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OBJECTIVES: This study employed a national longitudinal cohort to assess expected years of life lost (EYLL) in newly diagnosed psychiatric patients. METHODS: Data from Taiwan's National Death Registry and Health Insurance Research Database were scrutinized to identify patients with various psychiatric disorders. Disorders were ranked hierarchically, and age groups were categorized as young, middle-aged, and older adults. We utilized the semiparametric survival extrapolation method to estimate life expectancy (LE) and EYLL. Modifying effect of comorbid conditions and socioeconomic characteristics were also explored. RESULTS: Among the 5,757,431 cases, young adults with dementia, alcohol use disorder, schizophrenia, and bipolar disorder experienced an excess of 15 years of EYLL. Middle-aged adults faced approximately 9 years or more of EYLL, while older adults had lower EYLL values. Comorbid conditions, low income levels, and living in rural areas were associated with higher EYLL. CONCLUSIONS: This study underscores the substantial EYLL among young adults with psychiatric disorders and the significant impact of specific disorders on EYLL. Early intervention, tailored support, and healthcare system readiness are imperative for improved outcomes. Resource allocation and targeted interventions focusing on early detection and comprehensive treatment can alleviate the economic burden.

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BACKGROUND: Weaning outcomes of patients receiving mechanical ventilation (MV) are affected by multiple factors. A clinical feature of critically ill patients is the presence of lymphopenia, however the clinical significance of lymphopenia in patients receiving prolonged MV remains unclear. METHODS: We enrolled patients who received at least 21 consecutive days of MV in a medical center in Taiwan between 2007 and 2016. Patients with and without lymphopenia (mean count <1000/µL) were compared after propensity score matching. RESULTS: Of the 3460 patients included in the analysis, 1625 (47.0%) were liberated from MV within 100 days. Lymphopenia and severe lymphopenia (mean count <500/µL) during the first 21 days of MV were common (52.9% and 14.5%, respectively), and restricted cubic spline analysis showed a significant reduction in weaning success when the lymphocyte count dropped below 1000/µL. After propensity score matching, the patients with lymphopenia during the third week had a lower rate of weaning success within 100 days (p = 0.005) and a higher in-hospital mortality rate (p = 0.001) than those without lymphopenia. The lymphopenia group also had significantly reduced platelet (p < 0.001) and albumin (p < 0.001) levels. CONCLUSIONS: Our findings suggest that lymphopenia during the first 3 weeks may be a marker of poor weaning outcomes in patients with prolonged MV.

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Inflammatory bowel disease (IBD) is a chronic and progressive inflammatory intestinal disease that affects people around the world. The primary cause of IBD is an imbalance in the host immune response to intestinal flora. Several human genes, including IL10, STAT3, IRGM, ATG16L1, NOD2 and RUNX3, are associated with inappropriate immune responses in IBD. It has been reported that homozygous Runx3-knockout (ko) mice spontaneously develop colitis. However, the high mortality rate in these mice within the first two weeks makes it challenging to study the role of Runx3 in colitis. To address this issue, a spontaneous colitis (SC) mouse model carrying a C-terminal truncated form of Runx3 with Tyr319stop point mutation has been generated. After weaning, SC mice developed spontaneous diarrhea and exhibited prominent enlargement of the colon, accompanied by severe inflammatory cell infiltration. Results of immunofluorescence staining showed massive CD4+ T cell infiltration in the inflammatory colon of SC mice. Colonic IL-17A mRNA expression and serum IL-17A level were increased in SC mice. CD4+ T cells from SC mice produced stronger IL-17A than those from wildtype mice in Th17-skewing conditions in vitro. In addition, the percentages of Foxp3+ Treg cells as well as the RORγt+Foxp3+ Treg subset, known for its role in suppressing Th17 response in the gut, were notably lower in colon lamina propria of SC mice than those in WT mice. Furthermore, transfer of total CD4+ T cells from SC mice, but not from wildtype mice, into Rag1-ko host mice resulted in severe autoimmune colitis. In conclusion, the C-terminal truncated Runx3 caused autoimmune colitis associated with Th17/Treg imbalance. The SC mouse model is a feasible approach to investigate the effect of immune response on spontaneous colitis.

