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Chan-Lin Chu,1,2 Yueh-Peng Chen,3 Carl CP Chen,3,4 Chih-Kuang Chen,3,4 Hsiang-Ning Chang,4 Chien-Hung Chang,1,2,5,* Yu-Cheng Pei3,4,6,7,* 1Department of Neurology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 2School of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Center for Artificial Intelligence in Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 4Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 5Department of Electrical Engineering, College of Engineering, Chang Gung University, Taoyuan, Taiwan; 6Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan; 7Center of Vascularized Tissue Allograft, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan*These authors contributed equally to this workCorrespondence: Yu-Cheng Pei; Chien-Hung Chang Email yspeii@gmail.com; cva9514@gmail.comBackground: Tailored rehabilitation programs for stroke patients cannot be made without knowledge of their recovery potential. The aim of this study is to characterize the functional recovery patterns of ischemic stroke (IS) and intracerebral hemorrhage (ICH) patients under post-acute care stroke rehabilitation.Methods: This retrospective study analyzed the data of patients enrolled in the Post-Acute Care-Cerebrovascular Disease (PAC-CVD) rehabilitation program, which provides an individualized 1- to 3-hour intensive physical, occupational, and speech and language therapy for post-acute stroke patients in Taoyuan Chang Gung Memorial hospital in Taiwan. Our primary endpoint measure was Barthel Index (BI), and secondary endpoint measures included other 12 functional measures.Results: A total of 489 patients were included for analysis. Patients with stroke history had less BI improvement than those who suffered their first-ever stroke. In first-ever stroke patients who had completed 6 to 12 weeks of PAC-CVD program, subcortical ICH patients had greater BI, quality of life, sensation, and balance improvements, and had greater late-phase recovery than their IS counterparts. In IS patients, those with age > 75 had less BI improvement; those with National Institute of Health Stroke Scale (NIHSS) score 1– 5 had greater Motor Activity Log quality of use (MAL-quality) improvement than those with NIHSS score > 5; those with Mini-Mental State Examination (MMSE) score ≥ 24 had greater BI and instrumental activities of daily living (IADL) improvement. Using the general linear model, previous stroke (ß: − 6.148, p=0.01) and subcortical ICH (ß: 5.04, p=0.03) were factors associated with BI improvement.Conclusion: Subcortical ICH patients have greater functional improvement and greater late-phase recovery than their IS counterparts following PAC rehabilitation. More studies are needed to validate our findings and unravel the underlying mechanisms of stroke recovery to optimize the treatment strategy following a stroke.Keywords: activities of daily living, functional recovery, hemorrhagic stroke, ischemic stroke, post-acute care, rehabilitation

Lin-Ling Chiu,1,* Chun-Hao Liu,2,3,* Chun-Lin Chu,4 Huang-Li Lin,2 Shu-Chung Lii5,*1School of Medicine, Collage of Medicine, Chang Gung University, Taoyuan, Taiwan; 2Department of Psychiatry, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 3Department of Child Psychiatry, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 4Department of Psychiatry, Chang Gung Memorial Hospital at Taoyuan, Taoyuan, Taiwan; 5Humanistic & Social Medicine Division, College of Medicine, Chang Gung University, Taoyuan, Taiwan*These authors contributed equally to this workBackground: In this study, we applied a qualitative approach to explore patients’ subjective experiences of long-acting injectable antipsychotics (LAIs).Methods: Patients undergoing psychiatric treatment from the chronic ward or outpatient department of a medical center in northern Taiwan who had experience with LAI treatment were enrolled. Information was obtained through semi-structured in-depth interviews. The interviews were audio-recorded and then translated verbatim, and the data were collected and analyzed concurrently to develop major themes and categories.Result: In total, 14 participants (8 female) were interviewed. In a bio-psycho-social model, the participants used LAIs as a method to become “normal,” in order to achieve a balance between the “effects” and “side effects” that may influence their daily lives. Their past experiences constructed their concepts about and expectations regarding LAIs, and their relationships with their family members and co-workers also modeled their experiences.Conclusion: In our study, we sought to understand the experience of LAI in the daily life context of the patients. We attempted to use a bio-psycho-social model to evaluate the subjective experience of the patients; an improved understanding can help mental health specialists gain a closer insight into patient experience.Keywords: antipsychotics, experience, long-acting injectable, LAI, qualitative research

Chin-Pang Lee,1,2 Yu Chen,2–4 Kun-Hao Jiang,2,4,5 Chun-Lin Chu,1,2,4 Shih-Chieh Hsu,1,2,4 Jiun-Liang Chen,2,4,5 Ching-Yen Chen1,2,41Department of Psychiatry, Chang Gung Memorial Hospital, Linkou, Taiwan; 2Men’s Health Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 3Department of Urology, Chang Gung Memorial Hospital, Linkou, Taiwan; 4School of Medicine, Chang Gung University, Taoyuan; 5Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Linkou, TaiwanIntroduction: The Androgen Deficiency in the Aging Male (ADAM) questionnaire is widely used to screen for late-onset hypogonadism. The positive response to the ADAM questionnaire (positive ADAM) has been associated with depression and poorer quality of life in a number of studies. It is unclear whether there is any value of the ADAM questionnaire in psychiatric populations. In this study, we aimed to determine the utility of the ADAM questionnaire in a convenient sample of male psychiatric outpatients.Methods: One hundred and seventy-six men (mean age: 54.3 years; standard deviation: 10.7 years; range: 40–80 years) completed the ADAM questionnaire, the Hospital Anxiety and Depression Scale (HADS), and the Aging Males’ Symptoms (AMS) scale. Anxiety was defined as a HADS anxiety subscore ≥8; depression as a HADS depression subscore ≥8; and moderate/severe impairment of health-related quality of life (HQoL) as AMS ≥37. ADAM, anxiety, and depression was used to model the moderate/severe impairment of HQoL.Results: One hundred and sixty-four (93%) men had positive ADAM. Positive ADAM was associated with a lower body mass index (P0.05). Positive ADAM was associated with five symptoms of the AMS scale: “decline of one’s feeling of general well-being”, “depressive mood”, and three sexual symptoms. In regression analysis, positive ADAM was associated with increased risk of moderate/severe impairment of HQoL (unadjusted odds ratio 20.1, 95% confidence interval 3.77–372, P

Chun-Lin Chu,1–3 Yu Chen,1,3,4 Kun-Hao Jiang,1,3,5 Jiun-Liang Chen,1,3,5 Chin-Pang Lee,1–3 Yeuk-Lun Chau,1,2 Ching-Yen Chen1–3 1Men’s Health Center, 2Department of Psychiatry, Chang Gung Memorial Hospital at Linkou, 3School of Medicine, Chang Gung University, 4Department of Urology, 5Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan Introduction: Symptoms of depression in males, such as aggression and irritability, are different from those in females. However, there are no adequate scales for detecting possible diagnoses in the Chinese population. The aim of this study was to assess whether the Chinese version of the Gotland Male Depression Scale (CV-GMDS) could identify male depression as effectively as the English version. Materials and methods: A total of 231 male outpatients were sampled from a men’s health polyclinic. We used questionnaires to evaluate the characteristics and mood status of participants, including the CV-GMDS, the Chinese version of the Beck Depressive Inventory II (CV-BDI-II), and the Chinese version of the Aging Males’ Symptoms (CV-AMS) scale. Cronbach’s α-coefficient and Levene’s test were used to investigate internal consistency and homogeneity, respectively. External validity was evaluated using Spearman’s correlation coefficient. A factor analysis was conducted to evaluate the conceptual structure of the CV-GMDS, and a regression analysis was used to determine the relationship of the CV-AMS scale with the CV-GMDS and CV-BDI-II. Results: The mean age of the 231 participants was 46.1 years (standard deviation 11.0). Of the participants, 36.8% (n=85) were found to have depression according to the CV-GMDS and 34.6% (n=80) according to the CV-BDI-II. The internal consistency of the CV-GMDS was demonstrated by a Cronbach’s α of 0.933, and the test of homogeneity revealed a P-value of 0.762. The external validity for the CV-GDMS and CV-BDI-II was demonstrated by an intercorrelation of 0.835. The third and fourth items of the GMDS differed from the others, and the CV-GMDS showed a better relationship (R2=0.616) with the CV-AMS scale than the CV-BDI-II did. Conclusion: The CV-GMDS is a satisfactory and suitable psychometric questionnaire for detecting depression among a Chinese-speaking middle-aged or older male population. The results of this study could be used as a basis for investigating specific male depression and aging symptoms. Keywords: male depression, validation, utilization, Gotland Male Depression Scale, Aging Males’ Symptoms scale

