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Objectives: Pediatric palliative care (PPC), especially among noncancer pediatric patients, faces challenges including late referral, limited patient care, and insufficient data for Asian patients., Methods: This retrospective cohort study used the integrative hospital medical database between 2014 and 2018 to analyze the clinical characteristics, diagnoses, and end-of-life care for patients aged less than 20 who had died in our children's hospital, a tertiary referral medical center implementing PPC shared-care., Results: In our cohort of 323 children, 240 (74.3%) were noncancer patients who a younger median age at death (5 vs. 122 months, P < 0.001), lower rate of PPC involvement (16.7 vs. 66%, P < 0.001), and fewer survival days after PPC consult compared to cancer patients (3 vs. 11, P = 0.01). Patients not receiving PPC had more ventilator support (OR 9.9, P < 0.001), and less morphine use on their final day of life (OR 0.1, P < 0.001). Also, patients not receiving PPC had more cardiopulmonary resuscitation on the last day of life (OR 15.3, P < 0.001) and died in the ICU (OR 8.8, P < 0.001). There was an increasing trend of noncancer patients receiving PPC between 2014 and 2018 (P < 0.001)., Conclusions: High disparities exist between children receiving PPC in cancer versus noncancer patients. The concept of PPC is gradually becoming accepted in noncancer children and is associated with more pain-relief medication and less suffering during end-of-life care., (Copyright © 2023 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Rationale and Objectives: Diagnosis of breast cancer on MRI requires, first, the identification of suspicious lesions; second, the characterization to give a diagnostic impression. We implemented Mask Reginal-Convolutional Neural Network (R-CNN) to detect abnormal lesions, followed by ResNet50 to estimate the malignancy probability., Materials and Methods: Two datasets were used. The first set had 176 cases, 103 cancer, and 73 benign. The second set had 84 cases, 53 cancer, and 31 benign. For detection, the pre-contrast image and the subtraction images of left and right breasts were used as inputs, so the symmetry could be considered. The detected suspicious area was characterized by ResNet50, using three DCE parametric maps as inputs. The results obtained using slice-based analyses were combined to give a lesion-based diagnosis., Results: In the first dataset, 101 of 103 cancers were detected by Mask R-CNN as suspicious, and 99 of 101 were correctly classified by ResNet50 as cancer, with a sensitivity of 99/103 = 96%. 48 of 73 benign lesions and 131 normal areas were identified as suspicious. Following classification by ResNet50, only 16 benign and 16 normal areas remained as malignant. The second dataset was used for independent testing. The sensitivity was 43/53 = 81%. Of the total of 121 identified non-cancerous lesions, only 6 of 31 benign lesions and 22 normal tissues were classified as malignant., Conclusion: ResNet50 could eliminate approximately 80% of false positives detected by Mask R-CNN. Combining Mask R-CNN and ResNet50 has the potential to develop a fully-automatic computer-aided diagnostic system for breast cancer on MRI., (Copyright © 2022 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Some prior research has suggested that the brain-derived neurotrophic factor (BDNF) gene may amplify responses related to life stress (e.g., depression and anxiety) or associated with negative moods (e.g., self-harm and diminished cognitive functioning). The purpose of this study was to investigate whether stress/mood-related associations with depressive and anxiety symptoms, deliberate self-harm, and executive functioning (EF) are moderated by genotypic variations in BDNF rs10835210 (a relatively understudied BDNF polymorphism) in a nonclinical sample. As part of a larger study, European American social drinkers (N = 132; 43.9% female; M age = 26.0, SD = 7.6) were genotyped for BDNF rs10835210 and were administered self-report measures of subjective life stress, depressive and anxiety symptoms, and history of non-suicidal self-injury (NSSI) and behavioral measures of EF and deliberate self-harm. Results indicated that BDNF significantly moderated the life stress associations with depressive symptoms and NSSI, the anxious mood association with EF, and the depressed mood association with deliberate self-harm behavior. Each of these BDNF × stress/mood interactions were characterized by stress/mood associations that were stronger in individuals with the AA genotype (homozygous for the minor allele) than in individuals possessing a genotype that included the major allele (AC or CC). The main limitations of the present study were use of a cross-sectional design, modest sample size, and investigating only one BDNF polymorphism. Despite these limitations and though preliminary, current findings suggest that variations in BDNF may confer vulnerability to stress or mood, which may result in more adverse emotional, cognitive, or behavioral 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 Elsevier Ltd. All rights reserved.)

Background: Hereditary transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and fatal disease. A97S (p.Ala117Ser) is the most common transthyretin genetic mutation in Taiwan. Tafamidis is a transthyretin stabilizer, and it has been shown to improve outcomes. However, its effect on A97S ATTR-CM subtypes remains unknown., Objectives: This study aimed to investigate the efficacy of tafamidis in patients with hereditary A97S ATTR-CM after 6 months of treatment., Methods: We retrospectively analyzed ATTR-CM patients who received tafamidis (61 mg/day) treatment at National Taiwan University Hospital. Functional status, biochemistry and echocardiography were measured at baseline and after 6 months of tafamidis treatment. The outcome measure was to compare the N-terminal pro-brain natriuretic peptide (NT-proBNP) level at baseline and after 6 months of tafamidis treatment., Results: Twenty patients were enrolled in this study. Their mean age was 63.0 ± 5.8 years and 75% were men. The baseline left ventricular (LV) mass index was 200.9 ± 63.9 g/m 2 , and the baseline LV ejection fraction was 58.9 ± 13.5%. After 6 months of treatment, the log NT-proBNP level significantly improved from 2.9 ± 0.6 to 2.7 ± 0.5 (p = 0.036). Subgroup analysis showed that the LV posterior wall thickness and left atrial diameter were significantly higher in the patients with improved NT-proBNP, suggesting the benefits of tafamidis for ATTR-CM patients with severe cardiac involvement., Conclusions: The patients with hereditary A97S ATTR-CM in this study had decreased levels of NT-proBNP after 6 months of tafamidis treatment, and this reduction was especially pronounced in those with more severe cardiac involvement., Competing Interests: The authors have no conflicts of interest relevant to this article.

Objective: To quantitatively assess the pulmonary vasculature using non-contrast computed tomography (CT) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) pre- and post-treatment and correlate CT-based parameters with right heart catheterization (RHC) hemodynamic and clinical parameters., Materials and Methods: A total of 30 patients with CTEPH (mean age, 57.9 years; 53% female) who received multimodal treatment, including riociguat for ≥ 16 weeks with or without balloon pulmonary angioplasty and underwent both non-contrast CT for pulmonary vasculature analysis and RHC pre- and post-treatment were included. The radiographic analysis included subpleural perfusion parameters, including blood volume in small vessels with a cross-sectional area ≤ 5 mm² (BV5) and total blood vessel volume (TBV) in the lungs. The RHC parameters included mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac index (CI). Clinical parameters included the World Health Organization (WHO) functional class and 6-minute walking distance (6MWD)., Results: The number, area, and density of the subpleural small vessels increased after treatment by 35.7% ( P < 0.001), 13.3% ( P = 0.028), and 39.3% ( P < 0.001), respectively. The blood volume shifted from larger to smaller vessels, as indicated by an 11.3% increase in the BV5/TBV ratio ( P = 0.042). The BV5/TBV ratio was negatively correlated with PVR ( r = -0.26; P = 0.035) and positively correlated with CI ( r = 0.33; P = 0.009). The percent change across treatment in the BV5/TBV ratio correlated with the percent change in mPAP ( r = -0.56; P = 0.001), PVR ( r = -0.64; P < 0.001), and CI ( r = 0.28; P = 0.049). Furthermore, the BV5/TBV ratio was inversely associated with the WHO functional classes I-IV ( P = 0.004) and positively associated with 6MWD ( P = 0.013)., Conclusion: Non-contrast CT measures could quantitatively assess changes in the pulmonary vasculature in response to treatment and were correlated with hemodynamic and clinical parameters., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2023 The Korean Society of Radiology.)

Purpose: To build three prognostic models using radiomics analysis of the hemorrhagic lesions, clinical variables, and their combination, to predict the outcome of stroke patients with spontaneous intracerebral hemorrhage (sICH)., Materials and Methods: Eighty-three sICH patients were included. Among them, 40 patients (48.2%) had poor prognosis with modified Rankin scale (mRS) of 5 and 6 at discharge, and the prognostic model was built to differentiate mRS ≤ 4 vs. 5 + 6. The region of interest (ROI) of intraparenchymal hemorrhage (IPH) and intraventricular hemorrhage (IVH) were separately segmented. Features were extracted using PyRadiomics, and the support vector machine was applied to select features and build radiomics models based on IPH and IPH + IVH. The clinical models were built using multivariate logistic regression, and then the radiomics scores were combined with clinical variables to build the combined model., Results: When using IPH, the AUC for radiomics, clinical, and combined model was 0.78, 0.82, and 0.87, respectively. When using IPH + IVH, the AUC was increased to 0.80, 0.84, and 0.90, respectively. The combined model had a significantly improved AUC compared to the radiomics by DeLong test. A clinical prognostic model based on the ICH score of 0-1 only achieved AUC of 0.71., Conclusions: The combined model using the radiomics score derived from IPH + IVH and the clinical factors could achieve a high accuracy in prediction of sICH patients with poor outcome, which may be used to assist in making the decision about the optimal care., (© 2022. Fondazione Società Italiana di Neurologia.)

