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Background: A multi-method, multi-informant approach is crucial for evaluating attention-deficit/hyperactivity disorders (ADHD) in preschool children due to the diagnostic complexities and challenges at this developmental stage. However, most artificial intelligence (AI) studies on the automated detection of ADHD have relied on using a single datatype. This study aims to develop a reliable multimodal AI-detection system to facilitate the diagnosis of ADHD in young children. Methods: 78 young children were recruited, including 43 diagnosed with ADHD (mean age: 68.07 ± 6.19 months) and 35 with typical development (mean age: 67.40 ± 5.44 months). Machine learning and deep learning methods were adopted to develop three individual predictive models using electroencephalography (EEG) data recorded with a wearable wireless device, scores from the computerized attention assessment via Conners' Kiddie Continuous Performance Test Second Edition (K-CPT-2), and ratings from ADHD-related symptom scales. Finally, these models were combined to form a single ensemble model. Results: The ensemble model achieved an accuracy of 0.974. While individual modality provided the optimal classification with an accuracy rate of 0.909, 0.922, and 0.950 using the ADHD-related symptom rating scale, the K-CPT-2 score, and the EEG measure, respectively. Moreover, the findings suggest that teacher ratings, K-CPT-2 reaction time, and occipital high-frequency EEG band power values are significant features in identifying young children with ADHD. Conclusions: This study addresses three common issues in ADHD-related AI research: the utility of wearable technologies, integrating databases from diverse ADHD diagnostic instruments, and appropriately interpreting the models. This established multimodal system is potentially reliable and practical for distinguishing ADHD from TD, thus further facilitating the clinical diagnosis of ADHD in preschool young children. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is a leading malignant disease in numerous countries, including Taiwan with limited therapeutic options. Animal viruses including oncolytic avian reovirus (ARV) have the possibility to avoid pre-existing immunity in humans, while being safe and immunostimulatory. Here, we provide a novel insight into oncolytic ARV and UV-ARV-sensitized patient's peripheral blood mononuclear cells (P-PBMCs) and tumor infiltrating lymphocytes (TILs) killing primary GC (PGC) cells through the surface TLR3 and TRAIL/DR4/DR5 immunogenic apoptosis pathway. Methods: We conducted a comprehensive study to reveal whether ARV- or UV-inactivated ARV (UV-ARV)-modulated P-PBMCs or TILs killing ARV- and UV-ARV-sensitized AGS cells and PGC cells derived from clinical patients and to investigate the regulation of surface TLR3 receptor and upstream signaling pathways. Apoptosis analysis by flow cytometry and Western blot, suppression of signal pathway by specific inhibitors, in situ proximity ligation assay (PLA), time-resolved flurometry and lactate dehydrogenase (LDH) cytotoxicity assays, and an in vitro co-culture model were established to study the interplay between ARV- and UV-ARV-sensitized P-PBMCs and TILs to kill PGC cells and their upstream pathways. Results: Our results reveal that increased levels of DR4 and DR5 were observed in ARV and UV-ARV sensitized PGC cells through the TLR3/p38/p53 signaling pathway. Importantly, we found that the σC protein of ARV or UV-ARV interacted with surface TLR3 of CD8+ TILs, thereby triggering the TLR3/NF-κB/IFN-γ/TRAIL signaling pathway which induces immunogenic apoptosis of PGC cells. This study sheds further light on the molecular basis behind ARV oncolysis and facilitates the ARV or UV-ARV as a cancer therapeutic. Conclusions: The study provides novel insights into ARV- or UV-ARV-sensitized P-PBMCs and CD8+ TILs to kill PGC cells through the immunogenic apoptosis pathway. We conclude that P-PBMCs can easily be obtained from GC patients and provide a rich source as TILs to kill PGC cells. [ABSTRACT FROM AUTHOR]

