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Justine Cormier, Catherine J ChuMassachusetts General Hospital, Department of Neurology, Programs in Child Neurology and Neurophysiology, Boston, MA, USAAbstract: Epilepsy is a common neurological disorder in the pediatric population, affecting up to one percent of children, and for which the mainstay of treatment is anticonvulsant medication. Despite the frequent use of anticonvulsant drugs, remarkably little is known about the safety and efficacy of most of these medications in the pediatric epilepsy population. Of 34 anticonvulsants currently approved for use by the US Food and Drug Administration (FDA), only 13 have been approved for use in children. Although infants and young children are disproportionately affected by epilepsy, there are currently only three anticonvulsant medications that have been specifically evaluated and approved for use in children younger than 2 years of age. In 2012, the FDA approved levetiracetam as an adjunctive treatment for partial onset seizures in infants and children from one month of age. Here we review the available data on levetiracetam in the pediatric epilepsy population. We first discuss the pharmacological profile of levetiracetam, including its mechanism of action, formulations and dosing, and pharmacokinetics in children. We then review the available efficacy, safety, and tolerability data in children from one month of age with partial onset seizures. We conclude that the current data leading to the approval of levetiracetam for use in infants and children with partial onset seizures is encouraging, although more work needs to be done before definitive conclusions can be drawn about the efficacy of levetiracetam across different pediatric age groups.Keywords: levetiracetam, anticonvulsant drug, partial seizures, pediatric epilepsy

High-efficiency photon color conversion is an approach of great potential for implementing color display. Inspired by the observation of emission enhancement in a nanoscale cavity, a novel technique to fabricate an array of color converter by mixing colloidal quantum dots (QDs) with the electrolyte of an electrochemical etching (ECE) process is demonstrated. In this process, QDs flow with the electrolyte into the etched subsurface nanoscale porous structure (PS) and settle inside. Since the PS formation and hence QD insertion are controlled by the flow path of the applied electric current in the ECE process, this technique can be used for fabricating any graphic pattern. The nanostructure of such a QD-inserted mesa is examined to confirm QD insertion. Although only single-color mesa arrays are demonstrated in this paper, this technique can be used for fabricating a multiple-color mesa array if a QD or a light-emitting nanoparticle of higher thermal stability is available., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background: Cirrhosis is a major global cause of mortality, and upper gastrointestinal (GI) bleeding significantly increases the mortality risk in these patients. Although scoring systems such as the Child-Pugh score and the Model for End-stage Liver Disease evaluate the severity of cirrhosis, none of these systems specifically target the risk of mortality in patients with upper GI bleeding. In this study, we constructed machine learning (ML) models for predicting mortality in patients with cirrhosis and upper GI bleeding, particularly in emergency settings, to achieve early intervention and improve outcomes., Methods: In this retrospective study, we analyzed the electronic health records of adult patients with cirrhosis who presented at an emergency department (ED) with GI bleeding between 2001 and 2019. Data were divided into training and testing sets at a ratio of 90:10. The ability of three ML models-a linear regression model, an XGBoost (XGB) model, and a three-layer neural network model-to predict mortality in the patients was evaluated., Results: A total of 16,025 patients with cirrhosis and 32,826 ED visits for upper GI bleeding were included in the study. The in-hospital and ED mortality rates were 11.2% and 2.2%, respectively. The XGB model exhibited the highest performance in predicting both in-hospital and ED mortality (area under the receiver operating characteristic curve: 0.866 and 0.861, respectively). International normalized ratio, renal function, red blood cell distribution width, age, and white blood cell count were the strongest predictors in all the ML models. The median ED length of stay for the ED mortality group was 17.54 h (7.16-40.01 h)., Conclusions: ML models can be used to predict mortality in patients with cirrhosis and upper GI bleeding. Of the three models, the XGB model exhibits the highest performance. Further research is required to determine the actual efficacy of our ML models in clinical settings.

Epilepsy is a major neurological disorder characterized by recurrent, spontaneous seizures. For patients with drug-resistant epilepsy, treatments include neurostimulation or surgical removal of the epileptogenic zone (EZ), the brain region responsible for seizure generation. Precise targeting of the EZ requires reliable biomarkers. Spike ripples - high-frequency oscillations that co-occur with large amplitude epileptic discharges - have gained prominence as a candidate biomarker. However, spike ripple detection remains a challenge. The gold-standard approach requires an expert manually visualize and interpret brain voltage recordings, which limits reproducibility and high-throughput analysis. Addressing these limitations requires more objective, efficient, and automated methods for spike ripple detection, including approaches that utilize deep neural networks. Despite advancements, dataset heterogeneity and scarcity severely limit machine learning performance. Our study explores long-short term memory (LSTM) neural network architectures for spike ripple detection, leveraging data augmentation to improve classifier performance. We highlight the potential of combining training on augmented and in vivo data for enhanced spike ripple detection and ultimately improving diagnostic accuracy in epilepsy treatment., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In severe epileptic encephalopathies, epileptic activity contributes to progressive cognitive dysfunction. Epileptic encephalopathies share the trait of spike-wave activation during non-REM sleep (EE-SWAS), a sleep stage dominated by sleep spindles, which are brain oscillations known to coordinate offline memory consolidation. Epileptic activity has been proposed to hijack the circuits driving these thalamocortical oscillations, thereby contributing to cognitive impairment. Using a unique dataset of simultaneous human thalamic and cortical recordings in subjects with and without EE-SWAS, we provide evidence for epileptic spike interference of thalamic sleep spindle production in patients with EE-SWAS. First, we show that epileptic spikes and sleep spindles are both predicted by slow oscillations during stage two sleep (N2), but at different phases of the slow oscillation. Next, we demonstrate that sleep-activated cortical epileptic spikes propagate to the thalamus (thalamic spike rate increases after a cortical spike, P ≈ 0). We then show that epileptic spikes in the thalamus increase the thalamic spindle refractory period (P ≈ 0). Finally, we show that in three patients with EE-SWAS, there is a downregulation of sleep spindles for 30 s after each thalamic spike (P < 0.01). These direct human thalamocortical observations support a proposed mechanism for epileptiform activity to impact cognitive function, wherein epileptic spikes inhibit thalamic sleep spindles in epileptic encephalopathy with spike and wave activation during sleep., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Although >30% of epilepsy patients have drug-resistant epilepsy (DRE), typically those with generalized or multifocal disease have not traditionally been considered surgical candidates. Responsive neurostimulation (RNS) of the centromedian (CM) region of the thalamus now appears to be a promising therapeutic option for this patient population. We present outcomes following CM RNS for 13 patients with idiopathic generalized epilepsy (IGE) and eight with multifocal onsets that rapidly generalize to bilateral tonic-clonic (focal to bilateral tonic-clonic [FBTC]) seizures., Methods: A retrospective review of all patients undergoing bilateral CM RNS by the senior author through July 2022 were reviewed. Electrodes were localized and volumes of tissue activation were modeled in Lead-DBS. Changes in patient seizure frequency were extracted from electronic medical records., Results: Twenty-one patients with DRE underwent bilateral CM RNS implantation. For 17 patients with at least 1 year of postimplantation follow-up, average seizure reduction from preoperative baseline was 82.6% (SD = 19.0%, median = 91.7%), with 18% of patients Engel class 1, 29% Engel class 2, 53% Engel class 3, and 0% Engel class 4. There was a trend for average seizure reduction to be greater for patients with nonlesional FBTC seizures than for other patients. For patients achieving at least Engel class 3 outcome, median time to worthwhile seizure reduction was 203.5 days (interquartile range = 110.5-343.75 days). Patients with IGE with myoclonic seizures had a significantly shorter time to worthwhile seizure reduction than other patients. The surgical targeting strategy evolved after the first four subjects to achieve greater anatomic accuracy., Significance: Patients with both primary and rapidly generalized epilepsy who underwent CM RNS experienced substantial seizure relief. Subsets of these patient populations may particularly benefit from CM RNS. The refinement of lead targeting, tuning of RNS system parameters, and patient selection are ongoing areas of investigation., (© 2024 International League Against Epilepsy.)

