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Lung Chan,1 Chen-Huan Chen,2 Juey-Jen Hwang,3 San-Jou Yeh,4 Kou-Gi Shyu,5 Ruey-Tay Lin,6 Yi-Heng Li,7 Larry Z Liu,8 Jim Z Li,9 Wen-Yi Shau,10 Te-Chang Weng,10 1Department of Neurology, Shuang-Ho Hospital, School of Medicine, College of Medicine, Taipei Medical University, New Taipei, 2Department of Internal Medicine, Faculty of Medicine, National Yang-Ming University, 3Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, 4Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, 5Division of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, 6Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung, 7Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; 8Pfizer Inc, New York, NY, USA; 9Pfizer Inc, San Diego, CA ,USA; 10Pfizer Ltd., New Taipei City, Taiwan Abstract: Hypertension is a major risk factor for strokes and myocardial infarction (MI). Given its effectiveness and safety profile, the calcium channel blocker amlodipine is among the most frequently prescribed antihypertensive drugs. This analysis was conducted to determine the costs and quality-adjusted life years (QALYs) associated with the use of amlodipine and valsartan, an angiotensin II receptor blocker, in preventing stroke and MI in Taiwanese hypertensive patients. A state transition (Markov) model was developed to compare the 5-year costs and QALYs for amlodipine and valsartan. Effectiveness data were based on the NAGOYA HEART Study, local studies, and a published meta-analysis. Utility data and costs of MI and stroke were retrieved from the published literature. Medical costs were based on the literature and inflated to 2011 prices; drug costs were based on National Health Insurance prices in 2014. A 3% discount rate was used for costs and QALYs and a third-party payer perspective adopted. One-way sensitivity and scenario analyses were conducted. Compared with valsartan, amlodipine was associated with cost savings of New Taiwan Dollars (NTD) 2,251 per patient per year: costs were NTD 4,296 and NTD 6,547 per patient per year for amlodipine and valsartan users, respectively. Fewer cardiovascular events were reported in patients receiving amlodipine versus valsartan (342 vs 413 per 10,000 patients over 5 years, respectively). Amlodipine had a net gain of 58 QALYs versus valsartan per 10,000 patients over 5 years. Sensitivity analyses showed that the discount rate and cohort age had a larger effect on total cost and cost difference than on QALYs. However, amlodipine results were more favorable than valsartan irrespective of discount rate or cohort age. When administered to Taiwanese patients for hypertension control, amlodipine was associated with lower cost and more QALYs compared with valsartan due to a lower risk of stroke and MI events. Keywords: cost-effectiveness, pharmacoeconomic, Markov model, CCB, ARB

Aim. This paper is a report of a study to examine relationships among stress, coping and comorbidity and test the interaction effect of comorbidity. Background. Haemodialysis imposes a variety of physical and psychosocial stressors that challenge patients. Comorbidity is a risk factor for many health outcomes. Research on how comorbidity influences the relationship between coping and stress is limited. Method. In this cross-sectional study, conducted from October 2002 to January 2003, 2642 patients, who had been having haemodialysis for at least 3 months, were interviewed by nursing managers in the 27 participating centres. The Haemodialysis Stressor Scale measured stressors and the Jalowiec Coping Scale were used to measure coping strategies. Hierarchical regression was used to analyse the data. Results. Haemodialysis patients with comorbidities were found to have higher levels of stress. Comorbidity had a moderating effect between choice of problem-oriented responses and isolated thoughts as coping strategies. These findings show that haemodialysis patients with comorbidities often choose positive coping strategies. Conclusion. Comorbidity not only has a direct impact on stress but also has a moderating effect on the relationship between coping and stress. Comorbidity may hold the key to healthcare professionals' understanding of why patients having haemodialysis perceive different levels of stress and use various coping strategies. A personalized programme may be needed for each patient based on their different levels of comorbidity. [ABSTRACT FROM AUTHOR]

BACKGROUND: Under the universal health insurance system in Taiwan, policy makers seek new approaches to balance rising costs and quality of care. One policy, Ambulatory Care Reimbursement, enacted in 2001 has effectively reduced patient numbers in clinics by cutting per patient reimbursement when a physician has seen over predetermined number of patients. PURPOSE: To access the impact of this policy on physician satisfaction in regional hospitals and medical centers (MCs) from the point of view of their medical directors. METHODOLOGY: We conducted a cross-sectional survey of medical directors from 25 MCs and 78 regional hospitals in Taiwan. The survey used a 5-point Likert scale to identify both impacts of reduced ambulatory care visits and physician satisfaction. We randomly selected 30% of all medical directors from both types of medical institutions. Of the 248 medical directors contacted, 142 replied. Excluding 5 incomplete responses, our final sample was 137. Response rates were roughly equivalent for MCs (54.67%) and regional hospitals (57.89%). FINDINGS: Medical directors were typically male, aged 45.11 years, worked in MCs (60%), and were general practitioners (43.1%). Multiple regressions associated three independent predictors of physician satisfaction: physician-patient interaction (beta = .393, p = .001), mission (beta = .351, p = .007), and reduced health care expenditures (beta = .179, p = .014). Medical directors more often characterized the regulation of reducing number of visits as a means of encouraging MCs and regional hospitals to improve physician interaction with patients and, thus, associated it with greater patient satisfaction. Generally, directors did not believe that the regulation encouraged patients seeking care at other hospitals or that it resulted in reduced pay to physicians. PRACTICE IMPLICATION: Reducing ambulatory care visits has promoted the physician-patient relationship and allowed many physicians attain their medical mission. Such regulation had influence on the physicians' satisfaction. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Patients with stroke are often selected for epidemiological reporting and research using ICD-9-CM (ICD-9) diagnostic codes. This study addresses the accuracy of these codes in identifying patients with stroke. METHODS: A sample of 279 patients with new stroke and 392 non-stroke (no evidence of new stroke) patients were identified by medical record review from 11 Veterans Affairs Medical Centers. Administrative records containing ICD-9-CM diagnoses were matched with this sample. Coding sensitivity and specificity were determined using individual ICD-9 codes and two coding algorithms. RESULTS: Significant variation was found in the accuracy of cerebrovascular ICD-9-CM codes in identifying patients diagnosed with stroke. Two coding algorithms were identified with the following performance statistics based on the sampled populations: 1) 91-percent sensitivity, 40-percent specificity; and 2) 54-percent sensitivity, 87-percent specificity. DISCUSSION/CONCLUSIONS: Variability in identifying patients with stroke using ICD-9 codes has been reported in the literature and confirmed. Two coding algorithms for maximizing sensitivity or specificity are proposed. Caution is urged when using ICD-9-coded administrative data to identify patients with stroke. [ABSTRACT FROM AUTHOR]