Ching-Yen Chen,1,4,5 Chin-Pang Lee,1,4 Yu Chen,2,4,5 Jun-Ran Jiang,3,4,5 Chun-Lin Chu,1,4,5 Chun-Liang Chen3,4,5 1Department of Psychiatry, 2Department of Urology, 3Department of Traditional Chinese Medicine, 4Men’s Health Center, Chang Gung Memorial Hospital at Linkou, Taiwan; 5School of Medicine, Chang Gung University, Taoyuan, Taiwan Background: Andropause and psychiatric disorders are associated with various symptoms in aging males and are part of the differential diagnosis of depression and anxiety. This study was designed to investigate the relationship between symptoms of aging, anxiety, and depression, and to determine if sexual dysfunction could be a differentiating characteristic in the psychiatric outpatient clinic. Methods: One hundred seventy-six male psychiatric outpatients participated in the study and completed self-reported measures assessing symptoms of aging, depression, and anxiety. Symptoms of aging were assessed by the Aging Males’ Symptoms scale. Anxiety and depression were measured by the Hospital Anxiety and Depression Scale. Erectile dysfunction was considered if a response to item 15 on the Aging Males’ Symptoms scale (impaired sexual potency) was rated with 4 or 5 points. Affective disturbance was assessed by the total scores of the Hospital Anxiety and Depression Scale. Results: Age was correlated with less anxiety and more sexual symptoms. Anxiety and depression were associated with more severe symptoms of aging, and depression was associated with more sexual symptoms than was anxiety. Impaired sexual potency was the only sexual symptom not significantly associated with depression and anxiety. Depression was associated with an interspousal age gap of ≥6 years. The point prevalence of erectile dysfunction was 28.4%, and age and affective disturbance were associated with the risk of erectile dysfunction. Conclusion: Impaired sexual potency should raise the suspicion of androgen deficiency rather than depression and anxiety among middle-aged or older male psychiatric outpatients. Keywords: androgen deficiency, depression, anxiety, erectile dysfunction

BACKGROUND: Although a correlation between the central dopaminergic system and intelligence may exist, the results from imaging studies remain inconclusive. The aim of this study was to explore the relationship between striatal dopamine D2/D3 receptor availability and verbal intelligence quotient (VIQ) using single photon emission computed tomography (SPECT). METHOD: Striatal D2/D3 receptor availability of 64 healthy subjects was determined with the [123I]iodobenzamide ([123I]IBZM) ligand. Intelligence quotients (IQs) of the subjects were measured by the Wechsler Adult Intelligence Scale--Revised (WAIS-R). RESULTS: In addition to age, left striatal D2/D3 receptor availability correlated positively with VIQ. In females, left striatal D2/D3 receptor availability was the only variable that correlated significantly with the similarities subtest of VIQ. CONCLUSIONS: There is a relationship between left striatal D2/D3 receptor availability and verbal intelligence, which varies, predominantly in males. [ABSTRACT FROM AUTHOR]

Objective. Although studies have indicated that the human basal ganglia have a specific role in different memory systems, the functional significance of the striatal dopamine activities for the basal ganglia remains less clear. This study assessed the relationship between measures of striatal dopamine activities and indices of different memory systems in healthy individuals.Method. Single photon emission computed tomography and [[1][2][3]I]IBZM (iodobenzamide) were used to assess the striatal dopamine D[2]/D[3] receptor density in 62 healthy volunteers aged between 19 and 61 years. All subjects underwent a Wechsler Memory Scale-Revised test.Results. Dopamine D[2]/D[3] receptor densities in the striatum decline with age. Stepwise regression analysis showed that verbal delayed recall and working memory account for most of the variance in dopamine D[2]/D[3] measurements. These relationships remain significantly after controlling for age effects.Conclusions. Brain striatal dopamine activities are also significantly associated with various memory systems, in addition to motor functions. This may explain why patients with neuropsychiatric disorders may have both memory and motor impairments. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the contribution of myeloid differentiation primary-response gene 88 (MyD88) on the differentiation of T helper type 17 (Th17) and regulatory T (Treg) cells and the emerging subgingival microbiota dysbiosis in Porphyromonas gingivalis-induced experimental periodontitis., Methods: Alveolar bone loss, infiltrated inflammatory cells, immunostained cells for tartrate-resistant acid phosphatase (TRAP), the receptor activator of nuclear factor-kB ligand (RANKL), and osteoprotegerin (OPG) were quantified by microcomputerized tomography and histological staining between age- and sex-matched homozygous littermates (wild-type [WT, Myd88 +/+ ] and Myd88 -/- on C57BL/6 background). The frequencies of Th17 and Treg cells in cervical lymph nodes (CLNs) and spleen were determined by flow cytometry. Cytokine expression in gingival tissues, CLNs, and spleens were studied by quantitative polymerase chain reaction (qPCR). Analysis of the composition of the subgingival microbiome and functional annotation of prokaryotic taxa (FAPROTAX) analysis were performed., Results: P. gingivalis-infected Myd88 -/- mice showed alleviated bone loss, TRAP + osteoclasts, and RANKL/OPG ratio compared to WT mice. A significantly higher percentage of Foxp3 + CD4 + T cells in infected Myd88 -/- CLNs and a higher frequency of RORγt + CD4 + T cells in infected WT mice was noted. Increased IL-10 and IL-17a expressions in gingival tissue at D14-D28 then declined in WT mice, whereas an opposite pattern was observed in Myd88 -/- mice. The Myd88 -/- mice exhibited characteristic increases in gram-positive species and species having probiotic properties, while gram-negative, anaerobic species were noted in WT mice. FAPROTAX analysis revealed increased aerobic chemoheterotrophy in Myd88 -/- mice, whereas anaerobic chemoheterotrophy was noted in WT mice after P. gingivalis infection., Conclusions: MyD88 plays an important role in inflammation-induced bone loss by modulating the dynamic equilibrium between Th17/Treg cells and dysbiosis in P. gingivalis-induced experimental periodontitis., (© 2024 American Academy of Periodontology.)

Purpose: The transition from medical student to practicing physician affects the complex processes of professional identity formation and professionalism, which have a lasting effect on the physician's career development. This study explored two different transitional processes of medical students in Taiwan, the associated rituals during this transitional period (the 'liminal phase') and their effect on the formation of professional identity., Method: Using snowball sampling, we recruited 13 medical students from two training systems: six from the traditional postgraduate year programme and seven from the accelerated postgraduate year (A-PGY) programme. Semi-structured interviews were thematically analysed to identify significant themes that encapsulated trainees' experiences. A consistent and mutually confirmed discussion ensured the identification of robust recurring themes., Results: A comparative analysis of the two training modalities provided critical insights into the relative impact of the training dynamics. The A-PGY cohort, subjected to an altered 'incorporation' ritual, encountered an influx of unexpected symbolic social power, complicating their transformation within the liminal phase. Without a defined internship like in the PGY system, A-PGY trainees exhibited confusion and inconsistencies in professional identity formation marked by conflicting internal and external perceptions. This ambiguity affected their clinical training, social integration and overall development of professionalism. The absence of a structured, sequential liminal phase increased conflict and diminished motivation, culminating in an incomplete self-crafting journey for A-PGY trainees., Conclusions: This study highlights the impact of the well-sequenced implementation of rituals in liminality on professional identity formation. A good transition training programme for medical students should compass sequential rituals in the liminal phase, including clear starting and ending points, supervision by seniors, guided reflection and plenty of opportunities for observation and imitation in context. Optimal training and pivotal elements in a medical training system warrant delicate design and further research when developing and changing the structure of the training programme., (© 2024 Association for the Study of Medical Education and John Wiley & Sons Ltd.)

