20, 95% CI 1.32-3.64) was associated with higher odds of favorable outcome. By contrast, diffuse 18F-FDG-PET hypometabolism was associated with worse outcomes compared with focal hypometabolism (OR 0.34, 95% CI 0.22-0.54). DISCUSSION: Localizing 18F-FDG-PET hypometabolism is associated with favorable outcome after epilepsy surgery, irrespective of the presence of an epileptogenic lesion on MRI. The extent of 18F-FDG-PET hypometabolism provides additional information, with diffuse hypometabolism associated with worse surgical outcome than focal 18F-FDG-PET hypometabolism. These findings support the incorporation of 18F-FDG-PET into routine noninvasive investigations for patients being evaluated for epilepsy surgery to improve epileptogenic zone localization and to aid patient selection for surgery.

Memory/Active T-Cell Activation Is Associated with Immunotherapeutic Response in Fumarate Hydratase-Deficient Renal Cell Carcinoma.

PURPOSE: Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and lethal subtype of kidney cancer. However, the optimal treatments and molecular correlates of benefits for FH-deficient RCC are currently lacking. EXPERIMENTAL DESIGN: A total of 91 patients with FH-deficient RCC from 15 medical centers between 2009 and 2022 were enrolled in this study. Genomic and bulk RNA-sequencing (RNA-seq) were performed on 88 and 45 untreated FH-deficient RCCs, respectively. Single-cell RNA-seq was performed to identify biomarkers for treatment response. Main outcomes included disease-free survival (DFS) for localized patients, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for patients with metastasis. RESULTS: In the localized setting, we found that a cell-cycle progression signature enabled to predict disease progression. In the metastatic setting, first-line immune checkpoint inhibitor plus tyrosine kinase inhibitor (ICI+TKI) combination therapy showed satisfactory safety and was associated with a higher ORR (43.2% vs. 5.6%), apparently superior PFS (median PFS, 17.3 vs. 9.6 months, P = 0.016) and OS (median OS, not reached vs. 25.7 months, P = 0.005) over TKI monotherapy. Bulk and single-cell RNA-seq data revealed an enrichment of memory and effect T cells in responders to ICI plus TKI combination therapy. Furthermore, we identified a signature of memory and effect T cells that was associated with the effectiveness of ICI plus TKI combination therapy. CONCLUSIONS: ICI plus TKI combination therapy may represent a promising treatment option for metastatic FH-deficient RCC. A memory/active T-cell-derived signature is associated with the efficacy of ICI+TKI but necessitates further validation.

Amygdala enlargement in temporal lobe epilepsy: Histopathology and surgical outcomes.

OBJECTIVES: Amygdala enlargement is detected on magnetic resonance imaging (MRI) in some patients with drug-resistant temporal lobe epilepsy (TLE), but its clinical significance remains uncertain We aimed to assess if the presence of amygdala enlargement (1) predicted seizure outcome following anterior temporal lobectomy with amygdalohippocampectomy (ATL-AH) and (2) was associated with specific histopathological changes. METHODS: This was a case-control study. We included patients with drug-resistant TLE who underwent ATL-AH with and without amygdala enlargement detected on pre-operative MRI. Amygdala volumetry was done using FreeSurfer for patients who had high-resolution T1-weighted images. Mann-Whitney U test was used to compare pre-operative clinical characteristics between the two groups. The amygdala volume on the epileptogenic side was compared to the amygdala volume on the contralateral side among cases and controls. Then, we used a two-sample, independent t test to compare the means of amygdala volume differences between cases and controls. The chi-square test was used to assess the correlation of amygdala enlargement with (1) post-surgical seizure outcomes and (2) histopathological changes. RESULTS: Nineteen patients with and 19 patients without amygdala enlargement were studied. Their median age at surgery was 38 years for cases and 39 years for controls, and 52.6% were male. There were no statistically significant differences between the two groups in their pre-operative clinical characteristics. There were significant differences in the means of volume difference between cases and controls (Diff = 457.2 mm3, 95% confidence interval [CI] 289.6-624.8; p < .001) and in the means of percentage difference (p < .001). However, there was no significant association between amygdala enlargement and surgical outcome (p = .72) or histopathological changes (p = .63). SIGNIFICANCE: The presence of amygdala enlargement on the pre-operative brain MRI in patients with TLE does not affect the surgical outcome following ATL-AH, and it does not necessarily suggest abnormal histopathology. These findings suggest that amygdala enlargement might reflect a secondary reactive process to seizures in the epileptogenic temporal lobe.

Simulating the behavior of antioxidant to explore the mechanisms of oxidative stability in Pickering emulsion.