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OBJECTIVE: To investigate the extent of knowledge about breastfeeding and attitudes towards infant feeding among spouses of puerperas at the time of discharge from hospital, and explore the factors influencing spousal attitudes toward breastfeeding. METHODS: We conducted a questionnaire survey among 204 spouses of puerperas who were admitted in the maternity wards at a tertiary hospital in Shaanxi Province between October 2021 and December 2021. Respondents who fulfilled the inclusion criteria were identified using convenient sampling. RESULTS: (1) The score of breastfeeding knowledge among spouses prior to discharge from the hospital was (10.56 ± 3.78), with an accuracy rate of 59.6%, and the lowest accuracy rate was for Item 1 "Newborns should be fed on time, not on demand" (42.6%) and Item 5 "Breastfeeding can prevent infant rickets" (49.5%). (2) The average score of spouses' infant feeding attitudes was (58.15 ± 5.55), and the lowest scoring was for Item 17 "Daily urine volume of infants is a reliable indicator to judge whether they get enough breast milk" (1.99 ± 1.14). (3) Generalized linear model analysis showed a more positive attitude (higher score) among spousal attitudes towards infant feeding in those who had received breastfeeding education [OR = 4.588, 95% CI (0.160 ∼ 3.598)] and those with a master's degree or above [OR = 18.278, 95% CI (3.471 ∼ 9.346)]. CONCLUSION: (1) Spouses that received breastfeeding education and those that had a Masters Degree and above had more positive attitude towards infant feeding. (2) Medical staff should focus on puerperas'spouses with degrees below master's level who had not received breastfeeding education. We recommend using a variety of education methods to enable them to acquire more knowledge on breastfeeding and develop a more positive attitude towards breastfeeding, which will further enhance spousal support for breastfeeding, thus positivizing postpartum co-parenting attitudes and improving the rate of exclusive breastfeeding.

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Air pollution is inextricable from human activity patterns. This is especially true for nitrogen oxide (NOx), a pollutant that exists naturally and also as a result of anthropogenic factors. Assessing exposure by considering diurnal variation is a challenge that has not been widely studied. Incorporating 27 years of data, we attempted to estimate diurnal variations in NOx across Taiwan. We developed a machine learning-based ensemble model that integrated hybrid kriging-LUR, machine-learning, and an ensemble learning approach. Hybrid kriging-LUR was performed to select the most influential predictors, and machine-learning algorithms were applied to improve model performance. The three best machine-learning algorithms were suited and reassessed to develop ensemble learning that was designed to improve model performance. Our ensemble model resulted in estimates of daytime, nighttime, and daily NOx with high explanatory powers (Adj-R2) of 0.93, 0.98, and 0.94, respectively. These explanatory powers increased from the initial model that used only hybrid kriging-LUR. Additionally, the results depicted the temporal variation of NOx, with concentrations higher during the daytime than the nighttime. Regarding spatial variation, the highest NOx concentrations were identified in northern and western Taiwan. Model evaluations confirmed the reliability of the models. This study could serve as a reference for regional planning supporting emission control for environmental and human health.

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Ischemic stroke is a devastative nervous system disease associated with high mortality and morbidity rates. Unfortunately, no clinically effective neuroprotective drugs are available now. In ischemic stroke, S100 calcium-binding protein b (S100b) binds to receptor for advanced glycation end products (Rage), leading to the neurological injury. Therefore, disruption of the interaction between S100B and Rage can rescue neuronal cells. Here, we designed a peptide, termed TAT-W61, derived from the V domain of Rage which can recognize S100b. Intriguingly, TAT-W61 can reduce the inflammatory caused by ischemic stroke through the direct binding to S100b. The further investigation demonstrated that TAT-W61 can improve pathological infarct volume and reduce the apoptotic rate. Particularly, TAT-W61 significantly improved the learning ability, memory, and motor dysfunction of the mouse in the ischemic stroke model. Our study provides a mechanistic insight into the abnormal expression of S100b and Rage in ischemic stroke and yields an invaluable candidate for the development of drugs in tackling ischemic stroke. KEY MESSAGES: S100b expression is higher in ischemic stroke, in association with a high expression of many genes, especially of Rage. S100b is directly bound to the V-domain of Rage. Blocking the binding of S100b to Rage improves the injury after ischemic stroke.