Consistent observations across recording modalities, experiments, and neural systems find neural field spectra with 1/f-like scaling, eliciting many alternative theories to explain this universal phenomenon. We show that a general dynamical system with stochastic drive and minimal assumptions generates 1/f-like spectra consistent with the range of values observed in vivo without requiring a specific biological mechanism or collective critical behavior., (© 2024 Massachusetts Institute of Technology.)

We evaluated whether spike ripples, the combination of epileptiform spikes and ripples, provide a reliable and improved biomarker for the epileptogenic zone compared with other leading interictal biomarkers in a multicentre, international study. We first validated an automated spike ripple detector on intracranial EEG recordings. We then applied this detector to subjects from four centres who subsequently underwent surgical resection with known 1-year outcomes. We evaluated the spike ripple rate in subjects cured after resection [International League Against Epilepsy Class 1 outcome (ILAE 1)] and those with persistent seizures (ILAE 2-6) across sites and recording types. We also evaluated available interictal biomarkers: spike, spike-gamma, wideband high frequency oscillation (HFO, 80-500 Hz), ripple (80-250 Hz) and fast ripple (250-500 Hz) rates using previously validated automated detectors. The proportion of resected events was computed and compared across subject outcomes and biomarkers. Overall, 109 subjects were included. Most spike ripples were removed in subjects with ILAE 1 outcome (P < 0.001), and this was qualitatively observed across all sites and for depth and subdural electrodes (P < 0.001 and P < 0.001, respectively). Among ILAE 1 subjects, the mean spike ripple rate was higher in the resected volume (0.66/min) than in the non-removed tissue (0.08/min, P < 0.001). A higher proportion of spike ripples were removed in subjects with ILAE 1 outcomes compared with ILAE 2-6 outcomes (P = 0.06). Among ILAE 1 subjects, the proportion of spike ripples removed was higher than the proportion of spikes (P < 0.001), spike-gamma (P < 0.001), wideband HFOs (P < 0.001), ripples (P = 0.009) and fast ripples (P = 0.009) removed. At the individual level, more subjects with ILAE 1 outcomes had the majority of spike ripples removed (79%, 38/48) than spikes (69%, P = 0.12), spike-gamma (69%, P = 0.12), wideband HFOs (63%, P = 0.03), ripples (45%, P = 0.01) or fast ripples (36%, P < 0.001) removed. Thus, in this large, multicentre cohort, when surgical resection was successful, the majority of spike ripples were removed. Furthermore, automatically detected spike ripples localize the epileptogenic tissue better than spikes, spike-gamma, wideband HFOs, ripples and fast ripples., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background/aims: The performance of machine learning (ML) in predicting the outcomes of patients with hepatocellular carcinoma (HCC) remains uncertain. We aimed to develop risk scores using conventional methods and ML to categorize early-stage HCC patients into distinct prognostic groups., Methods: The study retrospectively enrolled 1,411 consecutive treatment-naïve patients with the Barcelona Clinic Liver Cancer (BCLC) stage 0 to A HCC from 2012 to 2021. The patients were randomly divided into a training cohort (n=988) and validation cohort (n=423). Two risk scores (CATS-IF and CATS-INF) were developed to predict overall survival (OS) in the training cohort using the conventional methods (Cox proportional hazards model) and ML-based methods (LASSO Cox regression), respectively. They were then validated and compared in the validation cohort., Results: In the training cohort, factors for the CATS-IF score were selected by the conventional method, including age, curative treatment, single large HCC, serum creatinine and alpha-fetoprotein levels, fibrosis-4 score, lymphocyte-tomonocyte ratio, and albumin-bilirubin grade. The CATS-INF score, determined by ML-based methods, included the above factors and two additional ones (aspartate aminotransferase and prognostic nutritional index). In the validation cohort, both CATS-IF score and CATS-INF score outperformed other modern prognostic scores in predicting OS, with the CATSINF score having the lowest Akaike information criterion value. A calibration plot exhibited good correlation between predicted and observed outcomes for both scores., Conclusion: Both the conventional Cox-based CATS-IF score and ML-based CATS-INF score effectively stratified patients with early-stage HCC into distinct prognostic groups, with the CATS-INF score showing slightly superior performance.

Background and Objectives: Sleep spindles are prominent thalamocortical brain oscillations during sleep that have been mechanistically linked to sleep-dependent memory consolidation in animal models and healthy controls. Sleep spindles are decreased in Rolandic epilepsy and related sleep-activated epileptic encephalopathies. We investigate the relationship between sleep spindle deficits and deficient sleep dependent memory consolidation in children with Rolandic epilepsy., Methods: In this prospective case-control study, children were trained and tested on a validated probe of memory consolidation, the motor sequence task (MST). Sleep spindles were measured from high-density EEG during a 90-minute nap opportunity between MST training and testing using a validated automated detector., Results: Twenty-three children with Rolandic epilepsy (14 with resolved disease), and 19 age- and sex-matched controls were enrolled. Children with active Rolandic epilepsy had decreased memory consolidation compared to control children (p=0.001, mean percentage reduction: 25.7%, 95% CI [10.3, 41.2]%) and compared to children with resolved Rolandic epilepsy (p=0.007, mean percentage reduction: 21.9%, 95% CI [6.2, 37.6]%). Children with active Rolandic epilepsy had decreased sleep spindle rates in the centrotemporal region compared to controls (p=0.008, mean decrease 2.5 spindles/min, 95% CI [0.7, 4.4] spindles/min). Spindle rate positively predicted sleep-dependent memory consolidation (p=0.004, mean MST improvement of 3.9%, 95% CI [1.3, 6.4]%, for each unit increase in spindles per minute)., Discussion: Children with Rolandic epilepsy have a sleep spindle deficit during the active period of disease which predicts deficits in sleep dependent memory consolidation. This finding provides a mechanism and noninvasive biomarker to aid diagnosis and therapeutic discovery for cognitive dysfunction in Rolandic epilepsy and related sleep activated epilepsy syndromes.

