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Abstract The anxiolytic effect of oxytocin (OXT) on psychosocial stress has been well documented, but the effectiveness under the interference of other factors still requires in-depth research. Previous studies have shown that nicotine addiction interacts with OXT on psychosocial stress on the behavioral level. However, the underlying neural mechanism of interaction between OXT and nicotine addiction on psychosocial stress has not been examined, and we conducted two experiments to reveal it. Firstly, after intranasal administration of randomized OXT or placebo (saline), a group of healthy participants (n = 27) and a group of smokers (n = 26) completed the Montreal Imaging Stress Task (MIST) in an MRI scanner. Secondly, a group of smokers (n = 22) was recruited to complete a transcranial direct current stimulation (tDCS) experiment, in which anodal tDCS was applied on subjects’ anterior right superior temporal gyrus (rSTG). In both experiment, subjective stress ratings, salivary cortisol samples and the amount of daily cigarette consumption were obtained from each participant. Analysis of variance were applied on both behavioral and neural data to examine the effects of OXT and nicotine addiction, and correlation analysis were used to examine relationships between neural and behavioral data. In first fMRI experiment, analysis of variance (ANOVA) revealed an interaction of OXT and nicotine addiction on subjective stress. In smokers, OXT failed to suppress the elevation of subjective stress and craving ratings after psychosocial stress. A voxel-wise ANOVA of fMRI data identified an interaction between OXT and nicotine addiction in anterior rSTG, and its functional connectivity with right middle frontal gyrus. Correlations between this functional connectivity and subjective psychosocial stress were also found abnormal in smokers. In second tDCS experiment, we found that under tDCS, OXT successfully suppressed the elevation of subjective stress and craving ratings after stress. In summary, we found that nicotine addiction blocked OXT’s anxiolytic on psychosocial stress, which was related to abnormalities in anterior rSTG. By applying anodal tDCS on anterior rSTG, OXT’s anxiolytic effect was restored in smokers. These findings will support further development on oxytocin’s intervention of psychosocial stress in nicotine addiction, and provides essential information for indicating OXT’s effectiveness.

Abstract A lack of adherence to long-term antiretroviral therapy may impact viral suppression. The current study examined the relationship between medication adherence and clinical outcomes in people with human immunodeficiency virus infection (PWH) receiving bictegravir, emtricitabine, and tenofovir alafenamide fumarate (B/F/TAF). A retrospective cohort study using two Japanese claims databases was conducted. Adherence was measured by the proportion of days covered (PDC). Patients were grouped into 3 PDC category and persistence was estimated by Kaplan-Meier method. Cox regression analysis was performed to investigate whether the PDC was associated with treatment discontinuation. Among 952 patients, 820 (86.1%), 95 (10.0%), and 37 (3.9%) patients were grouped into the PDC ≥ 90%, 80–

BackgroundWith the advancement of transcranial electrical stimulation (tES) technology, an increasing number of stimulation devices and treatment protocols have emerged. However, safety and tolerability remain critical concerns before new strategies can be implemented. Particularly, the use of gel particle electrodes brings new challenges to the safety and tolerability of tES, which hinders its widespread adoption and further research.ObjectiveOur study utilized a specially designed and validated transcranial electrical stimulation stimulator along with preconfigured gel particle electrodes placed at F3 and F4 in the prefrontal lobes. We aimed to assess the tolerance and safety of these electrodes in healthy subjects by administering different durations and types of tES.MethodsEach participant underwent ten sessions of either transcranial direct current stimulation (tDCS) or transcranial alternating current stimulation (tACS), with session durations varying. In the experiment, we collected various measurement data from participants, including self-report questionnaire data and behavioral keystroke data. Tolerability was evaluated through adverse events (AEs), the relationship of adverse events with tES (AEs-rela), the Self-Rating Anxiety Scale (SAS), and the Visual Analog Mood Scale-Revised (VAMS-R). Safety was assessed using the Visual Analog Scale (VAS), the Skin Sensation Rating (SSR), Montreal Cognitive Assessment (MoCA), and Stroop task. These data were analyzed to determine the impact of different parameters on the tolerability and safety of tES.ResultsThere were no significant changes in the results of the MoCA and SAS scales before and after the experiment. However, significant differences were observed in VAS, SSR, AEs, and AEs-rela between tDCS and tACS. Additionally, fatigue increased, and energy levels decreased on VAMS-R with longer durations. No significant differences were found in other neuropsychological tests.ConclusionOur study revealed significant differences in tolerability and safety between tDCS and tACS, underscoring the importance of considering the stimulation type when evaluating these factors. Although tolerance and safety did not vary significantly across different stimulation durations in this study, future research may benefit from exploring shorter durations to further assess tolerability and safety efficiently.