Purpose: Health care workers (HCWs), and in particular anesthesia providers, often must perform aerosol-generating medical procedures (AGMPs). However, no studies have analyzed droplet distributions on the bodies of HCWs during AGMPs. Therefore, the purpose of this study was to assess and analyze droplet distributions on the bodies of HCWs during suction of oral cavities with and without oral airways and during extubations., Design: Using a quasi-experiemental design, we assumed the HCWs perform suction and extubation on intubated patients, and we prepared an intubated mannequin mimicking a patient. This study performed the oral suction and extubation on the intubated mannequin (with or without oral airways in place) and analyzed the droplet distributions., Methods: We prepared a mannequin intubated with an 8.0 mm endotracheal tube, assuming the situation of general anesthesia. We designed the body mapping gown, and divided it into 10 areas including the head, neck, chest, abdomen, upper arms, forearms, and hands. We classified experiments into group O when suctions were performed on the mannequin with an oral airway, and into group X when the suctions were performed on the mannequin without an oral airway. An experienced board-certified anesthesiologist performed 10 oral suctions on each mannequin, and 10 extubations. We counted the droplets on the anesthesiologist's gown according to the divided areas after each procedure., Findings: The mean droplet count after suction was 6.20 ± 2.201 in group O and 13.6 ± 4.300 in group X, with a significant difference between the two groups (P < .001). The right and left hands were the most contaminated areas in group O (2.8 ± 1.033 droplets and 2.0 ± 0.943 droplets, respectively). The abdomen, right hand, left forearm, and left hand showed many droplets in group X. (1.3 ± 1.337 droplets, 3.1 ± 1.792 droplets, 3.2 ± 3.910 droplets, and 4.3 ± 2.214 droplets, respectively). The chest, abdomen, and left hand presented significantly more droplets in group X than in group O. The trunk area (chest and abdomen) was exposed to more droplets during extubations than during suctions., Conclusions: During suctions, more droplets are splattered from mannequins without oral airways than from those with oral airways. The right and left hands were the most contaminated areas in group O. Moreover, the abdomen, right hand, left forearm, and left hand presented a lot of droplets in group X. In addition, extubations contaminate wider areas (the head, neck, chest and abdomen) of an HCW than suctions., (Copyright © 2022 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

Dynamic contrast-enhanced MRI (DCE-MRI) is routinely included in the prostate MRI protocol for a long time; its role has been questioned. It provides rich spatial and temporal information. However, the contained information cannot be fully extracted in radiologists' visual evaluation. More sophisticated computer algorithms are needed to extract the higher-order information. The purpose of this study was to apply a new deep learning algorithm, the bi-directional convolutional long short-term memory (CLSTM) network, and the radiomics analysis for differential diagnosis of PCa and benign prostatic hyperplasia (BPH). To systematically investigate the optimal amount of peritumoral tissue for improving diagnosis, a total of 9 ROIs were delineated by using 3 different methods. The results showed that bi-directional CLSTM with ± 20% region growing peritumoral ROI achieved the mean AUC of 0.89, better than the mean AUC of 0.84 by using the tumor alone without any peritumoral tissue (p = 0.25, not significant). For all 9 ROIs, deep learning had higher AUC than radiomics, but only reaching the significant difference for ± 20% region growing peritumoral ROI (0.89 vs. 0.79, p = 0.04). In conclusion, the kinetic information extracted from DCE-MRI using bi-directional CLSTM may provide helpful supplementary information for diagnosis of PCa., (© 2023. International Federation for Medical and Biological Engineering.)

Despite the success of PD-1 blockade in melanoma and other cancers, effective treatment strategies to overcome resistance to cancer immunotherapy are lacking 1,2 . Here we identify the innate immune kinase TANK-binding kinase 1 (TBK1) 3 as a candidate immune-evasion gene in a pooled genetic screen 4 . Using a suite of genetic and pharmacological tools across multiple experimental model systems, we confirm a role for TBK1 as an immune-evasion gene. Targeting TBK1 enhances responses to PD-1 blockade by decreasing the cytotoxicity threshold to effector cytokines (TNF and IFNγ). TBK1 inhibition in combination with PD-1 blockade also demonstrated efficacy using patient-derived tumour models, with concordant findings in matched patient-derived organotypic tumour spheroids and matched patient-derived organoids. Tumour cells lacking TBK1 are primed to undergo RIPK- and caspase-dependent cell death in response to TNF and IFNγ in a JAK-STAT-dependent manner. Taken together, our results demonstrate that targeting TBK1 is an effective strategy to overcome resistance to cancer immunotherapy., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Mercaptopurine intolerance is an adverse effect of mercaptopurine administration in pediatric patients with acute lymphoblastic leukemia (ALL). NUDT15 variants have emerged as major determinants of mercaptopurine intolerance, especially in the Asian population. Two variants, c.55&#95;56insGAGTCG in exon 1 and c.415C > T in exon 3, were commonly detected in the same allele, named NUDT15*1/*2. Although rare, compound heterozygous mutations also occur, with the two variants on different alleles (NUDT15*3/*6), which may confer tolerance to considerably lesser mercaptopurine dosage. Sanger sequencing or pyrosequencing can determine the NUDT15 variants but not the phase. Here, we designed an allele-specific PCR (AS-PCR) with locked nucleic acid-modified primers. A cohort of 63 patients harboring heterozygous c.55&#95;56insGAGTCG and c.415C > T NUDT15 variations was selected for haplotyping using AS-PCR. Of the 63 patients, 60 harbored the NUDT15*1/*2 variant and three harbored compound heterozygous mutations, including two NUDT15*3/*6 and one NUDT15*2/*7 variants. These findings suggest that AS-PCR can determine NUDT15 diplotype and identify patients with compound heterozygous NUDT15 variants, which may enable precise genetic diagnosis of NUDT15. Nevertheless, a larger clinical trial is required to understand the clinical significance of NUDT15*3/*6 in pediatric patients with ALL because of its low incidence rate and challenges in detecting this variant., (© 2023. The Author(s).)

Purpose: To implement two Artificial Intelligence (AI) methods, radiomics and deep learning, to build diagnostic models for patients presenting with architectural distortion on Digital Breast Tomosynthesis (DBT) images., Materials and Methods: A total of 298 patients were identified from a retrospective review, and all of them had confirmed pathological diagnoses, 175 malignant and 123 benign. The BI-RADS scores of DBT were obtained from the radiology reports, classified into 2, 3, 4A, 4B, 4C, and 5. The architectural distortion areas on craniocaudal (CC) and mediolateral oblique (MLO) views were manually outlined as the region of interest (ROI) for the radiomics analysis. Features were extracted using PyRadiomics, and then the support vector machine (SVM) was applied to select important features and build the classification model. Deep learning was performed using the ResNet50 algorithm, with the binary output of malignancy and benignity. The Gradient-weighted Class Activation Mapping (Grad-CAM) method was utilized to localize the suspicious areas. The predicted malignancy probability was used to construct the ROC curves, compared by the DeLong test. The binary diagnosis was made using the threshold of ≥ 0.5 as malignant., Results: The majority of malignant lesions had BI-RADS scores of 4B, 4C, and 5 (148/175 = 84.6%). In the benign group, a substantial number of patients also had high BI-RADS ≥ 4B (56/123 = 45.5%), and the majority had BI-RADS ≥ 4A (102/123 = 82.9%). The radiomics model built using the combined CC+MLO features yielded an area under curve (AUC) of 0.82, the sensitivity of 0.78, specificity of 0.68, and accuracy of 0.74. If only features from CC were used, the AUC was 0.77, and if only features from MLO were used, the AUC was 0.72. The deep-learning model yielded an AUC of 0.61, significantly lower than all radiomics models (p<0.01), which was presumably due to the use of the entire image as input. The Grad-CAM could localize the architectural distortion areas., Conclusion: The radiomics model can achieve a satisfactory diagnostic accuracy, and the high specificity in the benign group can be used to avoid unnecessary biopsies. Deep learning can be used to localize the architectural distortion areas, which may provide an automatic method for ROI delineation to facilitate the development of a fully-automatic computer-aided diagnosis system using combined AI strategies., 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, Zhang, Zhou, Wang, Liu, Nie, Lin, He, Su, Cao and Wang.)