Background: Although tumor cells undergoing epithelial–mesenchymal transition (EMT) typically exhibit spindle morphology in experimental models, such histomorphological evidence of EMT has predominantly been observed in rare primary spindle carcinomas. The characteristics and transcriptional regulators of spontaneous EMT in genetically unperturbed non-spindled carcinomas remain underexplored. Methods: We used primary culture combined with RNA sequencing (RNA-seq), single-cell RNA-seq (scRNA-seq), and in situ RNA-seq to explore the characteristics and transcription factors (TFs) associated with potential spontaneous EMT in non-spindled breast carcinoma. Results: Our primary culture revealed carcinoma cells expressing diverse epithelial–mesenchymal traits, consistent with epithelial–mesenchymal plasticity. Importantly, carcinoma cells undergoing spontaneous EMT did not necessarily exhibit spindle morphology, even when undergoing complete EMT. EMT was a favored process, whereas mesenchymal–epithelial transition appeared to be crucial for secondary tumor growth. Through scRNA-seq, we identified TFs that were sequentially and significantly upregulated as carcinoma cells progressed through the EMT process, which correlated with increasing VIM expression. Once upregulated, the TFs remained active throughout the EMT process. ZEB1 was a key initiator and sustainer of EMT, as indicated by its earliest significant upregulation in the EMT process, its exact correlation with VIM expression, and the reversal of EMT and downregulation of EMT-upregulated TFs upon ZEB1 knockdown. The correlation between ZEB1 and vimentin expression in triple-negative breast cancer and metaplastic breast carcinoma tumor cohorts further highlighted its role. The immediate upregulation of ZEB2 following that of ZEB1, along with the observation that the knockdown of ZEB1 or ZEB2 downregulates both ZEB1 and ZEB2 concomitant with the reversal of EMT, suggests their functional cooperation in EMT. This finding, together with that of a lack of correlation of SNAI1, SNAI2, and TWIST1 expression with the mesenchymal phenotype, indicated EMT-TFs have a context-dependent role in EMT. Upregulation of EMT-related gene signatures during EMT correlated with poor patient outcomes, highlighting the biological importance of the model. Elevated EMT gene signatures and increased ZEB1 and ZEB2 expression in vimentin-positive compared to vimentin-negative carcinoma cells within the corresponding primary tumor tissue confirmed ZEB1 and ZEB2 as intrinsic, instead of microenvironmentally-induced, EMT regulators, and vimentin as an in vivo indicator of EMT. Conclusions: Our findings provide insights into the characteristics and transcriptional regulators of spontaneous EMT in primary non-spindled carcinoma. [ABSTRACT FROM AUTHOR]

Background: Due to cardiotoxicity concerns, the concurrent use of epirubicin and trastuzumab has not been fully studied. This study aimed to examine the cardiotoxicity and pathological complete response (pCR) rate associated with the concurrent regimens in patients with human epidermal growth factor receptor 2 (HER2)‐positive early breast cancer (EBC). Methods: We conducted a systematic search for relevant literature in the NCBI/PubMed, the Cochrane database, and international conference abstracts for phase II or III randomized controlled trials between January 1, 2000, and February 28, 2021, focusing on the concurrent regimens in patients with HER2‐positive EBC. To compare the risk of cardiotoxicity and the odds of the pCR rate, we performed linear meta‐regression analyses to investigate the effects of multiple covariates. Results: We analyzed 7 neoadjuvant trials involving the concurrent use of epirubicin and trastuzumab with 1797 patients. The median cumulative dose of epirubicin used was 300 mg/m2, with a total of 96 reported adverse cardiac events. The concurrent regimens did not result in a significant increase in cardiotoxicity compared to nonconcurrent regimens (risk ratio [RR] = 1.18, 95% confidence interval [CI] = 0.68–2.05). Compared with nonconcurrent or non‐anthracycline‐containing regimens, concurrent regimens were associated with a significant increase in the pCR rate (odds ratio = 1.48, 95% CI = 1.04–2.12). The linear fixed‐effects meta‐regression analysis indicated that in trials including more patients with hormone receptor‐positive EBC, the RR of cardiotoxicity significantly increased with concurrent regimens, and the pCR rate became less significant. Conclusions: The combination of trastuzumab and a low dose of epirubicin positively impacted the pCR rate without a significant increase in cardiotoxicity. We recommend exploring concurrent regimens for HR‐negative, HER2‐positive tumors to enhance pCR rates, with caution advised for HR‐positive tumors due to potential cardiotoxicity. [ABSTRACT FROM AUTHOR]

