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Interictal epileptiform discharges (IEDs) such as spikes and sharp waves represent pathological electrophysiological activities occurring in epilepsy patients between seizures. IEDs occur preferentially during non-rapid eye movement (NREM) sleep and are associated with impaired memory and cognition. Despite growing interest, most studies involving IED detections rely on visual annotations or employ simple amplitude threshold approaches. Alternatively, advanced computerized detection methods are not standardized or publicly available. To address this gap, we introduce a novel dataset comprising multichannel intracranial electroencephalography (iEEG) data recorded at two medical centers during overnight sleep with IED annotations performed by expert neurologists. Utilizing these annotations to train machine learning models via a gradient-boosting algorithm, we demonstrate automated IED detection with high precision (94.4%) and sensitivity (94.3%) that can generalize across individuals and surpass performance of a leading commercial software. The dataset featuring multi-channel annotations with sub-second resolution including hippocampus and medial temporal lobe (MTL) regions is made publicly available, together with the detection algorithm, to advance research on detection methodology, epilepsy, sleep, and cognition.

Objective To investigate the excitatory–inhibitory imbalance in drug‐resistant Juvenile Myoclonic Epilepsy (DR‐JME) patients using event‐related potentials during motor and cognitive tasks. Methods Eighteen JME patients and 11 healthy controls performed a visual Go No‐Go task while sitting (single‐task) and walking (dual‐task). EEG signals were analyzed using frequency‐domain techniques. Nonparametric tests compared groups and conditions. Results JME patients showed worse performance and slower reaction times than healthy controls (p < 0.04). DR‐JME patients demonstrated worse performance during Go cues (p = 0.001) but better withdrawal response to No‐Go cues (p = 0.03) compared to drug‐respondent JME. Significant differences in EEG spectral power were observed, particularly during dual‐task conditions. JME patients had lower power in the delta and alpha frequency bands compared to controls (p < 0.03). DR‐JME patients showed lower power in theta, alpha, and beta bands during dual‐task Go cues (p < 0.003) but higher power during dual‐task No‐Go cues compared to drug‐respondent JME (p < 0.02). Significance DR‐JME patients exhibited enhanced response inhibition, especially under dual‐task conditions, which likely indicates maladaptive neural processing and supports the notion of an excitatory–inhibitory imbalance in DR‐JME. This study provides new insights into the neurophysiological basis of drug resistance in JME, revealing distinct patterns of brain activity associated with inhibitory control. These findings could provide valuable insights into understanding the complex interactions between neuronal excitation and inhibition. Plain Language Summary Some patients with Juvenile Myoclonic Epilepsy (JME) do not respond to medication, but the reasons remain unclear. This study found that drug‐resistant JME patients show distinct brain activity and behavioral patterns, particularly during tasks requiring attention and movement. They had slower reactions but showed better inhibition to stop responses, along with altered brain rhythms, especially under dual‐task conditions. These results suggest an imbalance between brain excitation and inhibition, offering new insights into the neural mechanisms behind drug resistance in JME.