Purpose: To review the current and future approaches to investigating the intraocular immune response in human uveitis., Design: Perspective., Methods: Review of currently available methods for investigating the immune response in ocular tissues and fluids in patients with intraocular inflammation/ uveitis. The advantages and disadvantages of human studies have been compared to those of animal models of uveitis., Results: Animal models, while being excellent tools for mechanistic studies, do not replicate the clinical and immunologic heterogeneity of human uveitis. Opportunities for immunological studies in human uveitis are mostly limited to histological studies, or sampling of intraocular fluids and peripheral blood. Histopathological studies can be enhanced by revisiting published historical data, tissue repositories, or autopsy specimens. Intraocular fluids can be investigated by a variety of techniques. Among these, flow cytometry and single-cell RNA sequencing (scRNAseq) provide single-cell resolution. While the current technology is costly and labor-intensive, scRNAseq is less limited by the low cellular yield from intraocular fluids and allows unbiased immune profiling enabling discovery of new cellular subsets. Immunological phenotypes uncovered from human data can be further investigated in animal studies., Conclusion: The diversity of the intraocular immune response in uveitis patients remains challenging but can be studied by multiple techniques including histopathology, flow cytometry, and scRNAseq. Human data can be combined with animal studies for translating uveitis research into novel therapies., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Field factors play more important roles in predicting the outcomes of patients compared with tumor factors in early-stage hepatocellular carcinoma (HCC). However, the prognostic ability of noninvasive serum marker scores for hepatic fibrosis and liver functional reserve on very early-stage HCC is still not yet determined. We aimed to investigate the performance of these serum marker scores in predicting the prognoses of patients with very early-stage HCC., Methods: A total of 446 patients with very early-stage HCC from 2012 to 2022 were retrospectively enrolled. Serum biomarkers and prognostic scores determining overall survival (OS) were analyzed by Cox proportional hazards model. We compared the Akaike information criterion among the prognostic nutritional index (PNI), aspartate aminotransferase-to-platelet ratio index, albumin-bilirubin (ALBI) score, EZ (easy)-ALBI score, modified ALBI score, fibrosis-4 score, and lymphocyte-to-monocyte ratio to determine the predictability on the OS., Results: After a median follow-up of 41.0 months (interquartile range 36.9-45.1 months), 81 patients died, with a 5-year OS rate of 71.0%. Among the noninvasive serum marker scores, PNI had the best performance in predicting the OS with the lowest Akaike information criterion (846.407) compared with other scores. Moreover, we stratified the patients into high-risk (PNI <45) and low-risk (PNI ≥45) groups. It showed that the 5-year OS rates were 83.4% and 60.8% in the low-risk and high-risk PNI groups, respectively ( P < 0.001)., Discussion: PNI had the best performance in predicting the OS for patients with very early-stage HCC., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: The introduction of direct-acting antiviral agents (DAAs) has revolutionized the therapeutic landscape of chronic hepatitis C (CHC), however real-world data on the risk factors of hepatocellular carcinoma (HCC) recurrence following DAA treatment in CHC-HCC patients are limited in Taiwan. We aimed to evaluate the therapeutic efficacy of DAAs in Taiwanese patients with prior hepatitis C virus (HCV)-induced HCC and identify the posttreatment risk factors for HCC recurrence., Methods: Between January 2017 and August 2021, 208 CHC-HCC patients underwent DAA treatment at Taipei Veterans General Hospital. Among them, 94 patients met the inclusion criteria (Barcelona clinic liver cancer [BCLC] stage 0/A after treatment with complete radiological response) for analysis. Comprehensive demographic, clinical, and laboratory data were collected before and after DAA treatment. The primary outcome was HCC recurrence post-DAA treatment, and independent variables were assessed using multivariate Cox proportional hazards models., Results: The mean age of the enrolled patients was 75.9 ± 8.9 years; 44.7% were male, and 94.7% were Child-Pugh class A. Before DAA treatment, 31.9% experienced HCC recurrence. The median follow-up after DAA treatment was 22.1 months (interquartile range, 8.6-35.9 months). After treatment, 95.7% of the patients achieved a sustained virological response (SVR 12 ), but HCC recurrence occurred in 54.3%. Cumulative HCC recurrence rates after treatment were 31.1% at 1 year, 57.3% at 3 years, and 68.5% at up to 5.69 years. Multivariate analysis revealed that prior HCC recurrence before DAA treatment (hazard ratio [HR] = 3.15, p = 0.001), no SVR 12 after treatment (HR = 6.829, p = 0.016), 12-week posttreatment alpha-fetoprotein (AFP) level >10 ng/mL (HR = 2.34, p = 0.036), and BCLC A3 lesions (two or three nodules without any tumor exceeding 3 cm) (HR = 2.31, p = 0.039) were independent risk factors for HCC recurrence. We further developed a risk stratification system based on these significant independent factors., Conclusion: This investigation underscores the critical influence of factors such as prior HCC recurrence, successful attainment of SVR 12 , posttreatment AFP level, and specific tumor characteristics in determining the risk of HCC recurrence after treatment with DAAs. Our proposed innovative risk stratification system may not only contribute to enhanced personalized care but also holds the potential to optimize treatment outcomes., Competing Interests: Conflicts of interest: Dr. Chien-Wei Su, Dr. Fa-Yauh Lee, Dr. Yi-Hsiang Huang, and Dr. Ming-Chih Hou, editorial board members at Journal of the Chinese Medical Association , have no roles in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Machine learning (ML) models for predicting 72-hour unscheduled return visits (URVs) for patients with abdominal pain in the emergency department (ED) were developed in a previous study. This study refined the data to adjust previous prediction models and evaluated the model performance in future data validation during the COVID-19 era. We aimed to evaluate the practicality of the ML models and compare the URVs before and during the COVID-19 pandemic. We used electronic health records from Chang Gung Memorial Hospital from 2018 to 2019 as a training dataset, and various machine learning models, including logistic regression (LR), random forest (RF), extreme gradient boosting (XGB), and voting classifier (VC) were developed and subsequently used to validate against the 2020 to 2021 data. The models highlighted several determinants for 72-hour URVs, including patient age, prior ER visits, specific vital signs, and medical interventions. The LR, XGB, and VC models exhibited the same AUC of 0.71 in the testing set, whereas the VC model displayed a higher F1 score (0.21). The XGB model demonstrated the highest specificity (0.99) and precision (0.64) but the lowest sensitivity (0.01). Among these models, the VC model showed the most favorable, balanced, and comprehensive performance. Despite the promising results, the study illuminated challenges in predictive modeling, such as the unforeseen influences of global events, such as the COVID-19 pandemic. These findings not only highlight the significant potential of machine learning in augmenting emergency care but also underline the importance of iterative refinement in response to changing real-world conditions., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Periodontitis, a ubiquitous severe gum disease affecting the teeth and surrounding alveolar bone, can heighten systemic inflammation. We investigated the association between very severe periodontitis and early biomarkers of age-related macular degeneration (AMD), in individuals with no eye disease., Design: Cross-sectional analysis of the prospective community-based cohort United Kingdom (UK) Biobank., Participants: Sixty-seven thousand three hundred eleven UK residents aged 40 to 70 years recruited between 2006 and 2010 underwent retinal imaging., Methods: Macular-centered OCT images acquired at the baseline visit were segmented for retinal sublayer thicknesses. Very severe periodontitis was ascertained through a touchscreen questionnaire. Linear mixed effects regression modeled the association between very severe periodontitis and retinal sublayer thicknesses, adjusting for age, sex, ethnicity, socioeconomic status, alcohol consumption, smoking status, diabetes mellitus, hypertension, refractive error, and previous cataract surgery., Main Outcome Measures: Photoreceptor layer (PRL) and retinal pigment epithelium-Bruch's membrane (RPE-BM) thicknesses., Results: Among 36 897 participants included in the analysis, 1571 (4.3%) reported very severe periodontitis. Affected individuals were older, lived in areas of greater socioeconomic deprivation, and were more likely to be hypertensive, diabetic, and current smokers (all P < 0.001). On average, those with very severe periodontitis were hyperopic (0.05 ± 2.27 diopters) while those unaffected were myopic (-0.29 ± 2.40 diopters, P < 0.001). Following adjusted analysis, very severe periodontitis was associated with thinner PRL (-0.55 μm, 95% confidence interval [CI], -0.97 to -0.12; P  = 0.022) but there was no difference in RPE-BM thickness (0.00 μm, 95% CI, -0.12 to 0.13; P  = 0.97). The association between PRL thickness and very severe periodontitis was modified by age ( P < 0.001). Stratifying individuals by age, thinner PRL was seen among those aged 60 to 69 years with disease (-1.19 μm, 95% CI, -1.85 to -0.53; P < 0.001) but not among those aged < 60 years., Conclusions: Among those with no known eye disease, very severe periodontitis is statistically associated with a thinner PRL, consistent with incipient AMD. Optimizing oral hygiene may hold additional relevance for people at risk of degenerative retinal disease., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2024 by the American Academy of Ophthalmology.)