Objective: Recurrent stroke after revascularization surgeries predicts poor outcome in patients with moyamoya disease (MMD). Early identification of patients with stroke risk paves the way for rescue intervention. This study aimed to investigate the role of ultrasound in identifying patients at risk of post-operative ischemic events (PIEs)., Methods: This prospective study enrolled patients with symptomatic MMD who underwent indirect revascularization surgeries. Ultrasound examinations were performed preoperatively and at 3 mo post-operatively to evaluate the hemodynamic changes in extracranial and intracranial arteries on the operated side. PIE was defined as ischemic stroke or transient ischemic attack in the operated hemisphere within 1 y. The areas under receiver operating characteristic curves were compared between models for prediction of PIE., Results: A total of 56 operated hemispheres from 36 patients (mean age, 23.0 ± 18.5 y) were enrolled in this study, and 27% developed PIE. In multivariate logistic regression models, PIE was associated with lower end-diastolic velocity and flow volume (FV) of the ipsilateral external carotid artery (ECA), and lower FV of ipsilateral superficial temporal artery and occipital artery at 3 mo post-operatively (all p < 0.05). Moreover, the post-operative FV of the ipsilateral ECA was the only one factor that significantly increased the areas under receiver operating characteristic curves from 0.727 to 0.932 when adding to a clinical-angiographic model for prediction of PIE (p = 0.017). This parameter was significantly lower in hemispheres with PIE, both in adult and pediatric patients., Conclusion: After indirect revascularization, surgeries in patients with symptomatic MMD, FV of ipsilateral ECA at 3 mo helps clinicians to identify patients at risk of PIE., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2024 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Postural orthostatic tachycardia syndrome (POTS) presents excessive orthostatic tachycardia and orthostatic intolerance. POTS is a common and therapeutically challenging condition affecting numerous people worldwide. As many disease entities can be confused with POTS, it becomes critical to identify this syndrome. Moreover, unbalanced autonomic nervous activity can induce cardiovascular diseases and influence the bio-feedback mechanism: Baroreflex (BR) and cerebral autoregulation (CA). BR and CA are important bio-mechanisms that maintain a stable circulatory system via the autonomic nervous system. Therefore, an impaired autonomic nervous system would lead to imbalanced BRS and CA. Consequently, we propose an advanced cross-correlation function (ACCF) time-domain approach to analyze baroreflex and cerebral autoregulation using physiological signals. This study assesses relation changes in BR and CA using ACCF in POTS for early clinical detection and diagnosis. The ACCF analysis results has thresholds that reveal that the BR of healthy and POTS groups present significantly different maximum CCF values (p < 0.05). The complete CCF index shows that the BR phase changes significantly into phase lag in the POTS group. Although CA analysis using the maximum CCF index was mildly weak, it did not differ in the POTS group. Thus, POTS only affects BR. An increasing sympathetic activity might induce an unbalanced baroreflex effect and increase cerebral vasomotor tone with CA. Maximum CCF value correlation coefficients between BR and CA indicated positive in POTS groups and negative in the healthy group. It could be speculated that the sympathetic nervous system compensates to improve BR function, which remains CA function. The advantage of this ACCF algorithm is that it helps observe BR and CA for early detection., (© 2024. The Author(s).)

Aim: This study explored whether hospitals that allocate greater resources to their nursing staff provide better healthcare services than those that invest less in their nursing personnel., Design: Cross-sectional logistic and tobit analyses., Methods: We examined a sample of 314 California hospitals in 2017. We obtained a hospital's public recognition for treating nurses fairly between 2015 and 2017 from Nurse.org, the largest online community of nurses. We derived a hospital's healthcare quality in 2018 from the 2019-2020 Best Hospitals rankings released by U.S. News, a well-known media company publishing independent healthcare assessments periodically., Results: Our results showed that a nurse-friendly workplace was a crucial determinant of its overall healthcare quality., Conclusion and Implications: Healthcare administrators keen to enhance the quality of healthcare services should consider creating nurse-friendly workplaces. Furthermore, their evaluation of nurses' contributions to overall healthcare quality should not solely depend on the nurse-assessed quality of care, but rather comprise not only broad aspects of patient outcomes in primary care but also patient experiences, care-related factors and expert opinions., Patient or Public Contribution: Our study helped address the overwhelmed healthcare system, whose long-running shortage of nurses has been exacerbated by the COVID-19 pandemic. Our work suggested that a hospital's investment in a nurse-friendly workplace can enhance its acquisition, retention and devotion of the nursing staff. This, in turn, can have profound impacts on its overall healthcare quality., What Already Is Known: Existing empirical evidence on the relation between nurse-friendly workplace and healthcare quality is limited and inconclusive., What This Paper Adds: We documented evidence that the quality of healthcare services provided by hospitals varies with their treatment of nursing staff., Implications for Practice/policy: Our results provided insights into key policies that have the potential to improve healthcare quality., (© 2024 John Wiley & Sons Ltd.)

Background: Health care industries must consider their sustainable development, and employee well-being is a crucial environmental, social, and governance indicator that should be prioritized. During events such as the COVID-19 pandemic, information transparency is a concern for health care workers. Authentic leaders can build trust by openly sharing their thoughts and feelings. Understanding how authentic leadership affects employee well-being through job stress and how emotional intelligence reduces job stress is essential for health care workers., Purposes: This study investigated the effect of authentic leadership on employee well-being and considered the mediating role of job stress and moderating role of emotional intelligence in this effect., Methodology/approach: A time-lagged survey of 452 full-time health care workers (comprising nurses, allied health professionals, and administrative workers) from a general hospital in Taiwan was conducted., Findings: Authentic leadership was positively associated with employee well-being, and job stress mediated the effects of authentic leadership on employee well-being. Among the employees who perceived leadership to be authentic, those with higher emotional intelligence felt less job stress., Conclusion: From the perspective of conservation of resources theory, authentic leadership was identified as a crucial factor influencing how health care workers reduce job stress and improve their well-being. Emotional intelligence was identified as essential in enhancing the effects of authentic leadership on reducing the job stress of health care workers., Practice Implications: Organizations should promote authentic interactions between leaders and followers and provide training for developing authentic leadership. They should also provide training to improve their employees' emotional intelligence., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Neurological deterioration within 24 h after intravenous thrombolysis with tissue plasminogen activator (tPA) is associated with poor outcomes in patients with acute ischemic stroke (AIS). This study aimed to elucidate the features of neurological deterioration specifically during tPA infusion in these patients., Methods: We analyzed patients with AIS receiving thrombolysis between January 2018 and December 2021. Very early neurological deterioration (VEND) was defined as an increase of 4 or more points in the National Institutes of Health Stroke Scale (NIHSS) score during tPA infusion. Poor functional outcome was defined as a modified Rankin Scale score of 3-6 at three months., Results: Among the 345 patients with AIS who received tPA, 8.4% had VEND; all of which were caused by ischemic progression. Patients with VEND had a higher prevalence of intracranial atherosclerotic disease (41% vs. 17%, P = 0.005). VEND independently predicted poor functional outcome in both groups with minor (NIHSS score <6) and non-minor (NIHSS score >6) stroke. Among patients with minor stroke, those with VEND were more likely to undergo endovascular thrombectomy (EVT) than those without (38% vs. 5%, P = 0.019). In patients receiving EVT after VEND, the NIHSS scores at 24 h, which were correlated with 3-month functional outcome, were lower in those with successful recanalization than in those without (12 ± 9 vs. 26 ± 7, P = 0.047)., Conclusion: VEND predicted poor functional outcomes in patients with AIS. Timely and successful recanalization using EVT potentially alleviates the negative impact of VEND on long-term outcomes., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Gene expression profiling of new or modified cell lines becomes routine today; however, obtaining comprehensive molecular characterization and cellular responses for a variety of cell lines, including those derived from underrepresented groups, is not trivial when resources are minimal. Using gene expression to predict other measurements has been actively explored; however, systematic investigation of its predictive power in various measurements has not been well studied. Here, we evaluated commonly used machine learning methods and presented TransCell, a two-step deep transfer learning framework that utilized the knowledge derived from pan-cancer tumor samples to predict molecular features and responses. Among these models, TransCell had the best performance in predicting metabolite, gene effect score (or genetic dependency), and drug sensitivity, and had comparable performance in predicting mutation, copy number variation, and protein expression. Notably, TransCell improved the performance by over 50% in drug sensitivity prediction and achieved a correlation of 0.7 in gene effect score prediction. Furthermore, predicted drug sensitivities revealed potential repurposing candidates for new 100 pediatric cancer cell lines, and predicted gene effect scores reflected BRAF resistance in melanoma cell lines. Together, we investigated the predictive power of gene expression in six molecular measurement types and developed a web portal (http://apps.octad.org/transcell/) that enables the prediction of 352,000 genomic and cellular response features solely from gene expression profiles., (© The Author(s) 2024. Published by Oxford University Press and Science Press on behalf of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China.)