Background Juvenile myoclonic epilepsy (JME) is characterized by generalized seizures. Nearly 30% of JME patients are drug‐resistant (DR‐JME), indicating a widespread cortical dysfunction. Walking is an important function that necessitates orchestrated coordination of frontocentral cortical regions. However, gait alterations in JME have been scarcely investigated. Our aim was to assess changes in gait and motor‐evoked responses in DR‐JME patients. Methods Twenty‐nine subjects (11 JME drug‐responder, 8 DR‐JME, and 10 healthy controls) underwent a gait analyses during usual walking and dual‐task walking. Later, subjects underwent 64‐channel EEG recordings while performing a simple motor task. We calculated the motor‐evoked current source densities (CSD) at a priori chosen cortical regions. Gait and CSD measures were compared between groups and tasks using mixed model analysis. Results DR‐JME patients demonstrated an altered gait pattern that included slower gait speed (p = .018), reduced cadence (p = .003), and smaller arm‐swing amplitude (p = .011). The DR‐JME group showed higher motor‐evoked CSD in the postcentral gyri compared to responders (p = .049) and both JME groups showed higher CSD in the superior frontal gyri compared to healthy controls (p < .011). Moreover, higher CSD in the superior frontal gyri correlated with worse performance in dual‐task walking (r > |–0.494|, p < .008). Conclusions These alterations in gait and motor‐evoked responses in DRE‐JME patients reflect a more severe dysfunction of motor‐cognitive neural processing in frontocentral regions, leading to poorer gait performance. Further studies are needed to investigate the predictive value of altered gait and cortical motor processing as biomarkers for poor response to treatment in JME and other epilepsy syndromes. Patients with JME demonstrated abnormal gait pattern compared to healthy controls, which were even more accentuated in drug‐resistant patients. Furthermore, we found different spatial distribution of motor evoked potentials that strongly correlated with the abnormal gait measures. Overall, our results suggest that detailed gait assessment should be sought after in JME patients, as it possible reflects motor‐cognitive neural integrity and patients' responsiveness to medications.

A nationwide vaccination operation against Coronavirus disease 2019 (COVID-19) using the BNT162b2 mRNA vaccine commenced in Israel in December 2020. People older than 60 were prioritized, and most were vaccinated shortly after. Seizures are not infrequently attributed to the vaccine despite a lack of supporting evidence. People with epilepsy (PWE) are often reluctant to get the vaccine due to concerns of seizure aggravation. We aim to examine the effect of the vaccine effort on the frequency of both new-onset seizures and recurrent seizures in PWE. Methods: All adults who presented to the emergency department (ED) of Tel Aviv Sourasky Medical Center between January 1st and May 31st, 2017–2021, and were diagnosed with seizures were included. Demographic, clinical, and vaccination status parameters were collected using MDClone, a data acquisition tool. Vaccination rates in the general population were obtained from official governmental publications. Statistics included a sub-analysis of patients with the highest vaccination rate, people older than 60. Results: 1675 cases were included. The numbers of ED visits and hospital admissions due to seizures in 2021 were comparable to preceding years after adjusting for the total number of ED visits at the same time. Out of 339 cases in 2021, 134 patients older than 60 years old presented to the ED (39.5%) compared to 124–151 in 2017–2019 (37–44%) and 103 in 2020 (33%). The vaccination rate among patients hospitalized due to seizures was similar to the general population of the same age group during the same period in Israel. There was no temporal relation between vaccination and hospitalization due to a seizure. Significance: Despite very high vaccination rates in the general population in Israel and especially among people older than 60 years, no increase was observed in ED presentations due to seizures. No temporal relation was observed between vaccination and hospitalization due to a seizure. We conclude that the mass vaccination with the Pfizer BioNTech mRNA vaccine is not associated with increased seizure propensity. •Israel's national vaccination campaign commenced in December 2020 with the BNT162B2 vaccine.•We did not observe an increase in emergency department presentations due to seizures during the campaign.•No change in the frequency of both new-onset seizures and recurrent seizures was observed, including in patients over 60.•Vaccination rates among hospitalized patients were similiar to the general population of the same age.•There was no temporal association between vaccine administration and hospitalization with a seizure.