The study of cell signaling within tissues can be enhanced using highly multiplexed immunohistochemistry to localize the presence and spatial distribution of numerous pathways of interest simultaneously. Additional data can also be gained by placing the identified proteins into the context of adjacent structures, stroma, and interacting partners. Here, we outline a protocol for using the recently described IBEX method on tissues. This is an open and simple cyclic immunohistochemistry approach suited to this application. We describe a simplified protocol and provide guidance on the method, using a 12-marker panel on human retina to demonstrate the approach., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Epileptic encephalopathies are defined by the presence of frequent epileptiform activity that causes neurodevelopmental slowing or regression. Here, we review evidence that epilepsy surgery improves neurodevelopment in children with epileptic encephalopathies. We describe an example patient with epileptic encephalopathy without drug refractory seizures, who underwent successful diagnostic and therapeutic surgeries. In patients with epileptic encephalopathy, cognitive improvement alone is a sufficient indication to recommend surgical intervention in experienced centers., Competing Interests: Disclosure Dr C.J. Chu is a coinvestigator in the Neuropace Nautilus trial. Dr C.J. Chu receives research support from NIHNINDS, United States, NIHNIMH, United States, and the Epilepsy Foundation, United States New England and is a coinvestigator in the Neuropace Nautilus trial. Dr C.J. Chu has served as a consultant for Biogen Inc, Ionis Pharmaceuticals, Sun Pharmaceuticals, and Novartis within the last 2 years. Dr R.M. Richardson is PI in the Neuropace Nautilus trial and coinvestigator in the RNS System LGS Feasibility Study. Dr R.M. Richardson receives research support from NIH NINDS. Dr K.T. Kahle receives research support from NIH NINDS., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Hepatitis B virus (HBV) infection is prevalent in Asia including Taiwan. We retrospectively evaluated the risk of HBV reactivation and clinical outcomes in HBV+ and HBV- kidney transplant recipients., Methods: Patients who underwent kidney transplantation between January 2004 and December 2021 were reviewed. The outcomes of interest included risks of HBV reactivation and patient/graft survival., Results: We identified 337 patients (47.5 ± 12 years) in our final cohort. Fifty-two (15.4%) had hepatitis B surface antigen (HBsAg) positive at the time of transplantation. Seventeen developed viral reactivations, with 41.2% of them accompanied by active hepatitis. The graft survival, acute rejection rate, and cancer development after kidney transplantation did not differ in terms of HBsAg status. The Cox multivariate analysis indicated the HBV reactivation risk was increased by a lack of pretransplant anti-HBV medication (hazard ratio [HR], 5.95; 95% confidence interval [CI], 1.31-27.02; p = 0.021) or an absence of lifelong antiviral therapy (HR: 3.14; 95% CI: 1.01-9.74; p = 0.047)., Conclusion: Individuals, independent of HBsAg status, had similar prognosis in terms of patient and graft survival, acute rejection rate, and cancer development. The absence of either pretransplant anti-HBV medication or lifelong antiviral therapy was significantly associated with an increased risk of HBV reactivation., (© 2024 S. Karger AG, Basel.)

Rhythms are a common feature of brain activity. Across different types of rhythms, the phase has been proposed to have functional consequences, thus requiring its accurate specification from noisy data. Phase is conventionally specified using techniques that presume a frequency band-limited rhythm. However, in practice, observed brain rhythms are typically nonsinusoidal and amplitude modulated. How these features impact methods to estimate phase remains unclear. To address this, we consider three phase estimation methods, each with different underlying assumptions about the rhythm. We apply these methods to rhythms simulated with different generative mechanisms and demonstrate inconsistency in phase estimates across the different methods. We propose two improvements to the practice of phase estimation: (1) estimating confidence in the phase estimate, and (2) examining the consistency of phase estimates between two (or more) methods., Competing Interests: The authors declare no competing financial interests., (Copyright © 2023 Wodeyar et al.)

Objective: We investigated how diagnosis and injury location on neonatal brain MRI following onset of acute provoked seizures was associated with short term outcome., Study Design: A multicenter cohort of neonates with acute provoked seizures enrolled in the Neonatal Seizure Registry. MRIs were centrally evaluated by a neuroradiologist for location of injury and radiologic diagnosis. Clinical outcomes were determined by chart review. Multivariate logistic regression was used to examine the association between MRI findings and outcomes., Results: Among 236 newborns with MRI at median age 4 days (IQR 3-8), 91% had abnormal MRI. Radiologic diagnoses of intracranial hemorrhage (OR 3.2 [1.6-6.5], p < 0.001) and hypoxic-ischemic encephalopathy (OR 2.7 [1.4-5.4], p < 0.003) were associated with high seizure burden. Radiologic signs of intracranial infection were associated with abnormal neurologic examination at discharge (OR 3.9 [1.3-11.6], p < 0.01)., Conclusion: Findings on initial MRI can help with expectant counseling on short-term outcomes following acute provoked neonatal seizures., (© 2023. The Author(s).)