Background: Primary malignant mediastinal germ cell tumors (GCTs) are rare pediatric tumors that have a poorer prognosis compared to GCTs occurring elsewhere in the body. The current study aimed to assess the prognostic factors and treatment outcomes of children with primary malignant mediastinal GCT in Taiwan., Methods: The authors retrospectively reviewed children 0-18 years old who were newly diagnosed with primary malignant mediastinal GCT between January 1, 2005 and December 31, 2019 and were registered in the Taiwan Pediatric Oncology Group patient registry. The impact of presenting characteristics, including sex, age, tumor stage, histology subtype, surgical treatment, and chemotherapy regimens of the patients were analyzed., Results: This study enrolled 52 children with malignant mediastinal GCT who had a median age of 16.0 (range, 6.0-17.9) years at diagnosis. The most common histological subtypes were mixed GCTs (n = 20) and yolk sac tumors (n = 15). Advanced disease stage and choriocarcinoma histology subtype were associated inferior outcomes. Children who received surgical treatment exhibited better outcomes compared to those who did not (5-year overall survival, 78% vs. 7%, p < .001). After comparing patients who received first-line cisplatin- and carboplatin-based chemotherapy, no difference in treatment outcomes was observed. Multivariate analysis showed that surgical management was the only independent predictor for superior OS., Conclusions: Surgical treatment is recommended for mediastinal GCT. Cisplatin-based chemotherapy was not superior to carboplatin-based chemotherapy as first-line treatment and may be avoided due to toxicity concerns., (© 2022 American Cancer Society.)

Introduction/context: Healthcare workers (HCWs) play an important role in fighting against the COVID-19 pandemic. However, they have been exposed to mixed public responses more significantly during the COVID-19 pandemic, which have potentially affected their work and life., Aim: We aim to study what public responses toward HCWs existed, how and why such public responses impacted HCW's work engagement and well-being, and how Human Resource (HR) professionals navigate these impacts. These understandings are important for improving HCWs' work and life quality., Methods: We adopted a mixed approach including both quantitative and qualitative methods to investigate how the public responses impact HCWs' work engagement and well-being and how human resource management (HRM) shall intervene. Our quantitative study enables us to collect and analyze a large amount of public responses toward HCWs from the social media platform during the COVID-19 pandemic globally, and uncover the sentiments and topics of these pubic responses via big data and AI technologies. Our qualitative study allows us to understand how and why these public responses impact HCWs' work engagement and well-being via interviews and further identify how HR professionals shall navigate these impacts., Results: The sentiment analysis showed that 55.9% of the discussions toward HCWs were positive, 27.2% were neutral, and 16.9% were negative. The topic modeling analysis indicated that the commonly identified topics were related to fear (the negative responses) and gratitude (the positive responses). The interviews with 18 HCWs revealed that HCWs' work engagement and well-being were decreased by negative public responses through experiencing tension or disappointment due to social and physical ostracism, rejection, discrimination, and criticism. On the other hand, positive public responses in terms of encouragement, recognition, and tangible donations increased their work engagement and well-being. The analysis also suggested that occupational calling served as a mechanism that explained why public responses had such impacts on HCWs. The interview results also highlighted the significance of HRM in bridging positive public responses toward HCWs and revealed problems with communication from HRM during the pandemic. This research provides practical implications about how to improve HCWs work engagement and well-being during the pandemic via public and HRM efforts., 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 Shan, Wang and Su.)

Background: Previous studies have demonstrated that morphological changes in the suprascapular notch are closely associated with suprascapular nerve entrapment syndrome (SNES). Thus, we hypothesized that the suprascapular notch cross-sectional area (SSNCSA) could be a good diagnostic parameter to assess SNES., Methods: We acquired suprascapular notch data from 10 patients with SNES and 10 healthy individuals who had undergone shoulder magnetic resonance imaging (S-MRI) and had no evidence of SNES. T2-weighted coronal magnetic resonance images were acquired from the shoulder. We analyzed the SSNCSA at the shoulder on S-MRI using our image-analysis program (INFINITT PACS). The SSNCSA was measured as the suprascapular notch, which was the most affected site in coronal S-MRI images., Results: The mean SSNCSA was 64.50 ± 8.93 mm2 in the control group and 44.94 ± 10.40 mm2 in the SNES group. Patients with SNES had significantly lower SSNCSA (P < 0.01) than those in the control group. Receiver operating curve analysis showed that the best cut-off of the SSNCSA was 57.49 mm2, with 80.0% sensitivity, 80.0% specificity, and an area under the curve of 0.92 (95% CI [0.79, 1.00])., Conclusions: The SSNCSA was found to have acceptable diagnostic properties for detecting SNES. We hope that these results will help diagnose SNES objectively.

Glenohumeral joint (GHJ) space narrowing has been demonstrated to be an important morphologic parameter of glenohumeral osteoarthritis (GHO). However, the morphology of GHJ space is irregular because of degeneration of subchondral bone and articular cartilage. Thus, we devised GHJ cartilage cross-sectional area (GHJCCSA) as a new diagnostic morphological parameter to assess the irregular morphologic change of GHJ. GHJ samples were acquired from 33 patients with GHO and from 33 normal controls without evidence of GHO based on shoulder magnetic resonance imaging. T2-weighted coronal MRIs were collected at the GHJ level for all individuals. GHJCCSA and GHJ cartilage thickness (GHJCT) at the GHJ were measured on MRIs using a graphic measuring system. The GHJCCSA was measured as the whole cartilage cross-sectional area of the GHJ. The average GHJCCSA was 115.28 ± 17.36 mm2 in normal individuals and 61.77 ± 13.74 mm2 in the GHO group. The mean GHJCT was 2.06 ± 0.35 mm in normal individuals and 1.50 ± 0.28 mm in the GHO group. GHO patients had significantly lower GHJCCSA (P < .001) and GHJCT (P < .001) than normal individuals. Receiver operator characteristics curve analysis revealed that the optimal cutoff score of the GHJCCSA was 82.21 mm2, with a sensitivity of 97.0%, a specificity of 97.0%, and an area under the curve of 0.99 (95% CI: 0.97-1.00). Although GHJCCSA and GHJCT were both significantly associated with GHO, the GHJCCSA was a more sensitive measurement parameter., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

A narrowed sacroiliac joint (SIJ) space has been considered to be a major morphologic parameter of ankylosing spondylitis (AS). Previous studies revealed that the sacroiliac joint thickness (SIJT) correlated with AS in patients. However, irregular narrowing is different from thickness. Thus, we devised a method using the sacroiliac joint cross-sectional area (SIJA) as a new morphological parameter for use in evaluating AS. We hypothesized that the SIJA is a key morphologic parameter in diagnosing AS. SIJ samples were collected from 107 patients with AS, and from 85 control subjects who underwent SIJ-view X-rays that revealed no evidence of AS. We measured the SIJT and SIJA at the SIJ margin on X-rays using our picture archiving and communications system. The SIJT was measured at the narrowest point between the sacrum and the ilium. The SIJA was measured as the entire cross-sectional joint space area of the SIJ in the X-ray images. The average SIJT was 3.09 ± 0.61 mm in the control group, and 1.59 ± 0.52 mm in the AS group. The average SIJA was 166.74 ± 39.98 mm2 in the control group, and 68.65 ± 24.11 mm2 in the AS group. AS patients had significantly lower SIJT (P < .001) and SIJA (P < .001) than the control subjects. Receiver operating characteristics curve analysis showed that the best cutoff point for the SIJT was 2.33 mm, with 92.5% sensitivity, 94.1% specificity, and an area under the curve of 0.97 (95% confidence interval: 0.95-0.99). The optimal cutoff point for the SIJA was 106.19 mm2, with 93.5% sensitivity, 95.3% specificity, and an area under the curve of 0.98 (95% confidence interval: 0.97-1.00). Although the SIJT and SIJA were both significantly associated with AS, the SIJA parameter was a more sensitive measurement. We concluded that the SIJA is an easy-to-use, fast, cheap, and useful new morphological parameter for predicting AS., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Among patients undergoing head computed tomography (CT) scans within 3 h of spontaneous intracerebral hemorrhage (sICH), 28% to 38% have hematoma expansion (HE) on follow-up CT. This study aimed to predict HE using radiomics analysis and investigate the impact of intraventricular hemorrhage (IVH) compared with the conventional approach based on intraparenchymal hemorrhage (IPH) alone. Methods: This retrospective study enrolled 127 patients with baseline and follow-up non-contrast CT (NCCT) within 4~72 h of sICH. IPH and IVH were outlined separately for performing radiomics analysis. HE was defined as an absolute hematoma growth > 6 mL or percentage growth > 33% of either IPH (HEP) or a combination of IPH and IVH (HEP+V) at follow-up. Radiomic features were extracted using PyRadiomics, and then the support vector machine (SVM) was used to build the classification model. For each case, a radiomics score was generated to indicate the probability of HE. Results: There were 57 (44.9%) HEP and 70 (55.1%) non-HEP based on IPH alone, and 58 (45.7%) HEP+V and 69 (54.3%) non-HEP+V based on IPH + IVH. The majority (>94%) of HE patients had poor early outcomes (death or modified Rankin Scale > 3 at discharge). The radiomics model built using baseline IPH to predict HEP (RMP) showed 76.4% accuracy and 0.73 area under the ROC curve (AUC). The other model using IPH + IVH to predict HEP+V (RMP+V) had higher accuracy (81.9%) with AUC = 0.80, and this model could predict poor outcomes. The sensitivity/specificity of RMP and RMP+V for HE prediction were 71.9%/80.0% and 79.3%/84.1%, respectively. Conclusion: The proposed radiomics approach with additional IVH information can improve the accuracy in prediction of HE, which is associated with poor clinical outcomes. A reliable radiomics model may provide a robust tool to help manage ICH patients and to enroll high-risk ICH cases into anti-expansion or neuroprotection drug trials.