Background: Whether adjuvant chemotherapy should be different for patients with stage II and III gastric cancer is unknown., Methods: We retrospectively analyzed the effects of adjuvant chemotherapy on the outcomes of 140 and 256 patients with stage II and III gastric cancer, respectively, between January 2008 and December 2018. Chemotherapies were stratified as fluoropyrimidine plus platinum versus fluoropyrimidine alone, tegafur/gimeracil/octeracil (S-1)-containing versus non-S-1-containing regimens, and S-1 plus cisplatin versus S-1 alone., Results: The median age of patients was 67.0 (range 24.6-98.8) years. With a median follow-up of 105 months, recurrence occurred in 32 (22.9%) and 130 (50.8%) patients with stage II and III disease, respectively. Adjuvant chemotherapy was administered as fluoropyrimidine monotherapy to 68 (48.6%) and 73 (28.5%) patients, fluoropyrimidine plus platinum to 9 (6.4%) and 104 (40.6%) patients, and none to 63 (45.0%) and 79 (30.9%) patients with stage II and III gastric cancer, respectively. Doublet chemotherapy was associated with longer disease-free survival (DFS) (26.5 vs. 15.2 months, P = 0.001) and overall survival (OS) (41.2 vs. 22.0 months, P < 0.001) than fluoropyrimidine monotherapy for stage IIIB-IIIC disease. Furthermore, S-1-containing regimens prolonged DFS (57.4 vs. 21.9 months, P = 0.044) and OS (81.4 vs. 28.6 months, P = 0.023) compared with non-S-1-containing chemotherapy in stage III disease., Conclusion: Although fluoropyrimidine monotherapy is feasible for stage II-IIIA disease, doublet chemotherapy is significantly associated with longer survival than monotherapy for stage IIIB-IIIC disease. S-1-containing regimens might lead to longer survival than non-S-1-containing chemotherapy in stage III gastric cancer., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

(1) Background: Precise diagnosis and early intervention are crucial for toddlers with autism spectrum disorder (ASD) to achieve a better prognosis. This study investigated the efficacy of the Clancy Behavior Scale (CBS) and Modified Checklist for Autism in Toddlers (M-CHAT) in detecting ASD among toddlers under 30 months of age. (2) Methods: A total of 215 toddlers (117 with ASD and 98 with development delays) aged between 18 and 29 months participated in this study. All the primary caregivers of these toddlers were recruited to complete the CBS and M-CHAT. (3) Results: The findings indicated that the accuracy of the CBS and M-CHAT was promising, and the short forms of these two instruments performed better than their full versions. The CBS:9 critical items presented a sensitivity of 0.75 and a specificity of 0.74, while the M-CHAT:14 brief items showed a sensitivity of 0.72 and a specificity of 0.85. (4) Conclusions: The diagnostic accuracy of high-risk ASD toddlers improved via the combination of CBS and M-CHAT, particularly when the information gathered from these two instruments were consistent. The findings may provide implications for enhancing the early detection of ASD.

Background: T cell receptor (TCR) signaling and T cell activation are tightly regulated by gatekeepers to maintain immune tolerance and avoid autoimmunity. The TRAIL receptor (TRAIL-R) is a TNF-family death receptor that transduces apoptotic signals to induce cell death. Recent studies have indicated that TRAIL-R regulates T cell-mediated immune responses by directly inhibiting T cell activation without inducing apoptosis; however, the distinct signaling pathway that regulates T cell activation remains unclear. In this study, we screened for intracellular TRAIL-R-binding proteins within T cells to explore the novel signaling pathway transduced by TRAIL-R that directly inhibits T cell activation., Methods: Whole-transcriptome RNA sequencing was used to identify gene expression signatures associated with TRAIL-R signaling during T cell activation. High-throughput screening with mass spectrometry was used to identify the novel TRAIL-R binding proteins within T cells. Co-immunoprecipitation, lipid raft isolation, and confocal microscopic analyses were conducted to verify the association between TRAIL-R and the identified binding proteins within T cells., Results: TRAIL engagement downregulated gene signatures in TCR signaling pathways and profoundly suppressed phosphorylation of TCR proximal tyrosine kinases without inducing cell death. The tyrosine phosphatase SHP-1 was identified as the major TRAIL-R binding protein within T cells, using high throughput mass spectrometry-based proteomics analysis. Furthermore, Lck was co-immunoprecipitated with the TRAIL-R/SHP-1 complex in the activated T cells. TRAIL engagement profoundly inhibited phosphorylation of Lck (Y394) and suppressed the recruitment of Lck into lipid rafts in the activated T cells, leading to the interruption of proximal TCR signaling and subsequent T cell activation., Conclusions: TRAIL-R associates with phosphatase SHP-1 and transduces a unique and distinct immune gatekeeper signal to repress TCR signaling and T cell activation via inactivating Lck. Thus, our results define TRAIL-R as a new class of immune checkpoint receptors for restraining T cell activation, and TRAIL-R/SHP-1 axis can serve as a potential therapeutic target for immune-mediated diseases., (© 2024. The Author(s).)

Executive functions (EFs) play a pivotal role in daily functioning, academic and vocational achievement, well-being, and the regulation of cognitive processes that impact the quality of life. Physical exercise has been shown to have positive effects on EFs. However, there remains some controversy regarding whether exercise with greater cognitive loads may be more effective for improving EFs. Through this systematic review, we aimed to synthesize available cross-sectional and longitudinal intervention studies concerning the effects of exercise with varying cognitive loads on EFs. The literature search was conducted across three electronic databases, retrieving cross-sectional and longitudinal intervention (randomized controlled trials) studies, using a standardized EF measurement from inception until June 2023. Our search yielded a total of 1570 potentially relevant articles, of which 53 were considered for full-text reading, and 28 were included in the review after full-text reading. The present study utilized Gentile's (2000) taxonomy classification to determine the cognitive load levels in exercises. Overall, findings from the 28 included studies suggested that exercise training interventions are a promising way to promote overall EF. Noteworthy, there is preliminary empirical evidence to suggest that exercises with higher cognitive loads resulted in greater benefits for EF than those with lower cognitive loads., (Copyright © 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Hematopoietic progenitor kinase 1 (HPK1) is regarded as a highly validated target in pre-clinical immune oncology. HPK1 has been described as regulating multiple critical signaling pathway in both adaptive and innate cells. In support of this role, HPK1 KO T cells show enhanced sensitivity to TCR activation and HPK1 KO mice display enhanced anti-tumor activity. Taken together, inhibition of HPK1 has the potential to induce enhanced anti-tumor immune response. Herein, we described the discovery of highly potent HPK1 inhibitors starting form a weak HTS hit. Using a structure-based drug design, HPK1 inhibitors exhibiting excellent cellular single-digit nanomolar potency in both proximal (pSLP76) and distal (IL-2) biomarkers along with sustained elevation of IL-2 cytokine secretion were discovered., 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 © 2023 Elsevier Ltd. All rights reserved.)

Objectives: Patients with terminal cancer often experience physical and mental distress. Signing a do-not-resuscitate order (DNR) is crucial to protect against invalid treatment. This study aims to explore the effect of hospice shared care intervention by medical staff on the completion of a DNR-S (DNR order signed by surrogates) for patients with terminal cancer., Method: The cross-sectional study in this research involved secondary analysis of data from the 2011-2015 clinical cancer case management database of a medical center in central Taiwan. Those with a DNR order signed by patients (DNR-P) or DNR-S before the hospice shared care consultation were excluded from this study; a total of 1,306 patients with terminal cancer were selected., Results: This study demonstrated that the percentage of DNR-S after consultation involving both nurse and physician was 75.4%. With other variables controlled, the number of DNR-Ss after consultation with a nurse was significantly lower [odds ratio (OR) = 0.57, 95% confidence interval (CI) = 0.42-0.75] and that of DNR-Ss after consultation involving both nurse and physician was significantly higher (OR = 1.35, 95% CI = 1.01-1.79), than that of DNR-Ss after consultation with only the physician., Significance of Results: Joint involvement of the nurse and physician in hospice care provides sufficient information to patients and family with terminal cancer about their condition and enhances doctor-patient communication. This effectively assists patients with terminal cancer and their family members in making the major decision of signing a DNR, alleviates the concerns of patients and family members about signing a DNR, and reduces terminal cancer patients' pain at the end of life to ensure that they die in peace and dignity.