In this work, we demonstrate the performance enhancement of bottom-gated inductive line-tunneling TFET (iTFET) through the integration of bilateral sidewall engineering with SiGe mole fraction variation, considering the feasibility of the fabrication process. We also employ a metal-semiconductor interface for carrier induction to improve the I ON , resulting in a lower subthreshold swing average ( S.S avg ). Using Sentaurus TCAD simulations, we show that the dominant current mechanism is line tunneling, and the hump effect is mitigated by using SiGe with different mole fractions on the sidewalls. Compared to conventional tunnel field-effect transistors, which require at least three doping processes and annealing, the proposed device requires only one doping process and utilizes the metal-semiconductor interface for carrier induction, significantly reducing the fabrication cost and thermal budget. These measurement based simulations show that the S.S avg is improved to 21.5 mV dec -1 with an I ON / I OFF ratio of 106 at V D = 0.2 V. This is the first time that a TFT with a subthreshold swing of less than 60 mV dec -1 has been proposed, so it will save much more power in the future and displays with high energy efficiency can be realized and widely used in IoT applications., (© 2023 IOP Publishing Ltd.)

Background: The Child-Turcotte-Pugh (CTP) score is widely used for assessing the liver's functional reserve in patients with advanced chronic liver disease (ACLD) and hepatocellular carcinoma (HCC). This study aims to explore the outcomes of patients with HCC and CTP class B and to investigate the prognostic accuracy of prediction models for ACLD in these patients., Methods: We retrospectively enrolled 1143 patients with HCC and CTP class B between 2007 and 2022. We divided the patients into three subgroups based on their CTP scores: CTP-B7, CTP-B8, and CTP-B9. We compared the corrected Akaike information criterion among each mortality prediction model, including the CTP score, albumin-bilirubin (ALBI) score, modified ALBI score, the model for end-stage liver disease (MELD), and MELD 3.0., Results: Among the enrolled patients, 576 (50.3%) were in the CTP-B7 group, 363 (31.8%) were in the CTP-B8 group, and 204 (17.9%) were in the CTP-B9 group. After a median follow-up of 4.6 months (interquartile range IQR 1.8-17.2 months), 963 patients died, and the 5-year overall survival (OS) rate was 11.4%. The 5-year OS rates were 11.6%, 13.6%, and 8.3% in the CTP-B7, CTP-B8, and CTP-B9 groups, respectively. Patients in the CTP-B7 group and CTP-B8 group had comparable OS ( p = 0.089), both of which were better than those in the CTP-B9 group ( p < 0.001). Furthermore, the MELD 3.0 score had the lowest corrected akaike information criteria value and provided a more accurate mortality prediction than the MELD score, ALBI grade, modified ALBI grade, and CTP score., Conclusion: Patients in the CTP-B7 and CTP-B8 groups had comparable OS, both of which were better than those in the CTP-B9 group. Moreover, MELD 3.0 provided the most accurate mortality prediction in patients with HCC and CTP class B., Competing Interests: Conflicts of interest: Dr. Teh-Ia Huo, Dr. Yi-Hsiang Huang and Dr. Ming-Chih Hou, editorial board membesr at Journal of the Chinese Medical Association , have no roles in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Background: The treatment of chronic hepatitis C (CHC) infection underwent a significant transformation with the introduction of all-oral direct-acting anti-virals (DAAs). These medications offered a high success rate in treatment, shorter duration, good tolerability, and expanded treatment options. However, a residual risk of hepatocellular carcinoma (HCC) development remained for a few patients even after achieving sustained virological response (SVR). To date, there is a lack of real-world data on evaluating risk factors associated with de novo HCC in CHC patients post-SVR, particularly in Taiwan., Methods: Between January 2017 and December 2019, a total of 671 consecutive CHC patients who achieved SVR after receiving DAAs were included for analysis. Patients with a history of HCC or liver transplantation prior to DAAs, a short follow-up period (<1 year), or treatment failure with DAAs were excluded. The primary outcome was the development of HCC following the initiation of DAAs. Variables associated with the primary outcome were assessed using multivariate Cox proportional hazards models., Results: The mean age of the enrolled patients was 65.1 ± 12.8 years, with 39.6% of them being male. Among the patients, 30.6% had advanced (F3-4) fibrosis, and the median follow-up period was 2.90 years. The cumulative incidence of HCC in CHC patients post-SVR12 was 1.6% at 1 year, 4.4% at 2 years, 4.8% at 3 years, 5.3% at 4 years, and 6.1% at 4.8 years, respectively. Variables independently associated with de novo HCC were advanced liver fibrosis (hazard ratio [HR] = 6.745; 95% CI = 1.960-23.218; p = 0.002), end-of-treatment 12 weeks (EOT 12 ) alpha-fetoprotein (AFP) >7 ng/mL (HR = 3.059; 95% CI = 1.215-7.669; p = 0.018), EOT 12 albumin-bilirubin (ALBI) grade ≥ 2 (HR = 2.664; 95% CI = 1.158-6.128; p = 0.021), and body mass index (BMI) ≥ 25 kg/m 2 (HR = 2.214; 95% CI = 1.011-4.852; p = 0.047)., Conclusion: Despite achieving viral clearance with DAAs, CHC patients still face a residual risk of de novo HCC. Establishing a risk stratification model based on independent variables could facilitate the prediction of future HCC development and enhance screening strategies., Competing Interests: Conflicts of interest: Dr. Fa-Yauh Lee, Dr. Yi-Hsiang Huang and Dr. Ming-Chih Hou, editorial board members at Journal of the Chinese Medical Association , have no roles in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Objective: Median nerve somatosensory evoked fields (SEFs) conduction times reflect the integrity of neural transmission across the thalamocortical circuit. We hypothesized median nerve SEF conduction time would be abnormal in children with Rolandic epilepsy (RE)., Methods: 22 children with RE (10 active; 12 resolved) and 13 age-matched controls underwent structural and diffusion MRI and median nerve and visual stimulation during magnetoencephalography (MEG). N20 SEF responses were identified in contralateral somatosensory cortices. P100 were identified in contralateral occipital cortices as controls. Conduction times were compared between groups in linear models controlling for height. N20 conduction time was also compared to thalamic volume and Rolandic thalamocortical structural connectivity inferred using probabilistic tractography., Results: The RE group had slower N20 conduction compared to controls (p = 0.042, effect size 0.6 ms) and this difference was driven by the resolved RE group (p = 0.046). There was no difference in P100 conduction time between groups (p = 0.83). Ventral thalamic volume positively correlated with N20 conduction time (p = 0.014)., Conclusions: Children with resolved RE have focally decreased Rolandic thalamocortical connectivity., Significance: These results identify a persistent focal thalamocortical circuit abnormality in resolved RE and suggest that decreased Rolandic thalamocortical connectivity may support symptom resolution in this self-limited epilepsy., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: Among neonates with acute symptomatic seizures, we evaluated whether inability to take full feeds at time of hospital discharge from neonatal seizure admission is associated with worse neurodevelopmental outcomes, after adjusting for relevant clinical variables., Methods: This prospective, 9-center study of the Neonatal Seizure Registry (NSR) assessed characteristics of infants with seizures including: evidence of brainstem injury on MRI, mode of feeding upon discharge, and developmental outcomes at 12, 18, and 24 months. Inability to take oral feeds was identified through review of medical records. Brainstem injury was identified through central review of neonatal MRIs. Developmental outcomes were assessed with the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) at 12, 18, and 24 months corrected age., Results: Among 276 infants, inability to achieve full oral feeds was associated with lower total WIDEA-FS scores (160.2±25.5 for full oral feeds vs. 121.8±42.9 for some/no oral feeds at 24 months, p<0.001). At 12 months, a G-tube was required for 23 of the 49 (47%) infants who did not achieve full oral feeds, compared with 2 of the 221 (1%) who took full feeds at discharge (p<0.001)., Conclusions: Inability to take full oral feeds upon hospital discharge is an objective clinical sign that can identify infants with acute symptomatic neonatal seizures who are at high risk for impaired development at 24 months., Competing Interests: Dr. Robers has no disclosures. Dr. Barks receives research support from NIH. Dr. Glass receives research support from NIH. Dr. Soul has no disclosures. Dr. Chang has no disclosures. Dr. Wusthoff has no disclosures. Dr. Chu receives research support from Biogen Inc, and from NIH. Dr. Massey has no disclosures. Dr. Abend has no disclosures. Dr. Lemmon receives research support from NIH (K23NS116453). Dr. Thomas receives research support through NIH and UCB. Dr. Guillet has no disclosures. Dr. Rogers has no disclosures. Dr. Franck has no disclosures. Mr. McCaffrey has no disclosures. Dr. Li has no disclosures. Dr. McCulloch has no disclosures. Dr. Shellhaas receives research support from NIH. She receives royalties from UpToDate for authorship of topics related to neonatal seizures, serves as a consultant for the Epilepsy Study Consortium and is president-elect of the Pediatric Epilepsy Research Foundation™.