Carpal tunnel syndrome (CTS) is correlated with increased intracarpal canal pressure (ICP). The effect of palmaris longus tendon (PLT) loading on ICP is documented in previous researches. PLT loading induces the greatest absolute increase in ICP. Therefore, to analyze the connection between the PLT and CTS, we newly made the measurement of the PLT cross-sectional area (PLTCSA). We assumed that PLTCSA is a reliable diagnostic parameter in the CTS. PLTCSA measurement data were acquired from 21 patients with CTS, and from 21 normal subjects who underwent wrist magnetic resonance imaging (W-MRI). We measured the PLTCSA at the level of pisiform on W-MRI. The PLTCSA was measured on the outlining of PLT. The two different cutoff values in the analysis were determined using receiver operating characteristic (ROC) analysis. The mean PLTCSA was 2.34 ± 0.82 mm2 in the normal group and 3.97 ± 1.18 mm2 in the CTS group. ROC curve analysis concluded that the best cutoff point for the PLTCSA was 2.81 mm2, with 76.2% sensitivity, 71.4% specificity, and area under the curve of 0.88 (95% CI, 0.78-0.98). PLTCSA is a sensitive, new, objective morphological parameter for evaluating CTS., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

In recent years, with the vigorous development and gradual deployment of new energy vehicles, more attention has been paid to the research on lithium-ion batteries (LIBs). Compared with the booming LIBs, lithium primary batteries (LPBs) own superiority in specific energy and self-discharge rate and are usually applied in special fields such as medical implantation, aerospace, and military. Widespread application in special fields also means more stringent requirements for LPBs in terms of energy density, working temperature range and shelf life. Therefore, how to obtain LPBs with high energy density, wide operational temperature range and long storage life is of great importance in future development. In view of the above, this paper reviews the latest research on LPBs in cathode, anode and electrolyte over the years, and puts forward relevant insights for LPBs, along with the intention to explore avenues for the design of LPBs components in the coming decades and promote further development in this field., (© 2022 The Chemical Society of Japan & Wiley-VCH GmbH.)

Objectives: To evaluate the diagnostic performance of Kaiser score (KS) adjusted with the apparent diffusion coefficient (ADC) (KS+) and machine learning (ML) modeling., Methods: A dataset of 402 malignant and 257 benign lesions was identified. Two radiologists assigned the KS. If a lesion with KS > 4 had ADC > 1.4 × 10 -3 mm 2 /s, the KS was reduced by 4 to become KS+. In order to consider the full spectrum of ADC as a continuous variable, the KS and ADC values were used to train diagnostic models using 5 ML algorithms. The performance was evaluated using the ROC analysis, compared by the DeLong test. The sensitivity, specificity, and accuracy achieved using the threshold of KS > 4, KS+ > 4, and ADC ≤ 1.4 × 10 -3 mm 2 /s were obtained and compared by the McNemar test., Results: The ROC curves of KS, KS+, and all ML models had comparable AUC in the range of 0.883-0.921, significantly higher than that of ADC (0.837, p < 0.0001). The KS had sensitivity = 97.3% and specificity = 59.1%; and the KS+ had sensitivity = 95.5% with significantly improved specificity to 68.5% (p < 0.0001). However, when setting at the same sensitivity of 97.3%, KS+ could not improve specificity. In ML analysis, the logistic regression model had the best performance. At sensitivity = 97.3% and specificity = 65.3%, i.e., compared to KS, 16 false-positives may be avoided without affecting true cancer diagnosis (p = 0.0015)., Conclusion: Using dichotomized ADC to modify KS to KS+ can improve specificity, but at the price of lowered sensitivity. Machine learning algorithms may be applied to consider the ADC as a continuous variable to build more accurate diagnostic models., Key Points: • When using ADC to modify the Kaiser score to KS+, the diagnostic specificity according to the results of two independent readers was improved by 9.4-9.7%, at the price of slightly degraded sensitivity by 1.5-1.8%, and overall had improved accuracy by 2.6-2.9%. • When the KS and the continuous ADC values were combined to train models by machine learning algorithms, the diagnostic specificity achieved by the logistic regression model could be significantly improved from 59.1 to 65.3% (p = 0.0015), while maintaining at the high sensitivity of KS = 97.3%, and thus, the results demonstrated the potential of ML modeling to further evaluate the contribution of ADC. • When setting the sensitivity at the same levels, the modified KS+ and the original KS have comparable specificity; therefore, KS+ with consideration of ADC may not offer much practical help, and the original KS without ADC remains as an excellent robust diagnostic method., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Objective: Late-onset hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is often associated with heart involvement. Recent advances in cardiac imaging allow the detection of cardiac amyloidosis. This study aimed to explore cardiomyopathy by cardiac imaging and its clinical correlates with polyneuropathy in late-onset ATTRv-PN., Methods: Polyneuropathy was assessed by intraepidermal nerve fiber (IENF) density, nerve conduction study (NCS), autonomic function tests, quantitative sensory testing, and clinical questionnaires. Cardiomyopathy was evaluated by echocardiography, 99m Tc-pyrophosphate (PYP) single-photon emission computed tomography (SPECT) imaging, cardiac magnetic resonance imaging (CMR), and serum Pro-B-type natriuretic peptide. Healthy controls and patients with Brugada syndrome were enrolled for comparison of CMR., Results: Fifty late-onset ATTRv-PN patients (38 men, 46 with p. A117S mutation), aged 63.7 ± 5.5 years, of polyneuropathy disability stage 1-4 were enrolled. All patients presented polyneuropathy in NCS, and 74.5% of patients had reduced IENF density in distal legs. All patients showed significant radiotracer uptake in the heart on 99m Tc-PYP SPECT imaging, and 87.8% of patients had abnormally increased left ventricular (LV) septum thickness on echocardiography. CMR showed longer myocardial native T1, larger extracellular volume, greater LV mass index, and higher LV mass to end-diastolic volume ratio in ATTRv-PN patients than healthy controls and patients with Brugada syndrome. These CMR parameters were associated with skin denervation, absent sympathetic skin responses, elevated thermal thresholds, worsened NCS profiles, and functional deficits of polyneuropathy., Interpretation: Late-onset ATTRv-PN coexisted with cardiomyopathy regardless of the clinical severity of polyneuropathy. The cardiac amyloid burden revealed by CMR was correlated with pathophysiology and clinical disability of nerve degeneration., (© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: The use of biologic agents has become the cornerstone of therapy for moderate to severe IBD. Few studies have investigated the efficacy of vedolizumab (VDZ) induction for ulcerative colitis (UC) in Asian patients in a real practice setting., Aims: To evaluate the efficacy and safety of VDZ induction therapy for moderate to severe UC in Taiwan., Methods: This was a retrospective and observational study. Selected moderate to severe UC patients received VZD 300 mg i.v. at weeks 0, 2, and 6 as induction therapy. Mayo scores were calculated to evaluate the efficacy., Results: A total of 37 patients with UC who received VDZ and completed the induction therapy at Chang Gung Memorial Hospital (2017/10-2021/5) were included. The mean age was 46.5 year-old and the male to female ratio was 1:1 (19/18). 81.8% of the patients were biologic-naive. At weeks 8-10, a clinical response, clinical remission and endoscopic remission with VDZ induction therapy were achieved in 56.8% (21/37), 32.4% (12/37) and 58.3% (7/12) of the patients, respectively. 54.1% (20/37) were able to taper off at week 8. Overall, only 10.8% (4/37) of the patients were primary non-responders during induction therapy. No obvious VDZ-related severe adverse events were noted. Overall, 58.9% (11/19) of the patients relapsed after stopping VDZ, and the relapse rate after VDZ discontinuation was 42.1% (8/19) within first 6 months and 52.6% (10/19) within the first year., Conclusion: In real-world experience, induction therapy with VDZ showed promising clinical benefits and safety profile for patients with UC., Competing Interests: Declaration of competing interest There was no any financial interests or connections, direct or indirect, or other situations that might raise the question of bias in the work reported or the conclusions, implications, or opinions stated – including pertinent commercial or other sources of funding for the individual authors or for the associated departments or organizations, personal relationships, or direct academic competition., (Copyright © 2021 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Conflicts of interest None disclosed.