Background: Walking entails orchestration of the sensory, motor, balance, and coordination systems, and walking disability is a critical concern after stroke. How and to what extent these systems influence walking disability after stroke and recovery have not been comprehensively studied., Methods: We retrospectively analyzed patients with stroke in the Post-acute care-Cerebrovascular Diseases (PAC-CVD) program. We compared the characteristics of patient groups stratified by their ability to complete the 5-m walk test across various time points of rehabilitation. We then used stepwise linear regression to examine the degree to which each stroke characteristic and functional ability could predict patient gait performance., Results: Five hundred seventy-three patients were recruited, and their recovery of walking ability was defined by the timing of recovery in a 5-m walk test. The proportion of patients who could complete the 5-m walk test at admission, at 3 weeks of rehabilitation, at 6 weeks of rehabilitation, between 7 and 12 weeks of rehabilitation, and who could not complete the 5-m walk test after rehabilitation was 52.2%, 21.8%, 8.7%, 8.7%, and 8.6%, respectively. At postacute care discharge, patients who regained walking ability earlier had a higher chance of achieving higher levels of walking activity. Stepwise linear regression showed that Berg Balance Scale (BBS) (β: 0.011, p < .001), age (β: -0.005, p = .001), National Institutes of Health Stroke Scale (NIHSS) (6a + 6b; β: -0.042, p = .018), Mini-Nutritional assessment (MNA) (β: -0.007, p < .027), and Fugl-Meyer upper extremity assessment (FuglUE) (β: 0.002, p = .047) scores predicted patient's gait speed at discharge., Conclusion: Balance, age, leg strength, nutritional status, and upper limb function before postacute care rehabilitation are predictors of walking performance after stroke., Competing Interests: Conflicts of interest None., (Copyright © 2022 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

The fabrication of vertically stacked SiGe nanosheet (NS) field-effect transistors (FETs) was demonstrated in this study. The key process technologies involved in this device fabrication are low pressure chemical vapor deposition SiGe/Si multilayer epitaxy, selective etching of Si layers over SiGe layers using tetramethyl-ammonium-hydroxide wet solution, and atomic layer deposition of Y 2 O 3 gate dielectric. For the fabricated stacked SiGe NS p-GAAFETs with a gate length of 90 nm, I ON /I OFF ratio of around 5.0 × 10 5 and subthreshold swing of 75 mV/dec were confirmed via electrical measurements. Moreover, owing to its high quality of Y 2 O 3 gate dielectric, the device showed a very small drain-induced barrier-lowering phenomenon. These designs can improve the gate controllability of channel and device characteristics., (© 2023. The Author(s).)

CPT-11 (Irinotecan) remains an important chemotherapeutic agent against various solid tumors nowadays. Potential adverse effects, especially gastrointestinal toxicities, are the main limiting factor for its clinical utility. Ling Zhi-8 (LZ-8), a fungal immunomodulatory protein in Ganoderma lucidum mycelia, has potential for drug development due to its multiple bioactivities and functions. This study aimed to explore the influence of LZ-8 on CPT-11-treated IEC-6 cells in vitro and on mice with CPT-11-induced intestinal injury in vivo . The mechanism through which LZ-8 exerted its protective effects was also investigated. In the in vitro study, the viability and claudin-1 expression of IEC-6 cells decreased gradually with increasing concentrations of CPT-11, but LZ-8 treatment had no obvious influence on their viability, morphology, and claudin-1 expression. Pretreatment of LZ-8 significantly improved CPT-11-decreased cell viability and claudin-1 expression in IEC-6 cells. In mice with CPT-11-induced intestinal injury, LZ-8 treatment could ameliorate symptoms and mitigate intestinal damage. Meanwhile, LZ-8 restored claudin-1 expression in the intestinal membranes in CPT-11-treated mice. Collectively, our results demonstrated the protective effects of LZ-8 against CPT-11 damage in both IEC-6 cells and mice. LZ-8 can restore claudin-1 expression in intestinal cells following CPT-11 treatment, suggesting the role of claudin-1 in the scenario.

Background and Objectives: The effectiveness and safety of idarucizumab for the reversal of the effects of dabigatran have been proven. However, there remains a paucity of literature comprehensively investigating outcomes in real-world patients. This is especially true when comparing patients who were eligible for inclusion in the RE-VERSE AD trial with patients who were ineligible. As the prescription of dabigatran has become increasingly popular, the generalizability of the results to real-world populations has come into question due to the broad variability of real-world patients receiving dabigatran. Our study aimed to identify all patients who were prescribed idarucizumab and examined how effectiveness and safety varied among those patients who were eligible and ineligible for the trial. Materials and Methods : This retrospective cohort study analyzed the largest medical database in Taiwan. We enrolled all patients who were prescribed and received idarucizumab from when it became available in Taiwan up until May 2021. A Total of 32 patients were included and analyzed, and they were further divided into subgroups based on their eligibility for inclusion in the RE-VERSE AD trial. Multiple outcomes were evaluated, including successful hemostasis rate, complete reversal efficacy of idarucizumab, 90-day thromboembolic events, intra-hospital mortality, and adverse event rate. Results : In our study, we found that 34.4% of real-world cases of idarucizumab use were ineligible for the RE-VERSE AD trials. The eligible group had higher successful hemostasis rates (95.2% vs. 80%) and anticoagulant effect reversal rates compared to the ineligible group (73.3% vs. 0%). The mortality rates were 9.5%, compared to 27.3% in the ineligible group. Few adverse effects (n = 3) and 90-day thromboembolic events (n = 1) were observed in either group. Among the ineligible cases, all acute ischemic stroke patients (n = 5) received definite, timely treatments without complications. Conclusions: Our study demonstrated the real-world effectiveness and safety of idarucizumab infusion for trial-eligible patients and all acute ischemic stroke patients. However, although it seems to be effective and safe, idarucizumab appears to be less effective in other trial-ineligible patients. Despite this result, our study provides further evidence for extending the applicability of idarucizumab in real-world scenarios. Our study suggests that idarucizumab can be a safe and effective option for reversing the anticoagulant effect of dabigatran, particularly for eligible patients.

Background: Physical exercise as an intervention for improving cognitive function, especially executive function, is receiving increasing attention because it is easily accessible, cost-effective and promises many additional health-related benefits. While previous studies focused on aerobic exercise and resistance exercise, recent findings have suggested that exercise with high coordination demand elicits beneficial effects on executive function. We therefore examined the effects of an acute slackline exercise on the executive functions of young adults., Methods: In a crossover experimental design, 47 healthy participants (21 females), ranging in age from 18 to 27 years ( M  = 19.17, SD = 1.94) were randomly assigned to different sequences of two conditions (slackline exercise and film-watching). Before and after the 50 min intervention, a modified Simon task was used to assess participants' executive function (inhibitory control and cognitive flexibility)., Results: College students showed better inhibitory control performance as indicated by shorter reaction times following acute slackline exercise than those who participated in the film-watching session. As there was no difference in accuracy between the slackline exercise and film-watching sessions, the shortened reaction time after slackline exercise provides evidence against a simple speed-accuracy trade-off., Conclusion: Compared with film-watching, acute slackline exercise provides favorable effects on executive function necessitating inhibition in young adults. These findings provide insight into exercise prescription and cognition, and further evidence for the beneficial effects of coordination exercise on executive functions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wen, Chu, Chen, Chueh, Lin, Wu, Hsu, Huang and Hung.)

Purpose: To investigate the effects of various demographic, structural, radiographic, and clinical factors on the prognosis of patients with medial compartmental knee osteoarthritis with varus deformity undergoing medial opening wedge high tibial osteotomy (HTO) in combination with bone marrow concentrate (BMC) injection., Methods: In this prospective study, 20 patients underwent medial opening wedge HTO in combination with BMC injection with 12 months of follow-up. The structural and radiographic outcomes were evaluated by femorotibial angle and posterior tibial slope angle. The clinical outcomes were evaluated by visual analogue scale (VAS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), and The Knee injury and Osteoarthritis Outcome Score (KOOS). Multivariate nonlinear mixed-effects models with asymptotic regressions were used to model the trajectory of symptom improvement., Results: Medial opening wedge HTO in combination with BMC corrected the malalignment of the knee and led to significant symptom relief. The improvement of clinical symptoms reached a plateau 6 months after the surgery. Greater symptom severity at baseline and lower Kellgren-Lawrance (KL) grades were correlated with better post-operative clinical outcomes. Body-Mass-Index (BMI), femorotibial angle, age, and sex may also play a role in influencing the extent of symptom relief., Conclusion: Symptom severity at baseline is important for prognosis prediction. In clinical practice, we suggest that the evaluation of clinical features and functional status of the patients be more emphasised., (© 2023. The Author(s).)