Objective: Epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS) is a challenging neurodevelopmental disease characterized by abundant epileptiform spikes during non-rapid eye movement (NREM) sleep accompanied by cognitive dysfunction. The mechanism of cognitive dysfunction is unknown, but treatment with high-dose diazepam may improve symptoms. Spike rate does not predict treatment response, but spikes may disrupt sleep spindles. We hypothesized that in patients with EE-SWAS: (1) spikes and spindles would be anti-correlated, (2) high-dose diazepam would increase spindles and decrease spikes, and (3) spindle response would be greater in those with cognitive improvement., Methods: Consecutive EE-SWAS patients treated with high-dose diazepam that met the criteria were included. Using a validated automated spindle detector, spindle rate, duration, and percentage were computed in pre- and post-treatment NREM sleep. Spikes were quantified using a validated automated spike detector. The cognitive response was determined from a chart review., Results: Spindle rate was anti-correlated with the spike rate in the channel with the maximal spike rate (p = 0.002) and averaged across all channels (p = 0.0005). Spindle rate, duration, and percentage each increased, and spike rate decreased, after high-dose diazepam treatment (p ≤ 2e-5, all tests). Spindle rate, duration, and percentage (p ≤ 0.004, all tests) were increased in patients with cognitive improvement after treatment, but not those without. Changes in spindle rate but not changes in spike rate distinguished between groups., Interpretation: These findings confirm thalamocortical disruption in EE-SWAS, identify a mechanism through which benzodiazepines may support cognitive recovery, and introduce sleep spindles as a promising mechanistic biomarker to detect treatment response in severe epileptic encephalopathies., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Vicarious reward, essential to social learning and decision making, is theorized to engage select brain regions similarly to experienced reward to generate a shared experience. However, it is just as important for neural systems to also differentiate vicarious from experienced rewards for social interaction. Here, we investigated the neuronal interaction between the primate anterior cingulate cortex gyrus (ACCg) and the basolateral amygdala (BLA) when social choices made by monkeys led to either vicarious or experienced reward. Coherence between ACCg spikes and BLA local field potential (LFP) selectively increased in gamma frequencies for vicarious reward, whereas it selectively increased in alpha/beta frequencies for experienced reward. These respectively enhanced couplings for vicarious and experienced rewards were uniquely observed following voluntary choices. Moreover, reward outcomes had consistently strong directional influences from ACCg to BLA. Our findings support a mechanism of vicarious reward where social agency is tagged by interareal coordination frequency within the same shared pathway., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Gene therapy for kidney diseases has proven challenging. Adeno-associated virus (AAV) is used as a vector for gene therapy targeting other organs, with particular success demonstrated in monogenic diseases. We aimed to establish gene therapy for the kidney by targeting a monogenic disease of the kidney podocyte. The most common cause of childhood genetic nephrotic syndrome is mutations in the podocyte gene NPHS2 , encoding podocin. We used AAV-based gene therapy to rescue this genetic defect in human and mouse models of disease. In vitro transduction studies identified the AAV-LK03 serotype as a highly efficient transducer of human podocytes. AAV-LK03-mediated transduction of podocin in mutant human podocytes resulted in functional rescue in vitro, and AAV 2/9-mediated gene transfer in both the inducible podocin knockout and knock-in mouse models resulted in successful amelioration of kidney disease. A prophylactic approach of AAV 2/9 gene transfer before induction of disease in conditional knockout mice demonstrated improvements in albuminuria, plasma creatinine, plasma urea, plasma cholesterol, histological changes, and long-term survival. A therapeutic approach of AAV 2/9 gene transfer 2 weeks after disease induction in proteinuric conditional knock-in mice demonstrated improvement in urinary albuminuria at days 42 and 56 after disease induction, with corresponding improvements in plasma albumin. Therefore, we have demonstrated successful AAV-mediated gene rescue in a monogenic renal disease and established the podocyte as a tractable target for gene therapy approaches.

Background: Alpha fetoprotein (AFP) is the most widely used tumor marker for hepatocellular carcinoma (HCC). Nevertheless, few studies have investigated the prognostic factors of HCC patients with normal serum AFP levels., Methods: We retrospectively enrolled 2198 patients with HCC and normal serum AFP levels (<20 ng/mL) from 2007 to 2020. Overall survival (OS) rates were calculated by the Kaplan-Meier method, and analyses of the prognostic factors were performed using a Cox proportional hazard model., Results: Among the enrolled patients, 1385 (63%) patients were in the low-normal AFP group (serum AFP levels ≤7 ng/mL), and 813 (37%) patients were in the high-normal AFP group (serum AFP levels between 7 and 20 ng/mL). The high-normal AFP group had poorer liver functional reserve, more multiple tumors, and smaller tumor size compared to those in the low-normal AFP group. After a median follow-up of 32.4 months, 942 patients died, and the 5-year OS rate was 54.4%. The 5-year OS rates were 57.4% and 49.8% in the low-normal AFP group and high-normal AFP group, respectively (p = 0.001). A multivariate analysis showed the independent prognostic factors of poor OS were no anti-viral therapy, advanced albumin-bilirubin grades, the presence of vascular invasion, tumor size ≥5 cm, and non-curative treatment modalities. Serum AFP levels were not associated with OS according to the multivariate analysis., Conclusion: Liver functional reserve, anti-viral therapy, tumor size, vascular invasion, and treatment modalities, determined the outcomes of HCC patients with normal serum AFP levels, but serum AFP levels did not., Competing Interests: Declaration of competing interest There are no potential conflicts of financial and non-financial interests in the study., (Copyright © 2022. Published by Elsevier B.V.)