Purpose: To evaluate the volumetric change of COVID-19 lesions in the lung of patients receiving serial CT imaging for monitoring the evolution of the disease and the response to treatment., Materials and Methods: A total of 48 patients, 28 males and 20 females, who were confirmed to have COVID-19 infection and received chest CT examination, were identified. The age range was 21-93 years old, with a mean of 54 ± 18 years. Of them, 33 patients received the first follow-up (F/U) scan, 29 patients received the second F/U scan, and 11 patients received the third F/U scan. The lesion region of interest (ROI) was manually outlined. A two-step registration method, first using the Affine alignment, followed by the non-rigid Demons algorithm, was developed to match the lung areas on the baseline and F/U images. The baseline lesion ROI was mapped to the F/U images using the obtained geometric transformation matrix, and the radiologist outlined the lesion ROI on F/U CT again., Results: The median (interquartile range) lesion volume (cm 3 ) was 30.9 (83.1) at baseline CT exam, 18.3 (43.9) at first F/U, 7.6 (18.9) at second F/U, and 0.6 (19.1) at third F/U, which showed a significant trend of decrease with time. The two-step registration could significantly decrease the mean squared error (MSE) between baseline and F/U images with p < 0.001. The method could match the lung areas and the large vessels inside the lung. When using the mapped baseline ROIs as references, the second-look ROI drawing showed a significantly increased volume, p < 0.05, presumably due to the consideration of all the infected areas at baseline., Conclusion: The results suggest that the registration method can be applied to assist in the evaluation of longitudinal changes of COVID-19 lesions on chest CT., 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, Zhang, Cao, Zhou, Lin, Chen, Nie, Fu, Su and Wang.)

Background: Acute ST-elevation myocardial infarction (STEMI) elicits a robust cardiomyocyte death and inflammatory responses despite timely revascularization., Objectives: This phase 1, open-label, single-arm, first-in-human study aimed to assess the safety and efficacy of combined intracoronary (IC) and intravenous (IV) transplantation of umbilical cord-derived mesenchymal stem cells (UMSC01) for heart repair in STEMI patients with impaired left ventricular ejection fraction (LVEF 30-49%) following successful reperfusion by percutaneous coronary intervention., Methods: Consenting patients received the first dose of UMSC01 through IC injection 4-5 days after STEMI followed by the second dose of UMSC01 via IV infusion 2 days later. The primary endpoint was occurrence of any treatment-related adverse events and the secondary endpoint was changes of serum biomarkers and heart function by cardiac magnetic resonance imaging during a 12-month follow-up period., Results: Eight patients gave informed consents, of whom six completed the study. None of the subjects experienced treatment-related serious adverse events or major adverse cardiovascular events during IC or IV infusion of UMSC01 and during the follow-up period. The NT-proBNP level decreased (1362 ± 1801 vs. 109 ± 115 pg/mL, p = 0.0313), the LVEF increased (52.67 ± 12.75% vs. 62.47 ± 17.35%, p = 0.0246), and the wall motion score decreased (26.33 ± 5.57 vs. 22.33 ± 5.85, p = 0.0180) at the 12-month follow-up compared to the baseline values. The serial changes of LVEF were 0.67 ± 3.98, 8.09 ± 6.18, 9.04 ± 10.91, and 9.80 ± 7.56 at 1, 3, 6, and 12 months, respectively as compared to the baseline., Conclusion: This pilot study shows that combined IC and IV transplantation of UMSC01 in STEMI patients with impaired LVEF appears to be safe, feasible, and potentially beneficial in improving heart function. Further phase 2 studies are required to explore the effectiveness of dual-route transplantation of UMSC01 in STEMI patients., Competing Interests: C-HT was the founder of Ever Supreme Bio Technology. W-CS, D-YC, K-CC, and L-BJ were stockholders of the Ever Supreme Bio Technology. W-CS was employed by Ever Supreme Bio Technology and China Medical University Hospital. C-TH, C-KT, L-TC, and C-LC were employed by Ever Supreme Bio Technology. The remaining 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 Hsiao, Lin, Shyu, Ho, Lu, Chang, Wang, Chen, Lu, Wu, Li, Lin, Tseng, Su, Hsu, Tsai, Chiu, Chen, Lin, Hu, Cho, Tsai, Chang and Jeng.)

Purpose: To improve the performance of less experienced clinicians in the diagnosis of benign and malignant spinal fracture on MRI, we applied the ResNet50 algorithm to develop a decision support system., Methods: A total of 190 patients, 50 with malignant and 140 with benign fractures, were studied. The visual diagnosis was made by one senior MSK radiologist, one fourth-year resident, and one first-year resident. The MSK radiologist also gave the binary score for 15 qualitative imaging features. Deep learning was implemented using ResNet50, using one abnormal spinal segment selected from each patient as input. The T1W and T2W images of the lesion slice and its two neighboring slices were considered. The diagnostic performance was evaluated using tenfold cross-validation., Results: The overall reading accuracy was 98, 96, and 66% for the senior MSK radiologist, fourth-year resident, and first-year resident, respectively. Of the 15 imaging features, 10 showed a significant difference between benign and malignant groups with p <  = 0.001. The accuracy achieved by using the ResNet50 deep learning model for the identified abnormal vertebral segment was 92%. Compared to the first-year resident's reading, the model improved the sensitivity from 78 to 94% (p < 0.001) and the specificity from 61 to 91% (p < 0.001)., Conclusion: Our deep learning-based model may provide information to assist less experienced clinicians in the diagnosis of spinal fractures on MRI. Other findings away from the vertebral body need to be considered to improve the model, and further investigation is required to generalize our findings to real-world settings., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

(1) Background: Radiomics analysis of spontaneous intracerebral hemorrhages on computed tomography (CT) images has been proven effective in predicting hematoma expansion and poor neurologic outcome. In contrast, there is limited evidence on its predictive abilities for traumatic intraparenchymal hemorrhage (IPH). (2) Methods: A retrospective analysis of 107 traumatic IPH patients was conducted. Among them, 45 patients (42.1%) showed hemorrhagic progression of contusion (HPC) and 51 patients (47.7%) had poor neurological outcome. The IPH on the initial CT was manually segmented for radiomics analysis. After feature extraction, selection and repeatability evaluation, several machine learning algorithms were used to derive radiomics scores (R-scores) for the prediction of HPC and poor neurologic outcome. (3) Results: The AUCs for R-scores alone to predict HPC and poor neurologic outcome were 0.76 and 0.81, respectively. Clinical parameters were used to build comparison models. For HPC prediction, variables including age, multiple IPH, subdural hemorrhage, Injury Severity Score (ISS), international normalized ratio (INR) and IPH volume taken together yielded an AUC of 0.74, which was significantly ( p = 0.022) increased to 0.83 after incorporation of the R-score in a combined model. For poor neurologic outcome prediction, clinical variables of age, Glasgow Coma Scale, ISS, INR and IPH volume showed high predictability with an AUC of 0.92, and further incorporation of the R-score did not improve the AUC. (4) Conclusion: The results suggest that radiomics analysis of IPH lesions on initial CT images has the potential to predict HPC and poor neurologic outcome in traumatic IPH patients. The clinical and R-score combined model further improves the performance of HPC prediction.

Purpose: This project aimed to assess the significance of vascular endothelial growth factor (VEGF) and p53 for predicting progression-free survival (PFS) in patients with spinal giant cell tumor of bone (GCTB) and to construct models for predicting these two biomarkers based on clinical and computer tomography (CT) radiomics to identify high-risk patients for improving treatment., Material and Methods: A retrospective study was performed from April 2009 to January 2019. A total of 80 patients with spinal GCTB who underwent surgery in our institution were identified. VEGF and p53 expression and clinical and general imaging information were collected. Multivariate Cox regression models were used to verify the prognostic factors. The radiomics features were extracted from the regions of interest (ROIs) in preoperative CT, and then important features were selected by the SVM to build classification models, evaluated by 10-fold crossvalidation. The clinical variables were processed using the same method to build a conventional model for comparison., Results: The immunohistochemistry of 80 patients was obtained: 49 with high-VEGF and 31 with low-VEGF, 68 with wild-type p53, and 12 with mutant p53. p53 and VEGF were independent prognostic factors affecting PFS found in multivariate Cox regression analysis. For VEGF, the Spinal Instability Neoplastic Score (SINS) was greater in the high than low groups, p  < 0.001. For p53, SINS ( p  = 0.030) and Enneking stage ( p  = 0.017) were higher in mutant than wild-type groups. The VEGF radiomics model built using 3 features achieved an area under the curve (AUC) of 0.88, and the p53 radiomics model built using 4 features had an AUC of 0.79. The conventional model built using SINS, and the Enneking stage had a slightly lower AUC of 0.81 for VEGF and 0.72 for p53., Conclusion: p53 and VEGF are associated with prognosis in patients with spinal GCTB, and the radiomics analysis based on preoperative CT provides a feasible method for the evaluation of these two biomarkers, which may aid in choosing better management strategies., 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 Wang, Zhang, Zhang, Xing, Chen, Nie, Yuan, Su and Lang.)