Objective: Hypoactivity in the reward system among patients with attention deficit hyperactivity disorder (ADHD) is a well-known phenomenon. Whether the activity in the reward pathway is related to harm avoidance, such as in sensitivity to punishment, is unclear. Evidence regarding the potential difference between ADHD patients and controls in terms of this association is scarce., Methods: Event-related functional magnetic resonance imaging was conducted on subjects performing the Iowa gambling test. Fourteen adults with ADHD and 14 controls were enrolled in the study., Results: Harm avoidance was found to be positively correlated with the activities of the bilateral orbitofrontal cortex and right insula in individuals with ADHD. A group difference was also confirmed., Conclusion: Understanding the roles of harm avoidance and brain activation during risk tasks is important.

Background/purpose: Recent emerging evidence indicates that dysfunction of metabolic remodeling underlies aberrant T cell immune responses in systemic lupus erythematosus (SLE). This study was undertaken to investigate the expression of HIF-1α, a regulator of metabolic reprogramming, in T cells from SLE., Methods: HIF-1α expression in T lymphocytes from SLE patients was examined by quantitative polymerase chain reaction (PCR) and the protein expression was analyzed with intracellular staining in flow cytometry. HIF-1α was overexpressed in murine CD4 T cells via transducing T cells with HIF-1α containing lentivirus. The expression of HIF-1α, metabolic- and Th17-associated genes in T cells from SLE patients and its association with clinical manifestation was analyzed., Results: HIF-1α expression is increased in CD4 T cells from SLE patients both in intracellular staining and quantitative PCR analysis. In addition, there is enhanced HIF-1α expression in Th17-skewing murine T cells, and lentivirus-mediated HIF-1α overexpression promotes Th17 differentiation. Moreover, HIF-1α gene expression is positively correlated with the expression of glycolysis- and IL-17-associated genes in SLE patients., Conclusion: HIF-1α expression is increased in T cells from SLE patients, and is positively correlated with glycolysis- and Th17- associated pathway, implicating HIF-1α contributes to the activation of Th17 cells in SLE, and represents a potential novel therapeutic target., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Importance: As one of the chronic neurological degenerative diseases with the highest incidence of amnesia and dementia, Alzheimer's disease (AD) carried out the clinical treatment based on the 2 traditional Chinese medicine (TCM) of Chinese herbal compound and acupuncture (AP). With the vigorous development of TCM, doctors are facing the problem of choosing TCM or western medicine in clinical work. Hence there is an urge to make pairwise comparisons among these interventions to provide evidence for clinical practice., Objective: The used efficacy of the 2 TCM methods and combined with donepeziline were compared to compile the best treatment through network meta-analysis., Methods: Patients diagnosed with AD were included in the randomized clinical trial, who were treated with tonifying kidney decoction (TKD) or AP combined with donepezil hydrochloride (DH) as an intervention measure, while the control group was treated with DH. The total effective rate was the primary outcome, and mini-mental state examination (MMSE) score and activities of daily living (ADCS-ADL) scores were the secondary indicators., Results: Eventually 30 studies reporting 2236 patients underwent TKD or AP combined with DH were enrolled. In terms of total efficiency, compared with TKD and DH, TKD + DH was significantly preferable. In addition, TKD were classified into 2 categories, namely tonifying kidney with reducing phlegm formulas (TKRP) and tonifying kidney with filling lean marrow (TKFLM). Regarding to MMSE score of TKD, of the 3 interventions, only TKRP + DH (standard mean difference [SMD] = 4.84, 95% confidence interval [CI]: 0.86-8.82) and TKFLM + DH (SMD = 3.93, 95% CI: 1.06-6.80) had significant efficacy over TKFLM (SMD = 4.25, 95%CI: -2.58 to 11.08). Although no difference between TKRP and other groups, its effectiveness was higher than TKFLM + DH and TKFLM (surface under the cumulative ranking curve (SUCRA) = 61.5%). For the ADL score, compared with TKFLM + DH and DH, TKRP + DH had more effective (SUCRA = 70.2%). Regarding to the total effective rates, AP + DH was more statistically better than AP, and AP was statistically better than DH., Conclusion: TKD or AP in combination with DH are significantly superior in treating AD., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Kawasaki disease (KD), a multisystem inflammatory syndrome that occurs in children, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) may share some overlapping mechanisms. The purpose of this study was to analyze the differences in single-cell RNA sequencing between KD and COVID-19. We performed single-cell RNA sequencing in KD patients (within 24 hours before IVIG treatment) and age-matched fever controls. The single-cell RNA sequencing data of COVID-19, influenza, and health controls were downloaded from the Sequence Read Archive (GSE149689/PRJNA629752). In total, 22 single-cell RNA sequencing data with 102,355 nuclei were enrolled in this study. After performing hierarchical and functional clustering analyses, two enriched gene clusters demonstrated similar patterns in severe COVID-19 and KD, heightened neutrophil activation, and decreased MHC class II expression. Furthermore, comparable dysregulation of neutrophilic granulopoiesis representing two pronounced hyperinflammatory states was demonstrated, which play a critical role in the overactivated and defective aging program of granulocytes, in patients with KD as well as those with severe COVID-19. In conclusion, both neutrophil activation and MHC class II reduction play a crucial role and thus may provide potential treatment targets for KD and severe COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Huang, Wu, Chang, Chu and Kuo.)

Because nurse aides are one of the first-line care providers in hospitals, they should possess better knowledge, attitude, and behavioral intention toward COVID-19 during the pandemic. This study aimed to compare the improvements of COVID-19-related education on learning outcomes between multimedia-based and traditional face-to-face learning models for nurse aides. The parallel-group randomized controlled trial recruited 74 participants in both the experimental and control groups. Two 90 min interventions with the same contents, but in different ways, were delivered. A structured questionnaire was used to collect data of demographic information, knowledge, attitude, and behavioral intention toward COVID-19 before and after the interventions. Results from generalized estimation equations analysis indicated that the nurse aides in the multimedia-based learning group had greater improvement in the scores of knowledge (difference in change: 3.2, standard error: 0.97, p < 0.001), attitude (difference in change: 10.2, standard error: 2.97, p < 0.001), and behavioral intention (difference in change: 0.5, standard error: 0.04, p < 0.001) than those in the face-to-face learning group. During the outbreak of COVID-19, multimedia-based learning as an effective learning method could improve the learning outcomes related to COVID-19 and achieve learning goals without close contact.

Background: Many studies have been conducted to compare traditional trajectory (TT) and cortical bone trajectory (CBT) screws; however, how screw parameters affect the biomechanical properties of TT and CBT screws, and so their efficacy remains to be investigated., Methods: A finite element model was used to simulate screws with different trajectories, diameters, and lengths. Responses for implant and tissues at the adjacent and fixed segments were used as the comparison indices. The contact lengths and spanning areas of the inserted screws were defined and compared across the varieties., Results: The trajectory and diameter had a greater impact on the responses from the implant and tissues than the length. The CBT has shorter length than the TT; however, the contact length and supporting area of the CBT within the cortical bone were 19.6%. and 14.5% higher than those of the TT, respectively. Overall, the TT and CBT were equally effective at stabilizing the instrumented segment, except for bending and rotation. The CBT experienced less adjacent segment compensations than the TT. With the same diameter and length, the TT was considerably less stressed than the CBT, especially for flexion and extension., Conclusions: The CBT may provide less stress at adjacent segments compared with the TT. The CBT may provide more stiffer in osteoporotic segments than the TT due to greater contact with cortical bone and a wider supporting base between the paired screws. However, both entry point and insertion trajectory of the CBT should be carefully executed to avoid vertebral breach and ensure a stable cone-screw purchase., (© 2022. The Author(s).)