Abstract Introduction Although patients with HBV have a risk of reactivation after immunosuppressive therapy (IST), the status of their risk management is unclear in Japan. This study aims to describe the proportion of patients who received preventive management of HBV reactivation during ISTs in patients with chronic HBV infection of HBsAg or resolved HBV infection. Method A retrospective cohort study was conducted using the JMDC Japanese claims database from April 2011 to June 2021. Patients with HBV infections of HbsAg who received ISTs or patients who had resolved HBV infections who received ISTs were identified from the database and evaluated for appropriate management to prevent HBV reactivation. Results In total, 6242 eligible patients were identified. The proportions of patients with appropriate HBV reactivation management, stratified by the HBV reactivation risk level of IST, was 43.1% (276/641) for high-risk, 40.2% (223/555) for intermediate-risk and 14.9% (741/4965) for low-risk patients. When the evaluation period for the outcome calculation was shortened from 360 to 180 days, the proportion for high risk increased to 52.7%. The odds ratios of large hospitals for receiving appropriate management were 2.16 (95% CI 1.12–4.44) in the high-risk, 4.63 (95% CI 2.34–10.25) in the intermediate-risk and 3.60 (95% CI 3.07–4.24) in the low-risk patients. Conclusion HBV reactivation management was tailored according to the reactivation risk associated with IST. However, adherence to HBV reactivation management guidelines was sub-optimal, even among high-risk patients. This is especially the case for ensuring smaller-sized medical institutions, highlighting the need for further educational activities.

Emotions are fundamental to social interaction and deeply intertwined with interpersonal dynamics, especially in romantic relationships. Although the neural basis of interaction processes in romance has been widely explored, the underlying emotions and the connection between relationship quality and neural synchronization remain less understood. Our study employed EEG hyperscanning during a non-interactive video-watching paradigm to compare the emotional coordination between romantic couples and close friends. Couples showed significantly greater behavioral and prefrontal alpha synchronization than friends. Notably, couples with low relationship quality required heightened neural synchronization to maintain robust behavioral synchronization. Further support vector machine analysis underscores the crucial role of prefrontal activity in differentiating couples from friends. In summary, our research addresses gaps concerning how intrinsic emotions linked to relationship quality influence neural and behavioral synchronization by investigating a natural non-interactive context, thereby advancing our understanding of the neural mechanisms underlying emotional coordination in romantic relationships.