Long-term data on pediatric celiac disease (CD) patients after transition to adult care is scarce. We aimed to evaluate patients’ adherence to a gluten-free diet (GFD), the normalization of celiac serology and the frequency of follow-up before age 18, and to study changes in adherence and follow-up frequency after transition to adult care. Presenting symptoms, serology and biopsy results, patients’ reported GFD adherence, frequency of follow-up visits, and complications before and after 18 years were collected for CD patients diagnosed between 1998 and 2017. Of 441 CD patients diagnosed and followed in childhood, a quarter (108/441) were over 18 y (years) at data collection. Median age at diagnosis 7.1 y (9 months–18 y), at data collection 23 y (18–38 y), disease duration 11.3 y (2–36 y). Below the age of 18 y, most patients 386/436 (88.5%) reported adherence to GFD, and most 372/425 (85.7%) normalized serology. Of the 441 patients, only 3 failed to attend any follow-up visit, and 338/441 (76.6%) attended yearly visits. Over the age 18 y, serology testing was done in 78/108 (72.2%), every 1–3 y in 46/78 (59%). Serology normalized in 61/78 (78.2%). Most adult patients 77/108 (71.5%) never attended a gastroenterology clinic. CD-related complications were rare. Younger age at diagnosis, regular follow-up visits in childhood, resolution of symptoms, and normalization of serology before age 18 were identified as predictors of negative serology after the age of 18 y.Conclusions: Children who have regular follow-up and normalize serology before age 18 years are likely to maintain a GFD and have negative serology as adults.What is Known:• The rate of adherence to gluten-free diet (GFD) is higher among children compared to adults.• Data on long-term follow-up after transition to adult care is scarce.What is New:• Patients diagnosed with CD at a younger age (<12 y), who have yearly follow-up visits, resolution of symptoms, and negative serology in childhood are very likely to maintain GFD and have negative serology as adults.• Even though most patients do not attend GI clinics after transition to adulthood, most adhere to GFD, and complications are rare.

The mechanisms ensuring balanced growth remain a critical question in developmental biology. In plants, this balance relies on spatiotemporal integration of hormonal signaling pathways, but the understanding of the precise contribution of each hormone is just beginning to take form. Brassinosteroid (BR) hormone is shown here to have opposing effects on root meristem size, depending on its site of action. BR is demonstrated to both delay and promote onset of stem cell daughter differentiation, when acting in the outer tissue of the root meristem, the epidermis, and the innermost tissue, the stele, respectively. To understand the molecular basis of this phenomenon, a comprehensive spatiotemporal translatome mapping of Arabidopsis roots was performed. Analyses of wild type and mutants featuring different distributions of BR revealed autonomous, tissue-specific gene responses to BR, implying its contrasting tissue-dependent impact on growth. BR-induced genes were primarily detected in epidermal cells of the basal meristem zone and were enriched by auxin-related genes. In contrast, repressed BR genes prevailed in the stele of the apical meristem zone. Furthermore, auxin was found to mediate the growth-promoting impact of BR signaling originating in the epidermis, whereas BR signaling in the stele buffered this effect. We propose that context-specific BR activity and responses are oppositely interpreted at the organ level, ensuring coherent growth. Significance Brassinosteroid (BR) differentially regulates the number of stem cell daughters in the root meristem. How its activity coordinates and maintains the meristem size remains unknown. We show that BR signal coordinates root growth by evoking distinct and often opposing responses in specific tissues. Whereas epidermal BR signal promotes stem cell daughter proliferation, the stele-derived BR signal induces their differentiation. Using a comprehensive tissue-specific translatome survey, we uncovered a context-specific effect of BR signaling on gene expression. Auxin genes, activated by epidermal BR perception, are necessary for induction of cell division. Conversely, the stele BR perception, accompanied by gene repression, restrains the epidermal effect. Therefore, a site-specific BR signal is essential for balanced organ growth.