Purpose: To explore the potential protective effect of Kanglaite injection against radiotherapy-induced mucositis in patients with head and neck cancer., Patients and Methods: This was an open-label, single-arm, and phase II trial. The primary endpoint was the incidence of grade 3-4 radiation-induced mucositis. The secondary endpoints were hematological toxicity, non-hematological toxicity, nutritional status, and quality of life. All patients received 20g Kanglaite daily concurrently with radiotherapy., Results: The data of 46 patients were available for analysis. The incidence rates of grade 3 mucositis, pain, dysphagia, and neutropenia were 10.9%, 2.2%, 10.9%, and 6.5%, respectively, while the incidence of grade 4 acute toxicities was zero. The rate of opioid use was 2.2%. Radiotherapy dose reduction was 2.2% and no irradiation field was modified. The nutritional supports were oro-enteral nutritional supplements (13.0%), TPN (10.9%), and feeding tubes (0%) during radiotherapy. After radiotherapy, 52.2% of patients lost weight, and the weight loss was <10%. The mean pain score in the QLQ-H&N35 and QLQ-C30 was <50. Patients had nearly normal physical, emotional, and cognitive functions., Conclusions: A low incidence of grade 3-4 radiation-induced mucositis and no severe acute toxic events, with favorable nutritional status and quality of life, were observed in cancer patients after Kanglaite injection. Our findings highlight the need for a prospective, multicenter, and randomized study to investigate the effect of Kanglaite injection on the reduction of radiation-induced mucositis in patients with head and neck cancer., (Copyright © 2022 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Recent evidence from several autoimmune animal models has demonstrated that TRAIL suppresses the activation of T cells and inhibits autoimmune inflammation via an apoptosis-independent pathway. However, it remains unclear whether the immunosuppressive effects of TRAIL are dependent on its direct effects on T cells or on other immune cells to regulate T cells for the induction of disease. Therefore, we generated mice with T cell-specific TRAIL receptor (TRAIL-R) conditional knockout to investigate the impact of TRAIL on autoimmune inflammation and disease induction in experimental autoimmune encephalomyelitis (EAE). T cell-specific TRAIL-R knockout mice were found to completely reverse the TRAIL-mediated suppression of inflammation and disease induction, indicating that TRAIL-R on T cells is essential for TRAIL-mediated suppression of inflammation and disease induction in EAE. Moreover, the immune suppression effects were not due to the induction of cell apoptosis, but to the direct inhibition of T cell activation. In addition, RNA sequencing and transcriptome analysis revealed that TRAIL-R signaling significantly downregulated the genes involved in TCR signaling pathways, T cell differentiation, and proinflammatory cytokines. These results indicate that TRAIL-R on T cells is critical for pathologic T cell activation and induction of inflammation in EAE, suggesting that TRAIL-R serves as a novel immune checkpoint receptor in T cell-mediated autoimmune diseases., (Copyright © 2022 by The American Association of Immunologists, Inc.)

Background: Kawasaki disease (KD) is a form of systemic vasculitis that primarily affects children under the age of 5 years old. Antibiotics are often prescribed for KD patients even before a diagnosis is made due to their prolonged fever and elevated inflammatory markers. Therefore, the purpose of this study was to investigate the impact of antibiotics usage on the disease outcome of KD., Methods: We carried out a retrospective chart review of children between 2005 and 2017 for initial immunoglobulin (IVIG) treatment of KD. KD children with initial IVIG treatment more than 10 days after the onset of symptoms were excluded., Results: In total, 280 children were eligible for this study, among which 209 had been treated with antibiotic(s) and 71 had not been. The IVIG resistance rates were 5.6% (4/71), 8.9% (10/112), and 21.6% (21/97) in non-users, single-drug users, and multiple-drug users, respectively (r = 0.205, p = 0.003). The IVIG resistance rate of the multiple antibiotics drug users in KD patients was significantly higher than the other two groups. Furthermore, the likelihood of IVIG resistance was found to increase with elevated C-reactive protein (CRP) values (1.010/unit, p < 0.001) but not with total white blood cell (WBC) count (p = 0.466)., Conclusion: The probability of IVIG resistance increases with elevated CRP values and the use of multiple IV antibiotics, thus indicating that physicians should be prudent in administering multiple IV antibiotics when treating assumed infections in KD children., Competing Interests: Declaration of competing interest All of the authors hereby declare that they have no financial interests to disclose in relation to this article., (Copyright © 2021. Published by Elsevier B.V.)

Background: Patients' knowledge of how to care for their diabetes mellitus (DM) is critically influenced by health education, which is mostly provided by nurses. Therefore, effectively increasing nurses' knowledge of and skills in diabetes care is crucial. The aim of this study was to explore the effectiveness of the Diabetes Conversation Map™ Program (DCMP) in improving nurses' knowledge of DM care and skills in insulin injection., Method: A quasi-experimental design was adopted that used a pre-test and a posttest. A total of 18 nurses were included in the intervention group, while 19 nurses were in the control group receiving conventional teaching. A structured questionnaire regarding knowledge of and skills in DM care was administered before the program and then one month after., Results: Knowledge of DM and skills in insulin injection improved significantly in the intervention group compared to the control group ( p < .001 vs. p < .01)., Conclusion: The DCMP can be used to increase nurses' knowledge of DM and their skills in caring for DM. It leads to more effective learning than conventional teaching. [ J Contin Educ Nurs . 2022;53(2):90-96.] .

Horizontally stacked pure-Ge-nanosheet gate-all-around field-effect transistors (GAA FETs) were developed in this study. Large lattice mismatch Ge/Si multilayers were intentionally grown as the starting material rather than Ge/GeSi multilayers to acquire the benefits of the considerable difference in material properties of Ge and Si for realising selective etching. Flat Ge/Si multilayers were grown at a low temperature to preclude island growth. The shape of Ge nanosheets was almost retained after etching owing to the excellent selectivity. Additionally, dislocations were observed in suspended Ge nanosheets because of the absence of a Ge/Si interface and the disappearance of the dislocation-line tension force owing to the elongation of misfit dislocation at the interface. Forming gas annealing of the suspended Ge nanosheets resulted in a significant increase in the glide force compared to the dislocation-line tension force; the dislocations were easily removed because of this condition and the small size of the nanosheets. Based on this structure, a new mechanism of dislocation removal from suspended Ge nanosheet structures by annealing was described, which resulted in the structures exhibiting excellent gate control and electrical properties., (© 2022. The Author(s).)

The Child Behavior Checklist 1.5-5 (CBCL 1.5-5) is applied to identify emotional and behavioral problems on children with developmental disabilities (e.g., autism spectrum disorder [ASD] and developmental delays [DD]). To understand whether there are variations between these two groups on CBCL DSM-oriented scales, we took two invariance analyses on 443 children (228 children with ASD). The first analysis used measurement invariance and multiple-group factor analysis on the test structure. The second analysis used item-level analysis, i.e., differential item functioning (DIF), to discover whether group memberships responded differently on some items even though underlying trait levels were the same. It was discovered that, on the test structure, the Anxiety Problems scale did not achieve metric invariance. The other scales achieved metric invariance; DIF analyses further revealed that there were items that functioned differently across subscales. These DIF items were mostly about children's reactions to the surrounding environment. Our findings provide implications for clinicians to use CBCL DSM-oriented scales on differentiating children with ASD and children with DD. In addition, researchers need to be mindful about how items were responded differently, even though there were no mean differences on the surface.

Background: Spinal dural arteriovenous fistula (SDAVF) usually occurs during the 4 th to 6 th decades of life, and adolescent SDAVF is rarely reported. SDAVF arising around a tumor is also rare, and reported tumors are mostly schwannoma and lipoma., Case Presentation: We reported a 16-year-old male presented with progressive weakness and numbness of lower limbs for 3 months. A SDAVF was found, which was fed by right radicular arteries from segmental artery at L2 level and drained retrogradely into perimedullary veins. A concomitant spinal extradural nodular fasciitis at right L1/L2 intervertebral foramen was also noted. The SDAVF was completely obliterated by endovascular treatment and the tumor was debulked. The patient recovered well after the procedures., Conclusions: Our case report suggests SDAVF can occur in adolescent. The concomitant presence with a nodular fasciitis indicates that although it usually arises in subcutaneous tissue but can rarely form on the dura of spine., (© 2021. The Author(s).)