Background Internet gaming disorder (IGD) is a mental health issue that affects individuals worldwide. However, the lack of knowledge about the biomarkers associated with the development of IGD has restricted the diagnosis and treatment of this disorder.Aims We aimed to reveal the biomarkers associated with the development of IGD through resting-state brain network analysis and provide clues for the diagnosis and treatment of IGD.Methods Twenty-six patients with IGD, 23 excessive internet game users (EIUs) who recurrently played internet games but were not diagnosed with IGD and 29 healthy controls (HCs) performed delay discounting task (DDT) and Iowa gambling task (IGT). Resting-state functional magnetic resonance imaging (fMRI) data were also collected.Results Patients with IGD exhibited significantly lower hubness in the right medial orbital part of the superior frontal gyrus (ORBsupmed) than both the EIU and the HC groups. Additionally, the hubness of the right ORBsupmed was found to be positively correlated with the highest excessive internet gaming degree during the past year in the EIU group but not the IGD group; this might be the protective mechanism that prevents EIUs from becoming addicted to internet games. Moreover, the hubness of the right ORBsupmed was found to be related to the treatment outcome of patients with IGD, with higher hubness of this region indicating better recovery when undergoing forced abstinence. Further modelling analysis of the DDT and IGT showed that patients with IGD displayed higher impulsivity during the decision-making process, and impulsivity-related parameters were negatively correlated with the hubness of right ORBsupmed.Conclusions Our findings revealed that the impulsivity-related right ORBsupmed hubness could serve as a potential biomarker of IGD and provide clues for the diagnosis and treatment of IGD.

Abstract Natural language processing (NLP) is central to the communication with machines and among ourselves, and NLP research field has long sought to produce human‐quality language. Identification of informative criteria for measuring NLP‐produced language quality will support development of ever‐better NLP tools. The authors hypothesize that mentalizing network neural activity may be used to distinguish NLP‐produced language from human‐produced language, even for cases where human judges cannot subjectively distinguish the language source. Using the social chatbots Google Meena in English and Microsoft XiaoIce in Chinese to generate NLP‐produced language, behavioral tests which reveal that variance of personality perceived from chatbot chats is larger than for human chats are conducted, suggesting that chatbot language usage patterns are not stable. Using an identity rating task with functional magnetic resonance imaging, neuroimaging analyses which reveal distinct patterns of brain activity in the mentalizing network including the DMPFC and rTPJ in response to chatbot versus human chats that cannot be distinguished subjectively are conducted. This study illustrates a promising empirical basis for measuring the quality of NLP‐produced language: adding a judge's implicit perception as an additional criterion.

Background: In Japan, regional differences in asthma mortality have been reported; however, regional differences in asthma exacerbations have not been studied extensively. Therefore, using a health insurance claims database, we investigated the regional differences in the incidence of asthma exacerbations in Japan. Methods: This study used data from Medi-Scope (Japan Medical Information Research Institute Inc., Japan)—a nationwide health insurance claims database. Patients with asthma at the index date (the latest date of an asthma-related prescription with an asthma diagnosis before October 1, 2018) were included in the analysis. The pre-index period was defined as 1 year before the index date, and the follow-up period as 1 year after the index date. The incidence of asthma exacerbation events was analyzed for each region. Results: The primary analysis population comprised 24,883 patients who were continuously prescribed ICS or ICS/LABA at least four times during the pre-index period. The incidence rate of asthma exacerbations with hospitalization was the highest in Chugoku (2.95/100 person-years [95% CI, 1.97–4.43]) and the lowest in Kanto (1.52/100 person-years [95% CI, 1.26–1.83]). The incidence rate of asthma exacerbations for the composite outcome of hospitalization, injectable corticosteroid prescription, and oral corticosteroid burst was the highest in Fukui (105.00/100 person-years [95% CI, 64.53–170.85]) and the lowest in Nagasaki (15.69/100 person-years [95% CI, 10.84–22.72]). Conclusions: Regional differences in the incidence of asthma exacerbations as well as their treatments were observed in Japan.

Summary: According to the cognitive model of depression, memory bias, interpretation bias, and attention bias are associated with the development and maintenance of depression. Here, we present a protocol for investigating whether and how the novel coronavirus disease 2019 (COVID-19) pandemic may affect the relationship between current cognitive biases and future depression severity in a population with non-clinical depression. This protocol can also be used in other contexts, including cognitive bias-related studies and depression-related functional magnetic resonance imaging (fMRI) studies.For complete details on the use and execution of this protocol, please refer to Zhang et al. (2021).