Background: Caustic ingestion has gained increasing attention worldwide. However, the insight into whether to use esophagogastroduodenoscopy (EGD) or computed tomography (CT) for first-line investigation remains controversial. This study aimed to evaluate a diagnostic and management algorithm that combines EGD and CT for rapid triage., Methods: We established an algorithm for our hospital in 2013, aiming to maximize the benefits and minimize the limitations of EGD and CT. Then, we retrospectively analyzed the 163 enrolled patients treated between 2014 and 2019 and categorized them into 4 groups: A = 3 (1.8%): with perforation signs and directly confirmed by CT, B = 10 (6.1%): clinically suspected perforation but not initially proven by CT, C = 91 (55.8%): initial perforation less favored but with EGD grade ≥ 2b or GI/systemic complications, and D = 59 (36.2%): clinically stable with EGD grade ≤ 2a, according to initial signs/symptoms and EGD/CT grading. The morbidity and mortality of each group were analyzed. The predictive values of EGD and CT were examined by logistic regression analyses and receiver operating characteristic (ROC) curves., Results: The outcomes of such algorithm were reported. CT was imperative for patients with toxic signs and suspected perforation. For non-emergent operations, additional EGD was safe and helpful in identifying surgical necessity. For patients with an initially low perforation risk, EGD alone sufficiently determined admission necessity. Among inpatients, EGD provided excellent discrimination for predicting the risk for signs/symptoms' deterioration. Routine additional CT was only beneficial for those with deteriorating signs/symptoms., Conclusions: According to the analyses, initial signs/symptoms help to choose EGD or CT as the first-line investigative tool in caustic patients. CT is necessary for seriously injured patients, but it cannot replace EGD for moderate/mild injuries. The severity stratification and patient categorization help to simplify complex scenarios, accelerate decision-making, and prevent unnecessary intervention/therapy. External validation in a larger sample size is further indicated for this algorithm.

Background: Telomere length (TL) serves as a marker of cellular senescence and appears to plateau between the age of 4 y and young adulthood, after which the gut microbiota are supposed to be established. However, scarce data are available regarding the correlation between gut microbiota composition and TL in the pediatric population., Objectives: We aimed to investigate whether the gut microbiota and the concentrations of SCFAs in feces are associated with leukocyte TL in children., Methods: In total, 401 children aged 6-9 y from Guangzhou were enrolled in this cross-sectional study. qPCR was used to determine relative TL in peripheral blood leukocytes. The gut microbiota was characterized by 16S ribosomal RNA amplicon sequencing and the fecal concentrations of total SCFAs and SCFA subtypes were determined using HPLC. The multivariate methods with an unbiased variable selection (MUVR) algorithm and partial least square models were used to select predictable operational taxonomic units (OTUs). Further correlation analyses were performed based on multiple linear regression models with adjustment for covariates and false discovery rate., Results: With the use of MUVR, 35 relevant and minimal optimal OTUs were finally selected. Multiple linear regression analysis showed that the abundance of several OTUs, including OTU334 (belonging to the genus Family XIII AD3011 group), OTU726 (belonging to the species Lachnoclostridium phocaeense), OTU1441 (belonging to the genus Ruminococcus torques group), OTU2553 (belonging to the genus Lachnospiraceae UCG-010), and OTU3375 (belonging to the family Lachnospiraceae), was negatively associated with leukocyte TL (β: -0.187 to -0.142; false discovery rate (FDR)-corrected P value (PFDR) = 0.009-0.035]. However, neither SCFA subtype nor total SCFA content in feces exhibited significant associations with TL (β: -0.032 to 0.048; PFDR = 0.915-0.969)., Conclusions: The gut microbiota, but not fecal SCFA concentration, was significantly associated with TL in this pediatric population., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

The aim of this study was to apply registration and three-dimensional (3D) display tools to assess the evolution of intraparenchymal hemorrhage (IPH) in patients with traumatic brain injury (TBI). We identified 109 TBI patients who had two computed tomography (CT) scans within 4 days retrospectively. The IPH was manually outlined. The registration was performed in 39 lesions from 29 patients with lesion volume < 1.5 cm on both baseline and follow-up CT. The center of mass (COM) of each lesion was calculated, and the distance between baseline and follow-up CT was used to evaluate the registration effect. The mean distances of COM before registration in the XYZ, XY, and YZ coordinates were 20.5 ± 10.2 mm, 17.8 ± 9.4 mm, and 15.9 ± 9.4 mm, respectively, which decreased significantly (p < 0.001) to 7.9 ± 4.9, 7.8 ± 5.0, and 6.1 ± 4.1 mm after registration. A 3D short video displaying the rendering view of all lesions in 34 randomly selected patients from baseline and follow-up scans were presented side-by-side for comparison. The detection rate of new IPH lesions increased in 3D videos (100%) as compared with axial CT slices (78.6-92.9%). A very high interrater agreement (k = 0.856) on perceiving IPH lesion progression upon viewing 3D video was noted, and the absolute volume increase was significantly higher (p < 0.001) for progressive lesions (median 7.36 cc) over non-progressive lesions (median 0.01 cc). Compared to patients with spontaneous hemorrhagic stroke, evaluation of multiple small traumatic hemorrhages in TBI is more challenging. The applied image analysis and visualization methods may provide helpful tools for comparing changes between serial CT scans., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Magnetic resonance imaging (MRI) plays an important role in the modern radiation therapy (RT) workflow. In comparison with computed tomography (CT) imaging, which is the dominant imaging modality in RT, MRI possesses excellent soft-tissue contrast for radiographic evaluation. Based on quantitative models, MRI can be used to assess tissue functional and physiological information. With the developments of scanner design, acquisition strategy, advanced data analysis, and modeling, multiparametric MRI (mpMRI), a combination of morphologic and functional imaging modalities, has been increasingly adopted for disease detection, localization, and characterization. Integration of mpMRI techniques into RT enriches the opportunities to individualize RT. In particular, RT response assessment using mpMRI allows for accurate characterization of both tissue anatomical and biochemical changes to support decision-making in monotherapy of radiation treatment and/or systematic cancer management. In recent years, accumulating evidence have, indeed, demonstrated the potentials of mpMRI in RT response assessment regarding patient stratification, trial benchmarking, early treatment intervention, and outcome modeling. Clinical application of mpMRI for treatment response assessment in routine radiation oncology workflow, however, is more complex than implementing an additional imaging protocol; mpMRI requires additional focus on optimal study design, practice standardization, and unified statistical reporting strategy to realize its full potential in the context of RT. In this article, the mpMRI theories, including image mechanism, protocol design, and data analysis, will be reviewed with a focus on the radiation oncology field. Representative works will be discussed to demonstrate how mpMRI can be used for RT response assessment. Additionally, issues and limits of current works, as well as challenges and potential future research directions, will also be discussed., (© 2021 American Association of Physicists in Medicine.)

Cytomegalovirus (CMV) esophagitis is the second most common CMV disease of the gastrointestinal tract. This study aims to comprehensively analyze risk factors, clinical characteristics, endoscopic features, outcomes, and prognostic factors of CMV esophagitis. We retrospectively collected data of patients who underwent esophageal CMV immunohistochemistry (IHC) staining between January 2003 and April 2021 from the pathology database at the Chang Gung Memorial Hospital. Patients were divided into the CMV and non-CMV groups according to the IHC staining results. We enrolled 148 patients (44 CMV and 104 non-CMV patients). The risk factors for CMV esophagitis were male sex, immunocompromised status, and critical illness. The major clinical presentations of CMV esophagitis included epigastric pain (40.9%), fever (36.4%), odynophagia (31.8%), dysphagia (29.5%), and gastrointestinal bleeding (29.5%). Multiple diffuse variable esophageal ulcers were the most common endoscopic feature. The CMV group had a significantly higher in-hospital mortality rate (18.2% vs. 0%; p < 0.001), higher overall mortality rate (52.3% vs. 14.4%; p < 0.001), and longer admission duration (median, 24 days (interquartile range (IQR), 11−47 days) vs. 14 days (IQR, 7−24 days); p = 0.015) than the non-CMV group. Acute kidney injury (odds ratio (OR), 174.15; 95% confidence interval (CI), 1.27−23,836.21; p = 0.040) and intensive care unit admission (OR, 26.53; 95% CI 1.06−665.08; p = 0.046) were predictors of in-hospital mortality. In conclusion, the mortality rate of patients with CMV esophagitis was high. Physicians should be aware of the clinical and endoscopic characteristics of CMV esophagitis in high-risk patients for early diagnosis and treatment.