Background: We evaluated the diagnostic ability of macula retinal nerve fiber layer (mRNFL) thickness in preperimetric glaucoma (PPG) patients., Methods: This prospective study included 83 patients with PPG and 83 age- and refractive error-matched normal control subjects. PPG was defined as a localized RNFL defect corresponding to glaucomatous optic disc changes with a normal visual field test. We used spectral-domain (SD) optical coherence tomography (OCT) to measure the circumpapillary RNFL (cpRNFL) thickness and macular ganglion cell-inner plexiform layer (GCIPL) thickness. Swept-source (SS) OCT was used to measure cpRNFL thickness, macular ganglion cell layer + inner plexiform layer (IPL) thickness (GCL+), and macular ganglion cell layer + IPL+ mRNFL thickness (GCL++). The mRNFL thickness was defined as GCL++ minus GCL+. To evaluate the diagnostic power of each parameter, the area under the receiver operating characteristics curve (AUROC) was analyzed to differentiate PPG from the normal groups., Results: Using SD-OCT, all GCIPL parameters and most cpRNFL parameters, except at the nasal and temporal quadrant, were significantly lower in PPG versus normal controls. PPG eyes had significantly smaller values than normal controls for all cpRNFL and GCL parameters measured by SS-OCT, except mRNFL at the superonasal area. The inferotemporal GCL++ had the largest AUROC value (0.904), followed by inferotemporal GCL+ (0.882), inferotemporal GCIPL thickness (0.871), inferior GCL++ (0.866), inferior cpRNFL thickness by SS-OCT (0.846), inferior cpRNFL thickness by SD-OCT (0.841), and inferotemporal mRNFL thickness (0.840). The diagnostic performance was comparable between inferotemporal mRNFL thickness and the best measures of GCL (inferotemporal GCL++, p = 0.098) and cpRNFL (inferior cpRNFL thickness by SS-OCT, p = 0.546)., Conclusion: The diagnostic ability of mRNFL thickness was comparable to that of the best measures of cpRNFL and GCL analysis for eyes with PPG. Therefore, mRNFL thickness could be a new parameter to detect early structural changes in PPG., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Background: Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent (0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.9 mg/kg alteplase)., Methods: We enrolled consecutive patients in the multicenter Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke who had received combined thrombolysis (within 4.5 hours of onset) and thrombectomy treatment from January 2019 to April 2023. The choice of low- or standard-dose alteplase was based on the physician's discretion. The outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction score, 2b-3), symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score, and 90-day mortality. The outcomes between the 2 groups were compared using multivariable logistic regression and inverse probability of treatment weighting-adjusted analysis., Results: Among the 2242 patients in the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke, 734 (33%) received intravenous alteplase. Patients in the low-dose group (n=360) were older, had more women, more atrial fibrillation, and longer onset-to-needle time compared with the standard-dose group (n=374). In comparison to low-dose alteplase, standard-dose alteplase was associated with a lower rate of successful reperfusion (81% versus 87%; adjusted odds ratio, 0.63 [95% CI, 0.40-0.98]), a numerically higher incidence of symptomatic intracerebral hemorrhage (6.7% versus 3.9%; adjusted odds ratio, 1.81 [95% CI, 0.88-3.69]), but better 90-day modified Rankin Scale score (functional independence [modified Rankin Scale score, 0-2], 47% versus 31%; adjusted odds ratio, 1.91 [95% CI, 1.28-2.86]), and a numerically lower mortality rate (9% versus 15%; adjusted odds ratio, 0.73 [95% CI, 0.43-1.25]) after adjusting for covariates. Similar results were observed in the inverse probability of treatment weighting-adjusted models. The results were consistent across predefined subgroups and age strata., Conclusions: Despite the lower rate of successful reperfusion and higher risk of symptomatic intracerebral hemorrhage with standard-dose alteplase, standard-dose alteplase was associated with a better functional outcome in patients receiving combined thrombolysis and thrombectomy., Competing Interests: Disclosures None.

Objective: Despite amyloid deposition as a hallmark of hereditary transthyretin amyloidosis (ATTRv) with polyneuropathy, this pathology could not completely account for nerve degeneration. ATTRv patients frequently have vasomotor symptoms, but microangiopathy hypothesis in ATTRv was not systemically clarified., Methods: This study examined the vascular pathology of sural nerves in ATTRv patients with transthyretin (TTR) mutation of p.Ala117Ser (TTR-A97S), focusing on morphometry and patterns of molecular expression in relation to nerve degeneration. We further applied human microvascular endothelial cell (HMEC-1) culture to examine the direct effect of TTR-A97S protein on endothelial cells., Results: In ATTRv nerves, there was characteristic microangiopathy compared to controls: increased vessel wall thickness and decreased luminal area; both were correlated with the reduction of myelinated fiber density. Among the components of vascular wall, the area of collagen IV in ATTRv nerves was larger than that of controls. This finding was validated in a cell model of HMEC-1 culture in which the expression of collagen IV was upregulated after exposure to TTR-A97S. Apoptosis contributed to the endothelial cell degeneration of microvasculatures in ATTRv endoneurium. ATTRv showed prothrombotic status with intravascular fibrin deposition, which was correlated with (1) increased tissue factor and coagulation factor XIIIA and (2) reduced tissue plasminogen activator. This cascade led to intravascular thrombin deposition, which was colocalized with upregulated p-selectin and thrombomodulin, accompanied by complement deposition and macrophages infiltration, indicating thromboinflammation in ATTRv., Interpretation: Microangiopathy with thromboinflammation is characteristic of advanced-stage ATTRv nerves, which provides an add-on mechanism and therapeutic target for nerve degeneration., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

BACKGROUND An aortopulmonary window (APW) is an uncommon congenital defect of the septation between the ascending aorta and pulmonary trunk. The combination of APW and interrupted aortic arch (IAA) is even rarer, with the hallmark characteristics of high peri-operative mortality and postoperative obstruction of the aortic arch, pulmonary artery, and left main bronchus. These complications often need re-interventions. CASE REPORT We present 2 cases with diagnoses of APW and IAA that were treated with single-stage repair. Case 1: A male 32-week premature newborn (weight 1789 g) had APW type I and IAA type A. He had severe postoperative aortic arch obstruction on postoperative day 1, and we re-intervened promptly. He was still asymptomatic after 6 years. Case 2: A male term neonate had APW type III and IAA type A. He had left vocal cord paralysis and left bronchial compression postoperatively. We applied prolonged noninvasive respiratory supports. The complications resolved without re-intervention on postoperative day 66. Progressive arch stenosis at anastomosis after operation required close follow-up with echocardiography. CONCLUSIONS These 2 reports highlight the feasibility of single-stage surgical repair while addressing 2 challenges: (1) Recurrent arch stenosis: Lower body weight and direct end-to-side anastomosis without patch augmentation could be risk factors for re-intervention. (2) Bronchial compression: Presentation of the second reported case implied that bronchial compression may not warrant immediate re-intervention unless there is complete obstruction, persistent atelectasis, or recurrent infection. Further studies on long-term outcomes of different surgical procedure would help us to clarify the proper way to avoid re-intervention.