Introduction: Self-limited epilepsy with centrotemporal spikes is a transient developmental epilepsy with a seizure onset zone localized to the centrotemporal cortex that commonly impacts aspects of language function. To better understand the relationship between these anatomical findings and symptoms, we characterized the language profile and white matter microstructural and macrostructural features in a cohort of children with SeLECTS., Methods: Children with active SeLECTS (n = 13), resolved SeLECTS (n = 12), and controls (n = 17) underwent high-resolution MRIs including diffusion tensor imaging sequences and multiple standardized neuropsychological measures of language function. We identified the superficial white matter abutting the inferior rolandic cortex and superior temporal gyrus using a cortical parcellation atlas and derived the arcuate fasciculus connecting them using probabilistic tractography. We compared white matter microstructural characteristics (axial, radial and mean diffusivity, and fractional anisotropy) between groups in each region, and tested for linear relationships between diffusivity metrics in these regions and language scores on neuropsychological testing., Results: We found significant differences in several language modalities in children with SeLECTS compared to controls. Children with SeLECTS performed worse on assessments of phonological awareness (p = 0.045) and verbal comprehension (p = 0.050). Reduced performance was more pronounced in children with active SeLECTS compared to controls, namely, phonological awareness (p = 0.028), verbal comprehension (p = 0.028), and verbal category fluency (p = 0.031), with trends toward worse performance also observed in verbal letter fluency (p = 0.052), and the expressive one-word picture vocabulary test (p = 0.068). Children with active SeLECTS perform worse than children with SeLECTS in remission on tests of verbal category fluency (p = 0.009), verbal letter fluency (p = 0.006), and the expressive one-word picture vocabulary test (p = 0.045). We also found abnormal superficial white matter microstructure in centrotemporal ROIs in children with SeLECTS, characterized by increased diffusivity and fractional anisotropy compared to controls (AD p = 0.014, RD p = 0.028, MD p = 0.020, and FA p = 0.024). Structural connectivity of the arcuate fasciculus connecting perisylvian cortical regions was lower in children with SeLECTS (p = 0.045), and in the arcuate fasciculus children with SeLECTS had increased diffusivity (AD p = 0.007, RD p = 0.006, MD p = 0.016), with no difference in fractional anisotropy (p = 0.22). However, linear tests comparing white matter microstructure in areas constituting language networks and language performance did not withstand correction for multiple comparisons in this sample, although a trend was seen between FA in the arcuate fasciculus and verbal category fluency (p = 0.047) and the expressive one-word picture vocabulary test (p = 0.036)., Conclusion: We found impaired language development in children with SeLECTS, particularly in those with active SeLECTS, as well as abnormalities in the superficial centrotemporal white matter as well as the fibers connecting these regions, the arcuate fasciculus. Although relationships between language performance and white matter abnormalities did not pass correction for multiple comparisons, taken together, these results provide evidence of atypical white matter maturation in fibers involved in language processing, which may contribute to the aspects of language function that are commonly affected by the disorder., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The proliferation of new psychoactive substances (NPSs) in recent years has posed a significant challenge to public health. Traditional monitoring methods have proven insufficient in tracking these constantly evolving substances, leading to the development of alternative approaches such as wastewater-based epidemiology (WBE). The present study aims to utilize high-resolution mass spectrometry (HRMS)-based targeted and suspect screening to profile NPS, other illicit drugs, and drug-related compounds in a Taiwanese wastewater sample. For the targeted analysis, 8 out 18 standards of illicit drugs have been identified. The suspect screening approach based on approximately 3600 substances in the SWGDRUG library can further identify 92 compounds, including opiate analgesics, synthetic cathinones, phenylalkylamines derivatives, phenethylamine derivatives, tryptamine derivatives, steroids, and ephedrine-related compounds. Additionally, the presence of 5-methoxy-2-aminoindane (MEAI) in the wastewater indicates that drug dealers have recently sold this potential NPS to evade drug regulations. This study firstly reports the HRMS-based comprehensive profile of NPS, other illicit drugs, and drug-related compounds in Taiwan, which could be applied as biomarkers for estimating the consumption of drugs.

In clinical neuroscience, epileptic seizures have been associated with the sudden emergence of coupled activity across the brain. The resulting functional networks-in which edges indicate strong enough coupling between brain regions-are consistent with the notion of percolation, which is a phenomenon in complex networks corresponding to the sudden emergence of a giant connected component. Traditionally, work has concentrated on noise-free percolation with a monotonic process of network growth, but real-world networks are more complex. We develop a class of random graph hidden Markov models (RG-HMMs) for characterizing percolation regimes in noisy, dynamically evolving networks in the presence of edge birth and edge death. This class is used to understand the type of phase transitions undergone in a seizure, and in particular, distinguishing between different percolation regimes in epileptic seizures. We develop a hypothesis testing framework for inferring putative percolation mechanisms. As a necessary precursor, we present an EM algorithm for estimating parameters from a sequence of noisy networks only observed at a longitudinal subsampling of time points. Our results suggest that different types of percolation can occur in human seizures. The type inferred may suggest tailored treatment strategies and provide new insights into the fundamental science of epilepsy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: We evaluated whether interictal epileptiform discharge (IED) rate and morphological characteristics predict seizure risk., Methods: We evaluated 10 features from automatically detectable IEDs in a stereotyped population with self-limited epilepsy with centrotemporal spikes (SeLECTS). We tested whether the average value or the most extreme values from each feature predicted future seizure risk in cross-sectional and longitudinal models., Results: 10,748 individual centrotemporal IEDs were analyzed from 59 subjects at 81 timepoints. In cross-sectional models, increases in average spike height, spike duration, slow wave rising slope, slow wave falling slope, and the most extreme values of slow wave rising slope each improved prediction of an increased risk of a future seizure compared to a model with age alone (p < 0.05, each). In longitudinal model, spike rising height improved prediction of future seizure risk compared to a model with age alone (p = 0.04) CONCLUSIONS: Spike height improves prediction of future seizure risk in SeLECTS. Several other morphological features may also improve prediction and should be explored in larger studies., Significance: Discovery of a relationship between novel IED features and seizure risk may improve clinical prognostication, visual and automated IED detection strategies, and provide insights into the underlying neuronal mechanisms that contribute to IED pathology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

To improve color conversion performance for color display application, we study the near-field-induced nanoscale-cavity effects on the emission efficiency and Förster resonance energy transfer (FRET) under the condition of surface plasmon (SP) coupling by inserting colloidal quantum dots (QDs) and synthesized Ag nanoparticles (NPs) into surface nano-holes fabricated on a GaN template and an InGaN/GaN quantum-well (QW) template. In the QW template, the inserted Ag NPs are close to either QWs or QDs for producing three-body SP coupling to enhance color conversion. Time-resolved and continuous-wave photoluminescence (PL) behaviors of the QW- and QD-emitting lights are investigated. The comparison between the nano-hole samples and the reference samples of surface QD/Ag NP shows that the nanoscale-cavity effect of the nano-hole leads to the enhancements of QD emission, FRET between QDs, and FRET from QW into QD. The SP coupling induced by the inserted Ag NPs can enhance the QD emission and FRET from QW into QD. Its result is further enhanced through the nanoscale-cavity effect. The relative continuous-wave PL intensities among different color components also show the similar behaviors. By introducing SP coupling to a color conversion device with the FRET process in a nanoscale cavity structure, we can significantly improve the color conversion efficiency. Simulation results confirm the basic observations in experiment.