Introduction: Approximately 60 million individuals worldwide used opioids in 2021, constituting 1.2% of the global adult population. This study aimed to evaluate the effectiveness of integrated treatment strategies for opioid use disorder and nicotine use disorder by assessing the impact of smoking cessation within a methadone treatment framework. Methods: In a retrospective cohort study, 53 methadone maintenance patients were divided into 16 treatment-seeking smokers (TSS) and 37 treatment-rejecting smokers (TRS) based on their participation in the Ottawa model for smoking cessation plus 16 weeks of varenicline treatment. Both groups received standard methadone treatment for 68 weeks. TSS were followed up for 44 weeks to assess smoking cessation outcomes, while TRS had none due to their lack of participation in smoking cessation treatment. Results: The median age of the TSS group was 48 years, while that of the TRS group was 45.5 years. Males comprised 75% of TSS and 94.6% of the TRS. TSS exhibited an 83% decrease in positive opioid screen results compared to TRS (p=0.023). In TSS, peak smoking cessation success was observed at week 20, with 57% of participants maintaining carbon monoxide levels <5 ppm. Conclusions: The significant reduction in positive opioid screens and the high smoking cessation rate in the TSS group highlight the efficacy of combined treatment methods. This study underscores the advantages of integrating smoking cessation with methadone maintenance treatment, indicating that comprehensive approaches can substantially improve treatment outcomes. [ABSTRACT FROM AUTHOR]

There are limited therapeutic options for patients with Dravet syndrome (DS). The equilibrative nucleoside transporters 1 (ENT1) mediate both the influx and efflux of adenosine across the cell membrane exerted beneficial effects in the treatment of epilepsy. This study aimed to evaluate the anticonvulsant effect of the ENT1 inhibitor in an animal model of DS (Scn1aE1099X/+ mice). J7 (5 mg/kg) treatment was efficacious in elevating seizure threshold in Scn1aE1099X/+ mice after hyperthermia exposure. Moreover, the J7 treatment significantly reduced the frequency of spontaneous excitatory post‐synaptic currents (sEPSCs, ~35% reduction) without affecting the amplitude in dentate gyrus (DG) granule cells. Pretreatment with the adenosine A1 receptor (A1R) antagonist, DPCPX, abolished the J7 effects on sEPSCs. These observations suggest that the J7 shows an anticonvulsant effect in hyperthermia‐induced seizures in Scn1aE1099X/+ mice. This effect possibly acts on presynaptic A1R‐mediated signaling modulation in granule cells. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is a leading malignant disease in numerous countries, including Taiwan with limited therapeutic options. Animal viruses including oncolytic avian reovirus (ARV) have the possibility to avoid pre-existing immunity in humans, while being safe and immunostimulatory. Here, we provide a novel insight into oncolytic ARV and UV-ARV-sensitized patient's peripheral blood mononuclear cells (P-PBMCs) and tumor infiltrating lymphocytes (TILs) killing primary GC (PGC) cells through the surface TLR3 and TRAIL/DR4/DR5 immunogenic apoptosis pathway., Methods: We conducted a comprehensive study to reveal whether ARV- or UV-inactivated ARV (UV-ARV)-modulated P-PBMCs or TILs killing ARV- and UV-ARV-sensitized AGS cells and PGC cells derived from clinical patients and to investigate the regulation of surface TLR3 receptor and upstream signaling pathways. Apoptosis analysis by flow cytometry and Western blot, suppression of signal pathway by specific inhibitors, in situ proximity ligation assay (PLA), time-resolved flurometry and lactate dehydrogenase (LDH) cytotoxicity assays, and an in vitro co-culture model were established to study the interplay between ARV- and UV-ARV-sensitized P-PBMCs and TILs to kill PGC cells and their upstream pathways., Results: Our results reveal that increased levels of DR4 and DR5 were observed in ARV and UV-ARV sensitized PGC cells through the TLR3/p38/p53 signaling pathway. Importantly, we found that the σC protein of ARV or UV-ARV interacted with surface TLR3 of CD8 + TILs, thereby triggering the TLR3/NF-κB/IFN-γ/TRAIL signaling pathway which induces immunogenic apoptosis of PGC cells. This study sheds further light on the molecular basis behind ARV oncolysis and facilitates the ARV or UV-ARV as a cancer therapeutic., Conclusions: The study provides novel insights into ARV- or UV-ARV-sensitized P-PBMCs and CD8 + TILs to kill PGC cells through the immunogenic apoptosis pathway. We conclude that P-PBMCs can easily be obtained from GC patients and provide a rich source as TILs to kill PGC cells., (© 2024. The Author(s).)