Purpose: Psychological and social support are crucial in treating cancer. Cancer resource centers provide patients with cancer and their families with services that can help them through cancer treatment, ensure that patients receive adequate treatment, and reduce cancer-related stress. These centers offer various services, including medical guidance, health education, emotional assistance (e.g., consultations for cancer care), and access to resources such as financial aid and post recovery programs. In this study, we comprehensively analyzed how cancer resource centers assist patients with cancer and improve their clinical outcomes., Methods: The study participants comprised patients initially diagnosed with head and neck cancer or esophageal cancer. A total of 2442 patients from a medical center in Taiwan were included in the study. Data were analyzed through logistic regression and Cox proportional hazards regression., Results: The results indicate that unemployment, blue-collar work, and a lower education level were associated with higher utilization of cancer resource center services. The patients who were unemployed or engaged in blue-collar work had higher risks of mortality than did their white-collar counterparts. Patient education programs can significantly improve the survival probability of patients with cancer. On the basis of our evaluation of the utilization and benefits of services provided by cancer resource centers, we offer recommendations for improving the functioning of support systems for patients with cancer and provide suggestions for relevant future research., Conclusions: We conclude that cancer resource centers provide substantial support for patients of low socioeconomic status and improve patients' survival., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ferroptosis, an iron-dependent form of cell death, is characterized by intracellular accumulation of iron and reactive oxygen species-induced lipid peroxidation. Animal experiments have shown the important roles of ferroptosis in ischemic stroke, but the evidence in human stroke is insufficient. This prospective study evaluated the associations between plasma ferroptosis biomarkers at hyperacute stage and long-term outcomes in patients with acute ischemic stroke undergoing endovascular thrombectomy (EVT). The plasma samples were collected immediately before and after EVT (T1 and T2) and at 24 h (T3) for the 126 stroke patients and once for the 50 stroke-free control subjects. Compared with controls, stroke patients had higher 4-hydroxynonenal (4-HNE) levels at T1 and T2 while lower homocysteine and soluble transferrin receptor (sTfR) levels at T3. In stroke patients, higher National Institutes of Health Stroke Scale scores at admission were correlated with higher 4-HNE and lower sTfR levels. Lower Alberta Stroke Program Early CT (ASPECT) scores and larger infarct core volumes on CT perfusion before EVT were correlated with higher 4-HNE and homocysteine levels. After adjusting for significant parameters, homocysteine levels at T2 were significantly associated with poor functional outcome and mortality at 3 months. In the receiver operating characteristic (ROC) models, adding homocysteine levels at T2 and hemoglobin levels to the reference model for predicting poor functional outcome significantly increased the area under the ROC curve. In summary, this study provides evidence that ferroptosis is associated with stroke severity and outcomes in patients with acute ischemic stroke undergoing EVT., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We investigated the hemodynamic parameters of pediatric PDA patients and focused on the influence of PDA size on pulmonary arterial pressure and the prevalence of pulmonary hypertension. A total of 52 patients aged between 2 months and 20 years who received transcatheter closure of a PDA from January 2018 to June 2022 in our institution were retrospectively recruited. Their hemodynamic parameters collected both by echocardiography and by cardiac catheterization were analyzed to delineate the influence of PDA size on the pulmonary vascular system. The echocardiographic-based ductal size and indexed PDA size were 1.93 mm (1.15-6 mm) and 4.05 mm/m 2 (2.03-25.47 mm/m 2 ), respectively. The pulmonary artery pressure measured was 20.83 mmHg (8-45 mmHg). We found a positive correlation between indexed PDA size and mean pulmonary arterial pressure (mPAP) (Pearson correlation coefficient = 0.47, p < 0.001). A subgroup analysis showed that 28 patients (53.8%) developed pulmonary hypertension (PH) (defined as mPAP > 20 mmHg). The median age of the PH group was 1.02 years [range: 0.19-8.64], which was significantly younger than the non-PH group's median age of 3.43 years [range: 0.42-19.96] (p = 0.001). The indexed PDA size for the PH group, 4.69 mm/m 2 , was significantly higher than that of the non-PH group, 3.2 mm/m 2 (p = 0.004). The major risk factor for patients with PH was the PDA/BSA index, with an OR of 2.181 (95% CI, 1.224-3.887). Our demographic data showed younger patients with a higher PDA/BSA index are more likely to develop pulmonary hypertension., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Postradiotherapy carotid vasculopathy is a clinically relevant complication in patients with head and neck cancer receiving radiotherapy. In this study, we investigated the factors associated with the development and progression of carotid artery stenosis (CAS) in such patients., Methods: Patients who received radiotherapy for head and neck cancers between October 2011 and May 2019 at a medical center in Taiwan were eligible for inclusion in this study. This study included patients who underwent two consecutive carotid duplex examinations within an interval of 1 to 3 years. The factors associated with ≥50% CAS at baseline and follow-up were analyzed., Results: In total, 694 patients (mean age, 57.8 ± 9.9 years; men, 75.2%; nasopharyngeal cancer, 73.3%) were included. The mean interval between radiotherapy and carotid duplex examination was 9.9 ± 5.9 years. At baseline, 103 patients had ≥50% CAS, which was significantly associated with tobacco smoking, hypercholesterolemia, and a prolonged interval between radiotherapy and carotid duplex examination. A total of 586 patients did not have CAS at baseline; of them, 68 developed ≥50% CAS during follow-up. Hypertension and hypercholesterolemia were identified as independent risk factors for CAS progression., Conclusion: Modifiable vascular risk factors, such as hypertension and hypercholesterolemia, appear to be significantly associated with the rapid progression of postradiotherapy CAS in patients with head and neck cancer., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Stroke is a leading cause of serious long-term disability and the major cause of mortality worldwide. Experimental ischemic stroke models play an important role in realizing the mechanism of cerebral ischemia and evaluating the development of pathological extent. An accurate and reliable image segmentation tool to automatically identify the stroke lesion is important in the subsequent processes. However, the intensity distribution of the infarct region in the diffusion weighted imaging (DWI) images is usually nonuniform with blurred boundaries. A deep learning-based infarct region segmentation framework is developed in this paper to address the segmentation difficulties. The proposed solution is an encoder-decoder network that includes a hybrid block model for efficient multiscale feature extraction. An in-house DWI image dataset was created to evaluate this automated stroke lesion segmentation scheme. Through massive experiments, accurate segmentation results were obtained, which outperformed many competitive methods both qualitatively and quantitatively. Our stroke lesion segmentation system is potential in providing a decent tool to facilitate preclinical stroke investigation using DWI images.Clinical Relevance- This facilitates neuroscientists the investigation of a new scoring system with less examination time and better inter-rater reliability, which helps to understand the function of specific brain areas underlying neuroimaging signatures clinically.

Objectives: To mitigate the shortage of homograft sources, the use of handmade trileaflet expanded polytetrafluoroethylene valves in pulmonary valve replacement has shown excellent results from multicentre studies conducted in Japan. However, world-wide data outside Japan are relatively insufficient. This study presents the long-term results of a single surgeon's use of flipped-back trileaflet method in a 10-year case series., Methods: We have developed an efficient way to make a trileaflet-valved conduit utilizing flipped-back method for pulmonary valve replacement and have employed the technique since 2011. Retrospective data were studied between October 2010 and January 2020. Echocardiography, electrocardiogram, Pro-Brain Natriuretic Peptide and Magnetic Resonance Imaging data were analysed., Results: Fifty-five patients were reviewed and median follow-up duration was 2.9 years. The majority of diagnoses was Tetralogy of Fallot (n = 41), and these patients subsequently underwent secondary pulmonary valve replacement at a median age of 15.6 years. Survival was 92.7% with the longest follow-up period being 10 years. There was no need for reoperation, and freedom from reintervention was 98.0% at 10 years. There were 4 deaths (3 in-hospital and 1 outpatient). One patient eventually received transcatheter pulmonary valve implantation. Postoperative echocardiography showed mild or less pulmonary stenosis and pulmonary regurgitation degree in 92.2% and 92.0% of patients, respectively. Comparable magnetic resonance imaging data (n = 25) showed significant reduction in right ventricular volumes but not in ejection fractions., Conclusions: Our series showed satisfactory long-term function of handmade flipped-back trileaflet-valved conduit used in our patients. The simple design is efficiently reproducible without complex fabrication process., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Introduction: Temporalis muscle thickness (TMT) is a surrogate marker for sarcopenia. This study investigated the association of TMT with clinical outcomes in patients receiving endovascular thrombectomy (EVT) for stroke involving acute large vessel occlusion (LVO)., Material and Methods: We enrolled consecutive patients who had undergone EVT between September 2014 and December 2021 at three thrombectomy-capable institutes. TMT was measured through preprocedural computerized tomography angiography. The clinical variables affecting TMT were investigated. The associations between TMT and clinical functional outcomes, defined using the modified Rankin scale, were also studied., Results: A total of 657 patients were included (mean age: 72.0 ± 12.7 years; male: 52.1%). The mean TMT was 6.35 ± 1.84 mm. Younger age, male sex, higher body mass index, and premorbid functional independence were associated with larger TMT in both univariate and multivariate linear regression (P <.05). Ordinal logistic regression revealed that TMT was associated with better clinical outcomes at 90 days (P trend  = 0.047); multivariate logistic regression indicated that larger TMT was an independent predictor (adjusted odds ratio: 1.14, 95% confidence interval: 1.03-1.27, P = 0.02) of favorable functional independence (modified Rankin scale score: 0-2). The effect was stronger in older patients (≥80 years) than younger patients, as revealed by interaction modeling analysis (P interaction  = 0.06)., Conclusion: TMT is associated with age, sex, body mass index, and premorbid functional status. Larger TMT is associated with better outcomes after EVT. The effects of TMT are more pronounced in older adults, indicating that sarcopenia may have influence on stroke outcomes., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