In this study, we investigated the changes in global methylation status and its functional relevance in childhood atopic dermatitis (AD). Differences in epigenome-scale methylation events in peripheral blood associated with childhood AD were screened using DNA methylation arrays of 24 patients with AD compared with 24 control subjects. Of the 16,840 differentially methylated CpG regions between AD and control subjects, >97% CpG loci revealed hypomethylation in patients with childhood AD. Among the globally hypomethylated loci, we identified two CpG clusters within the golli-mbp locus of the MBP gene, which was functionally enriched by subnetwork enrichment analysis as an orchestrator among associated genes. The differential hypomethylation of the top-ranked cg24700313 cluster in the golli-mbp locus was validated by pyrosequencing in an independent cohort of 224 children with AD and 44 control subjects. DNA methylation was found to be negatively correlated with disease severity but showed no significant correlation with IgE levels after age adjustment. The multivariate correlation analysis represents a higher score in AD intensity with significantly increased IgE levels and decreased methylation levels in cg27400313. We concluded that methylation loss in the golli-mbp locus is an epigenetic factor associated with disease severity of childhood AD., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Tentorial dural arteriovenous fistula is a rare subtype of intracranial dural arteriovenous fistula (DAVF) with a deteriorating natural course, which may be attributed to its pial angioarchitecture. TDAVF often harbors feeders arising from pial arteries (FPAs). Reports have revealed that, if these feeders are not obliterated early, the restricted venous outflow during the embolization process may cause upstream congestion in the fragile pial network, which increases the risk of hemorrhagic complications. Because most reported cases of TDAVF were embolized through feeders from non-pial arteries (FNPAs), little is known of the feasibility of direct embolization through FPAs. Methods: We present three patients with medial TDAVFs that were embolized through the dural branches of the posterior cerebral and superior cerebellar arteries. Findings from brain magnetic resonance imaging, computed tomography, angiography, and clinical outcomes are described. Furthermore, we performed a review of the literature on TDAVFs with FPAs. Results: The fistulas were completely obliterated in two patients; both recovered well with no procedure-related complications. The fistula was nearly obliterated in one patient, who developed left superior cerebellum and midbrain infarct due to the reflux of the embolizer into the left superior cerebellar artery. Including our cases, eight cases of TDAVFs with direct embolization through the FPAs have been reported, and ischemic complications occurred in three (37.5%). Conclusions: Advancing microcatheter tips as close to the fistula point as possible and remaining highly aware of potential embolizer flow back into the pial artery are key factors in achieving successful embolization. Balloon-assisted embolization may be an option for treating TDAVFs with FPAs in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chu, Chu, Lam, Lee, Chien, Yeh, Wu and Wong.)

Prediction of post-stroke functional outcomes is crucial for allocating medical resources. In this study, a total of 577 patients were enrolled in the Post-Acute Care-Cerebrovascular Disease (PAC-CVD) program, and 77 predictors were collected at admission. The outcome was whether a patient could achieve a Barthel Index (BI) score of >60 upon discharge. Eight machine-learning (ML) methods were applied, and their results were integrated by stacking method. The area under the curve (AUC) of the eight ML models ranged from 0.83 to 0.887, with random forest, stacking, logistic regression, and support vector machine demonstrating superior performance. The feature importance analysis indicated that the initial Berg Balance Test (BBS-I), initial BI (BI-I), and initial Concise Chinese Aphasia Test (CCAT-I) were the top three predictors of BI scores at discharge. The partial dependence plot (PDP) and individual conditional expectation (ICE) plot indicated that the predictors' ability to predict outcomes was the most pronounced within a specific value range (e.g., BBS-I < 40 and BI-I < 60). BI at discharge could be predicted by information collected at admission with the aid of various ML models, and the PDP and ICE plots indicated that the predictors could predict outcomes at a certain value range.

Endovascular thrombectomy (EVT) is the standard of care for anterior circulation acute ischemic stroke (AIS) with large vessel occlusion (LVO). Young patients with AIS-LVO have distinctly different underlying stroke mechanisms and etiologies. Much is unknown about the safety and efficacy of EVT in this population of young AIS-LVO patients. All consecutive AIS-LVO patients aged 50 years and below were included in this multicenter cohort study. The primary outcome measured was functional recovery at 90 days, with modified Rankin Scale of 0-2 deemed as good functional outcome. A total of 275 AIS-LVO patients that underwent EVT from 10 tertiary centers in Germany, Sweden, Singapore, and Taiwan were included. Successful reperfusion was achieved in 85.1% (234/275). Good functional outcomes were achieved in 66.0% (182/275). Arterial dissection was the most prevalent stroke etiology (42/195, 21.5%). National Institutes of Health Stroke Scale (NIHSS) score at presentation was inversely related to good functional outcomes (aOR: 0.92, 95% CI: 0.88-0.96 per point increase, p < 0.001). Successful reperfusion (aOR: 3.22, 95% CI: 1.44-7.21, p = 0.005), higher ASPECTS (aOR: 1.21, 95% CI: 1.01-1.44, p = 0.036), and bridging intravenous thrombolysis (aOR: 2.37, 95% CI: 1.29-4.34, p = 0.005) independently predicted good functional outcomes. Successful reperfusion was inversely associated with in-hospital mortality (aOR: 0.14, 95% CI: 0.03-0.57, p = 0.006). History of hypertension strongly predicted in-hospital mortality (aOR: 4.59, 95% CI: 1.10-19.13, p = 0.036). While differences in functional outcomes exist across varying stroke aetiologies, high rates of successful reperfusion and good outcomes are generally achieved in young AIS-LVO patients undergoing EVT., (© 2021 European Academy of Neurology.)

Encouraging citizens to use health checkup services is a health promotion strategy. In nations with aging populations, ensuring equitable use of health check-ups by senior citizens is a public health concern. The objective of this research was to quantify income-related inequality and its effect on the use of health checkup services in Taiwan during the 2007-2008 global financial crisis. We used the 2005 and 2009 datasets of the Taiwan National Health Interview Surveys to assess how income-related inequality influenced health check-up use among older adults in Taiwan during the 2007-2008 financial crisis. Corrected concentration indices (CCIs) were calculated and decomposed to determine the influences of explanatory variables. The dependent variable was whether participants had used free senior health check-ups in the past year, and the determinant factors were health behavior, health situation, socioeconomic and demographic factors, and area health care resources accessibility factors. The study assessed 2,460 older adults from the 2005 dataset and 2,514 such individuals from the 2009 dataset. The utilization of health check-ups increased from 21.6% in 2005 to 34.0% in 2009. Income-related inequality in the use of health check-up services was generally tilted toward the higher income individuals among both women and men in 2005 and 2009, and income-related inequality decreased among women group and increased among men group with non significantly from 2005 to 2009 (women: CCI decreased from.0738 in 2005 to.0658 in 2009; men: CCI increased from.1068 in 2005 to.1256 in 2009). We analyzed the effect of explanatory factors on men's and women's intention to use health check-ups by using a probit model. After controlling for other factors, we determined that income significantly influenced women's health check-up service use in 2005 and men's in 2005 and 2009. Positive health behavior significantly increased health check-up services use among men and women group after the financial crisis, and negative health behavior significantly reduced health check-ups use among men across financial crisis. The 2008 global financial crisis strengthened the effect on health check-ups use of income-related inequality of elderly men, especially in older adults with negative health behaviors. Elderly men with negative health behaviors tended to contribute more income-related inequality in use health check-up services after the financial crisis. Health promotion initiatives should focus their efforts on elderly men with negative health behaviors., Competing Interests: The authors have declared that no competing interests exist.

The Fc gamma receptor family contains several activating receptors and the only inhibitory receptor, FcγR2B . In this study, we investigated the dynamic methylation change of FcγR2B in different stages of Kawasaki disease (KD). We enrolled a total of 116 participants, which included patients with febrile diseases as controls and KD patients. Whole blood cells of KD patients were collected prior to intravenous immunoglobulin (IVIG) treatment (KD1), three to seven days after IVIG (KD2), three weeks after IVIG treatment (KD3), six months after IVIG (KD4), and one year after IVIG treatment (KD5). In total, 76 KD patients provided samples in every stage. Leukocytes of controls were also recruited. We performed DNA extraction and pyrosequencing. FcγR2B methylation levels were higher in KD3 compared to both the controls and KD1. A significantly higher methylation of FcγR2B was found in KD5 when compared with KD1. FcγR2B methylation levels in the IVIG-resistant group were lower than those in the IVIG-responsive group at KD1-3 ( p = 0.004, 0.004, 0.005 respectively). This study is the first to report the dynamic change of FcγR2B methylation and to demonstrate long-term hypermethylation one year after disease onset. Hypomethylation of FcγR2B is associated with IVIG resistance.