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Background: Adult preventive health checkups with depression screening were launched in August 2011 in Taiwan; however, its impact has not yet been evaluated. This study aimed to use real-world data to assess the effectiveness of depression screening among middle-aged and older adults. Methods: A total of 4,972,228 adults aged 40 years and above who participated in a health checkup with depression screening between 2013 and 2019 and the same number of unscreened counterparts were included. The target trial emulation study was conducted to estimate the hazard ratios (HRs) for newly treated depression, psychiatric hospitalisation, and suicide. The changes in HRs during the study period were assessed using interval Cox models. Findings: The screening group had a higher rate of newly treated depression (HR 1.63 [95% CI 1.62, 1.64]) and a lower risk of psychiatric hospitalisation (HR 0.93 [95% CI 0.91, 0.95]). There was a null association between depression screening and suicide; however, a higher suicide risk was found in screened older adults aged 65 years and above. Only 10.8% received depression treatment during the study period among the screen-positive individuals. Interpretation: Health checkups with depression screening could potentially promote depression treatment and reduce the risk of psychiatric hospitalisation; however, there was no effect on suicide. The treatment rate for depression remained low after screening for depression. Further attention to enhance referral and treatment is required. Funding: The study was funded by the National Health Research Institutes, Taiwan.

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Virus-like particles (VLPs) have natural structural antigens similar to those found in viruses, making them valuable in vaccine immunization. Furthermore, VLPs have demonstrated significant potential in drug delivery, and emerged as promising vectors for transporting chemical drug, genetic drug, peptide/protein, and even nanoparticle drug. With virus-like permeability and strong retention, they can effectively target specific organs, tissues or cells, facilitating efficient intracellular drug release. Further modifications allow VLPs to transfer across various physiological barriers, thus acting the purpose of efficient drug delivery and accurate therapy. This article provides an overview of VLPs, covering their structural classifications, deliverable drugs, potential physiological barriers in drug delivery, strategies for overcoming these barriers, and future prospects.

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Prenatal diagnosis of congenital heart disease (CHD) relies primarily on fetal echocardiography conducted at mid-gestational age-the sensitivity of which varies among centers and practitioners. An objective method for early diagnosis is needed. Here, we conducted a case-control study recruiting 103 pregnant women with healthy offspring and 104 cases with CHD offspring, including VSD (42/104), ASD (20/104), and other CHD phenotypes. Plasma was collected during the first trimester and proteomic analysis was performed. Principal component analysis revealed considerable differences between the controls and the CHDs. Among the significantly altered proteins, 25 upregulated proteins in CHDs were enriched in amino acid metabolism, extracellular matrix receptor, and actin skeleton regulation, whereas 49 downregulated proteins were enriched in carbohydrate metabolism, cardiac muscle contraction, and cardiomyopathy. The machine learning model reached an area under the curve of 0.964 and was highly accurate in recognizing CHDs. This study provides a highly valuable proteomics resource to better recognize the cause of CHD and has developed a reliable objective method for the early recognition of CHD, facilitating early intervention and better prognosis.