Temporal interference transcranial alternating current stimulation (TI-tACS) is a new technique of noninvasive brain stimulation. Previous studies have shown the effectiveness of TI-tACS in stimulating brain areas in a selective manner. However, its safety in modulating human brain neurons is still untested. In this study, 38 healthy adults were recruited to undergo a series of neurological and neuropsychological measurements regarding safety concerns before and after active (2 mA, 20/70 Hz, 30 min) or sham (0 mA, 0 Hz, 30 min) TI-tACS. The neurological and neuropsychological measurements included electroencephalography (EEG), serum neuron-specific enolase (NSE), the Montreal Cognitive Assessment (MoCA), the Purdue Pegboard Test (PPT), an abbreviated version of the California Computerized Assessment Package (A-CalCAP), a revised version of the Visual Analog Mood Scale (VAMS-R), a self-assessment scale (SAS), and a questionnaire about adverse effects (AEs). We found no significant difference between the measurements of the active and sham TI-tACS groups. Meanwhile, no serious or intolerable adverse effects were reported or observed in the active stimulation group of 19 participants. These results support that TI-tACS is safe and tolerable in terms of neurological and neuropsychological functions and adverse effects for use in human brain stimulation studies under typical transcranial electric stimulation (TES) conditions (2 mA, 20/70 Hz, 30 min).

Because of the impact of close partner's touch on psychological and physical well-being by alleviating stress, it is important to explore the influence factors that underlie the stress-alleviating effect of close partner's touch. Previous studies suggested that the stress-alleviating effect was different when individuals were touched by different persons. Specifically, the stress was reduced significantly when the individual was touched by the close partner compared with the acquaintance and the stranger. However, whether the stress-alleviating effect of touch was modulated by the close relationship quality is unknown. To examine this question, the participants (n = 61) performed a 3 (i.e., alone, partner no-touch, and partner touch) × 2 (i.e., safety and threat) within-subjects experiment. The results revealed that the stress of the participants alleviated significantly while close partners present with touch compared with without touch during facing a threat. We also found that the relationship quality of couple-members (i.e., participants perceiving the quality of alternatives and the partners' commitment level) modulated touch-induced stress alleviation. Participants perceiving the low quality of alternatives and the high partners' commitment level showed stronger touch-induced stress-alleviating effect than participants perceiving the high quality of alternatives and the low partners' commitment level. The explained variance was around 16.8% jointly for actor and partner effects. These findings provide evidence for explaining the reasons for touch-induced alleviating stress and have important implications for predicting the future effect of interactive behaviors.

Summary: The outbreak of the novel coronavirus disease 2019 (COVID-19) has increased concern about people's mental health under such serious stressful situation, especially depressive symptoms. Cognitive biases have been related to depression degree in previous studies. Here, we used behavioral and brain imaging analysis, to determine if and how the COVID-19 pandemic affects the relationship between current cognitive biases and future depression degree and the underlying neural basis in a nonclinical depressed population. An out-expectation result showed that a more negative memory bias was associated with a greater decrease in future depressive indices in nonclinical depressed participants during the COVID-19 pandemic, which might be due to decreased social stress. These data enhance our understanding of how the depressive degree of nonclinical depressed populations will change during the COVID-19 pandemic and also provide support for social distancing policies from a psychological perspective.

Addicts are often vulnerable to drug use in the presence of drug cues, which elicit significant drug cue reactivity. Mounting neuroimaging evidence suggests an association between functional magnetic resonance imaging connectivity networks and smoking cue reactivity; however, there is still little understanding of the electroencephalography (EEG) coherence basis of smoking cue reactivity. We therefore designed two independent experiments wherein nicotine-dependent smokers performed a smoking cue reactivity task during EEG recording. Experiment I showed that a low-theta EEG coherence network occurring 400–600 ms after onset during long-range (mainly between frontal and parieto-occipital) scalp regions, which was involved in smoking cue reactivity. Moreover, the average coherence of this network was significantly correlated with participants’ level of cigarette craving. In experiment II, we tested an independent group of smokers and demonstrated that the low-theta coherence network significantly predicted changes in individuals’ cigarette craving. Thus, the low-theta EEG coherence in smokers’ brains might be a biomarker of smoking cue reactivity and can predict addiction behavior.

