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With the growth of chatbots, concerns about implementing artificial intelligence (AI) chatbots in educational settings have consistently arisen, especially for the purpose of language learning. This study introduced a task-based voice chatbot called “Ellie”, newly developed by the researchers, and examined the appropriateness of its task design and performance as an English conversation partner and students’ perceptions on using it in EFL class. Korean EFL learners (N = 314) aged 10–15 years performed three speaking tasks with Ellie in their school classroom. The participants took 9.63 turns per session on average using the first 1,000-word band, indicating that the chatbot highly encouraged students to engage in conversation, which rarely occurs in general EFL classes in Korea. The high task success rates (88.3%) showed the design appropriateness of both L2 tasks and operational intents in terms of users’ successful understanding and completeness of the given chatbot tasks. The participants’ responses to the survey not only supported the positive potential of the chatbot in EFL settings but also revealed limitations to be resolved. Future suggestions for advancing and implementing AI chatbots in EFL classrooms are discussed.

Spectral ripple discrimination (SRD) has been widely used to evaluate the spectral resolution in cochlear implant (CI) recipients based on its strong correlation with speech perception performance. However, despite its usefulness for predicting speech perception outcomes, SRD performance exhibits large across-subject variabilities even among subjects implanted with the same CIs and sound processors. The potential factors of this observation include current spread, nerve survival, and CI mapping. Previous studies have found that the spectral resolution reduces with increasing distance of the stimulation electrode from the auditory nerve fibers (ANFs), attributable to increasing current spread. However, it remains unclear whether the spread of excitation is the only cause of the observation, or whether other factors such as temporal interaction also contribute to it. In this study, we used a computational model to investigate channel interaction upon non-simultaneous stimulation with respect to the electrode-ANF distance, and evaluated the SRD performance for five electrode-ANF distances. The SRD performance was determined based on the similarity between two neurograms in response to standard and inverted stimuli and used to evaluate the spectral resolution in the computational model. The spread of excitation was observed to increase with increasing electrode-ANF distance, consistent with previous findings. Additionally, the preceding pulses delivered from neighboring channels induced a channel interaction that either inhibited or facilitated the neural responses to subsequent pulses depending on the electrode-ANF distance. The SRD performance was also found to decrease with increasing electrode-ANF distance. The findings of this study suggest that variation of the neural responses (inhibition or facilitation) with the electrode-ANF distance in CI users may cause spectral smearing, and hence poor spectral resolution. A computational model such as that used in this study is a useful tool for understanding the neural factors related to CI outcomes, such as cannot be accomplished by behavioral studies alone.

Background Trimethyltin (TMT) is a potent neurotoxicant that leads to hippocampal neurodegeneration. Regulatory T cells (Tregs) play an important role in maintaining the immune balance in the central nervous system (CNS), but their activities are impaired in neurodegenerative diseases. In this study, we aimed to determine whether adoptive transfer of Tregs, as a living drug, ameliorates hippocampal neurodegeneration in TMT-intoxicated mice. Methods CD4 + CD25 + Tregs were expanded in vitro and adoptively transferred to TMT-treated mice. First, we explored the effects of Tregs on behavioral deficits using the Morris water maze and elevated plus maze tests. Biomarkers related to memory formation, such as cAMP response element-binding protein (CREB), protein kinase C (PKC), neuronal nuclear protein (NeuN), nerve growth factor (NGF), and ionized calcium binding adaptor molecule 1 (Iba1) in the hippocampus were examined by immunohistochemistry after killing the mouse. To investigate the neuroinflammatory responses, the polarization status of microglia was examined in vivo and in vitro using real-time reverse transcription polymerase chain reaction (rtPCR) and Enzyme-linked immunosorbent assay (ELISA). Additionally, the inhibitory effects of Tregs on TMT-induced microglial activation were examined using time-lapse live imaging in vitro with an activation-specific fluorescence probe, CDr20. Results Adoptive transfer of Tregs improved spatial learning and memory functions and reduced anxiety in TMT-intoxicated mice. Additionally, adoptive transfer of Tregs reduced neuronal loss and recovered the expression of neurogenesis enhancing molecules in the hippocampi of TMT-intoxicated mice. In particular, Tregs inhibited microglial activation and pro-inflammatory cytokine release in the hippocampi of TMT-intoxicated mice. The inhibitory effects of TMT were also confirmed via in vitro live time-lapse imaging in a Treg/microglia co-culture system. Conclusions These data suggest that adoptive transfer of Tregs ameliorates disease progression in TMT-induced neurodegeneration by promoting neurogenesis and modulating microglial activation and polarization.