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PURPOSE: Although the therapy-related bone loss attracts increasing attention nowadays, the differences in chemotherapy-induced bone loss and bone metabolism indexes change among breast cancer (BC) women with different menstrual statuses or chemotherapy regimens are unknown. The aim of the study is to explore the effects of different regimens of chemotherapy on bone health. METHOD: The self-control study enrolled 118 initially diagnosed BC women without distant metastasis who underwent dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) screening and (or) bone metabolism index monitoring during chemotherapy at Chongqing Breast Cancer Center. Mann-Whitney U test, Cochran's Q test, and Wilcoxon sign rank test were performed. RESULTS: After chemotherapy, the BMD in the lumbar 1-4 and whole lumbar statistically decreased (- 1.8%/per 6 months), leading to a significantly increased proportion of osteoporosis (27.1% vs. 20.5%, P < 0.05), which were mainly seen in the premenopausal group (- 7.0%/per 6 months). Of the chemotherapeutic regimens of EC (epirubicin + cyclophosphamide), TC (docetaxel + cyclophosphamide), TEC (docetaxel + epirubicin + cyclophosphamide), and EC-T(H) [epirubicin + cyclophosphamide-docetaxel and/or trastuzumab], EC regimen had the least adverse impact on BMD, while the EC-TH regimen reduced BMD most (P < 0.05) inspite of the non-statistical difference between EC-T regimen, which was mainly seen in the postmenopausal group. Chemotherapy-induced amenorrhea (estradiol 94 pg/ml vs, 22 pg/ml; FSH 9.33 mIU/ml vs. 61.27 mIU/ml) was proved in premenopausal subgroup (P < 0.001). Except the postmenopausal population with calcium/VitD supplement, the albumin-adjusted calcium increased significantly (2.21 mmol/l vs. 2.33 mmol/l, P < 0.05) after chemotherapy. In postmenopausal group with calcium/VitD supplement, ß-CTX decreased significantly (0.56 ng/ml vs. 0.39 ng/ml, P < 0.05) and BMD were not affected by chemotherapy (P > 0. 05). In premenopausal group with calcium/VitD supplement, PTH decreased significantly (52.90 pg/ml vs. 28.80 pg/ml, P = 0. 008) and hip BMD increased after chemotherapy (0.845 g/m2 vs. 0.952 g/m2, P = 0. 006). As for both postmenopausal and premenopausal group without calcium/VitD supplement, there was a significant decrease in bone mass in hip and lumbar vertebrae after chemotherapy (0.831 g/m2 vs. 0.776 g/m2; 0.895 g/m2 vs. 0.870 g/m2, P < 0.05). CONCLUSION: Chemotherapy might induce lumbar vertebrae BMD loss and spine osteoporosis with regimen differences among Chinese BC patients. Calcium/VitD supplementation could improve bone turnover markers, bone metabolism indicators, and bone mineral density. Early interventions on bone health are needed for BC patients during chemotherapy.

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AIMS: We explored long-term employment status and income before and after depression diagnosis among men and women and at different working ages in Taiwan. METHODS: Data from 2006 to 2019 were obtained from the National Health Insurance Research Database (NHIRD). Individuals with newly diagnosed depressive disorder aged 15 to 64 years during the study period were identified. An equal number of individuals without depression were matched for their demographic and clinical characteristics. Employment outcomes included employment status, which was categorized into employed or unemployed, and annual income. Based on the occupation categories and monthly insurance salary recorded in the Registry for Beneficiaries of the NHIRD, a subject was defined as unemployed if he or she differed from the income earner or the occupation category was unemployed. Monthly income was defined as zero for unemployed subjects and proxied as monthly insurance salary for others. Annual income was the sum of monthly income in each observation year. RESULTS: A total of 420,935 individuals with depressive disorder were included in the study, and an equal number of individuals with not diagnosed depression served as controls. Employment rate and income were lower in the depression group than in the control group before the year of diagnosis, with a difference of 5.7% in employment rate and USD 1,173 in annual income. This gap increased considerably after the year of diagnosis (7.3% in employment rate and USD 1,573 in annual incomes) and further widened in the subsequent years (8.1% in employment rate and USD 2,006 in annual incomes in the 5th following year). The drops in the employment rate and income caused by depression were more evident in men and older age groups than in women and younger age groups, respectively. However, the reduction in employment rate and income in the following years after the diagnosis was more considerable among younger age groups. CONCLUSIONS: The effect of depression on employment status and income was significant during the year of diagnosis and continued afterwards. The effect on employment outcomes varied between genders and across all age groups.