The prevalence of heart failure is increasing, causing a tremendous burden on health care systems around the world. Although mortality rate of heart failure has been significantly reduced by several effective agents in the past 3 decades, yet it remains high in observational studies. More recently, several new classes of drugs emerged with significant efficacy in reducing mortality and hospitalization in chronic heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). To integrate these effective therapies and prioritize them in the management of Asian patients, Taiwan Society of Cardiology has recently appointed a working group to formulate a consensus of pharmacological treatment in patients with chronic heart failure. Based on most updated information, this consensus provides rationales for prioritization, rapid sequencing, and in-hospital initiation of both foundational and additional therapies for patients with chronic heart failure., Competing Interests: Dr. C.-E. Chiang has received honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Menarini, MSD, Novartis, Pfizer, and Sanofi. Dr. C.-L. Hung has received honorarium from Astrazeneca, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Pfizer, and Sanofi. Dr. Y.-W. Wu has received honorarium from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, MSD, Novartis, Pfizer, Sanofi, and Takeda. Dr. T.-H. Lin has received honorarium from Astrazeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, MSD, Novartis, Pfizer, Sanofi, Bayer, Viatris, Menariri, Tanabe, and Takeda. Dr. K.-C. Ueng has received honorarium from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Merck Sharp and Dohme, Novartis, Pfizer, and Sanofi. Dr. S.-H. Sung has received honorarium from Astrazeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Novartis, Pfizer, Sanofi, Abbott, and Edward. Dr. C.-K. Wu has received honorarium from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Novartis, Pfizer, Sanofi, and Abbott. Dr. T.-H. Chao has received honorarium from Bayer, AstraZeneca, Eli Lilly, Boehringer Ingelheim, Daiichi-Sankyo, Tanabe Taiwan, and Novartis. Dr. Y.-H. Lin has received honorarium from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, MSD, Novartis, Pfizer, and Sanofi. Dr. M. YC Chen has received honorarium from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, and Pfizer. Dr. P.-L. Lin has received honorarium from AstraZeneca, Abbott, Boehringer Ingelheim, Bayer, Daiichi-Sankyo, Eli Lilly, Novartis, Novo Nordisk, Pfizer, and Sanofi. Dr. T.-F. Chao has received speaker honorarium from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Novartis, Pfizer, and Sanofi. Dr. H.-M. Cheng has received honorarium from AstraZeneca, Pfizer, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, SERVIER, Sanofi, Takeda, and Eli Lilly. Dr. M.-E. Liu has received honorarium from Abbott, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Medtronic, MSD, Novartis, Pfizer, and Sanofi. Dr. H.-I. Yeh has received honorarium from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, MSD, Novartis, Novo Nordisk, Pfizer, and Sanofi. Dr. Y.-H. Li has received honorarium from AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Novartis, Pfizer, and Sanofi. Dr. I.-C. Hsieh has received honorarium from AstraZeneca, Boehringer Ingelheim, Novartis, Bayer, MSD, Sanofi, Daiichi Sankyo, Pfizer, and Eli Lilly. Dr. C.-C. Wang has received honorarium from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Novartis, and Pfizer. Dr. C.-H. Chen reports honoraria from Novartis and Daiichi Sankyo. Dr. P.-H. Chu has received honorarium from AstraZeneca. Dr. S.-J. Yeh has received honorarium from Tanabe. Dr. W.-J. Chen has received honorarium from Astrazeneca, Boehringer Ingelheim, Daiichi-Sankyo, MSD, Novartis, Pfizer, and Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Experimental ischemic stroke models play a fundamental role in interpreting the mechanism of cerebral ischemia and appraising the development of pathological extent. An accurate and automatic skull stripping tool for rat brain image volumes with magnetic resonance imaging (MRI) are crucial in experimental stroke analysis. Due to the deficiency of reliable rat brain segmentation methods and motivated by the demand for preclinical studies, this paper develops a new skull stripping algorithm to extract the rat brain region in MR images after stroke, which is named Rat U-Net (RU-Net)., Methods: Based on a U-shape like deep learning architecture, the proposed framework integrates batch normalization with the residual network to achieve efficient end-to-end segmentation. A pooling index transmission mechanism between the encoder and decoder is exploited to reinforce the spatial correlation. Two different modalities of diffusion-weighted imaging (DWI) and T2-weighted MRI (T2WI) corresponding to two in-house datasets with each consisting of 55 subjects were employed to evaluate the performance of the proposed RU-Net., Results: Extensive experiments indicated great segmentation accuracy across diversified rat brain MR images. It was suggested that our rat skull stripping network outperformed several state-of-the-art methods and achieved the highest average Dice scores of 98.04% (p < 0.001) and 97.67% (p < 0.001) in the DWI and T2WI image datasets, respectively., Conclusion: The proposed RU-Net is believed to be potential for advancing preclinical stroke investigation and providing an efficient tool for pathological rat brain image extraction, where accurate segmentation of the rat brain region is fundamental., (© 2023. The Author(s).)

Objective: The purpose of this study was to use a deep learning model and a traditional statistical regression model to predict the long-term care insurance decisions of registered nurses., Methods: We Prospectively surveyed 1,373 registered nurses with a minimum of 2 years of full-time working experience at a large medical center in Taiwan: 615 who already owned long-term care insurance (LTCI), 332 who had no intention to purchase LTCI (group 1), and 426 who intended to purchase LTCI (group 2)., Results: After inverse probability of treatment weighting (IPTW), no statistically significant differences were identified in the study characteristics of the two groups. All the performance indices for the deep neural network (DNN) model were significantly higher than those of the multiple logistic regression (MLR) model (P<0.001). The strongest predictor of an individual's long-term care insurance decision was their risk propensity score, followed by their caregiving responsibilities, whether they live with older adult relatives, their experiences of catastrophic illness, and their openness to experience., Conclusions: The DNN model is useful for predicting long-term care insurance decisions. Its prediction accuracy can be increased through training with temporal data collected from registered nurses. Future research can explore designs for two-level or multilevel models that explain the contextual effects of the risk factors on long-term care insurance decisions., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Aim: The study examined whether occupational stress mediated the relationship between abusive supervision and well-being of nursing staff., Design: A cross-sectional questionnaire survey was administered., Methods: Data were collected at three-time points between July 2020 and January 2021. A total of 313 valid responses were obtained from nurses working in a general hospital in Taiwan. The data were analysed using descriptive statistics, Pearson's correlation analysis and the bootstrap method., Results: Abusive supervision was positively associated with occupational stress (β = 0.288, SE = 0.069, 95% CI [0.152, 0.423]) and negatively associated with employee well-being, including psychological (β = -0.350, SE = 0.084, 95% CI [-0.515, -0.186]), physical (β = -0.301, SE = 0.080, 95% CI [-0.459, -0.143]) and social well-being (β = -0.422, SE = 0.121, 95% CI [-0.661, -0.183]). Occupational stress was negatively related to employee well-being. A mediation analysis with bootstrapping revealed that occupational stress mediated the relationship between abusive supervision and employee well-being, which included psychological (95% bootstrap CI [-0.183, -0.046]), physical (95% bootstrap CI [-0.212, -0.062]) and social well-being (95% bootstrap CI [-0.178, -0.040])., Conclusion: Abusive supervision influences employee well-being. Occupational stress mediates the relationship between abusive supervision and employee well-being. To improve employee well-being, hospital administrators should develop policies for effectively managing nursing supervisors' abusive behaviour and subordinates' stress management., Impact: Abusive supervision increased the occupational stress of employees and influenced their well-being. Thus, educational courses should be implemented to train supervisors to practice positive leadership and treat employees fairly. Promoting stress management among nursing staff may lead to the prompt reporting of abusive events and improved employee well-being., No Patient or Public Contribution: This study investigated the relationship between the abusive supervision and employee well-being of nursing employees. No patient or public contribution is involved in this study., (© 2022 John Wiley & Sons Ltd.)