We previously reported that rice bran extract supplement (RBS) administration to mice decreased sleep latency and induced non-rapid eye movement (NREM) sleep via inhibition of the histamine H 1 receptor. Based on this, we performed the first clinical trial to investigate whether RBS would be beneficial to subjects with disturbed sleep. We performed a randomized, double‐blinded, placebo‐controlled, 2-week study. Fifty subjects with sleep disturbance were enrolled and received either RBS (1,000 mg/day) or placebo. Polysomnography was performed, and Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale (ESS), and Fatigue Severity Scale were administered at the initiation and termination of the study. Compared with the placebo, RBS led to significant polysomnographic changes, including decreased sleep latency (adjusted, P = 0.047), increased total sleep time (P = 0.019), and improved sleep efficiency (P = 0.010). Additionally, the amount of stage 2 sleep significantly increased in the RBS group. When adjusted for caffeine intake, wakefulness after sleep onset, total wake time, and delta activity tended to decrease in the RBS group. RBS administration decreased ESS scores. There were no reported serious adverse events in both groups. RBS improved sleep in adults with sleep disturbance. Trial registration: WHO ICTRP, KCT0001893.

Modern members of society tend to feel stressed in their workplace and at home, but exercising has been shown to effectively reduce stress and increase quality of life and satisfaction. This study aimed to investigate and compare stress relief, life satisfaction, and quality of life based on marriage status and gender among members of society who participate in exercise. We used a questionnaire survey with 311 participants, and the data were analyzed using descriptive statistics, validity and reliability, a multivariate analysis of variance (MANOVA), and a post hoc analysis. The study results showed that the single groups demonstrated higher mean scores in stress relief than the married groups. Conversely, the married groups showed higher mean scores in life satisfaction and quality of life compared with the single groups, and there were no gender differences in any of the results. In conclusion, it seems that these results were affected by the single groups’ high autonomy and the married groups’ sense of stability in the family.

Although oxaliplatin is a well-known anti-cancer agent used for the treatment of colorectal cancer, treated patients often experience acute cold and mechanical allodynia as side effects. Unfortunately, no optimal treatment has been developed yet. In this study, [6]-shogaol (10 mg/kg, i.p.), which is one of the major bioactive components of Zingiber officinale roscoe (Z. officinale), significantly alleviated allodynia induced by oxaliplatin (6 mg/kg, i.p.) injection. Cold and mechanical allodynia were assessed by acetone drop and von Frey filament tests, respectively. The analgesic effect of [6]-shogaol was blocked by the intrathecal injection of 5-HT1A, 5-HT3, and GABAB receptor antagonists, NAN-190 (1 μg), MDL-72222 (15 μg), and CGP 55845 (10 μg), respectively. Furthermore, oxaliplatin injection lowered the GABA concentration in the superficial laminae of the spinal dorsal horn, whereas [6]-shogaol injection significantly elevated it. The GAD (glutamic acid decarboxylase) 65 concentration also increased after [6]-shogaol administration. However, pre-treatment of NAN-190 completely inhibited the increased GABA induced by [6]-shogaol in the spinal dorsal horn, whereas MDL-72222 partially blocked the effect. Altogether, these results suggest that [6]-shogaol could attenuate oxaliplatin-induced cold and mechanical allodynia through 5-HT1A and 5-HT3 receptor antagonists located in the GABAergic neurons in the spinal dorsal horn in mice.

Background Glucocorticoid therapy has a beneficial effect in several diseases, but chronic treatment has adverse effects, including muscle atrophy, which refers to the gradual decrease in muscle mass, size and strength. It is important to know how the muscle atrophy occurs, but the underlying mechanism is not yet fully understood. This study shows that dexamethasone decreases levels of the transcriptional co‐activator with PDZ binding motif (TAZ), which facilitates dexamethasone‐induced muscle atrophy. Methods To induce muscle atrophy, C2C12 myotubes were treated with dexamethasone, and mice were fed with water containing dexamethasone. Muscle atrophy was analysed for the expression of myosin heavy chain, MuRF1 and Atrogin‐1 using immunofluorescence staining, immunoblot analysis and qRT‐PCR. Muscle tissue was analysed by haematoxylin and eosin staining. Adeno‐associated virus was used for overexpression of wild‐type and mutant TAZ. Results TAZ levels decrease in dexamethasone‐treated mice (0.36‐fold, p < 0.001) and C2C12 myotubes (0.44‐fold, p = 0.024). Overexpression of the TAZ mutant, which resists its proteolytic degradation, inhibits dexamethasone‐induced muscle atrophy. Atrogin‐1 and MuRF1 interact with TAZ and facilitate its degradation in dexamethasone‐treated C2C12 myotubes. TAZ mutant stimulates protein synthesis through activation of mTOR signalling via induction of RhebL1 (DEX; Con vs, TAZ4SA: 5.1‐fold, p < 0.001) in dexamethasone‐treated mice. Ginsenoside Rb3 increases TAZ levels in dexamethasone‐treated mice (1.49‐fold, p = 0.007) and C2C12 myotubes (1.63‐fold, p = 0.01), which stimulates mTOR signalling and inhibits dexamethasone‐induced muscle atrophy. Conclusions Our results demonstrate a novel regulatory mechanism of dexamethasone‐induced muscle atrophy by TAZ, suggesting that stabilisation of TAZ in muscle cells ameliorates the muscle atrophy. These results suggest that TAZ may be a drug target for the dexamethasone‐induced muscle atrophy.