Excessive activation of mTOR has been observed in the brains of mouse models for Dravet syndrome. We aim to confirm whether that the overactivation of mTOR contributes to the neuropathological changes leading to epileptogenesis and neurobehavior deficits to support a novel pharmacological therapeutic approach for Dravet syndrome. The mTOR inhibitor everolimus, as a clinical antiseizure medication, was utilized to investigate whether mTOR is involved in hyperthermia-induced seizures, anxiety-like, and autism-like behaviors, as well as to explore potential pathogenic mechanisms in Scn1a E1099X/+ mice, a model of Dravet syndrome. First, we found that mTOR signaling was upregulated in hippocampus tissues and neural cultures derived from Scn1a E1099X/+ mice prior to seizure onset. Behaviorally, everolimus increased the seizure threshold and improved anxiety-like and autism-like behaviors in Scn1a E1099X/+ mice. Electrophysiologically, everolimus reduced the frequency of spontaneous excitatory postsynaptic currents in dentate granule neurons from Scn1a E1099X/+ mice. Biochemically, everolimus prevented hyperthermia-induced phosphorylation of hippocampal S6 ribosome in hippocampus, and it delayed hyperthermia-induced increase of cytosolic Ca 2+ level in primary neuronal cultures derived from Scn1a E1099X/+ mice. Our results provide the evidence that overactivated mTOR as an important neuropathological change which regulates seizure threshold, impairments of neurobehavior, neuronal glutamatergic transmission and intracellular Ca 2+ levels in Scn1a E1099X/+ mice. Inhibition of mTOR is a potential pharmacological therapeutic approach., 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 © 2024. Published by Elsevier Ltd.)

The sustainability of lithium-based energy storage or conversion systems, e.g., lithium-ion batteries, can be enhanced by establishing methods of efficient lithium extraction from harsh brines. In this work, we describe a decoupled membrane-free electrochemical cell that cycles lithium ions between iron-phosphate electrodes and features cathode (brine) and anode (fresh water) compartments that are isolated from each other yet electrochemically connected through a pair of silver/silver-halide redox electrodes. This design is compatible with harsh brines having magnesium/lithium molar ratios of up to 3258 and lithium concentrations down to 0.15 millimolar, enabling the production of battery-grade (>99.95% pure) lithium carbonate. Energy savings of up to ~21.5% were realized by efficiently harvesting the osmotic energy of the brines. A pilot-scale cell with an electrode surface area of 33.75 square meters was used to realize lithium extraction from Dead Sea brine with a recovery rate of 84.0%.

Objective: The identification and diagnosis of children with attention deficit hyperactivity disorder (ADHD) traits is challenging during the preschool stage. Neuropsychological measures may be useful in early assessments. Furthermore, analysis of event-related behavior appears to be an unmet need for clinical treatment planning. Conners' Kiddie Continuous Performance Test (K-CPT) is the most popular well-established neuropsychological measurement but lacks event markers to clarify the heterogeneous behaviors among children. This study utilized a novel commercially available neuropsychological measure, the ΣCOG, which was more game-like and provided definite event markers of individual trial in the test., Methods: Thirty-three older preschool children (14 were diagnosed with ADHD, mean age: 66.21 ± 5.48 months; 19 demonstrated typical development, mean age: 61.16 ± 8.11 months) were enrolled and underwent comprehensive medical and developmental evaluations. All participants underwent 2 versions of neuropsychological measures, including the K-CPT, Second Edition (K-CPT 2) and the ΣCOG, within a short interval., Results: The study indicated the omissions and response time scores measured in this novel system correlated with clinical measurement of the behavioral scales in all participants and in the group with ADHD; additionally, associations with the traditional K-CPT 2 were observed in commissions and response time scores. Furthermore, this system provided a within-task behavioral analysis that identified the group differences in the specific trial regarding omission and commission errors., Conclusions: This innovative system is clinically feasible and can be further used as an alternative to the K-CPT 2 especially in research by revealing within-task event-related information analysis., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)