Background: The likelihood of advanced or synchronous neoplasms is significantly higher in fecal immunochemical test (FIT)-positive individuals than in the general population. The magnitude of the colonoscopy-related complication rate in FIT-positive individuals remains unknown. This study aimed to elucidate the colonoscopy-related complication rate after a positive FIT result and compare it with the rate when colonoscopy was performed for other purposes., Methods: Information regarding colonoscopy-related severe complications after a positive FIT result (FIT-colonoscopy) and ordinary colonoscopy during 2010-2014 was collected from the Taiwanese Colorectal Cancer Screening Program Database and National Health Insurance Research Database. Severe complications included significant bleeding, perforation, and cardiopulmonary events ≤ 14 days after colonoscopy. The number of events per 1000 procedures was used to quantify complication rates. Multivariate analysis was conducted to assess the association of various factors with severe complications associated with FIT-colonoscopy compared with ordinary colonoscopy., Results: 319 114 FIT-colonoscopies (214 955 patients) were identified, 51 242 (16.1 %) of which included biopsy and 94 172 (29.5 %) included polypectomy. Overall, 2125 significant bleedings (6.7 ‰) and 277 perforations (0.9 ‰) occurred ≤ 14 days after FIT-colonoscopy. Polypectomy, antiplatelet use, and anticoagulant use were associated with higher risk of complications (adjusted odds ratio [aOR] 4.41, 95 % confidence interval [CI] 4.05-4.81); aOR 1.35, 95 %CI 1.12-1.53; aOR 1.88, 95 %CI 0.61-5.84, respectively). Compared with ordinary colonoscopy, FIT-colonoscopy involved significantly higher risk of significant bleeding (aOR 3.10, 95 %CI 2.90-3.32)., Conclusions: FIT-colonoscopy was associated with a more than two-fold risk of significant bleeding, especially when polypectomy was performed., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Cytomegalovirus (CMV) infection of the gastrointestinal (GI) tract can be fatal. However, very few studies have provided comprehensive analyses and specified the differences in symptoms observed in different parts of the GI tract. This study aimed to comprehensively analyze clinical manifestations and management of GI CMV disease. This retrospective cohort study enrolled the patients who had CMV diseases of the GI tract proved by CMV immunohistochemistry stain from the pathology database in a 4000-bed tertiary medical center between January 2000 and May 2021. The patient characteristics, clinical manifestations, endoscopic features, treatments, outcomes, and prognostic factors were analyzed. A total of 356 patients were enrolled, including 46 infected in the esophagus, 76 in the stomach, 30 in the small intestine, and 204 in the colon. In total, 49.4% patients were immunocompromised. The overall in-hospital mortality rate was 20.8%: CMV enteritis had the highest rate (23.3%). Sixty percent of patients received antiviral treatment and 16% were administered both intravenous and oral anti-viral drugs (Combo therapy, minimal and mean treatment duration were 14 and 39.9 ± 25 days). Prognostic factors of in-hospital mortality included age, immune status, albumin level, platelet count, GI bleeding, time-to-diagnosis, and Combo therapy. In the survival analysis, immunocompetent patients receiving Combo therapy had the best survival curve, and immunocompromised patients receiving non-Combo therapy had the worst survival curve. Combo therapy ≥14 days resulted in a better outcome for both immunocompromised and immunocompetent patients. In conclusion, CMV GI diseases affect both immunocompromised and immunocompetent hosts, and a complete treatment course should be considered for patients with poor prognostic factors.

In this study, a liquid chromatography-tandem multi-stage mass spectrometry (LC/MS n ) method was established to characterize the metabolites of TRG in monkeys and dogs. A total of seven metabolites of TRG besides the prototype were found, which were identified as TR (M1), TRN (M2), trans -resveratrol-4'- O -glucuronide (M2'), trans -resveratrol-3- O -glucoside-4'- O -glucuronide (M3), trans -resveratrol-3- O -glucoside-5- O -glucuronide (M3'), trans -resveratrol-3-sulfate (M4) and trans -resveratrol-4'-sulfate (M4'). Additionally, the metabolic pathways of TRG in monkeys and dogs were proposed. There were also species differences of metabolism of TRG between monkeys and dogs.

Objective: Sepsis is the leading cause of in-hospital mortality in the United States (US). Quality improvement initiatives for improving sepsis care depend on accurate estimates of sepsis mortality. While hospital 30-day risk-standardized mortality rates have been published for patients hospitalized with acute myocardial infarction, heart failure, and pneumonia, risk-standardized mortality rates for sepsis have not been well characterized. We aimed to construct a sepsis risk-standardized mortality rate map for the United States, to illustrate disparities in sepsis care across the country., Methods: This cross-sectional study included adults from the US Nationwide Inpatient Sample who were hospitalized with sepsis between 1 January 2010 and 30 December 2011. Hospital-level risk-standardized mortality rates were calculated using hierarchical logistic modelling, and were risk-adjusted with predicted mortality derived from (1) the Sepsis Risk Prediction Score, a logistic regression model, and (2) gradient-boosted decision trees, a supervised machine learning (ML) algorithm., Results: Among 1,739,033 adults hospitalized with sepsis, 50% were female, and the median age was 71 years (interquartile range: 58-81). The national median risk-standardized mortality rate for sepsis was 18.4% (interquartile range: 17.0, 21.0) by the boosted tree model, which had better discrimination than the Sepsis Risk Prediction Score model (C-statistic 0.87 and 0.78, respectively). The highest risk-standardized mortality rates were found in Wyoming, North Dakota, and Mississippi, while the lowest were found in Arizona, Colorado, and Michigan., Conclusions: Wide variation exists in sepsis risk-standardized mortality rates across states, representing opportunities for improvement in sepsis care. This represents the first map of state-level variation of risk-standardized mortality rates in sepsis., (© The Author(s) 2022.)

Rationale and Objectives: Computer-aided methods have been widely applied to diagnose lesions on breast magnetic resonance imaging (MRI). The first step was to identify abnormal areas. A deep learning Mask Regional Convolutional Neural Network (R-CNN) was implemented to search the entire set of images and detect suspicious lesions., Materials and Methods: Two DCE-MRI datasets were used, 241 patients acquired using non-fat-sat sequence for training, and 98 patients acquired using fat-sat sequence for testing. All patients have confirmed unilateral mass cancers. The tumor was segmented using fuzzy c-means clustering algorithm to serve as the ground truth. Mask R-CNN was implemented with ResNet-101 as the backbone. The neural network output the bounding boxes and the segmented tumor for evaluation using the Dice Similarity Coefficient (DSC). The detection performance, and the trade-off between sensitivity and specificity, was analyzed using free response receiver operating characteristic., Results: When the precontrast and subtraction image of both breasts were used as input, the false positive from the heart and normal parenchymal enhancements could be minimized. The training set had 1469 positive slices (containing lesion) and 9135 negative slices. In 10-fold cross-validation, the mean accuracy = 0.86 and DSC = 0.82. The testing dataset had 1568 positive and 7264 negative slices, with accuracy = 0.75 and DSC = 0.79. When the obtained per-slice results were combined, 240 of 241 (99.5%) lesions in the training and 98 of 98 (100%) lesions in the testing datasets were identified., Conclusion: Deep learning using Mask R-CNN provided a feasible method to search breast MRI, localize, and segment lesions. This may be integrated with other artificial intelligence algorithms to develop a fully automatic breast MRI diagnostic system., (Copyright © 2020 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Aim: We aimed to compare the outcomes of different therapeutic modalities in rectal carcinoid tumors., Method: We retrospectively collected 145 patients with rectal carcinoid tumors which were pathologically diagnosed from 2005/01/01 to 2016/12/31. We compared tumor size, complete resection rate and recurrent rate between different therapeutic modalities. Then, prospectively compared the treatment outcomes of 28 patients treated with ligation assisted endoscopic mucosal resection (LEMR) and 25 patients treated with endoscopic mucosal resection with cap (EMRC)., Result: The mean size of tumors was 6.5 mm (1-25 mm), and the mean follow-up duration was 26 months (6-118 months). The therapeutic modalities included ligation-assisted endoscopic mucosal resection (LEMR) (25 tumors, 17%), endoscopic mucosal resection (EMR) (31 tumors, 21%), snare polypectomy (30 tumors, 21%), biopsy forceps removal (46 tumors, 32%) and surgical resection (13 tumors, 11%), including 6 tumors treated with transanal endoscopic microsurgery (TEM) method. In view of pathologically complete resection rate, LEMR was highest (100%), followed by surgical resection (85%). However, EMR only had 42% pathologically complete resection rate. Besides, LEMR and surgical resection had no local recurrence and significantly higher clinically complete resection rate, compared to other treatments. For the further prospective study, complete resection was noted in 28 (100%) patients in LEMR group and 13 (52%) patients in EMRC group., Conclusion: In the treatment of rectal carcinoid tumors, LEMR is safe and effective compared with traditional endoscopic treatments., (© 2021. The Author(s).)