Atherosclerosis is a chronic inflammatory disease caused by lipids and calcareous accumulations in the vascular wall due to an inflammatory reaction. Recent reports have demonstrated that regulatory T (Treg) cells have an important role as a new treatment for atherosclerosis. This study suggests that bee venom phospholipase A2 (bvPLA2) may be a potential therapeutic agent in atherosclerosis by inducing Treg cells. We examined the effects of bvPLA2 on atherosclerosis using ApoE-/- and ApoE-/-/Foxp3DTR mice. In this study, bvPLA2 increased Treg cells, followed by a decrease in lipid accumulation in the aorta and aortic valve and the formation of foam cells. Importantly, the effect of bvPLA2 was found to depend on Treg cells. This study suggests that bvPLA2 can be a potential therapeutic agent for atherosclerosis.

Background/Objectives: This study aimed to investigate the preoperative clinicopathologic and imaging features associated with subsequent breast cancer events detected on postoperative abbreviated MRI in early-stage breast cancer patients following breast and axillary surgery. Methods: A retrospective analysis was conducted on 1171 patients (median age, 53 years; range, 24–90 years) diagnosed with clinical stage I or II breast cancer between January 2013 and December 2017. Logistic regression analysis was used to evaluate preoperative imaging features—including breast density assessed on mammography and MRI descriptors—along with clinicopathologic characteristics, to identify factors independently associated with subsequent breast cancer events during abbreviated MRI screening. Results: Among the patients, 57 (4.9%) experienced subsequent breast cancer events at a median follow-up of 74 months. In the multivariable analysis, high nuclear grade (odds ratio [OR] = 2.821; 95% confidence interval [CI], 1.427–5.577; p = 0.003), dense breast tissue on mammography (OR = 4.680; 95% CI, 1.113–19.684; p = 0.035), and absence of heterogeneous internal enhancement on preoperative MRI (OR = 0.429; 95% CI, 0.206–0.891; p = 0.023) were independently associated with subsequent breast cancer events detected using an abbreviated breast MRI protocol. Age ≥ 40 years (OR = 0.448; 95% CI, 0.193–1.039; p = 0.061) and clinical T2 stage (OR = 1.744; 95% CI, 0.969–3.139; p = 0.064) showed borderline significance. Conclusions: High nuclear grade, dense breast tissue on mammography, and absence of heterogeneous internal enhancement on preoperative MRI were associated with an increased risk of subsequent breast cancer events in patients undergoing abbreviated MRI surveillance following surgery for early-stage breast cancer.

Rationale In psychopharmacology, researchers have been interested in the hypnotic effects of terrestrial plant polyphenols and their synthetic derivatives. Phlorotannins, a marine plant polyphenol, could have potential as a source of novel hypnotic drugs. Objectives The effects of phlorotannins and major phlorotannin constituent eckstolonol on sleep–wake profiles in mice were evaluated in comparison with diazepam, and their hypnotic mechanism was also investigated. Methods The effects of phlorotannin preparation (PRT) and eckstolonol orally given on sleep–wake profiles were measured by recording electroencephalograms (EEG) and electromyograms in C57BL/6N mice. Flumazenil, a GABA A -benzodiazepine (BZD) receptor antagonist, was injected 15 min before PRT and eckstolonol to reveal its hypnotic mechanism. Results PRT administration (>250 mg/kg) produced a significant decrease in sleep latency and an increase in the amount of non-rapid eye movement sleep (NREMS). Eckstolonol significantly decreased sleep latency (>12.5 mg/kg) and increased the amount of NREMS (50 mg/kg). PRT and eckstolonol had no effect on EEG power density of NREMS. The hypnotic effects of PRT or eckstolonol were completely abolished by pretreatment with flumazenil. Conclusions We demonstrated that phlorotannins promote NREMS by modulating the BZD site of the GABA A receptor. These results suggest that phlorotannins can be potentially used as an herbal medicine for insomnia and as a promising structure for developing novel sedative–hypnotics.