This study explores effective strategies for bolstering emulsion oxidative stability via optimized interfacial distribution of varying hydrophobicity antioxidants (gallic acid, propyl gallate, octyl gallate) in zein nanoparticle (ZP) stabilized Pickering emulsions. Experimental and simulation methods revealed that antioxidant (AO) with higher hydrophobicity or loaded into ZP demonstrated stronger hydrogen bonding and van der Waals interactions with ZP. This increased interfacial loading of antioxidants resulted in improved oxidative stability in Pickering emulsions. The flow, distribution and orientation of AO, as revealed by dissipative dynamics simulations, highlighted the role of hydrophobic interactions during initial AO migration, influenced by varied alkyl chain lengths. Subsequent interface rearrangements arose from conservative force interactions between the AO's phenol hydroxyl ends and ZP. These findings inform effective interfacial engineering to optimize antioxidant efficiency, guiding practical applications in emulsion systems for improved oxidative stability.

Sodium butyrate activates the KATP channels to regulate the mechanism of Parkinson's disease microglia model inflammation.

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disorder. Microglia-mediated neuroinflammation has emerged as an involving mechanism at the initiation and development of PD. Activation of adenosine triphosphate (ATP)-sensitive potassium (KATP ) channels can protect dopaminergic neurons from damage. Sodium butyrate (NaB) shows anti-inflammatory and neuroprotective effects in some animal models of brain injury and regulates the KATP channels in islet ß cells. In this study, we aimed to verify the anti-inflammatory effect of NaB on PD and further explored potential molecular mechanisms. METHODS: We established an in vitro PD model in BV2 cells using 1-methyl-4-phenylpyridinium (MPP+ ). The effects of MPP+ and NaB on BV2 cell viability were detected by cell counting kit-8 assays. The morphology of BV2 cells with or without MPP+ treatment was imaged via an optical microscope. The expression of Iba-1 was examined by the immunofluorescence staining. The intracellular ATP content was estimated through the colorimetric method, and Griess assay was conducted to measure the nitric oxide production. The expression levels of pro-inflammatory cytokines and KATP channel subunits were evaluated by reverse transcription-quantitative polymerase chain reaction and western blot analysis. RESULTS: NaB (5 mM) activated the KATP channels through elevating Kir6.1 and Kir6.1 expression in MPP+ -challenged BV2 cells. Both NaB and pinacidil (a KATP opener) suppressed the MPP+ -induced activation of BV2 cells and reduced the production of nitrite and pro-inflammatory cytokines in MPP+ -challenged BV2 cells. CONCLUSION: NaB treatment alleviates the MPP+ -induced inflammatory responses in microglia via activation of KATP channels.

Preliminary findings on diagnostic performance of computed tomography perfusion images for intracranial arterial stenosis: a retrospective study.

OBJECTIVES: Computed tomographic perfusion (CTP) can play an auxiliary role in the selection of patients with acute ischemic stroke for endovascular treatment. However, data on CTP in non-stroke patients with intracranial arterial stenosis are scarce. We aimed to investigate images in patients with asymptomatic intracranial arterial stenosis to determine the detection accuracy and interpretation time of large/medium-artery stenosis or occlusion when combining computed tomographic angiography (CTA) and CTP images. METHODS: We retrospectively reviewed 39 patients with asymptomatic intracranial arterial stenosis from our hospital database from January 2021 to August 2023 who underwent head CTP, head CTA, and digital subtraction angiography (DSA). Head CTA images were generated from the CTP data, and the diagnostic performance for each artery was assessed. Two readers independently interpreted the CTA images before and after CTP, and the results were analyzed. RESULTS: After adding CTP maps, the accuracy (area under the curve) of diagnosing internal carotid artery (R1: 0.847 vs. 0.907, R2: 0.776 vs. 0.887), middle cerebral artery (R1: 0.934 vs. 0.933, R2: 0.927 vs. 0.981), anterior cerebral artery (R1: 0.625 vs. 0.750, R2: 0.609 vs. 0.750), vertebral artery (R1: 0.743 vs. 0.764, R2: 0.748 vs. 0.846), and posterior cerebral artery (R1: 0.390 vs. 0.575, R2: 0.390 vs. 0.585) occlusions increased for both readers (p < 0.05). Mean interpretation time (R1: 72.4 ± 6.1 s vs. 67.7 ± 6.4 s, R2: 77.7 ± 3.8 s vs. 72.6 ± 4.7 s) decreased when using a combination of both images both readers (p < 0.001). CONCLUSIONS: The addition of CTP images improved the accuracy of interpreting CTA images and reduced the interpretation time in asymptomatic intracranial arterial stenosis. These findings support the use of CTP imaging in patients with asymptomatic intracranial arterial stenosis.