BackgroundAlcadein proteins (Alcs; Alcα, Alcβand Alcγ) are predominantly expressed in neurons, as is Alzheimer's β-amyloid (Aβ) precursor protein (APP). Both Alcs and APP are cleaved by primary α- or β-secretase to generate membrane-associated C-terminal fragments (CTFs). Alc CTFs are further cleaved by γ-secretase to secrete p3-Alc peptide along with the release of intracellular domain fragment (Alc ICD) from the membrane. In the case of APP, APP CTFβ is initially cleaved at the ε-site to release the intracellular domain fragment (AICD) and consequently the γ-site is determined, by which Aβ generates. The initial ε-site is thought to define the final γ-site position, which determines whether Aβ40/43 or Aβ42 is generated. However, initial intracellular ε-cleavage sites of Alc CTF to generate Alc ICD and the molecular mechanism that final γ-site position is determined remains unclear in Alcs.MethodologyUsing HEK293 cells expressing Alcs plus presenilin 1 (PS1, a catalytic unit of γ-secretase) and the membrane fractions of these cells, the generation of p3-Alc possessing C-terminal γ-cleavage site and Alc ICD possessing N-terminal ε-cleavage site were analysed with MALDI-TOF/MS. We determined the initial ε-site position of all Alcα, Alcβ and Alcγ, and analyzed the relationship between the initially determined ε-site position and the final γ-cleavage position.ConclusionsThe initial ε-site position does not always determine the final γ-cleavage position in Alcs, which differed from APP. No additional γ-cleavage sites are generated from artificial/non-physiological positions of ε-cleavage for Alcs, while the artificial ε-cleavage positions can influence in selection of physiological γ-site positions. Because alteration of γ-secretase activity is thought to be a pathogenesis of sporadic Alzheimer's disease, Alcs are useful and sensitive substrate to detect the altered cleavage of substrates by γ-secretase, which may be induced by malfunction of γ-secretase itself or changes of membrane environment for enzymatic reaction.

Background Internet gaming disorder (IGD) is a mental health issue that affects individuals worldwide. However, the lack of knowledge about the biomarkers associated with the development of IGD has restricted the diagnosis and treatment of this disorder. Aims We aimed to reveal the biomarkers associated with the development of IGD through resting-state brain network analysis and provide clues for the diagnosis and treatment of IGD. Methods Twenty-six patients with IGD, 23 excessive internet game users (EIUs) who recurrently played internet games but were not diagnosed with IGD and 29 healthy controls (HCs) performed delay discounting task (DDT) and Iowa gambling task (IGT). Resting-state functional magnetic resonance imaging (fMRI) data were also collected. Results Patients with IGD exhibited significantly lower hubness in the right medial orbital part of the superior frontal gyrus (ORBsupmed) than both the EIU and the HC groups. Additionally, the hubness of the right ORBsupmed was found to be positively correlated with the highest excessive internet gaming degree during the past year in the EIU group but not the IGD group; this might be the protective mechanism that prevents EIUs from becoming addicted to internet games. Moreover, the hubness of the right ORBsupmed was found to be related to the treatment outcome of patients with IGD, with higher hubness of this region indicating better recovery when undergoing forced abstinence. Further modelling analysis of the DDT and IGT showed that patients with IGD displayed higher impulsivity during the decision-making process, and impulsivity-related parameters were negatively correlated with the hubness of right ORBsupmed. Conclusions Our findings revealed that the impulsivity-related right ORBsupmed hubness could serve as a potential biomarker of IGD and provide clues for the diagnosis and treatment of IGD. [ABSTRACT FROM AUTHOR]