Background: Post-stroke inflammation contributes to poor outcomes, but its impact on patients with stroke receiving endovascular thrombectomy (EVT) remains unknown., Methods: We enrolled adult patients with stroke who received EVT, with blood sampling immediately before (T1) and after EVT (T2), and at 24 hours after EVT (T3). Non-stroke controls and patients with non-EVT stroke were also enrolled. The medical information, image findings and levels of serum amyloid A (SAA) and C-reactive protein (CRP) were analyzed to clarify the association with poor functional outcome (modified Rankin Scale 4-6) at 3 months after stroke., Results: A total of 93 patients with stroke receiving EVT, 51 non-stroke controls, and 64 with non-EVT stroke were enrolled in this study. The SAA and CRP levels at T1 to T3 in patients with stroke receiving EVT were higher compared with those in controls (all p<0.001), and their levels at T3 were significantly higher than those at T1 (both p<0.0001) while similar to those in patients with non-EVT stroke. The SAA levels at the three time points were significantly associated with poor functional outcome (p=0.003 to 0.009). Furthermore, adding SAA level at T3 significantly improved the basic prediction model for 3-month poor functional outcome by receiver operating characteristic (ROC) analysis (areas under ROC curves from 0.803 to 0.878, p=0.03)., Conclusions: Our findings demonstrate that plasma levels of SAA at an early stage are significant predictors for poor functional outcomes at 3 months in patients with stroke receiving EVT, indicating the substantial role of systemic inflammation in shaping stroke outcomes following EVT., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Perihematomal edema of intracerebral hemorrhage (ICH) is caused by a hematoma-induced inflammatory reaction, which usually contributes to delayed deterioration of neurological function and poor outcomes. Celecoxib is a commonly used nonsteroidal anti-inflammatory drug that selectively inhibits cyclooxygenase-2. High-dose celecoxib (400 mg twice daily) for 14 days has been shown to reduce perihematomal edema and hematoma enlargement in patients with ICH, but without improvement in long-term functional outcome, which may be confounded by the heterogeneity of hematoma location. Low-dose celecoxib may be an effective management for symptoms caused by perihematomal edema in patients with ICH, particularly those involving the thalamus., Case Report: We reported two patients with acute thalamic ICH; a common symptom between the two was delayed onset of drowsiness caused by perihematomal edema involving the thalamus. Their consciousness improved after low-dose celecoxib (200 mg once daily) administration for 3 and 2 days in case A and B, respectively. Furthermore, other symptoms that concomitantly improved included poor appetite caused by perihematomal edema involving the left hypothalamus in case A, and limb weakness caused by perihematomal edema of the internal capsule in case B., Conclusion: These cases revealed that low-dose celecoxib may be an effective management for symptoms caused by perihematomal edema in patients with ICH, particularly those involving the thalamus.

Purpose: Autonomic dysfunction is an underrecognized complication of acute ischemic stroke. The cortical regulation of sympathetic activation is predominantly lateralized to the right hemisphere and parasympathetic activation to the left hemisphere. However, prior evidence is lacking regarding ischemic lesions in unilateral hemisphere that concomitantly cause sympathetic and parasympathetic dysfunction., Case Report: We present the case of a 73-year-old woman with acute ischemic stroke in the left middle cerebral artery territory, whose neurological symptoms improved significantly after thrombolysis and endovascular thrombectomy. She presented residual scattered small infarctions involving the left insula and lateral parietal cortex. However, she experienced obvious autonomic symptoms that included orthostatic hypotension, which is indicative of sympathetic dysfunction, and micturition difficulty with exaggerated reflex tachycardia, indicative of parasympathetic dysfunction. The sympathetic and parasympathetic functions sequentially resolved on days 10 and 20 after stroke onset, respectively., Conclusion: The case revealed insight into the phenomenon and recovery course of concurrent sympathetic and parasympathetic dysfunction associated with ischemic lesions in the left hemisphere.

Purposes: This study investigated the impact of posterior limb of internal capsule (PLIC) infarct on outcomes of acute internal carotid artery (ICA) occlusion after endovascular thrombectomy (EVT) and the diagnostic accuracy of pretreatment noncontrast computerized tomography (NCCT) and computerized tomography angiography (CTA) findings., Methods: Patients who underwent EVT for acute ICA occlusion between September 2014 and August 2020 were included in the study. The patients were dichotomized as PLIC infarct or spared. The risk factors for PLIC infarct were investigated, and the association between infarct patterns and clinical outcomes were assessed using logistic regression analysis. Pretreatment NCCT and CTA findings, including PLIC hypodensity, choroid plexus enhancement (CPE), and posterior cerebral artery (PCA) flow status, were calculated for diagnosis of PLIC infarct., Results: Among 72 patients, the mean age was 70.9 years, and the mean stroke scale was 19.4. PLIC infarct was identified in 15 patients (20.8%). PLIC infarct was associated with worse 90-day functional outcome (P = 0.01, shift test). Lack of CPE is the only independent predictor of PLIC infarct (odds ratio: 127.48, P = 0.001). Lack of CPE and impaired PCA flow produce greater diagnostic accuracy for PLIC infarct than does NCCT hypodensity (area under the receiver operating characteristics curve: 0.85 and 0.76, P = 0.0005 and 0.02, respectively)., Conclusions: In acute ICA occlusion, PLIC infarct is an independent risk factor for worse clinical outcome at 90 days. The lack of CPE was associated with PLIC infarct, and pretreatment CTA can be useful for early diagnosis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objective: Indirect revascularization surgery reduce the risk of recurrent vascular events in patients with moyamoya disease (MMD), but the roles of postoperative angiography and ultrasonography in predicting these events remain unclear., Methods: This prospective study enrolled patients with MMD who would undergo their first unilateral indirect revascularization surgery. They received preoperative and postoperative ultrasound examination at 1, 3, and 6 months and conventional cerebral angiography. On ultrasonography, postoperative emerging flow (PEF) in an intracranial artery was defined as emerging flow postoperatively with absence of flow preoperatively. Predictors of vascular event frequency reduction were identified from angiographic and ultrasonographic parameters., Results: In total, 52 patients (including 24 pediatric and 24 male patients), who underwent 52 preoperative and 82 postoperative ultrasound examinations, were enrolled. Significant postoperative changes were noted in all the ultrasonographic parameters of ipsilateral superficial temporal artery (STA) and the end-diastolic velocity and flow volume in contralateral STA. During a median follow-up of 5.3 years, indirect revascularization surgery significantly reduced the occurrence of ipsilateral vascular events. Predictors of vascular event frequency reduction included Matsushima grade A or B on the ipsilateral side on angiography (odds ratio [OR] = 22.00, P = 0.002) and lower resistance index (RI) in ipsilateral STA (OR = 0.0001, P = 0.012) but no PEF pattern in ipsilateral middle cerebral artery (OR = 0.14, P = 0.029) on ultrasonography performed within 6 months., Conclusions: Reduction of long-term vascular event frequency probably can be predicted through postoperative angiography and ultrasonography within 6 months after indirect revascularization surgery., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Gastric cancer (GC) is the third leading cause of cancer death in the world. It is associated with the stimulation of microenvironment, aberrant epigenetic modification, and chronic inflammation. However, few researches discuss the GC molecular progression mechanisms from the perspective of the system level. In this study, we proposed a systems medicine design procedure to identify essential biomarkers and find corresponding drugs for GC. At first, we did big database mining to construct candidate protein-protein interaction network (PPIN) and candidate gene regulation network (GRN). Second, by leveraging the next-generation sequencing (NGS) data, we performed system modeling and applied system identification and model selection to obtain real genome-wide genetic and epigenetic networks (GWGENs). To make the real GWGENs easy to analyze, the principal network projection method was used to extract the core signaling pathways denoted by KEGG pathways. Subsequently, based on the identified biomarkers, we trained a deep neural network of drug-target interaction (DeepDTI) with supervised learning and filtered our candidate drugs considering drug regulation ability and drug sensitivity. With the proposed systematic strategy, we not only shed the light on the progression of GC but also suggested potential multiple-molecule drugs efficiently.