Objectives: To explore the predictive value of preoperative imaging in patients with spinal giant cell tumor of bone (GCTB) for postoperative recurrence and risk stratification., Methods: Clinical data for 62 cases of spinal GCTB diagnosed and treated at our hospital from 2008 to 2018 were identified. All patients were followed up for more than 2 years according to the clinical guidelines after surgery. Medical history data including baseline demographic and clinical characteristics, computed tomography (CT) and magnetic resonance imaging (MRI) findings of recurrent and non-recurrent patients were compared. Two musculoskeletal radiologists read the images and were blinded to the clinical data. The imaging features associated with postoperative recurrence were analyzed by multivariate logistic regression, and receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff value of the largest lesion diameter predicting recurrence after surgery., Results: According to whether the disease recurred within the follow-up period, patients were divided into the recurrence group and the non-recurrence group. Of 62 patients (29 males and 33 females), 17 had recurrence and 45 did not. The recurrence rate was 27.4%. The mean follow-up time was 73.66 (± 32.92) months. The three major treatments were total en bloc spondylectomy (n = 26), intralesional spondylectomy (n = 20), and curettage(n = 16). A total of 16 CT and MRI features were analyzed. A univariate analysis showed no significant difference in age, sex, treatment, multi-vertebral body involvement, location, boundary, expansile mass, residual bone crest, paravertebral soft tissue mass, CT value, and MRI signal on T1-weighted imaging (WI), T2-WI, and T2-WI fat suppression (FS) sequences (P > 0.05). The largest lesion diameter [(4.68 ± 1.79) vs (5.92 ± 2.17) cm, t = 2.287, P = 0.026] and the vertebral compression fracture (51% vs 82%, χ 2  = 5.005, P = 0.025) were significantly different between the non-recurrence and recurrence groups. Logistic regression analysis showed that both largest lesion diameter (odds ratio [OR], 1.584; 95% confidence interval [CI], 1.108-2.264; P = 0.012) and compression fracture (OR, 8.073; 95%CI, 1.481-11.003; P = 0.016) were independent predictors of postoperative recurrence. When we set the cutoff value for the largest lesion diameter at 4.2 cm, the sensitivity and specificity for distinguishing the recurrence and non-recurrence of GCTB were 94.1% and 42.2%, respectively, and the area under the curve (AUC) was 0.671. The combined model achieved a sensitivity, specificity and accuracy of 47.1%, 97.8% and 83.9%, respectively., Conclusions: In spinal GCTB, maximum lesion diameter and the vertebral compression fracture are associated with tumor recurrence after surgery, which may provide helpful information for planning personalized treatment., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Objectives: To evaluate the performance of deep learning using ResNet50 in differentiation of benign and malignant vertebral fracture on CT., Methods: A dataset of 433 patients confirmed with 296 malignant and 137 benign fractures was retrospectively selected from our spinal CT image database. A senior radiologist performed visual reading to evaluate six imaging features, and three junior radiologists gave diagnostic prediction. A ROI was placed on the most abnormal vertebrae, and the smallest square bounding box was generated. The input channel into ResNet50 network was 3, including the slice with its two neighboring slices. The diagnostic performance was evaluated using 10-fold cross-validation. After obtaining the malignancy probability from all slices in a patient, the highest probability was assigned to that patient to give the final diagnosis, using the threshold of 0.5., Results: Visual features such as soft tissue mass and bone destruction were highly suggestive of malignancy; the presence of a transverse fracture line was highly suggestive of a benign fracture. The reading by three radiologists with 5, 3, and 1 year of experience achieved an accuracy of 99%, 95.2%, and 92.8%, respectively. In ResNet50 analysis, the per-slice diagnostic sensitivity, specificity, and accuracy were 0.90, 0.79, and 85%. When the slices were combined to ve per-patient diagnosis, the sensitivity, specificity, and accuracy were 0.95, 0.80, and 88%., Conclusion: Deep learning has become an important tool for the detection of fractures on CT. In this study, ResNet50 achieved good accuracy, which can be further improved with more cases and optimized methods for future clinical implementation., Key Points: • Deep learning using ResNet50 can yield a high accuracy for differential diagnosis of benign and malignant vertebral fracture on CT. • The per-slice diagnostic sensitivity, specificity, and accuracy were 0.90, 0.79, and 85% in deep learning using ResNet50 analysis. • The slices combined with per-patient diagnostic sensitivity, specificity, and accuracy were 0.95, 0.80, and 88% in deep learning using ResNet50 analysis., (© 2021. European Society of Radiology.)

This study investigated the antimicrobial resistance of isolates from patients with refractory Helicobacter pylori. The resistance rate was 34.1% for amoxicillin, 92.7% for clarithromycin, 65.9% for metronidazole, 85.4% for levofloxacin, and 29.3% for rifabutin. Dual resistance to both clarithromycin and levofloxacin was found in 73.2%. The antimicrobial resistance rate of refractory H. pylori was extremely high, which had become a major consideration in therapeutic challenge., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2021. Published by Elsevier B.V.)

Background and Aims: Patients with Meckel's diverticulum (MD) are difficult to preoperatively diagnose because of its endoscopic inaccessibility. Balloon-assisted enteroscopy (BAE) allows endoscopic access to the entire small intestine. The aim of the current study was to investigate patients with MD diagnosed by BAE in Taiwan., Methods: We conducted a retrospective, multicenter study of patients with MD who were diagnosed by BAE in Taiwan. The clinical characteristics, endoscopic features, histopathological findings, treatment methods, and outcomes were analyzed., Results: A total of 55 patients with MD were enrolled (46 males and 9 females). The mean age at diagnosis was 34.1 years. Overt gastrointestinal bleeding (87.3%) was the primary indication for BAE, followed by abdominal pain (9.1%), suspected small bowel tumor (1.8%), and Crohn's disease follow-up (1.8%). The mean distance between the ileocecal valve and MD was 71.6 cm (regarding diagnostic yields: BAE-100%, capsule endoscopy-40%, Meckel's scan-35.7%, computed tomography-14.6%, small bowel series-12.5%, and angiography-11.1%; regarding endoscopic features of MD: a large ostium-89.1%, a small ostium-7.3%, and a polypoid mass-3.6%). Surgical treatment was performed in 76.4% patients, and conservative treatment was performed in 23.6% patients. The mean length of MD in 42 patients who underwent surgical resection was 5.2 cm (in 43 patients of MD with available histopathology: heterotopic gastric tissue, 42.4%, heterotopic gastric and pancreatic tissues, 7%; heterotopic pancreatic tissue, 4.7%; heterotopic colonic tissue, 2.3%; and a neuroendocrine tumor, 2.3%)., Conclusions: The current study showed BAE is a very useful modality for detecting MD compared with other conventional modalities., Competing Interests: No conflicts of interest exist., (Copyright © 2021 Jen-Wei Chou et al.)

Objective: To build radiomics models using features extracted from DCE-MRI and mammography for diagnosis of breast cancer., Materials and Methods: 266 patients receiving MRI and mammography, who had well-enhanced lesions on MRI and histologically confirmed diagnosis were analyzed. Training dataset had 146 malignant and 56 benign, and testing dataset had 48 malignant and 18 benign lesions. Fuzzy-C-means clustering algorithm was used to segment the enhanced lesion on subtraction MRI maps. Two radiologists manually outlined the corresponding lesion on mammography by consensus, with the guidance of MRI maximum intensity projection. Features were extracted using PyRadiomics from three DCE-MRI parametric maps, and from the lesion and a 2-cm bandshell margin on mammography. The support vector machine (SVM) was applied for feature selection and model building, using 5 datasets: DCE-MRI, mammography lesion-ROI, mammography margin-ROI, mammography lesion+margin, and all combined., Results: In the training dataset evaluated using 10-fold cross-validation, the diagnostic accuracy of the individual model was 83.2% for DCE-MRI, 75.7% for mammography lesion, 64.4% for mammography margin, and 77.2% for lesion+margin. When all features were combined, the accuracy was improved to 89.6%. By adding mammography features to MRI, the specificity was significantly improved from 69.6% (39/56) to 82.1% (46/56), p<0.01. When the developed models were applied to the independent testing dataset, the accuracy was 78.8% for DCE-MRI and 83.3% for combined MRI+Mammography., Conclusion: The radiomics model built from the combined MRI and mammography has the potential to provide a machine learning-based diagnostic tool and decrease the false positive diagnosis of contrast-enhanced benign lesions on MRI., 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 Zhao, Chen, Zhang, Zhou, Chen, Lee, Combs, Parajuli, Mehta, Wang and Su.)

Objective: To compare the clinical efficacy of abdominal acupoint thread embedding therapy based on "brain-intestinal connection" combined with donepezil hydrochloride tablets and oral donepezil hydrochloride tablets alone for mild-to-moderate Alzheimer's disease (AD) and observe its effects on amyloid precursor protein (APP) and β-amyloid protein 1-42 (Aβ 1-42 )., Methods: Sixty patients with AD were randomly divided into an observation group (30 cases, 3 cases dropped off) and a control group (30 cases, 3 cases dropped off). The patients in the control group were treated with donepezil hydrochloride tablets (5 mg per day); based on the treatment in the control group, the patients in the observation group were treated with abdominal acupoint thread embedding therapy at Zhongwan (CV 12), Xiawan (CV 10), Huaroumen (ST 24), Wailing (ST 26), Daheng (SP 15), etc., once every 10 days. Both groups were treated for 2 months. The mini-mental state examination (MMSE), Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog), activity of daily living scale (ADL), neuropsychiatric inventory questionnaire (NPI) as well as the serum levels of APP and Aβ 1-42 were observed before and after treatment in the two groups., Results: After treatment, the MMSE scores in the two groups were higher than those before treatment ( P <0.05), and the ADAS-Cog, ADL and NPI scores were lower than those before treatment ( P <0.05). After treatment, the MMSE score in the observation group was higher than that in the control group ( P <0.05), and the ADAS-Cog, ADL and NPI scores were lower than those in the control group ( P <0.05). After treatment, the serum levels of APP and Aβ 1-42 were lower than those before treatment ( P <0.05), and the serum levels of APP and Aβ 1-42 in the observation group was lower than those in the control group ( P <0.05)., Conclusion: The abdominal acupoint thread embedding therapy based on the theory of "brain-intestinal connection" combined with donepezil hydrochloride tablets can improve cognitive function, self-care ability of daily life and mental behavior, and reduce the serum levels of APP and Aβ 1-42 in patients with mild-to-moderate AD, which have superior clinical effect to donepezil hydrochloride tablets alone.