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Universal antenatal education has been offered to expectant mothers in Taiwan since 2014. Depression screening is included in the offered education sessions. This study aimed to examine the association of antennal education and depression screening with mental health outcomes, including perinatal depression diagnosis and psychiatrist visits. Data was obtained from the antenatal education records and Taiwan's National Health Insurance claims database. A total of 789,763 eligible pregnant women were included in the current study. The psychiatric-related outcomes were measured between antenatal education and the six-month after delivery. It was found that the antenatal education was widely used in Taiwan, and the attendance rate has increased to 82.6% since its launch. The attenders were more likely to be from disadvantaged backgrounds, and 5.3% of them were screened positive for depressive symptoms. They were also more likely to visit a psychiatrist but less likely to be diagnosed with depression than the non-attenders. Factors including young age, high healthcare utilization, and comorbid psychiatric disorder history were consistently associated with depression symptoms, perinatal depression diagnoses and psychiatrist visits. Further research is needed to understand the reasons for the nonattendance at antenatal education programmes and the barriers to utilizing mental health services.

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Purpose: Acupuncture is widely used to relieve shoulder pain. A survey was conducted in order to recognize hotspots and frontiers of acupuncture for shoulder pain from the year 2000-2022. Methods: The Web of Science Core Collection was used to collect literature related to acupuncture therapy for shoulder pain, which spanned January 2000 to August 2022. The number of publications yearly, countries/institutions, journals, and keywords was analyzed and visualized in shoulder pain with acupuncture therapy by CiteSpace v.5.7.R5. Results: We totally analyzed 214 articles that met the inclusion criteria. The overall trend of publication volume continues to increase. The most productive authors in the field were César Fernández las Peñas and José L Arias-Buría, and the most influential author was Green S. Kyung Hee University and the People's Republic of China had the highest volume of publications, respectively. The most influential journal is Pain with high citation and impact factor. The hot keywords were "acupuncture", "shoulder pain", "dry needling", "randomized trial", and "injection". The research frontier in acupuncture for treating chronic shoulder pain was mainly "mechanism". Conclusion: Over the last 22 years, the findings of this bibliometric analysis have provided research trends and frontiers in clinical research on acupuncture therapy for patients with shoulder pain, which identifying hot topics and exploring new directions for the future may be helpful to researchers. Studying mechanisms underlying acupuncture therapy for shoulder pain remains a focus of future research.

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CONTEXT: Thyroid function variation within the thyroxine reference range has negative metabolic effects. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a recently proposed definition. OBJECTIVE: We aim to explore the effects of thyroid function status on prevalence and mortality of MAFLD. METHODS: Data of 10 666 participants from the Third National Health and Nutrition Examination Survey (NHANES III) were used. MAFLD was diagnosed based on the new definition. Thyroid function variation within the thyroxine reference range was defined based on thyroid-stimulating hormone (TSH) levels: subclinical hyperthyroidism, <0.39 mIU/L; strict-normal thyroid function, 0.39-2.5 mIU/L; and low thyroid function, >2.5 mIU/L, which comprised low-normal thyroid function (2.5-4.5 mIU/L) and subclinical hypothyroidism (> 4.5 mIU/L). Logistic and Cox regression were used in multivariate analysis. RESULTS: Low thyroid function is independently associated with MAFLD (odds ratio: 1.27). Compared with strict-normal thyroid function, subclinical hypothyroidism was significantly associated with increased risk for all-cause and cardiovascular mortality in the total population (hazard ratio [HR] for all-cause: 1.23; cardiovascular: 1.65) and MAFLD population (HR for all-cause: 1.32; cardiovascular: 1.99); meanwhile, in the low-normal thyroid function group, an increasing trend in mortality risk was observed. Furthermore, low thyroid function also showed significant negative impact on mortality in the total and MAFLD population. Among thyroid function spectrum, mild subclinical hypothyroidism showed the highest HRs on mortality. CONCLUSIONS: Low thyroid function is independent risk factor of MAFLD and is associated with increased risk for all-cause and cardiovascular mortality in the MAFLD population. Reevaluation of TSH reference range should be considered.