Background: Machine learning algorithms for predicting 30-day stroke readmission are rarely discussed. The aims of this study were to identify significant predictors of 30-day readmission after stroke and to compare prediction accuracy and area under the receiver operating characteristic (AUROC) curve in five models: artificial neural network (ANN), K nearest neighbor (KNN), random forest (RF), support vector machine (SVM), naive Bayes classifier (NBC), and Cox regression (COX) models., Methods: The subjects of this prospective cohort study were 1,476 patients with a history of admission for stroke to one of six hospitals between March, 2014, and September, 2019. A training dataset ( n = 1,033) was used for model development, and a testing dataset ( n = 443) was used for internal validation. Another 167 patients with stroke recruited from October, to December, 2019, were enrolled in the dataset for external validation. A feature importance analysis was also performed to identify the significance of the selected input variables., Results: For predicting 30-day readmission after stroke, the ANN model had significantly ( P < 0.001) higher performance indices compared to the other models. According to the ANN model results, the best predictor of 30-day readmission was PAC followed by nasogastric tube insertion and stroke type ( P < 0.05). Using a machine learning ANN model to obtain an accurate estimate of 30-day readmission for stroke and to identify risk factors may improve the precision and efficacy of management for these patients., Conclusion: Using a machine-learning ANN model to obtain an accurate estimate of 30-day readmission for stroke and to identify risk factors may improve the precision and efficacy of management for these patients. For stroke patients who are candidates for PAC rehabilitation, these predictors have practical applications in educating patients in the expected course of recovery and health outcomes., 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, Chung, Yeh, Lou, Lin, Lin, Hsien, Hung, Yeh and Shi.)

Diffuse large B cell lymphoma (DLBCL) is an aggressive heterogeneous disease. The most common subtypes of DLBCL include germinal center b-cell (GCB) type and activated b-cell (ABC) type. To learn more about the pathogenesis of two DLBCL subtypes (i.e., DLBCL ABC and DLBCL GCB), we firstly construct a candidate genome-wide genetic and epigenetic network (GWGEN) by big database mining. With the help of two DLBCL subtypes' genome-wide microarray data, we identify their real GWGENs via system identification and model order selection approaches. Afterword, the core GWGENs of two DLBCL subtypes could be extracted from real GWGENs by principal network projection (PNP) method. By comparing core signaling pathways and investigating pathogenic mechanisms, we are able to identify pathogenic biomarkers as drug targets for DLBCL ABC and DLBCL GCD, respectively. Furthermore, we do drug discovery considering drug-target interaction ability, drug regulation ability, and drug toxicity. Among them, a deep neural network (DNN)-based drug-target interaction (DTI) model is trained in advance to predict potential drug candidates holding higher probability to interact with identified biomarkers. Consequently, two drug combinations are proposed to alleviate DLBCL ABC and DLBCL GCB, respectively.

Diabetes mellitus (DM) is a chronic disease characterized by elevated blood glucose levels, which leads over time to serious damage to the heart, blood vessels, eyes, kidneys, and nerves. DM is of two types-types 1 or 2. In type 1, there is a problem with insulin secretion, and in type 2-insulin resistance. About 463 million people worldwide have diabetes, and 80% of the majority live in low- and middle-income countries, and 1.5 million deaths are directly attributed to diabetes each year. Autonomic neuropathy (AN) is one of the common diabetic complications, leading to failure in blood pressure (BP) control and causing cardiovascular disease. Therefore, early detection of AN becomes crucial to optimize treatment. We propose an advanced cross-correlation function (ACCF) between BP and heart rate with suitable threshold parameters to analyze and detect early changes in baroreflex sensitivity (BRS) in DM with AN (DM+). We studied heart rate (HR) and systolic BP responses during tilt in 16 patients with diabetes mellitus only (DM-), 19 diabetes mellitus with autonomic dysfunction (DM+), and 10 healthy subjects. The ACCF analysis revealed that the healthy and DM groups had different filtered percentages of significant maximum cross-correlation function (CCF) value ( p < 0.05), and the maximum CCF value after thresholds was significantly reduced during tilt in the DM+ group ( p < 0.05). The maximum CCF index, a parameter for the phase between HR and BP, separated the healthy group from the DM groups ( p < 0.05). Due to the maximum CCF index in DM groups being located in the positive range and significantly different from healthy ones, it could be speculated that BRS dysfunction in DM and AN could cause a phase change from lead to lag. ACCF could detect and separate DM+ from DM groups. This fact could represent an advantage of the ACCF algorithm. A common cross-correlation analysis was not easy to distinguish between DM- and DM+. This pilot study demonstrates that ACCF analysis with suitable threshold parameters could explore hidden changes in baroreflex control in DM+ and DM-. Furthermore, the superiority of this ACCF algorithm is useful in distinguishing whether AN is present or not in DM., 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 Yeh, Lung, Jan and Liau.)

Prostate cancer (PCa) is the second most frequently diagnosed cancer for men and is viewed as the fifth leading cause of death worldwide. The body mass index (BMI) is taken as a vital criterion to elucidate the association between obesity and PCa. In this study, systematic methods are employed to investigate how obesity influences the noncutaneous malignancies of PCa. By comparing the core signaling pathways of lean and obese patients with PCa, we are able to investigate the relationships between obesity and pathogenic mechanisms and identify significant biomarkers as drug targets for drug discovery. Regarding drug design specifications, we take drug-target interaction, drug regulation ability, and drug toxicity into account. One deep neural network (DNN)-based drug-target interaction (DTI) model is trained in advance for predicting drug candidates based on the identified biomarkers. In terms of the application of the DNN-based DTI model and the consideration of drug design specifications, we suggest two potential multiple-molecule drugs to prevent PCa (covering lean and obese PCa) and obesity-specific PCa, respectively. The proposed multiple-molecule drugs (apigenin, digoxin, and orlistat) not only help to prevent PCa, suppressing malignant metastasis, but also result in lower production of fatty acids and cholesterol, especially for obesity-specific PCa.