Volvariella volvacea, also known as straw mushroom, is a common edible mushroom in Chinese cuisine. It contains many nutrients for human health. A fungal immunomodulatory protein (FIP) has been isolated from V. volvacea and named FIP-vvo. Although the regulatory effects of many FIPs on immunity have been identified, the impact of FIP-vvo in modulating dendritic cells (DCs), which play a key role to connect the innate and the adaptive immunity, is not known. In this study, we aim to study the effect of FIP-vvo on the DC maturation and function. We found that FIP-vvo slightly increased the generation of CD11c + bone marrow-derived DC (BMDC). In addition, the surface expression of MHCII was promoted in BMDCs after the treatment of FIP-vvo, suggesting that FIP-vvo induces DC maturation. Furthermore, FIP-vvo enhanced the ability of BMDCs to activate antigen-specific T cell responses in vitro. In the in vivo study, the FIP-vvo treatment facilitated T cell response in lymph nodes. Therefore, for the first time, our data demonstrated that FIP-vvo promoted DC maturation and function and suggested that FIP-vvo could have benefits for human health by enhancing immunity.

Lay Abstract: The benefits of early intervention for young children with autism spectrum disorder highlight the importance of early diagnosis. Reliable diagnoses of autism spectrum disorder can be made before 24 months of age. However, many children are diagnosed with autism spectrum disorder at a later age. Delayed diagnosis can occur for children with less severe symptoms and lead to missed opportunities for early intervention. This current study was executed to examine the Taiwanese version of the Screening Tool for Autism in Two-Year-Olds in detecting autism spectrum disorder in toddlers between 18 and 24 months of age. One strength of this study was the inclusion of toddlers with autism spectrum disorder or mild-autism spectrum disorder using the strict and relaxed Diagnostic and Statistical Manual of Mental Disorders (5th ed.) criteria for autism spectrum disorder simultaneously. The results of this study supported that diagnosis of toddlers with autism spectrum disorder could be made reliable before 24 months of age. And the Taiwanese version of the Screening Tool for Autism in Two-Year-Olds was a Level 2 autism-specific screening tool for toddlers aged from 18 to 24 months in Taiwan.

Kawasaki disease (KD) is a systemic vasculitis that primarily affects children under the age of 5 years old. The most significant complication is coronary artery lesions, but several ocular manifestations have also been reported. Recently, one study revealed an increasing incidence of myopia among KD patients. Therefore, the aim of this study was to assess the difference in myopic incidence between Kawasaki disease (KD) patients treated with aspirin and intravenous immunoglobulin (IVIG). Materials and methods: We carried out a nationwide retrospective cohort study by analyzing the data of KD patients (ICD-9-CM code 4461) from Taiwan's National Health Insurance Research Database (NHIRD) during the period of 1996-2013. Results: A total of 14,102 diagnosed KD were found in Taiwan during the study period. After excluded missing data, treatment strategy and age distribution, a total of 1446 KD patients were enrolled for analysis including 53 of which received aspirin (without IVIG) and 1393 of which were treated with IVIG. Patients who had myopia, astigmatism, glaucoma, cataract, etc. prior to their KD diagnosis were excluded. The age range was 0 to 6 years old. According to the cumulative curves, our results demonstrated that the myopic incidence in the IVIG group was significantly lower than the aspirin group (hazard ratio: 0.59, 95% confidence intervals: 0.36~0.96, p = 0.02). Treatment with IVIG for KD patients may have benefit for myopia control. Conclusion: Compared to aspirin, IVIG may decrease the myopic risk in KD patients. However, it needs further investigation including clinical vision survey of myopia due to the limitations of this population-based study.

Immune checkpoints play critical roles in the regulation of T-cell effector function, and the effectiveness of their inhibitors in cancer therapy has been established. Immune checkpoint inhibitors (ICIs) constitute a paradigm shift in cancer therapy in general and cancer immunotherapy in particular. Immunotherapy has been indicated to reinvigorate antitumor T-cell activity and dynamically modulate anticancer immune responses. However, despite the promising results in the use of immunotherapy in some cancers, numerous patients do not respond to ICIs without the existence of a clear predictive biomarker. Overall, immunotherapy involves a certain degree of uncertainty and complexity. Research on the exploration of cellular and molecular factors within the tumor microenvironment (TME) aims to identify possible mechanisms of immunotherapy resistance, as well as to develop novel combination strategies involving the specific targeting of the TME for cancer immunotherapy. The combination of this approach with other types of treatment, including immune checkpoint blockade therapy involving multiple agents, most of the responses and effects in cancer therapy could be significantly enhanced, but the appropriate combinations have yet to be established. Moreover, the in-depth exploration of complexity within the TME allows for the exploration of pathways of immune dysfunction. It may also aid in the identification of new therapeutic targets. This paper reviews recent advances in the improvement of therapeutic efficacy on the immune context of the TME and highlights its contribution to cancer immunotherapy.

The fungal immunomodulatory protein Ling Zhi-8 (LZ-8) isolated from Ganoderma lucidum (GL) regulates immune cells and inhibits tumor growth; however, the role of LZ-8 in protecting intestinal epithelial cells (IECs) is unknown. In this study, we aim to investigate the functional effect of LZ-8 on IECs. LZ-8 effectively rescued the pro-inflammatory cytokine-induced loss of tight junctions (TJs) by enhancing transepithelial electrical resistance (TEER), reducing permeability, and maintaining the distribution of TJ proteins, in Caco-2 cells. Mechanistically, LZ-8 blocked the upregulation of myosin light chain kinase (MLCK) and NF-kB activation by TLR2-mediated suppression of cytokine signaling (SOCS)-1 expression. Furthermore, LZ-8 pre-treatment reduced the pathological scores of dextran sulfate sodium (DSS)-induced colitis in mice. These results indicated that LZ-8 protected the barrier function of IECs against inflammation. Thus, LZ-8 may potentially be a novel candidate for treating inflammatory bowel disease (IBD).

Background: To identify predictors of carotid artery stenosis (CAS) progression in head and neck cancer (HNC) patients after radiation therapy (RT)., Methods: We included 217 stroke-naïve HNC patients with mild carotid artery stenosis after RT in our hospital. These patients underwent annual carotid duplex ultrasound (CDU) studies to monitor CAS progression. CAS progression was defined as the presence of ≥50% stenosis of the internal/common carotid artery on follow-up CDU. We recorded total plaque score (TPS) and determined the cut-off TPS to predict CAS progression. We categorized patients into high (HP) and low plaque (LP) score groups based on their TPS at enrolment. We analyzed the cumulative events of CAS progression in the two groups., Results: The TPS of the CDU study at enrolment was a significant predictor for CAS progression (adjusted odds ratio [aOR] = 1.69, p = 0.002). The cut-off TPS was 7 (area under the curve: 0.800), and a TPS ≥ 7 strongly predicted upcoming CAS progression (aOR = 41.106, p = 0.002). The HP group had a higher risk of CAS progression during follow-up (adjusted hazard ratio = 6.15; 95% confident interval: 2.29-16.53) in multivariable Cox analysis, and also a higher trend of upcoming ischemic stroke (HP vs. LP: 8.3% vs. 2.2%, p = 0.09)., Conclusions: HNC patients with a TPS ≥ 7 in any CDU study after RT are susceptible to CAS progression and should receive close monitoring within the following 2 years., Competing Interests: The authors have declared that no competing interests exist.

Introduction: This study analyzes the severity of dementia status with clinical dementia rating (CDR) score distribution among patients according to various family functional and sociodemographic issues., Methods: A cross-sectional study was performed in a regional hospital in Central Taiwan. The sample consisted of 318 patients who came to the clinic from May 2018 to April 2019, and who were diagnosed by the physicians with CDR scores ≧ 0.5. The Chi-Square test and binary logistic regression analyses were performed for inferential statistical analysis., Results: The mean age of the sample was 78.7 ± 8.51 years, and 61.6% of the samples' CDR scores were equal or less than 1.0. Patients visiting the clinic were accompanied by spouses (21.7%), sons or daughters-in-law (40.6%), daughters (23.6%). Of the sample, 142 (44.3%) patients live with sons. Patients with a lower educational level had higher CDR scores. Compared to the patients who went to the clinic by themselves, the higher OR values of CDR scores ≧ 2 are found in patients who were accompanied by other relatives (OR = 18.871, 95% C.I. = 3.117-114.237, p = 0.001), or spouse (OR = 10.783, 95% C.I. = 1.996-58.245, p = 0.006)., Conclusion: The family member who accompanied the patient to a clinic visit and the patient's educational level are both significant issues relating to the severity of dementia.