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OBJECTIVES: Sleep variability levels are unknown in heavy goods vehicle (HGV) drivers yet are associated with adverse health outcomes and reduced driver vigilance when high. METHODS: Two hundred and thirty-three HGV drivers recruited across 25 UK depots provided sleep variability, sleep duration, and sleep efficiency data via wrist-worn accelerometry (GENEActiv) over 8 days. Sleep variability indicators included social jetlag (the difference in midpoint of the sleep window between work and nonworkdays) and intraindividual variability of sleep window onset time, out-of-bed time, and sleep duration. RESULTS: Fifty-three percent of drivers experienced social jetlag (≥1 hour), and 27% experienced high (>2 hours) social jetlag. Drivers with the highest sleep variability had the shortest sleep duration and lowest sleep efficiency during workdays. CONCLUSIONS: Drivers with high sleep variability may experience more fatigue when driving given the poor sleep outcomes during workdays observed.

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OBJECTIVES: This study aimed to investigate the impact of a 6-month health intervention on truck drivers' cardiovascular reactivity to stress and whether cardiovascular reactivity was predictive of depression, anxiety, or fatigue symptoms at 6-month follow-up. METHODS: Two hundred thirty-eight truck drivers completed a 6-month cluster randomized controlled trial to increase physical activity and completed a stress protocol (Stroop and mirror-tracing tasks) with measurements of heart rate, systolic blood pressure, and diastolic blood pressure taken, alongside fatigue, anxiety, and depressive symptoms assessment. Measures were taken at 0 and 6 months. RESULTS: Analyses showed a negative relationship between 0-month diastolic blood pressure reactivity and 6-month persistent fatigue. Trends toward negative relationships between systolic blood pressure reactivity and future anxiety and fatigue symptoms at 6 months were evident. CONCLUSIONS: Our findings may have serious implications, as fatigue can be a major cause of road traffic collisions in truck drivers.

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MicroRNAs (miRNAs) can regulate the expression of genes involved in the establishment of the window of implantation (WOI) in the endometrium. Recent studies indicated that cell-free miRNAs in uterine fluid and blood samples could act as alternative and non-invasive sample types for endometrial receptivity analysis. In this study, we attempt to systematically evaluate whether the expression levels of cell-free microRNAs in blood samples could be used as non-invasive biomarkers for assessing endometrial receptivity status. We profiled the miRNA expression levels of 111 blood samples using next-generation sequencing to establish a predictive model for the assessment of endometrial receptivity status. This model was validated with an independent dataset (n = 73). The overall accuracy is 95.9%. Specifically, we achieved accuracies of 95.9%, 95.9%, and 100.0% for the pre-receptive group, the receptive group, and the post-respective group, respectively. Additionally, we identified a set of differentially expressed miRNAs between different endometrial receptivity statuses using the following criteria: p-value < 0.05 and fold change greater than 1.5 or less than -1.5. In conclusion, the expression levels of cell-free miRNAs in blood samples can be utilized in a non-invasive manner to distinguish different endometrial receptivity statuses.

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One of the characteristics of individuals on the autism spectrum is the restricted, repetitive patterns of behaviors, interests, or activities which have been considered the result of a direct deficit in self-regulation skills. Peer-mediated intervention (PMI) is one of the ways to support young children on the autism spectrum for following school routines independently. PMI is an evidence-based practice based on behavioral principles to train typical peers to help with students on the autism spectrum. By using PMI, students on the autism spectrum can have more interaction opportunities with typical peers. Students on the autism spectrum can become less dependent on adult support to complete the expectations independently or with peers' support. The aim of this study is to use PMI to support students with autism and ADHD aged 7-8 in a regular classroom to complete the behavioral expectations in Taiwan. This study used a multiple probe design across three participants to determine the effects of the intervention. The researchers trained seven typically developing peers on how to prompt and reinforce the target children. This study took both peers and target children's data. The data shows a positive result for target children to follow the expectations independently and most peer models can prompt and reinforce the target children after being trained. Our study has extended the effectiveness and usage of PMI in teaching behavioral expectations in Taiwan.