Objective: The COVID-19 pandemic has increased psychological distress among common people and has caused health care providers, such as nurses, to experience tremendous stress., Methods: This prospective cross-sectional study assessed the psychological impacts on nurses in a community hospital in Taiwan, including major depressive disorder (MDD), posttraumatic stress (PTS), and pessimism. According to transactional theory, coping strategies and personal factors have psychological impacts. We hypothesized that behavioral responses to COVID-19 (problem-focused coping) are more effective in reducing psychological impacts than emotional responses to COVID-19 (emotion-focused coping). Independent variables were the use of behavioral and emotional coping strategies for COVID-19 and 3 personal factors, namely sleep disturbance, physical component summary (PCS-12), and mental component summary (MCS-12) of the 12-Item Short Form Health Survey (SF-12) obtained from the Medical Outcomes Study. Dependent variables comprised 3 psychological impacts, namely MDD, PTS, and pessimism., Results: We determined that behavioral coping strategies had significant negative effects on PTS and pessimism; however, emotional coping strategies had significantly positive effects on PTS and pessimism. Sleep disturbance was significantly associated with increased MDD and pessimism. PCS-12 had a significant negative effect on PTS, whereas MCS-12 was not significantly associated with any of the 3 psychological impacts., Conclusions: Nurses who adopted protective behavior against COVID-19, such as washing hands, wearing masks, avoiding touching eyes, and mouth, and avoiding personal contact, were associated with less posttraumatic stress and pessimism. Healthcare providers should consider strategies for improving preventive behaviors to help ease their worries and fears concerning COVID-19.

Background: Prolongation of the QT interval is associated with the risk of sudden infant death syndrome. QT interval differs depending on age at the time of screening. Screening protocols have yet to be established for Taiwanese patients., Objectives: To construct QT interval reference values during early infancy, to investigate whether QT interval change differs according to age calculation methods, and to identify an optimal QT correction method and associated infant factors., Methods: Electrocardiographic readings and QT intervals were recorded cross-sectionally in 595 healthy infants and screened prospectively for long QT interval. Corrected QT intervals with Bazett's (QTc-B) and Fridericia's (QTc-F) formulas were compared by post-natal and post-menstrual screening age, sex, body mass index (BMI), heart rate (HR), birth and family history., Results: QTc-B and QTc-F decreased in the second month (31-60 days), and peaked in the third month (61-90 days). QT interval length was similar between post-menstrual and post-natal ages for QTc-B. Simple linear regression showed that post-menstrual age, post-natal age, HR and BMI were associated with QTc-F, while only sex and HR were associated with QTc-B. Although both QTc-B and QTc-F were significantly associated with HR, QTc-B was less affected by HR than QTc-F (β = -0.1, p < 0.05 for QTc-B vs. β = -0.3, p < 0.001 for QTc-F). Female infants tended to have slightly longer QTc intervals., Conclusions: QT interval in early infancy changed physiologically, peaking in the third month. The rate of QT change was not affected by different age correction methods. QTc-B was less affected by age, BMI and HR, although differences in sex should be noted.

Machine learning algorithms have proven to be effective for predicting survival after surgery, but their use for predicting 10-year survival after breast cancer surgery has not yet been discussed. This study compares the accuracy of predicting 10-year survival after breast cancer surgery in the following five models: a deep neural network (DNN), K nearest neighbor (KNN), support vector machine (SVM), naive Bayes classifier (NBC) and Cox regression (COX), and to optimize the weighting of significant predictors. The subjects recruited for this study were breast cancer patients who had received breast cancer surgery (ICD-9 cm 174-174.9) at one of three southern Taiwan medical centers during the 3-year period from June 2007, to June 2010. The registry data for the patients were randomly allocated to three datasets, one for training ( n = 824), one for testing ( n = 177), and one for validation ( n = 177). Prediction performance comparisons revealed that all performance indices for the DNN model were significantly ( p < 0.001) higher than in the other forecasting models. Notably, the best predictor of 10-year survival after breast cancer surgery was the preoperative Physical Component Summary score on the SF-36. The next best predictors were the preoperative Mental Component Summary score on the SF-36, postoperative recurrence, and tumor stage. The deep-learning DNN model is the most clinically useful method to predict and to identify risk factors for 10-year survival after breast cancer surgery. Future research should explore designs for two-level or multi-level models that provide information on the contextual effects of the risk factors on breast cancer survival.

Ischemic stroke with a mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) or T2-weighted images indicates onset within 4.5 h, but the pathological substrates in the DWI-T2 mismatch and T2(+) areas remain elusive. In this study, proteomics was used to explore (1) the protein expression profiles in the T2(+), mismatch, and contralateral areas, and (2) the protein with the highest expression in the T2(+) area in the brains of male Sprague-Dawley rats within 4.5 h after middle cerebral artery occlusion (MCAO). The expression of the candidate protein was further validated in (1) rat brain subjected to MCAO, (2) rat primary cortical neuronal culture with oxygen-glucose deprivation (OGD), and (3) infarcted human brain tissues. This study showed that apoptosis was observed in the T2(+) and mismatch regions and necroptosis in the T2(+) region of rat brains after MCAO. We identified capping protein regulator and myosin 1 linker 3 (CARMIL3) as the candidate molecule in the T2(+) and mismatch areas, exclusively in neurons, predominantly in the cytoplasm, and most abundant in the mismatch area. The CARMIL3(+) neurons and neurites in the mismatch and T2(+) areas were larger than those in the control area, and associated with (1) increased expression of sulfonylurea receptor 1 (SUR1), indicating edema, (2) accumulation of p62, indicating impaired autophagy, and (3) increase in 8-hydroxy-2'-deoxyguanosine (8-OHdG), indicating oxidative stress. The increased expression of CARMIL3 was validated in a cell model of cortical neurons after OGD and in infarcted human brain tissues. In conclusion, this study shows that the mismatch and T2(+) areas within 4.5 h after ischemia are characterized by upregulated expression of CARMIL3 in neurons, particularly the mismatch area, which is associated with neuronal edema, impaired autophagy, and oxidative stress, indicating that CARMIL3 serves as a molecular signature of brain ischemia., 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 Yeh, Hsu, Yeh, Yang, Chang, Chiang, Tang, Tsai, Jeng and Hsieh.)

Cardiovascular diseases have been the leading causes of mortality in Taiwan and the world at large for decades. The composition of cardiovascular and cerebrovascular systems is quite complicated. Therefore, it is difficult to detect or trace the related signs of cardiovascular and cerebrovascular diseases. The characteristics and changes in cardiopulmonary system disease can be used to track cardiovascular and cerebrovascular disease prevention and diagnosis. This can effectively reduce the occurrence of cardiovascular and cerebrovascular diseases. This study analyzes the variability in blood pressure, cerebral blood flow velocity and the interaction characteristics using linear and nonlinear approaches in stroke, hypertension and healthy groups to identify the differences in cardiovascular control in these groups. The results showed that the blood pressure and cerebral blood flow of stroke patients and hypertensive patients were significantly higher than those of healthy people (statistical differences ( p < 0.05). The cerebrovascular resistance (CVR) shows that the CVR of hypertensive patients is higher than that of healthy people and stroke patients ( p < 0.1), indicating that the cerebral vascular resistance of hypertensive patients is slightly higher. From the patient's blood flow and vascular characteristics, it can be observed that the cardiovascular system is different from those in healthy people. Baroreflex sensitivity (BRS) decreased in stroke patients ( p < 0.05). Chaotic analysis revealed that the blood pressure disturbance in hypertensive patients has a higher chaotic behavior change and the difference in initial state sensitivity. Cross-correlation (CCF) analysis shows that as the course of healthy→hypertension→stroke progresses, the maximum CCF value decreases significantly ( p < 0.05). That means that blood pressure and cerebral blood flow are gradually not well controlled by the self-regulation mechanism. In conclusion, cardiovascular control performance in hypertensive and stroke patients displays greater variation. This can be observed by the bio-signal analysis. This analysis could identify a measure for detecting and preventing the risk for hypertension and stroke in clinical practice. This is a pilot study to analyze cardiovascular control variation in healthy, hypertensive and stroke groups., 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 Yeh, Lung, Jan, Kuo and Liau.)