Study Objective: Sleep spindles are present from birth and reflect cognitive functions across the lifespan, but normative values for this cognitive biomarker across development are lacking. This study aims to establish normative spindle features over development., Methods: All available normal 19-channel electroencephalograms from developmentally normal children between February 2002 and June 2021 in the MGH EEG lab were analyzed. Approximately, 20 000 spindles were hand-marked to train and validate an automated spindle detector across ages. Normative values for spindle rate, duration, frequency, refractory period, and interhemispheric lag are provided for each channel and each age., Results: Sleep EEGs from 567 developmentally normal children (range 0 days to 18 years) were included. The detector had excellent performance (F1 = 0.47). Maximal spindle activity is seen over central regions during infancy and adolescence and frontopolar regions during childhood. Spindle rate and duration increase nonlinearly, with the most rapid changes during the first 4 months of life and between ages 3 and 14 years. Peak spindle frequency follows a U-shaped curve and discrete frontal slow and central fast spindles are evident by 18 months. Spindle refractory periods decrease between ages 1 and 14 years while interhemispheric asynchrony decreases over the first 3 months of life and between ages 1 and 14 years., Conclusions: These data provide age- and region-specific normative values for sleep spindles across development, where measures that deviate from these values can be considered pathological. As spindles provide a noninvasive biomarker for cognitive function across the lifespan, these normative measures can accelerate the discovery and diagnosis in neurodevelopmental disorders., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Both sleep and wake encephalograms (EEG) change over the lifespan. While prior studies have characterized age-related changes in the EEG, the datasets span a particular age group, or focused on sleep and wake macrostructure rather than the microstructure. Here, we present sex-stratified data from 3372 community-based or clinic-based otherwise neurologically and psychiatrically healthy participants ranging from 11 days to 80 years of age. We estimate age norms for key sleep and wake EEG parameters including absolute and relative powers in delta, theta, alpha, and sigma bands, as well as sleep spindle density, amplitude, duration, and frequency. To illustrate the potential use of the reference measures developed herein, we compare them to sleep EEG recordings from age-matched participants with Alzheimer's disease, severe sleep apnea, depression, osteoarthritis, and osteoporosis. Although the partially clinical nature of the datasets may bias the findings towards less normal and hence may underestimate pathology in practice, age-based EEG reference values enable objective screening of deviations from healthy aging among individuals with a variety of disorders that affect brain health., (Copyright © 2023 Elsevier Inc. All rights reserved.)

What is the common denominator of consciousness across divergent regimes of cortical dynamics? Does consciousness show itself in decibels or in bits? To address these questions, we introduce a testbed for evaluating electroencephalogram (EEG) biomarkers of consciousness using dissociations between neural oscillations and consciousness caused by rare genetic disorders. Children with Angelman syndrome (AS) exhibit sleep-like neural dynamics during wakefulness. Conversely, children with duplication 15q11.2-13.1 syndrome (Dup15q) exhibit wake-like neural dynamics during non-rapid eye movement (NREM) sleep. To identify highly generalizable biomarkers of consciousness, we trained regularized logistic regression classifiers on EEG data from wakefulness and NREM sleep in children with AS using both entropy measures of neural complexity and spectral (i.e., neural oscillatory) EEG features. For each set of features, we then validated these classifiers using EEG from neurotypical (NT) children and abnormal EEGs from children with Dup15q. Our results show that the classification performance of entropy-based EEG biomarkers of conscious state is not upper-bounded by that of spectral EEG features, which are outperformed by entropy features. Entropy-based biomarkers of consciousness may thus be highly adaptable and should be investigated further in situations where spectral EEG features have shown limited success, such as detecting covert consciousness or anesthesia awareness., (© 2022. The Author(s).)

Background: Limited data exist regarding seizure burden, electroencephalogram (EEG) background, and associated outcomes in neonates with acute intracranial infections., Methods: This secondary analysis was from a prospective, multicenter study of neonates enrolled in the Neonatal Seizure Registry with seizures due to intracranial infection. Sites used continuous EEG monitoring per American Clinical Neurophysiology Society guidelines. High seizure burden was defined a priori as seven or more EEG-confirmed seizures. EEG background was categorized using standardized terminology. Primary outcome was neurodevelopment at 24-months corrected age using Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS). Secondary outcomes were postneonatal epilepsy and motor disability., Results: Twenty-seven of 303 neonates (8.9%) had seizures due to intracranial infection, including 16 (59.3%) bacterial, 5 (18.5%) viral, and 6 (22.2%) unknown. Twenty-three neonates (85%) had at least one subclinical seizure. Among 23 children with 24-month follow-up, the WIDEA-FS score was, on average, 23 points lower in children with high compared with low seizure burden (95% confidence interval, [-48.4, 2.1]; P = 0.07). After adjusting for gestational age, infection etiology, and presence of an additional potential acute seizure etiology, the effect size remained unchanged (β = -23.8, P = 0.09). EEG background was not significantly associated with WIDEA-FS score. All children with postneonatal epilepsy (n = 4) and motor disability (n = 5) had high seizure burden, although associations were not significant., Conclusion: High seizure burden may be associated with worse neurodevelopment in neonates with intracranial infection and seizures. EEG monitoring can provide useful management and prognostic information in this population., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To investigate the correlation between periodontal parameters and cell-free DNA (cfDNA) concentrations in gingival crevicular fluid (GCF), saliva, and plasma. Methods: Full mouth periodontal parameters, including probing depth (PD), bleeding on probing (BOP), and plaque index (PI) were recorded from 25 healthy volunteers, 31 patients with untreated gingivitis, and 25 patients with untreated periodontitis. GCF, saliva, and plasma samples were collected from all subjects. Extraction and quantification assays were undertaken to determine cfDNA concentrations of each sample. Results: GCF and salivary cfDNA levels were increased with aggravation of periodontal inflammation (GCF p < 0.0001; saliva p < 0.001). Plasma cfDNA concentrations in patients with periodontitis were significantly higher than those in healthy volunteers and patients with gingivitis. GCF and salivary cfDNA were positively correlated with mean PD, max PD, BOP, and mean PI (p < 0.0001), whereas plasma cfDNA was not correlated with BOP (p = 0.099). Conclusion: GCF, saliva, and plasma concentrations of cfDNA were significantly elevated in patients with periodontal disease. There were also positive correlations between cfDNA levels in GCF and saliva and periodontal parameters.