Introduction There is scarce data regarding the incidence of venous thromboembolism (VTE) and arterial thromboembolism (ATE) in the molecular subtypes of non-small cell lung cancer (NSCLC). We aimed to investigate the association between Anaplastic Lymphoma Kinase (ALK)-positive NSCLC and thromboembolic events. Methods A retrospective population-based cohort study of the Clalit Health Services database, included patients with NSCLC diagnosed between 2012 and 2019. Patients exposed to ALK-tyrosine-kinase inhibitors (TKIs) were defined as ALK-positive. The outcome was VTE (at any site) or ATE (stroke or myocardial infarction) 6 months prior to the diagnosis of cancer, until 5 years post-diagnosis. The cumulative incidence of VTE and ATE and hazard-ratios (HR) with 95% CIs were calculated (at 6- 12- 24 and 60-months), using death as a competing risk. Cox proportional hazards multivariate regression was performed, with the Fine and Gray correction for competing risks. Results The study included 4762 patients, of which 155 (3.2%) were ALK-positive. The overall 5-year VTE incidence was 15.7% (95% CI, 14.7-16.6%). ALK-positive patients had a higher VTE risk compared to ALK-negative patients (HR 1.87 [95% CI, 1.31-2.68]) and a 12-month VTE incidence of 17.7% (13.9-22.7%) compared to 9.9% (9.1-10.9%) in ALK-negative patients. The overall 5-year ATE incidence was 7.6% [6.8-8.6%]. ALK positivity was not associated with ATE incidence (HR 1.24 [0.62-2.47]). Conclusions In this study, we observed a higher VTE risk, but not ATE risk, in patients with ALK-rearranged NSCLC relative to those without ALK rearrangement. Prospective studies are warranted to evaluate thromboprophylaxis in ALK-positive NSCLC. There is scarce data regarding the incidence of venous thromboembolism and arterial thromboembolism in the molecular subtypes of non-small cell lung cancer (NSCLC). This study investigated the association between ALK-positive NSCLC and thromboembolic events.

Plants feature remarkable developmental plasticity, enabling them to respond to and cope with environmental cues, such as limited availability of phosphate, an essential macronutrient for all organisms. Under this condition, Arabidopsis (Arabidopsis thaliam) roots undergo striking morphological changes, including exhaustion of the primary meristem, impaired unidirectional cell expansion, and elevated density of lateral roots, resulting in shallow root architecture. Here, we show that the activity of two homologous brassinosteroid (BR) transcriptional effectors, BRASSINAZOLE RESISTANT1 (BZR1) and BRASSINOSTEROID INSENSITIVE1-ETHYL METHANESULFONATE-SUPPRESSOR1 (BES1)/BZR2, blocks these responses, consequently maintaining normal root development under low phosphate conditions without impacting phosphate homeostasis. We show that phosphate deprivation shifts the intracellular localization of BES1/BZR2 to yield a lower nucleus-to-cytoplasm ratio, whereas replenishing the phosphate supply reverses this ratio within hours. Phosphate deprivation reduces the expression levels of BR biosynthesis genes and the accumulation of the bioactive BR 28-norcastasterone. In agreement, low and high BR levels sensitize and desensitize root response to this adverse condition, respectively. Hence, we propose that the environmentally controlled developmental switch from deep to shallow root architecture involves reductions in BZR1 and BES1/BZR2 levels in the nucleus, which likely play key roles in plant adaptation to phosphate-deficient environments.

Background. Kaposi sarcoma is a rare vascular mesenchymal neoplasm, associated with Human Herpes Virus 8 (HHV8). Gout is a condition clinically characterized by recurrent flares of arthritis and hyperuricemia. Following our clinical impression that patients with classical Kaposi sarcoma (CKS) have a high rate of gout, we explored this in a retrospective manner. Methods. All consecutive patients diagnosed with sarcoma or carcinosarcoma within a single tertiary center between 1/2012–12/2017 were identified through the pathology department database. A cohort of CKS patients was compared with the non-Kaposi sarcoma and carcinosarcoma cohort. Data were extracted from patients’ electronic medical records. Patients younger than 18 and patients without clinical data available were excluded. Association between diagnosis of gout and CKS was assessed and adjusted for risk factors. Results. Three hundred and sixty-one patients were eligible for this analysis, 61 were diagnosed with CKS and 300 with other types of sarcoma. We found a higher incidence of gout in CKS patients, 11/61 (18%) patients, compared with 8/300 (2.6%) with other types of sarcoma, odds ratio (OR) 8.0 (P<0.00001). This association persisted when adjusted for age >39 years (OR = 6.7, P<0.00001), age and male sex (OR = 4.97, P<0.0001), and when adjusting for multiple confounding factors and medical comorbidities. Conclusions. We have demonstrated a statistically significant association between gout and CKS. As risk factors for gout were accounted for, this association may be explained by HHV8 immune-related effects. This should be further explored in vitro and in population-based studies.